bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB115: Simultaneous whole-body ultrasound contrast imaging: a novel high throughput preclinical platform for targeted molecular imaging studies
Authors: Natarajan Arutselvan , Tabesh Farbod , Hyun Dongwoon , Paulmurugan Ramasamy , Dahl Jeremy
Published: April 2023

Ultrasound contrast agent (UCA) based molecular imaging is a rapidly growing field in biomedical research. Ultrasound (US) is a non-radiative imaging modality that is frequently used to investigate various human diseases in the clinic. US molecular imaging is a novel imaging modality that utilizes targeted contrast agents to add molecular information about the imaging target, including vascular biomarkers of cancer. Pre-clinical animal models are commonly used to evaluate and validate targeted contrast agents before extending them for FDA-approval. Key impediments in the preclinical evaluations are the short in vivo half-life of microbubbles (MBs) (less than 30 minutes), limited transducer scanning area, and focusing one target at a time, which all make this strategy low throughput. Moreover, whole-body imaging strategy is not available for US imaging compared to other imaging modalities, such as PET, CT, and MRI. To overcome these imitations, we have developed a multi-mouse US imaging platform using an Automated Breast Volume Scanner (ABVS) system. In addition, we have synthesized a novel breast cancer vascular-specific B7-H3 targeted microbubbles (TMBs) using a microfluidic device. We tested these TMBs in a genetically engineered transgenic mice model [FVB/N-Tg (MMTV-PyMT)634Mul/J] (n=32) that develops breast cancer in the mammary fat pad. The US imaging results of conventional Vevo 2100 system indicated that B7-H3-TMBs could provide target specific contrast signals in the tumor vasculature compared to control MBs. We used this MBs for whole-body imaging using an ABVS system with two mice simultaneously in a stage. We imaged multiple tumors (10 tumors/mouse, 2 mice per scan, n=20 tumors) with a single bolus injection of TMBs per mouse. The results successfully showed tumor specific contrast signals from tumors independent of tumor size. Introduction of this whole-body scanner, and its ability to scan multiple mice simultaneously allows rapid imaging of multiple tumors with 3D quantification of tumor size by administering a single TMB injection enabling without significant contrast loss. Our approach makes this US-MI as high throughput and can be used to test multiple contrast agents for investigating different aspects of biological problems including screening of vascular biomarkers of human diseases.

Citation Format: Arutselvan Natarajan, Farbod Tabesh, Dongwoon Hyun, Ramasamy Paulmurugan, Jeremy Dahl. Simultaneous whole-body ultrasound contrast imaging: a novel high throughput preclinical platform for targeted molecular imaging studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB115.
Abstract LB119: Recurrence score for recurrence over survival outcome in the landmark TAILORx trial
Authors: Yang Sherry X. , Yu John , Wang Molin
Published: April 2023

Overall survival is the most relevant endpoint in clinical research and patient care. Nonetheless, cancer recurrence has been frequently utilized as a surrogate endpoint, particularly in the context of multi-gene assays and molecular signatures. The 21-gene recurrence score (RS) was originally established against distant recurrence for prognosis in breast cancer. However, it is unclear whether RS has a weight for the recurrence over survival prognosis. We investigated RS on the choice of clinical endpoints in the Trial Assigning Individualized Options for Treatment (TAILORx), which had OS, invasive disease-free survival (DFS), and recurrence-free interval (RFI) in addition to distant recurrence-free interval as the clinical endpoints. Both midrange (11-25) and high-range (26-100) scores were associated with RFI, high-range only with DFS, but not significantly associated with OS in the multivariable Cox proportional-hazards regression models. Of 462 death events, 33.1% (153 events) were ascribed to breast cancer and 91.8% (424) were due to DFS-related events that included 24.5% other cancers, 34.2% unknown and 33.1% breast cancer. It is DFS that was wound up as the most representative surrogate endpoint for survival. The lack of survival significance was probably due to the nature of 21-gene assay weighted for recurrence rather than not having enough event numbers in the TAILORx clinical trial. The data call for establishing biomarkers directly towards OS or DFS to increase survival with more precision.

Citation Format: Sherry X. Yang, John Yu, Molin Wang. Recurrence score for recurrence over survival outcome in the landmark TAILORx trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB119.
Abstract LB179: Automated viable circulating tumor cell (CTC) isolation enables efficient single-cell multi-omics analysis in a clinical setting
Authors: Dickerson Janet , Dufek Dylan , Huff Robbie , Jones Stephenie , Barber-Singh Jennifer , Brandt Christopher , Muller-Cohn Judy , Muller Rolf , Wang Yipeng
Published: April 2023

Circulating tumor cells (CTCs) are rare cells found in peripheral blood or other body fluids of cancer patients. Single-cell multi-omics analysis of CTCs can provide critical information and insights for tumor heterogeneity, early detection, residual disease, recurrence, and response and resistance to therapies. However, the adoption of single cell analysis in a clinical setting has been challenging due to complicated and lengthy workflows, lack of automation, low throughput, cell loss, inefficient cell picking, and nucleic acid degradation. To overcome these challenges, we have developed the fully automated LiquidScan liquid biopsy platform as a solution for CTC enrichment and single cell isolation. Whole blood samples were collected from breast, prostate, and lung cancer patients using BioFluidica blood collection tubes. CTCs were enriched with LiquidScan platform coupled with microfluidic affinity selection of rare cells with antibodies against cancer specific surface markers. Cell eluates released from microfluidic chips were further sorted and individual cells were placed into individual wells of PCR plates. The isolated single cells were processed with either whole genome amplification for DNA analysis or pre-amplification of RNA for transcriptome profiling. Cell viability and RNA integrity were assessed for enriched cells post LiquidScan processing. Whole blood samples were directly loaded to microfluidic chips and processed (capture, wash, release and elute) using Hamilton robot for automated processing with no require to red blood cell lysis. The sample processing time was approximately 3 hours with up to 8 samples processed simultaneously. Enriched cells were 70% viable on average post LiquidScan sample processing. The RNA RIN score for the enriched cells was 6 on average. Success rate of DNA amplifications and RNA pre-Amplifications were both over 90% across all samples processed.

The LiquidScan platform provides a solution for fast, automated single viable cell isolation making downstream molecular analysis possible in a clinical setting. Protocols for RNA pre-amplification and DNA sequencing including copy number analysis and targeted resequencing have been developed. Single cell DNA methylation and proteomics assay development is in progress.

Citation Format: Janet Dickerson, Dylan Dufek, Robbie Huff, Stephenie Jones, Jennifer Barber-Singh, Christopher Brandt, Judy Muller-Cohn, Rolf Muller, Yipeng Wang. Automated viable circulating tumor cell (CTC) isolation enables efficient single-cell multi-omics analysis in a clinical setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB179.
Abstract LB279: Targeting microglial metabolic rewiring synergizes with immune checkpoint blockade therapy for glioblastoma
Authors: Ye Zengpanpan , Ai Xiaolin , Zhao Linjie , Rich Jeremy N. , Zhou Shengtao
Published: April 2023

Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2 +/−) or microglia-specific Nr4a2 (Nr4a2 fl/fl Cx3cr1 cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacological NR4A2 inhibition attenuated the pro-tumorigenic TIME, and targeting the NR4A2 or SQLE enhanced therapeutic efficacy of immune checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer.

Citation Format: Zengpanpan Ye, Xiaolin Ai, Linjie Zhao, Jeremy N. Rich, Shengtao Zhou. Targeting microglial metabolic rewiring synergizes with immune checkpoint blockade therapy for glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB279.
Abstract LB301: Molecular pharmacology and broad synergy of the novel ATR inhibitor M1774 with DNA damaging anticancer agents
Authors: Jo Ukhyun , Arakawa Yasuhiro , Zimmermann Astrid , Taniyama Daiki , Mizunuma Makito , Jenkins Lisa M , Kumar Suresh , Zenke Frank T , Pommier Yves
Published: April 2023

Ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase orchestrates DNA damage response and repair pathways stimulated by replicative stresses. Recent studies have established that pharmacological inhibition of ATR is clinically promising. As M1774 is an oral ATR inhibitor in clinical development, we explored the molecular basis by which M1774 induces cancer cell death. As a single agent, we found that M1774 suppresses cancer cell viability at nanomolar concentrations with a potency higher than ceralasertib and berzosertib, but lower than gartisertib (M4344) and elimusertib in the small cell lung cancer (SCLC) cell lines H146, H82, and DMS114. We found that M1774 efficiently suppresses the ATR/CHK1 checkpoints. While M1774 alone induced apoptosis and G2/M cell cycle arrest at micromolar concentrations, at a non-toxic low dose, M1774 enhanced TOP1 inhibitor-mediated cancer cell death by preventing replication arrest and inducing DNA damage detected by EdU and γH2AX staining. Tandem mass tagging (TMT) coupled with mass spectrometry revealed that M1774 combined with SN-38 increases the expression of replication-related proteins (TIPIN, CDC45, TIMELESS, and RPA1) and G2/M-related proteins (PLK1 and CCNB1). To establish the synergistic combinations of M1774 with clinical anticancer DNA damaging agents in preclinical models, we performed experiments in cancer cell lines, patient-derived organoids, and xenograft models. Low doses of M1774 significantly synergized with the clinical TOP1 inhibitor SN-38, the TOP2 inhibitor etoposide, cisplatin, and the PARP inhibitor talazoparib in SCLC cell lines. We also found that M1774 significantly reversed chemoresistance to DNA-damaging agents in cancer cells lacking SLFN11 expression, suggesting that SLFN11 expression can be utilized for combination therapy with M1774 as a biomarker. The synergistic efficacy between M1774 and DNA-damaging agents was confirmed in SCLC patient-derived organoids, colon cancer patient-derived organoids, and H82 SCLC xenografts. Together, these results provide insights into the molecular mechanism and potential combination strategies for M1774 in cancer therapy.

Citation Format: Ukhyun Jo, Yasuhiro Arakawa, Astrid Zimmermann, Daiki Taniyama, Makito Mizunuma, Lisa M Jenkins, Suresh Kumar, Frank T Zenke, Yves Pommier. Molecular pharmacology and broad synergy of the novel ATR inhibitor M1774 with DNA damaging anticancer agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB301.
Abstract LB347: A lung-mimicking synthetic metastatic niche reveals N1 neutrophils drive breast cancer metastatic dormancy in the lungs
Authors: Wang Jing , Ocadiz-Ruiz Ramon , Hall Matthew , Bushnell Grace , Orbach Sophia , Decker Joseph , Raghani Ravi , Zhang Yining , Morris Aaron , Jeruss Jacqueline , Shea Lonnie
Published: April 2023

3D scaffolds mimicking the environment in the primary tumor or metastatic organs can deconstruct complex niche signals and facilitate the study of cancer progression and metastasis. Here, we reported that a subcutaneous 3D scaffold implant acted as a lung-mimicking dormant metastatic niche in mouse models of metastatic breast cancer, recruiting lung-tropic circulating tumor cells yet suppressing their growth through potent in situ antitumor immunity. We compared it with the immunosuppressive lungs developing lethal metastases and the dormant lungs suppressing tumor growth derived from breast cancer models with varying tumor aggressiveness and host immunity. Our data suggested that breast cancer-induced Gr1+CD11b+Ly6G+ granulocytic myeloid cells (neutrophils) infiltrated the scaffold implants and lungs, secreting the same signal to facilitate the metastatic seeding of lung-tropic cancer cells in these two types of niches. However, circulating neutrophils with opposing phenotypes and functions (N1 and N2) were selectively recruited and enriched in the dormant scaffolds/lungs and immunosuppressive lungs, respectively, responding to two distinct groups of chemoattractants. N1 or N2 neutrophils established activated or suppressive immune environments in the metastatic niches, directing different fates of cancer cells. The clinical relevance of these scientific findings was validated by the strong positive correlation of a high N1-to-N2 neutrophil chemoattractant ratio with a low-grade primary tumor, a low metastases incidence, and a better prognosis in breast cancer patients. Overall, our study revealed the multifaceted roles of neutrophils in regulating lung metastasis and underscored the importance of N1 neutrophils in driving breast cancer metastatic dormancy in the lungs, inspiring next-generation immunotherapy.

Citation Format: Jing Wang, Ramon Ocadiz-Ruiz, Matthew Hall, Grace Bushnell, Sophia Orbach, Joseph Decker, Ravi Raghani, Yining Zhang, Aaron Morris, Jacqueline Jeruss, Lonnie Shea. A lung-mimicking synthetic metastatic niche reveals N1 neutrophils drive breast cancer metastatic dormancy in the lungs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB347.
Abstract LB348: A controlled high fiber dietary intervention alters metabolome and gut microbiome in melanoma survivors
Authors: Jiang Yan
Published: April 2023

Background: Multiple studies support the gut microbiome as playing a key role in response to immune checkpoint blockade (ICB). Habitual dietary fiber intake has been associated with improved response to ICB. We conducted a pilot feasibility study of a high-fiber dietary intervention (HFDI) in melanoma survivors.

Methods: Melanoma survivors (BMI <40 kg/m2, currently not on active therapy) were enrolled to a 6-week controlled feeding study in which all meals were provided by MD Anderson Cancer Center Bionutrition Research Core. Target daily fiber intake was up to 50 g/day derived from whole foods. The primary outcome was compliance. Blood and stool were collected q 2 weeks. Whole genome shotgun sequencing (WGS) was performed on fecal specimens, and metabolomics was conducted using mass spectroscopy on blood and stool.

Results: Ten participants were enrolled, of which 60% were female. Average BMI was 31.4 kg/m2, and average baseline fiber intake was 17.8 g/day (range 7.4-28.3 g/day). Overall compliance was 88% (95% CI 83%-93%) with 45.8 g/day fiber reached (range 40.0-50.0 g/day). HFDI was well-tolerated with 1 participant experiencing grade 2 diarrhea and all other AEs were grade 1: diarrhea (40%), bloating (50%), flatulence (60%) and abdominal pain (10%). Exploratory analyses of global and targeted metabolomics showed increases in the short chain fatty acid acetate, shifts in omega-3/6 PUFAs, and indole/tryptophan metabolism. Stool WGS analyses showed that the largest shifts in gut microbiome structure in those who started with the lowest baseline fiber intake.

Conclusion: A HFDI is well-tolerated and feasible in a melanoma population. The expected shifts in metabolome and gut microbiome observed with HFDI support that participants were compliant. Thus, this intervention is currently being tested in a Phase II study in metastatic melanoma patients receiving ICB.

Citation Format: Yan Jiang. A controlled high fiber dietary intervention alters metabolome and gut microbiome in melanoma survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB348.
Data from Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047
Authors: Shiels Meredith S. , Lipkowitz Stanley , Campos Nicole G. , Schiffman Mark , Schiller John T. , Freedman Neal D. , de González Amy Berrington
Published: April 2023

Abstract
On February 2, 2022, President Biden and First Lady Dr. Biden reignited the Cancer Moonshot, setting a new goal to reduce age-standardized cancer mortality rates by at least 50% over the next 25 years in the United States. We estimated trends in U.S. cancer mortality during 2000 to 2019 for all cancers and the six leading types (lung, colorectum, pancreas, breast, prostate, liver). Cancer death rates overall declined by 1.4% per year from 2000 to 2015, accelerating to 2.3% per year during 2016 to 2019, driven by strong declines in lung cancer mortality (−4.7%/year, 2014 to 2019). Recent declines in colorectal (−2.0%/year, 2010–2019) and breast cancer death rates (−1.2%/year, 2013–2019) also contributed. However, trends for other cancer types were less promising. To achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. We reviewed opportunities to prevent, detect, and treat these common cancers that could further reduce population-level cancer death rates and also reduce disparities.
Significance:
We reviewed opportunities to prevent, detect, and treat common cancers, and show that to achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed.
Data from Hedgehog Signaling Regulates Treg to Th17 Conversion Through Metabolic Rewiring in Breast Cancer
Authors: Hinshaw Dominique C. , Benavides Gloria A. , Metge Brandon J. , Swain Courtney A. , Kammerud Sarah C. , Alsheikh Heba A. , Elhamamsy Amr , Chen Dongquan , Darley-Usmar Victor , Rathmell Jeffrey C. , Welner Robert S. , Samant Rajeev S. , Shevde Lalita A.
Published: April 2023

Abstract
The tumor immune microenvironment dynamically evolves to support tumor growth and progression. Immunosuppressive regulatory T cells (Treg) promote tumor growth and metastatic seeding in patients with breast cancer. Deregulation of plasticity between Treg and Th17 cells creates an immune regulatory framework that enables tumor progression. Here, we discovered a functional role for Hedgehog (Hh) signaling in promoting Treg differentiation and immunosuppressive activity, and when Hh activity was inhibited, Tregs adopted a Th17-like phenotype complemented by an enhanced inflammatory profile. Mechanistically, Hh signaling promoted O-GlcNAc modifications of critical Treg and Th17 transcription factors, Foxp3 and STAT3, respectively, that orchestrated this transition. Blocking Hh reprogramed Tregs metabolically, dampened their immunosuppressive activity, and supported their transdifferentiation into inflammatory Th17 cells that enhanced the recruitment of cytotoxic CD8+ T cells into tumors. Our results demonstrate a previously unknown role for Hh signaling in the regulation of Treg differentiation and activity and the switch between Tregs and Th17 cells in the tumor microenvironment.
Data from Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia
Authors: Kotini Andriana G. , Carcamo Saul , Cruz-Rodriguez Nataly , Olszewska Malgorzata , Wang Tiansu , Demircioglu Deniz , Chang Chan-Jung , Bernard Elsa , Chao Mark P. , Majeti Ravindra , Luo Hanzhi , Kharas Michael G. , Hasson Dan , Papapetrou Eirini P.
Published: April 2023

Abstract
The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.
Significance:
We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation.

See related commentary by Doulatov, p. 252.

This article is highlighted in the In This Issue feature, p. 247
Table S3 from IOA-244 is a Non–ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

Table showing the raw data of the AUC value of figure 2A
Figure S3 from IOA-244 is a Non–ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

Correlation analysis of PI3Kd levels and the response to IOA-244 and Idelalisib
Figure S1 from IOA-244 is a Non–ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance
Authors: Johnson Zoë , Tarantelli Chiara , Civanelli Elisa , Cascione Luciano , Spriano Filippo , Fraser Amy , Shah Pritom , Nomanbhoy Tyzoon , Napoli Sara , Rinaldi Andrea , Niewola-Staszkowska Karolina , Lahn Michael , Perrin Dominique , Wenes Mathias , Migliorini Denis , Bertoni Francesco , van der Veen Lars , Di Conza Giusy
Published: April 2023

IC50 curve of the ATP competitive assay and pie chart of the Kinativ assay
Carbon Stored on Seagrass Beds in Gili Maringkik, Lombok, Indonesia
Authors: Rahman Firman Ali , Qayim Ibnul , Wardiatno Yusli
Published: April 2023

Seagrass beds are an important vegetation for reducing the impact of global warming besides the function of forest and mangroves vegetation. The research aims to find the composition of seagrass species, density, seagrass coverage, seagrass standing biomass, seagrass standing carbon and substrate carbon. The research was conducted in Gili Maringkik, Lombok, Indonesia. The research included observation of species composition and the sample was collected from 0.5 ×0.5 m plot area. Total plot area was 25 on five lanes with the space between plots 25 m and between lanes 100 m. The researcher found that there were eight seagrass species (two families, six genera): Cymodocea rotundata, Cymodocea serrulata, Enhalus acoroides, Halodule pinifolia, Halophila minor, Halophila spinulosa, Syringodium isoetifolium and Thalassia hemprichii. Cymodocea rotundata (506.40±187.809 stand.m-2) was the species of highest density and while the species of Thalassia hemprichii (36.52±30.004 %) was the species of highest coverage. Total of seagrass standing biomass in Gili Maringkik was 1081.85 g.DW.m-2 with the carbon stock of seagrass beds was 483.86 g.C.m-2 and substrate carbon content was 0.09%–0.49%. the total carbon stock of seagrass beds in Gili Maringkik has 153.96 ton.C (4.84 ton.C.Ha-1).
Zadovoljstvo roditelja organizacijom dječje otorinolaringološke jednodnevne kirurgije u Dječjoj bolnici Srebrnjak
Authors: Igrec Marija , Šklebar Ivan
Published: April 2023

Uvod: Jednodnevna kirurgija podrazumijeva izvođenje terapijskog postupka i odlazak kući u istom danu. Takav je način liječenja idealan za djecu i roditelje jer su stres i strah od boravka u bolnici svedeni na minimum. Pružanje zdravstvene skrbi putem jednodnevne dječje kirurgije može uvelike povećati zadovoljstvo roditelja i percepciju kvalitete pruženih zdravstvenih usluga, a istovremeno racionalizirati troškove. Cilj: Cilj je istraživanja ispitati zadovoljstvo roditelja organizacijom rada na otorinolaringološkoj jednodnevnoj dječjoj kirurgiji te detektirati potencijalna područja za poboljšanje. Metode i ispitanici: Istraživanje je presječna prospektivna studija koja je provedena u Dječjoj bolnici Srebrnjak na otorinolaringološkoj jednodnevnoj dječjoj kirurgiji u razdoblju od 1. siječnja 2021. do 1. lipnja 2021. godine. Uzorak je činilo 100 ispitanika. Ispitanici su bili roditelji, skrbnici ili pratnja djeci koja su dolazila na operaciju u Dječju bolnicu Srebrnjak. Pristupalo im se na Odjelu otorinolaringološke jednodnevne dječje kirurgije prije otpusta kući sa zamolbom da ispune upitnik uz osiguranje dobrovoljnosti i anonimnosti. Za potrebe istraživanja koristio se validirani upitnik o zadovoljstvu pacijenata pruženom skrbi u dnevnoj bolnici pod nazivom Core questionnaire for the assessment of Patient Satisfaction – Day care (COPS-D). Upitnik je preveden na hrvatski jezik i modificiran za potrebe istraživanja. Rezultati: Rezultati su pokazali visoku razinu zadovoljstva u svim ispitanim domenama. U domenama prijeoperacijske pripreme, Odjela otorinolaringološke jednodnevne dječje kirurgije, operacijske sale i sestrinske skrbi zadovoljno je svih 100 ispitanika. Liječničkom skrbi zadovoljno je 98 ispitanika, informacijama 99 ispitanika, a 97 ispitanika iskazalo je zadovoljstvo na području autonomije. Cjelokupnom organizacijom rada zadovoljno je svih 100 ispitanika. Ispitanici su najmanju razinu zadovoljstva iskazali kod pitanja o privatnosti tijekom posjete i pregleda, pa je to potencijalno područje za poboljšanje rada otorinolaringološke jednodnevne dječje kirurgije. Zaključak: Na temelju dobivenih rezultata utvrđena je visoka razina zadovoljstva roditelja organizacijom rada otorinolaringološke jednodnevne dječje kirurgije. Ovakav model organizacije rada možemo preporučiti svim ustanovama i odjelima koji pružaju kirurško liječenje djeci.
First records of Perithous Holmgren (Hymenoptera: Ichneumonidae: Pimplinae) and Neoxorides Clément (Poemeniinae) from Mexico
Authors: KHALAIM ANDREY I. , RUÍZ-CANCINO ENRIQUE , CORONADO-BLANCO JUANA MARÍA
Published: April 2023

Two genera, Perithous Holmgren (Pimplinae) and Neoxorides Clément (Poemeniinae), are recorded for the first time from Mexico. Two species are described as new to science: Perithous escondidus Khalaim & Ruíz-Cancino, sp. nov. (Mexico: Nuevo León) and Neoxorides borderai Khalaim, sp. nov. (Mexico: Hidalgo). A brief review of the North American species of Perithous and Neoxorides is given, along with identification keys for North American taxa are provided.
A new species of Colpolopha Stål, 1873 (Orthoptera: Romaleidae) from Brazil
Authors: MARIÑO-PÉREZ RICARDO , POCCO MARTINA E.
Published: April 2023

Colpolopha minuta sp. nov. (Orthoptera: Romaleidae) is described from Floresta Nacional do Aripe near Crato in Ceará State, Brazil from 17 specimens collected by Moacyr Alvarenga deposited at the Insect Collection of the University of Michigan Museum of Zoology. This new species is characterized by its small size and brachypterous tegmina compared to other known Colpolopha species. A comparison with other short-winged Colpolopha species is provided. A discussion about some iNaturalist records is provided in order to help us identify possible new records or species in the region.
Specificity of fleas associated with opossums in a landscape gradient in the Paranaense Rainforest Ecoregion
Authors: URDAPILLETA MARA , LAMATTINA DANIELA , BURGOS ELIANA FLORENCIA , SALOMÓN OSCAR DANIEL , LARESCHI MARCELA
Published: April 2023

The degree of host specificity of fleas varies from highly specific (monoxenous) to opportunistic (polyxenous). Specific parasite-host associations can be observed among some flea families and tribes and mammalian orders, such as fleas of the tribe Tritopsyllini (Ctenophthalmidae, Doratopsyllinae) and opossums (Didelphimorphia). Specimens of the family Didelphidae are common hosts of fleas of the genus Adoratopsylla (Ewing, 1925). In northern Argentina, Adoratopsylla (Adoratopsylla) antiquorum antiquorum (Rothschild, 1904) and Adoratopsylla (Tritopsylla) intermedia intermedia (Wagner, 1901) were recorded preferentially parasitizing opossums. In order to study parasite/host relationships, fleas were collected from opossums captured in different environments in the Paranaense Rainforest ecoregion, northern Misiones province between 2016 and 2018. A total of 287 fleas were collected from 110 opossums. The fleas were identified as Pulicidae: Ctenocephalides felis felis (Bouché, 1835); Rhopalopsyllidae: Polygenis (Polygenis) rimatus (Jordan, 1932), Polygenis (Polygenis) roberti roberti (Rothschild, 1905); Ctenophthalmidae: A. (T.) i. intermedia, A. (A.) a. antiquorum, Adoratopsylla (Adoratopsylla) antiquorum ronnai (Guimarães, 1954). We report for the first time in Argentina a male specimen of A. (A.) a. ronnai collected on Didelphis albiventris (Lund, 1840) (Didelphidae), and male and female specimens of P. (P.) r. roberti collected on Didelphis aurita (Wied-Neuwied, 1826), and we describe the expansion of the geographic and host distribution of fleas to the Paranaense Rainforest ecoregion. Our records reinforce the specific association between Adoratopsylla and Polygenis fleas and didelphid opossums, mentioned in the literature for the Atlantic Forest ecoregion in Brazil. Furthermore, we observed that flea communities in opossums change in a landscape gradient, with invasive cat fleas and euryxenous fleas common in anthropized areas, and endemic fleas common in natural areas. Our results underline the importance for public health and veterinary medicine the analysis of flea circulation between wild and urban environments due to the risk of pathogen transmission.
Scaling Approaches to Quasigeostrophic Theory for Moist, Precipitating Air
Authors: Bäumer Daniel , Hittmeir Sabine , Klein Rupert
Published: April 2023

Quasigeostrophic (QG) theory is of fundamental importance in the study of large-scale atmospheric flows. In recent years, there has been growing interest in extending the classical QG plus Ekman friction layer model (QG–Ekman) to systematically include additional physical processes known to significantly contribute to real-life weather phenomena. This paper lays the foundation for combining two of these developments, namely, Smith and Stechmann’s family of precipitating quasigeostrophic (PQG) models on the one hand, and the extension of QG–Ekman for dry air by a strongly diabatic layer (DL) of intermediate height (QG–DL–Ekman) on the other hand. To this end, Smith and Stechmann’s PQG equations for soundproof motions are first corroborated within a general asymptotic modeling framework starting from a full compressible flow model. The derivations show that the PQG model family is naturally embedded in the asymptotic hierarchy of scale-dependent atmospheric flow models introduced by one of the present authors. Particular emphasis is then placed on an asymptotic scaling regime for PQG that accounts for a generic Kessler-type bulk microphysics closure and is compatible with QG–DL–Ekman theory. The detailed derivation of a moist QG–DL–Ekman model is deferred to a future publication.
Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post–CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey
Authors: van Doesum Jaap A. , Salmanton-García Jon , Marchesi Francesco , Di Blasi Roberta , Falces-Romero Iker , Cabirta Alba , Farina Francesca , Besson Caroline , Weinbergerová Barbora , Van Praet Jens , Schönlein Martin , López-García Alberto , Lamure Sylvain , Guidetti Anna , De Ramón-Sánchez Cristina , Batinić Josip , Gavriilaki Eleni , Tragiannidis Athanasios , Tisi Maria Chiara , Plantefeve Gaëtan , Petzer Verena , Ormazabal-Vélez Irati , Marques de Almeida Joyce , Marchetti Monia , Maertens Johan , Machado Marina , Kulasekararaj Austin , Hernández-Rivas José-Ángel , Gomes da Silva Maria , Fernández Noemí , Espigado Ildefonso , Drgoňa Ľuboš , Dragonetti Giulia , Metafuni Elisabetta , Calbacho Maria , Blennow Ola , Wolf Dominik , van Anrooij Bjorn , Nunes Rodrigues Raquel , Nordlander Anna , Martín-González Juan-Alberto , Liévin Raphaël , Jiménez Moraima , Gräfe Stefanie K. , García-Sanz Ramón , Córdoba Raúl , Rahimli Laman , van Meerten Tom , Cornely Oliver A. , Pagano Livio
Published: April 2023

Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.
T-RHEX-RNAseq – a tagmentation-based, rRNA blocked, random hexamer primed RNAseq method for generating stranded RNAseq libraries directly from very low numbers of lysed cells
Authors: Gustafsson Charlotte , Hauenstein Julia , Frengen Nicolai , Krstic Aleksandra , Luc Sidinh , Månsson Robert
Published: April 2023

Background

RNA sequencing has become the mainstay for studies of gene expression. Still, analysis of rare cells with random hexamer priming – to allow analysis of a broader range of transcripts – remains challenging.

Results

We here describe a tagmentation-based, rRNA blocked, random hexamer primed RNAseq approach (T-RHEX-RNAseq) for generating stranded RNAseq libraries from very low numbers of FACS sorted cells without RNA purification steps.

Conclusion

T-RHEX-RNAseq provides an easy-to-use, time efficient and automation compatible method for generating stranded RNAseq libraries from rare cells.
BSA modification of bacterial surface: a promising anti-cancer therapeutic strategy
Authors: He Zhongming , Chen Kun , An Yu , He Jie , Zhang Xiaoli , Tang Lannan , Sun Fa , Jiang Kehua
Published: April 2023

Background

Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics.

Methods and objective

Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated.

Results

BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines.

Conclusion

BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.
Graphical analysis of multi-environmental trials for wheat grain yield based on GGE-biplot analysis under diverse sowing dates
Authors: Saeidnia Fatemeh , Taherian Majid , Nazeri Seyed Mahmoud
Published: April 2023

Background

Information on the nature and extent of genetic and genotype × environment (GE) interaction is extremely rare in wheat varieties under different sowing dates. In the present study, the GGE biplot method was conducted to investigate genotype × environment interaction effects and evaluate the adaptability and yield stability of 13 wheat varieties across eight sowing dates, in order to facilitate comparison among varieties and sowing dates and identify suitable varieties for the future breeding studies.

Results

Considerable genotypic variation was observed among genotypes for all of the evaluated traits, demonstrating that selection for these traits would be successful. Low broad sense heritability obtained for grain yield showed that, both genetic and non-genetic gene actions played a role in the control of this trait, and suggested that indirect selection based on its components which had high heritability and high correlation with yield, would be more effective to improve grain yield in this germplasm. Hence, selection based on an index may be more useful for improvement of this trait in recurrent selection programs. The results of the stability analysis showed that the environmental effect was a major source of variation, which captured 72.21% of total variation, whereas G and GE explained 6.94% and 18.33%, respectively. The partitioning of GGE through GGE biplot analysis showed that, the first two PCs accounted for 54.64% and 35.15% of the GGE sum of squares respectively, capturing a total of 89.79% variation. According to the GGE biplot, among the studied varieties, the performance of Gascogen was the least stable, whereas Sirvan, Roshan, and Pishtaz had superior performance under all sowing dates, suggesting that they have a broad adaptation to the diverse sowing dates. These varieties may be recommended for genetic improvement of wheat with a high degree of adaptation.

Conclusion

The results obtained in this study demonstrated the efficiency of the GGE biplot technique for selecting high yielding and stable varieties across sowing dates.
The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol
Authors: Bregman Noa , Shiner Tamara , Kavé Gitit , Alcalay Roy , Gana-Weisz Mali , Goldstein Orly , Glinka Tal , Aizenstein Orna , Bashat Dafna Ben , Alcalay Yifat , Mirelman Anat , Thaler Avner , Giladi Nir , Omer Nurit
Published: April 2023

Background

Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.

Methods

The study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an “in-depth” visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a “brief” visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one “in-depth” visit, similar to the baseline visit of healthy relatives.

Discussion

This continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions.

Trial registration

The study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.
Symptom management care pathway adaptation process and specific adaptation decisions
Authors: Vettese Emily , Sherani Farha , King Allison A. , Yu Lolie , Aftandilian Catherine , Baggott Christina , Agarwal Vibhuti , Nagasubramanian Ramamoorthy , Kelly Kara M. , Freyer David R. , Orgel Etan , Bradfield Scott M. , Kyono Wade , Roth Michael , Klesges Lisa M. , Beauchemin Melissa , Grimes Allison , Tomlinson George , Dupuis L. Lee , Sung Lillian
Published: April 2023

Background

There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions.

Methods

Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications.

Results

Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection.

Conclusions

Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes.

Trial registration

clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1.