bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Dual targeting of apoptotic and signaling pathways in T-lineage acute lymphoblastic leukemia
Authors: Saygin Caner , Giordano Giorgia , Shimamoto Kathryn , Eisfelder Bart , Thomas-Toth Anika , Venkataraman Girish , Ananthanarayanan Vijayalakshmi , Vincent Tiffaney L. , DuVall Adam , Patel Anand A. , Chen Yi , Tan Fenlai , Anthony Stephen P. , Chen Yu , Shen Yue , Odenike Olatoyosi , Teachey David T. , Kee Barbara L. , LaBelle James , Stock Wendy
Published: July 2023

Abstract
Purpose: Relapsed T-acute lymphoblastic leukemia (T-ALL) has limited treatment options. We investigated mechanisms of resistance to BH3 mimetics in T-ALL in order to develop rational combination strategies. We also looked at the preclinical efficacy of NWP-0476, a novel BCL-2/BCL-xL inhibitor, as single agent and combination therapy in T-ALL. Methods: We used BH3 profiling as a predictive tool for BH3 mimetic response in T-ALL. Using isogenic control, venetoclax-resistant (ven-R) and NWP-0476-resistant (NWP-R) cells, phosphokinase array was performed to identify differentially regulated signaling pathways. Results: Typical T-ALL cells had increased dependence on BCL-xL, while early T-precursor (ETP)-ALL cells had higher BCL-2 dependence for survival. BCL-2/BCL-xL dual inhibitors were effective against both subtypes of T-lineage ALL. A 71-protein human phosphokinase array showed increased LCK activity in ven-R cells, and increased ACK1 activity in ven-R and NWP-R cells. We hypothesized that pre-TCR and ACK1 signaling pathways are drivers of resistance to BCL-2 and BCL-xL inhibition, respectively. First, we silenced LCK gene in T-ALL cell lines, which resulted in increased sensitivity to BCL-2 inhibition. Mechanistically, LCK activated NF-κB pathway and the expression of BCL-xL. Silencing ACK1 gene resulted in increased sensitivity to both BCL-2 and BCL-xL inhibitors. ACK1 signaling up-regulated AKT pathway, which inhibited the pro-apoptotic function of BAD. In a T-ALL patient-derived xenograft model, combination of NWP-0476 and dasatinib demonstrated synergy without major organ toxicity. Conclusions:LCK and ACK1 signaling pathways are critical regulators of BH3 mimetic resistance in T-ALL. Combination of BH3 mimetics with tyrosine kinase inhibitors might be effective against relapsed T-ALL.
Data from Associations between AI-assisted tumor amphiregulin and epiregulin IHC and outcomes from anti-EGFR therapy in the routine management of metastatic colorectal cancer
Authors: Williams Christopher J.M. , Elliott Faye , Sapanara Nancy , Aghaei Faranak , Zhang Liping , Muranyi Andrea , Yan Dongyao , Bai Isaac , Zhao Zuo , Shires Michael , Wood Henry M. , Richman Susan D. , Hemmings Gemma , Hale Michael , Bottomley Daniel , Galvin Leanne , Cartlidge Caroline , Dance Sarah , Bacon Chris M. , Mansfield Laura , Young-Zvandasara Kathe , Sudan Ajay , Lambert Katy , Bibby Irena , Coupland Sarah E. , Montazeri Amir , Kipling Natalie , Hughes Kathryn , Cross Simon S. , Dewdney Alice , Pheasey Leanne , Leng Cathryn , Gochera Tatenda , Mangham D Chas , Saunders Mark , Pritchard Martin , Stott Helen , Mukherjee Abhik , Ilyas Mohammad , Silverman Rafael , Hyland Georgina , Sculthorpe Declan , Thornton Kirsty , Gould Imogen , O'Callaghan Ann , Brown Nicholas , Turnbull Samantha , Shaw Lisa , Seymour Matthew T. , West Nicholas P. , Seligmann Jenny F. , Singh Shalini , Shanmugam Kandavel , Quirke Philip
Published: July 2023

Abstract
Purpose: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG immunohistochemistry (IHC) was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. Experimental Design: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival FFPE tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: 494 of 541 patients (91.3%) had adequate tissue for analysis. 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n=360; 80.2%) was associated with significantly prolonged PFS (median: 8.5 vs 4.4 months; HR 0.73; 95% CI, 0.56-0.95; p=0.02) and OS (median: 16.4 vs 8.9 months; HR 0.66 [0.50-0.86]; p=0.002). The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection. Conclusions: High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice.
Data from B-cell receptor pathway mutations are infrequent in patients with chronic lymphocytic leukemia on continuous ibrutinib therapy
Authors: Woyach Jennifer A. , Ghia Paolo , Byrd John C. , Ahn Inhye E. , Moreno Carol , O'Brien Susan M. , Jones Daniel , Cheung Leo W.K. , Chong Elizabeth , Kwei Kevin , Dean James P. , James Danelle F. , Wiestner Adrian
Published: July 2023

Abstract
Purpose: Acquired mutations in Bruton’s tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited. Experimental Design: We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients (n=238) or relapsed/refractory (n=150) CLL across 5 clinical trials. Results: With median follow-up of 35 months (range, 0-72) without PD at last sampling, mutations in BTK (3%), PLCG2 (2%) or both genes (1%) were rare in previously untreated patients. With median follow-up of 35 months (range, 1-70) without PD at last sample, mutations in BTK (30%), PLCG2 (7%), or both genes (5%) were more common in patients with relapsed/refractory CLL. Median time to first detection of BTK C481S mutation was not reached in previously untreated patients and was >5 years in patients with relapsed/refractory CLL. Among patients evaluable at PD, previously untreated patients (n=12) had lower rates than those with relapsed/refractory disease (n=45) of BTK (25% vs 49%) and PLCG2 mutations (8% vs 13%). Time from first detection of BTK C481S mutation to PD was 11.3 months in 1 previously untreated patient and median 8.5 months (range, 0-35.7) among 23 patients with relapsed/refractory CLL. Conclusions: This systematic investigation describes development of mutations over time in patients without PD and informs the potential clinical opportunity to optimize ongoing benefits for such patients.
Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages
Authors: Yuan Wei , Zhang Qian , Gu Danling , Lu Chenfei , Dixit Deobrat , Gimple Ryan C. , Gao Yisu , Gao Jiancheng , Li Daqi , Shan Danyang , Hu Lang , Li Lu , Li Yangqing , Ci Shusheng , You Hao , Yan Linping , Chen Kexin , Zhao Ningwei , Xu Chuanhai , Lan Jianyun , Liu Dong , Zhang Junxia , Shi Zhumei , Wu Qiulian , Yang Kailin , Zhao Linjie , Qiu Zhixin , Lv Deguan , Gao Wei , Yang Hui , Lin Fan , Wang Qianghu , Man Jianghong , Li Chaojun , Tao Weiwei , Agnihotri Sameer , Qian Xu , Mack Stephen C. , Zhang Nu , You Yongping , Rich Jeremy N. , Sun Guan , Wang Xiuxing
Published: July 2023

Purpose:

The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state.

Experimental Design:

We performed an integrative multi-omics analyses of RNA sequencing, GBM mRNA expression datasets, immune signatures, and epigenetic profiling to define the specific genes expressed in the mesenchymal GSC subsets. We then used patient-derived GSCs and a xenograft murine model to investigate the mechanisms of tumor-intrinsic and extrinsic factor to maintain the mesenchymal state of GSCs and induce TAM polarization.

Results:

We identified that CXCL8 was preferentially expressed and secreted by mesenchymal GSCs and activated PI3K/AKT and NF-κB signaling to maintain GSC proliferation, survival, and self-renewal through a cell-intrinsic mechanism. CXCL8 induced signaling through a CXCR2–JAK2/STAT3 axis in TAMs, which supported an M2-like TAM phenotype through a paracrine, cell-extrinsic pathway. Genetic- and small molecule–based inhibition of these dual complementary signaling cascades in GSCs and TAMs suppressed GBM tumor growth and prolonged survival of orthotopic xenograft-bearing mice.

Conclusions:

CXCL8 plays critical roles in maintaining the mesenchymal state of GSCs and M2-like TAM polarization in GBM, highlighting an interplay between cell-autonomous and cell-extrinsic mechanisms. Targeting CXCL8 and its downstream effectors may effectively improve GBM treatment.
Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: July 2023

Purpose:

Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI.

Experimental Design:

In two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3′ RNA sequencing was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed.

Results:

In the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A (“stromalHIGH-proliferationLOW”), cluster B (“stromalHIGH-proliferationMED”), and cluster C (“stromalLOW-proliferationHIGH”), with an enrichment of patients progressing at first disease assessment under ICI in cluster A (30% vs. 12% in cluster B and 8.1% in cluster C; P = 0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared with clusters B or C (P < 0.001) with 2-year PFS rates of 33.5%, 80.5%, and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08–0.45; P < 0.001] and cluster C (HR, 0.25; 95% CI, 0.10–0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non–ICI-based regimens was not significantly different according to cluster.

Conclusions:

This unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The “stromalHIGH-proliferationLOW” cluster is associated with a poorer prognosis with ICI treatment.
Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W.
Published: July 2023

Purpose:

Clinical evidence indicates that treatment with estrogens elicits anticancer effects in ∼30% of patients with advanced endocrine-resistant estrogen receptor α (ER)-positive breast cancer. Despite the proven efficacy of estrogen therapy, its mechanism of action is unclear and this treatment remains underused. Mechanistic understanding may offer strategies to enhance therapeutic efficacy.

Experimental Design:

We performed genome-wide CRISPR/Cas9 screening and transcriptomic profiling in long-term estrogen-deprived ER+ breast cancer cells to identify pathways required for therapeutic response to the estrogen 17β-estradiol (E2). We validated findings in cell lines, patient-derived xenografts (PDX), and patient samples, and developed a novel combination treatment through testing in cell lines and PDX models.

Results:

Cells treated with E2 exhibited replication-dependent markers of DNA damage and the DNA damage response prior to apoptosis. Such DNA damage was partially driven by the formation of DNA:RNA hybrids (R-loops). Pharmacologic suppression of the DNA damage response via PARP inhibition with olaparib enhanced E2-induced DNA damage. PARP inhibition synergized with E2 to suppress growth and prevent tumor recurrence in BRCA1/2-mutant and BRCA1/2-wild-type cell line and PDX models.

Conclusions:

E2-induced ER activity drives DNA damage and growth inhibition in endocrine-resistant breast cancer cells. Inhibition of the DNA damage response using drugs such as PARP inhibitors can enhance therapeutic response to E2. These findings warrant clinical exploration of the combination of E2 with DNA damage response inhibitors in advanced ER+ breast cancer, and suggest that PARP inhibitors may synergize with therapeutics that exacerbate transcriptional stress.
Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction
Authors: Salari Keyan , Sundi Debasish , Lee Jason J. , Wu Shulin , Wu Chin-Lee , DiFiore Gabrielle , Yan Q. Robert , Pienkny Andrew , Lee Chi K. , Oberlin Daniel , Barme Greg , Piser Joel , Kahn Robert , Collins Edward , Phillips Kevin G. , Caruso Vincent M. , Goudarzi Mahdi , Garcia-Ransom Monica , Lentz Peter S. , Evans-Holm Martha E. , MacBride Andrew R. , Fischer Daniel S. , Haddadzadeh Iden J. , Mazzarella Brian C. , Gray Joe W. , Koppie Theresa M. , Bicocca Vincent T. , Levin Trevor G. , Lotan Yair , Feldman Adam S.
Published: July 2023

Purpose:

Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk.

Experimental Design:

This is a multicenter case–control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology.

Results:

uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%.

Conclusions:

uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.
Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial
Authors: Fleshner Neil E. , Sayyid Rashid K. , Hansen Aaron R. , Chin Joseph L.K. , Fernandes Ricardo , Winquist Eric , van der Kwast Theodorus , Sweet Joan , Lajkosz Katherine , Kenk Miran , Hersey Karen , Veloso Rosette , Berlin Doron , Herrera-Caceres Jaime O. , Sridhar Srikala , Moussa Madeleine , Finelli Antonio , Hamilton Robert J. , Kulkarni Girish S. , Zlotta Alexandre R. , Joshua Anthony M.
Published: July 2023

Purpose:

Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer.

Patients and Methods:

This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile.

Results:

The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0–68.0] and 21.9 ng/mL (IQR, 14.6–42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078).

Conclusions:

Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.
Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: July 2023

As a result of tumor heterogeneity and solid cancers harboring multiple molecular defects, precision medicine platforms in oncology are most effective when both genetic and pharmacologic determinants of a tumor are evaluated. Expandable patient-derived xenograft (PDX) mouse tumor and corresponding PDX culture (PDXC) models recapitulate many of the biological and genetic characteristics of the original patient tumor, allowing for a comprehensive pharmacogenomic analysis. Here, the somatic mutations of 23 matched patient tumor and PDX samples encompassing four cancers were first evaluated using next-generation sequencing (NGS). 19 antitumor agents were evaluated across 78 patient-derived tumor cultures using clinically relevant drug exposures. A binarization threshold sensitivity classification determined in culture (PDXC) was used to identify tumors that best respond to drug in vivo (PDX). Using this sensitivity classification, logic models of DNA mutations were developed for 19 antitumor agents to predict drug response. We determined that the concordance of somatic mutations across patient and corresponding PDX samples increased as variant allele frequency increased. Notable individual PDXC responses to specific drugs, as well as lineage-specific drug responses were identified. Robust responses identified in PDXC were recapitulated in vivo in PDX-bearing mice and logic modeling determined somatic gene mutation(s) defining response to specific antitumor agents. In conclusion, combining NGS of primary patient tumors, high-throughput drug screen using clinically relevant doses, and logic modeling, can provide a platform for understanding response to therapeutic drugs targeting cancer.
Data from Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study
Authors: Koyama Takafumi , Shimizu Toshio , Kojima Yuki , Sudo Kazuki , Okuma Hitomi Sumiyoshi , Shimoi Tatsunori , Ichikawa Hitoshi , Kohsaka Shinji , Sadachi Ryo , Hirakawa Akihiro , Yoshida Akihiko , Ando Reiko Makihara , Ueno Toshihide , Yanagaki Mitsuru , Matsui Naoko , Nakamura Kenichi , Yamamoto Noboru , Yonemori Kan
Published: July 2023

Abstract
Intimal sarcoma is an extremely rare, life-threatening malignant neoplasm. Murine double minute 2 (MDM2) amplification is observed in >70% of intimal sarcomas. Milademetan, an MDM2 inhibitor, may provide clinical benefit in this patient population. We conducted a phase Ib/II study in patients with MDM2-amplified, wild-type TP53 intimal sarcoma as a substudy of a large nationwide registry for rare cancers in Japan. Milademetan (260 mg) was administered orally once daily for 3 days every 14 days, twice in a 28-day cycle. Of 11 patients enrolled, 10 were included in the efficacy analysis. Two patients (20%) showed durable responses for >15 months. Antitumor activity correlated with TWIST1 amplification (P = 0.028) and negatively with CDKN2A loss (P = 0.071). Acquired TP53 mutations were detected in sequential liquid biopsies as a novel exploratory resistance mechanism to milademetan. These results suggest that milademetan could be a potential therapeutic strategy for intimal sarcoma.
Significance:
Strategies to optimize outcomes could include the use of new biomarkers (TWIST1 amplification and CDKN2A loss) to select patients with MDM2-amplified intimal sarcoma who might benefit from milademetan and combination with other targeted treatments. Sequential liquid biopsy of TP53 can be used to evaluate disease status during treatment with milademetan.
Activation of the Complement and Coagulation Systems in the Small Airways in Asthma
Authors: Kokelj Spela , Östling Jörgen , Fromell Karin , Vanfleteren Lowie E.G.W. , Olsson Henric K. , Nilsson Ekdahl Kristina , Nilsson Bo , Olin Anna-Carin
Published: July 2023

Background: Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma. Objectives: We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control. Method: Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry. Results: 53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways. Conclusions: The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.
The Modernization of the Energy Charter Treaty: Dead in the Water?
Authors: Roiger-Simek Koloman
Published: July 2023

The Agreement in Principle of the Modernisation of the Energy Charter Treaty succeeded in adjusting many of the ECT’s provisions to cover developments in international investment law in the 28 years since the ECT’s conclusion, particularly specifying the scope of standards of protection. The modernization has also addressed other global and regional issues such as climate change and the importance of transitioning from fossil fuels to renewable sources of energy, and criticism of arbitral tribunals for intra-EU disputes respectively. Despite these results, criticism of the ECT had not abated but instead led to several EU member states declaring their intention to withdraw and it is questionable whether the Agreement in Principle will be accepted at all considering that investments in fossil fuels will continue to be protected in most state parties.
Viability and fertility of cryopreserved pollen of Brinjal and its wild relatives
Authors: Rajasekharan P.E. , Ravi Harsha
Published: July 2023

The Solanum wild relatives are valuable for developing pest and disease-resistant lines in the breeding program of S. melongena (brinjal). However, breeding new varieties that are superior to the existing ones in S. melongena faces several challenges. To overcome geographical and seasonal barriers, a breeding strategy involving pollen cryopreservation may be helpful. Fifteen different Solanum species/accessions of wild relatives and two accessions from cultivated species were studied for in vitro germination and fertility. Among these S. indicum accessions exhibited the highest fresh pollen germination of 92.7 ± 0.7 (JRPH/15–154) and 88.2 ± 3.2% after 1 year and 4 months of cryostorage. In vivo fertility was estimated by quantifying fruit set after pollination with both fresh and cryopreserved pollen. The cryopreserved pollen was able to set fruit (91.5 ± 0.5 in JRPH/15–154) compared to fresh pollen (100%). Scanning Electron Microscopic studies (SEM) were conducted on both fresh and cryopreserved pollen, and various morphological parameters such as pollen length, breadth, and perimeter were recorded for all the accessions and species. These studies explore the possibility of establishing a pollen cryobank for Solanum wild species.
Chimairacoris flavipes sp. nov., (Hemiptera, Heteroptera, Miridae, Phylinae) from New Caledonia
Authors: TASZAKOWSKI ARTUR , MASŁOWSKI ADRIAN , CASSIS GERASIMOS
Published: July 2023

A new species, Chimairacoris flavipes Taszakowski & Cassis sp. nov. (Hemiptera, Heteroptera, Miridae, Phylinae), is described from New Caledonia. Habitus and SEM images of the female and necessary morphological structures are presented. The structure of the female genitalia is also shown in detail. An identification key and distributional map of known Chimairacoris species are provided.
Unsupervised Clustering of Geostationary Satellite Cloud Properties for Estimating Precipitation Probabilities of Tropical Convective Clouds
Authors: Kim Doyi , Kim Hee-Jae , Choi Yong-Sang
Published: July 2023

Understanding the growth of tropical convective clouds (TCCs) is of vital importance for the early detection of heavy rainfall. This study explores the properties of TCCs that can cause them to develop into clouds with a high probability of precipitation. Remotely sensed cloud properties, such as cloud-top temperature (CTT), cloud optical thickness (COT), and cloud effective radius (CER) as measured by a geostationary satellite are trained by a neural network. First, the image segmentation algorithm identifies TCC objects with different cloud properties. Second, a self-organizing map (SOM) algorithm clusters TCC objects with similar cloud microphysical properties. Third, the precipitation probability (PP) for each cluster of TCCs is calculated based on the proportion of precipitating TCCs among the total number of TCCs. Precipitating TCCs can be distinguished from nonprecipitating TCCs using Integrated Multi-Satellite Retrievals for Global Precipitation Measurement precipitation data. Results show that SOM clusters with a high PP (>70%) satisfy a certain range of cloud properties: CER ≥ 20 μm and CTT < 230 K. PP generally increases with increasing COT, but COT cannot be a clear cloud property to confirm a high PP. For relatively thin clouds (COT < 30), however, CER should be much larger than 20 μm to have a high PP. More importantly, these TCC conditions associated with a PP ≥ 70% are consistent across regions and periods. We expect our results will be useful for satellite nowcasting of tropical precipitation using geostationary satellite cloud properties.

Significance Statement

We aim to identify the properties of tropical convective clouds (TCCs) that have a high precipitation probability. We designed a two-step framework to identify TCC objects and the conditions of cloud properties for TCCs to have a high precipitation probability. The TCCs with a precipitation probability > 70% tend to have a low cloud-top temperature and a cloud particle effective radius ≥ 20 μm. Cloud optical thicknesses are distributed over a wide range, but thinning requires a particle radius larger than 20 μm. These conditions of cloud properties appear to be unchanged under various spatial–temporal conditions over the tropics. This important observational finding advances our understanding of the cloud–precipitation relationship in TCCs and can be applied to satellite nowcasting of precipitation in the tropics, where numerical weather forecasts are limited.
Temporal Error Monitoring Does Not Depend on Working Memory
Authors: Öztel Tutku , Balci Fuat
Published: July 2023

Working memory (WM) and metacognition has been documented to be in a reciprocal relationship. This study aims to address if temporal error monitoring performance can be diminished with increased working memory load. We hypothesized that if temporal error monitoring has commonalities with perceptual error monitoring, temporal error monitoring performance should be diminished by increased working memory load. Participants completed a temporal error monitoring task in a dual task design in which the secondary task was a letter alphabetization task. Results revealed no disrupting effect of WM load on either confidence or short-long judgments as being different metrics of temporal error monitoring ability. These results demonstrate that unlike perceptual error monitoring, WM and temporal error monitoring have distinct processing mechanisms. With this result, the current study suggests that temporal and perceptual error monitoring may partially rely on different mechanisms. Results are discussed within A Theory of Magnitude (ATOM), pacemaker-accumulator model and temporal error monitoring frameworks.
John Robinson and primitive Christian eschatology: contexts and comparisons then and now
Authors: Laird Stephen
Published: July 2023

This article explores Bishop John Robinson’s approaches to New Testament eschatology in the 1950s and documents some scholars’ parallels and responses.
Study on the effect of structural parameters of the convergence flow conditioner on eccentric jet flow rectification
Authors: Liu Qi , Chen Hang-bo , Tian Shuai , Lin Zhe
Published: July 2023

In flow measurement and control industrial application, installing a flow conditioner is an effective way to rectify irregular and unstable flow to stable flow state within a short flow distance. To effectively rectify the eccentric jet flow caused by valve regulation in pipeline, the convergence flow conditioner with convergent orifice angles has been innovatively designed and investigated. However, the effect of structural parameters (such as flow conditioner thickness and flow area) on improving unstable eccentric jet flow rectification was still not elaborated. Thus, the effect of structural parameters of the convergence flow conditioner on rectifying eccentric jet flow was examined in this paper. The structural parameters of the flow conditioner thickness and the flow area were considered under the fixed convergence angle of 12°. The experimental system of monitoring pressures upstream and downstream of the convergence flow conditioner along the pipeline was developed and corresponding numerical simulation was employed. The flow coefficient and resistance coefficient of a convergence flow conditioner under various valve openings were accessed, and monitored pressures along the pipeline were also discussed for numerical simulation verification. The velocity and streamline distributions downstream the convergence flow conditioners were comparatively analyzed. In addition, the axial velocities on various downstream cross-sections were extracted to evaluate the velocity uniformity. A dimensionless parameter of velocity deviation ratio was introduced to quantify the rectification effect of eccentric jet flow evolving in the downstream pipeline. Results showed that the convergence flow conditioner with the thickness of 6 mm and the flow area of 50% owned a better effect on rectifying the valve-induced eccentric jet flow, that is, a shorter flow length was required for changing the valve-induced eccentric unstable flow to uniform stable flow by installing a convergence flow conditioner with above structural parameters.
Capacity building and professional development in contemporary music careers: An Australian contemporary music case study
Authors: Ballico Christina , Foran Sean
Published: July 2023

This paper examines capacity building and professional development in Western Australia’s contemporary popular music sector. It reports on a mixed-methods qualitative-quantitative study into the lived experiences and needs of musicians and industry practitioners alike. It examines learning which is undertaken outside of formal education settings, and includes conferencing, one-on-one mentorship and other workshop based modes of delivery. As is reported, participants are overall positive about their experiences when engaging in such activities however several barriers exist as they relate to the required investments of time and money, modes of delivery and the focus of specific opportunities. A range of recommendations are made in order to address these barriers and support a diversification within the capacity building and professional development space.
Infant Alstrom syndrome diagnosed by a new gene mutation: a case report
Authors: Ye Yujiao , Wang Xianmin , Li Guixia , Xiao Xia , Ji Xuehong
Published: July 2023

Alstrom syndrome is a rare autosomal recessive disorder resulting from an ALMS1 gene mutation. Here, we present the clinical data of a case of an infant diagnosed with Alstrom syndrome through whole-exome sequencing. A 2-month-old male infant was admitted to Sichuan Provincial Maternity and Child Health Care Hospital on 30 May 2019 after “coughing for half a day and dyspnea for 2 hours”. He was diagnosed with severe pneumonia, acute congestive heart failure, Grade III cardiac function, acute respiratory failure, and myocarditis. After treatment, he was discharged with a prescription for oral medication. After a 4-month follow-up, the patient’s left ventricle exhibited spherical enlargement and a decrease in left ventricular function. The infant’s whole-exome sequencing results revealed compound heterozygous mutations in the ALMS1 gene: c.2179dup (p. Y727Lfs*12), a frameshift mutation, that was heterozygous and originated from the mother, while c.11140C>T (p. Q3714*) was a heterozygous nonsense mutation that originated from the father. Both mutations are classified as “category 1-pathogenic mutations” according to the American College of Medical Genetics and Genomics (ACMG) assessment. A novel ALMS1 mutation was identified in this case report, highlighting the importance of genetic testing for the early diagnosis of Alstrom syndrome.
Flight Time and Flight Traffic Before, During, and After the Pandemic: What Has Changed?
Authors: Xu Jing , Dai Lu , Hansen Mark
Published: July 2023

This paper develops a model for quantifying the relationship between flight volume and its operational performance at the macro level and investigating whether there are any changes before, during, and after the pandemic. Inspired by the market basket concept from economics, we first calculate macro-level effective flight time (EFT) for the U.S. domestic flight market by constructing a flight basket. Semi-log-linear models are developed to formulate the relationship between the total number of flights and macro-level EFT and its components. The estimation results indicate that the total number of flights has a positive and significant impact on EFT and its components, with 29.244 min longer for the weighted EFT for the analysis period compared with a zero-traffic scenario. Further investigations into the post-pandemic period verify the performance of the model and indicate that deteriorating operational performance in this period, especially with regard to gate delay and taxi-in time, is not only a result of the recovery of the flight market.
Proof of ID: Building Access and Personhood in the Social Service Ecosystem Through Exchange
Authors: Pierce Meghan E.
Published: July 2023

Engaging in exchange fosters a sense of connectedness and contributes to the metaperception that one is part of a society. Being excluded from exchange is dehumanizing, leaving those who are excluded to feel disconnected and subhuman. Consumers experiencing deep poverty and homelessness are denied access to many aspects of the mainstream marketplace, necessitating their use of the social service ecosystem. A key currency to receive social services from government and nonprofit entities is a valid, government-issued photo identification (ID) document. Many consumers experiencing homelessness and deep poverty do not have a valid ID and are often denied access to the very services they depend on for their survival, services that were created for this purpose. The current work investigates the impact of ID documents on consumer access to the marketplace. Through the conceptual lens of personhood, findings indicate that ID documents increase access to services and contribute to the confidence and well-being of consumers experiencing deep poverty and homelessness. Public policy implications relating to social service access, “stop and frisk” policies, and how social service organizations can play an important role in (re)building personhood are discussed.
Development of Zn/Ce containing bioactive glasses for bone regeneration applications
Authors: Naruphontjirakul Parichart , Suwanakitti Nattida
Published: July 2023

The impact of either Zn or Ce substituted with Ca in bioactive glasses based on the 45SiO2 - 6P2O5 - 11SrO - (38-(x + y) CaO) - xZnO or yCe2O3 (xZn-yCeBGs) system on bone regeneration has not yet been reported. The aim of this study was to develop new formulations of sol-gel-derived bioactive glass to use as a synthetic bone graft. xZn-yCeBGs were synthesized through the sol-gel process with 0.01 M nitric acid catalyst. xZn-yCeBG formation was investigated using SEM and FTIR. The bioactivity of xZn-yCeBGs was evaluated using SEM, EDX-SEM, and XRD. Cell viability and ability to form mineralization of MC3T3-E1 treated with xZn-yCeBGs were detected using MTT assay and Alizarin Red S staining, respectively. xZn-yCeBGs were successfully prepared. Zn or Ce substituted with Ca in BGs stimulated bioactivity through apatite formation, enhanced bone mineralization, and were not toxic to the bone cells. Moreover, these particles had an antibacterial effect against Escherichia coli ( E. coli) and Staphylococcus aureus ( S. aureus) via the disc diffusion method. Therefore, xZn-yCeBGs are a promising unique biomaterial with a potential future role as bone graft substitutes.
Failure Privilege in Policymaking: Exploitation, (In)visibilization, and Future Projection in Abortion Policy in Poland
Authors: Mica Adriana , Pawlak Mikołaj , Kubicki Paweł
Published: July 2023

Who gets to benefit from failure is a hot topic in recent research on science and innovation. This article articulates the phenomenon of failure privilege on the terrain of public policy, that is, circumstantial and institutionally ingrained dispositions to use policy downfalls, derailments, and crises as resources of policy action, tools of integration, and dynamism. Building on analyses of policy failures, the article advances a typology of three forms of privilege: exploitation, (in)visibilization, and projection of policy futures. It brings illustrations from abortion policymaking in Poland. Here, failure privilege interacts with a bio-political and culturally polarized setting that further blends neoliberal mechanisms of failing with post-Communist transformation of cultures of failure. This leads to the argument that exploitation and controversial interventions in public policy demand legitimacy that is today constructed by advancing imaginaries and models of failure that allow actors to both visibilize new futures and advance a policy stalemate. Failure is a powerful resource of integration and even surveillance, as well as a factor furthering the politics of waiting. Redefining it is a crucial policy win and entails complex and implicit mechanisms impacting policy agendas.
Techniques, applications, and prospects of recycled polyethylene terephthalate bottle: A review
Authors: Hossain Md Tanvir , Shahid Md Abdus , Mahmud Nadim , Darda Md Abu , Samad Abdullah Bin
Published: July 2023

Growing industrialization and population deposit huge amounts of waste materials into nature every day. Environmental pollution is the biggest threat to life on earth, and one of the major polluters of nature is the throwaway plastic bottles made from polyethylene terephthalate (PET), a harmful fossil fuel/petroleum-based material. This review focuses on the recent development of recycling techniques of PET waste and their potential applications including fiber production, nanofibrous membrane, air filtering materials, water filtering materials, reinforced concrete formation, energy harvesting etc. In addition, the two most promising methods for recycling: chemical recycling and mechanical recycling are discussed. The most appropriate technologies and waste disposal procedures are suggested for energy harvesting based on the socio-economic aspects of the problem. The recent progress of this topic has been discussed. The prospect of these recycled bottles has been mentioned at the end of the article.
Construct-Irrelevant Variance on the ASWB Clinical Social Work Licensing Exam: A Replication of Prior Validity Concerns
Authors: Victor Bryan G. , McNally Kellan , Qi Zia , Perron Brian E.
Published: July 2023

Purpose: This study sought to replicate a previous investigation of construct-irrelevant variance on the Association of Social Work Boards (ASWB) clinical licensing exam completed by Albright and Thyer over a decade ago. Method: The performance of ChatGPT was assessed on a modified version of 50 newly developed clinical exam questions currently distributed by the ASWB, where only the four multiple-choice options for each item were presented without the question. Results: ChatGPT achieved an average accuracy rate of 73.3% across three rounds of testing, providing strong evidence of construct-irrelevant variance. Discussion: These results raise concerns about the construct validity of the clinical exam and emphasize the need for reassessment of its structure and content to ensure fairness and accuracy. Based on the findings, state legislators and regulators are encouraged to temporarily discontinue the use of the ASWB exam in the clinical licensure process until its validity flaws are resolved.
Global prevalence of myopic macular degeneration in general population and patients with high myopia: A systematic review and meta-analysis
Authors: Shi Hekai , Guo Nuojin , Zhao Zeming , He Xiaoyu , Li Jiahang , Duan Jialiang
Published: July 2023

The prevalence of myopic macular degeneration (MMD) in the general population and patients with high myopia worldwide has not been fully investigated. Therefore, we screened all population-based studies that reported the prevalence of MMD, and pooled prevalence of MMD using a random-effect model. Subgroup analyses were performed to explore the differences in MMD prevalence in the general population and patients with high myopia according to ethnicity, region of residence (urban/rural), and grading system. Finally, 16 studies were included in this meta-analysis. Results obtained from 2,963 patients from seven countries on four continents indicated that the pooled prevalence of MMD in patients with high myopia was 49.0% (95% CI: 31.5%–66.7%). Results obtained from 71,052 participants from 10 countries on four continents suggested that the pooled prevalence of MMD in the general population was 1.7% (95% CI: 1.1%–2.6%). In the general population, living in urban areas and East Asians were associated with a high prevalence of MMD. Among patients with high myopia, only East Asians were at a higher risk of developing MMD. In conclusion, MMD was particularly prevalent in patients with high myopia. Compared with Europeans, East Asians (Chinese and Japanese) have a higher propensity of developing MMD, both in the general population and in patients with high myopia. It remains unclear whether the higher prevalence of MMD in patients with high myopia in East Asia is caused by differences in given age or given degree of myopia.

Systematic review registration number: 202270014 (INPLASY.COM).
The perilous promise of productivity: Affective politics of farming media and its consequences for the future of agriculture
Authors: Carolan Michael
Published: July 2023

This article brings together historically disparate literatures, including rural sociology, critical food studies, new media studies, and affect theory to think critically, and productively, about digital agriculture—for example, robotic milking machines, precision techniques, data-intensive and algorithm-enabled predictive software. To make this argument, the article triangulates multiple forms of data, including that collected through recurring interviews with 25 farmers in Colorado, Kansas, and Nebraska who employed agricultural digital platforms. When taken together, these data tell a story about how new farm media enact worlds by affording networked affective subjectivities. They do this not because they tell users things—as suggested by their “smart” moniker. Perhaps most importantly, they animate what farmers feel through affordances tied to expressions of desire, risk, and promise; anticipatory-affects with immense political potential.