bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Characterisation of Seed-Borne Fungal Pathogens Associated with Maize (Zea mays L.)
Authors: Goko M. L. , Murimwa J. C. , Gasura E. , Rugare J. T. , Ngadze E. 
Published: September 2021

A research study was conducted to identify and characterise seed-borne fungal pathogens associated with maize (Zea mays L.) in storage. Seed-borne fungal pathogenic infections of maize were studied using seed samples collected from Gokwe South District in Zimbabwe. The agar plating method using PDA medium was used to detect fungal pathogens on the maize seeds. A total of 150 treatments were used for this experiment, which were replicated three times in a randomised complete block design (RCBD). Analysis of the grain showed the presence of Fusarium moniliforme, Rhizopus stolonifer, Penicillium citrinum, and mostly Aspergillus species, namely, Aspergillus flavus, Aspergillus parasiticus, Aspergillus niger, and Aspergillus tamarii. Significant differences (

p

< 0.05) between treatments were detected for the pathogens. A total of ten samples were used for mycotoxin determination, and all of them were 100% positive with aflatoxin total, zearalenone, fumonisin, and deoxynivalenol (DON) having an average of 0.255 ppb, 2.425 ppb, 2.65 ppb, and 0.07 ppb, respectively. The present study showed that most grain samples are contaminated with different species of fungi with mycotoxigenic potential. The data on the diversity and magnitude of pathogen infection by fungal species will have a significant effect even at the regional level for predicting the extent of pre- and postinfections. Measures to reduce mycotoxin contamination are needed for maize grains.
Constructions and Properties for a Finite-Dimensional Modular Lie Superalgebra
K

n
,
m
Authors: Mao Dan , Zheng Keli 
Published: September 2021

In this paper, a finite-dimensional Lie superalgebra

K

n
,
m

over a field of prime characteristic is constructed. Then, we study some properties of

K

n
,
m

. Moreover, we prove that

K

n
,
m

is an extension of a simple Lie superalgebra, and if

m
=
n
−
1

, then it is isomorphic to a subalgebra of a restricted Lie superalgebra.
Tumor neuroendocrino, mucocele y adenoma tubulo-velloso: tres lesiones infrecuentes en el apéndice cecal
Authors: Piamo Morales Alberto José , Chávez Jiménez Digna , Arzuaga Anderson Isnerio , Ferrer Marrero Daisy , Palma Machado Lourdes , Montano Loandy Sotolongo 
Published: September 2021

Introducción: Los tumores del apéndice cecal constituyen un grupo heterogéneo de neoplasias con evolución y pronóstico variables; representan una pequeña parte de todas las neoplasias gastrointestinales y de las apendicetomías.
Objetivo: Realizar la comunicación de la presentación de tumores infrecuentes del apéndice cecal y revisar la literatura con énfasis la importancia del diagnóstico histopatológico.
Presentación de caso: Durante la necropsia del paciente HC: 199584 se realizó el diagnóstico histopatológico de un tumor carcinoide y mucocele apendicular y en la pieza quirúrgica del paciente HC: 223360 correspondiente a una apendicectomía se realizó el diagnóstico de adenoma tubulo-velloso, dadas que estas lesiones son poco frecuente se decide su comunicación y la revisión del tema en la literaturaen idioma inglés y español a través de las bases de datos MEDLINE/PubMed, ELSEVIER, SciELO, EBSCO, Hinari y Búsqueda Avanzada en Google Schcolar, encontrándose un total de 29 publicaciones entre 1990 a 2019.
Conclusiones: El diagnóstico de tumores del apéndice cecal se realiza en forma incidental en el estudio anatomopatológico después de una apendicectomía por apendicitis aguda, es por ello que siempre se debe realizar el estudio histológico de la pieza quirúrgica, no solo para confirmar o negar el diagnostico que motivo la apendicetomía sino para descartar la presencia de lesiones neoplásicas benignas o malignas.
caso de aducanumab ¿Más esperanza que ciencia?
Authors: Sánchez-Montoya Eliana , Andresen Max , Corrales Raúl , Gallardo Jorge , Noriega Viviana , Weinstein-Oppenheimer Caroline R. 
Published: September 2021

En junio, la Agencia de Alimentos y medicamentos de los Estados Unidos (FDA) otorgó aprobación mediante vía acelerada al medicamento aducanumab, desarrollado por Biogen, Inc. para tratamiento de la enfermedad de Alzheimer (EA). Esta autorización no ha estado exenta de controversia, ya que no se basó en un criterio de beneficio clínico demostrado, sino en un resultado de valoración sustituto, como es la reducción de la placa β-amieloide (Aβ). Primero con mecanismo novedoso aprobado para EA desde 2003 (Jaffe, 2021).
Racial/Ethnic Disparities in Childhood Cancer Survival in the United States
Authors: Zhao Jingxuan , Han Xuesong , Zheng Zhiyuan , Nogueira Leticia , Lu Amy D. , Nathan Paul C. , Yabroff K. Robin 
Published: September 2021

Abstract

Background:
Non-white patients with childhood cancer have worse survival than Non-Hispanic (NH) White patients for many childhood cancers in the United States. We examined the contribution of socioeconomic status (SES) and health insurance on racial/ethnic disparities in childhood cancer survival.

Methods:
We used the National Cancer Database to identify NH White, NH Black, Hispanic, and children of other race/ethnicities (&lt;18 years) diagnosed with cancer between 2004 and 2015. SES was measured by the area-level social deprivation index (SDI) at patient residence and categorized into tertiles. Health insurance coverage at diagnosis was categorized as private, Medicaid, and uninsured. Cox proportional hazard models were used to compare survival by race/ethnicity. We examined the contribution of health insurance and SES by sequentially adjusting for demographic and clinical characteristics (age group, sex, region, metropolitan statistical area, year of diagnosis, and number of conditions other than cancer), health insurance, and SDI.

Results:
Compared with NH Whites, NH Blacks and Hispanics had worse survival for all cancers combined, leukemias and lymphomas, brain tumors, and solid tumors (all P &lt; 0.05). Survival differences were attenuated after adjusting for health insurance and SDI separately; and further attenuated after adjusting for insurance and SDI together.

Conclusions:
Both SES and health insurance contributed to racial/ethnic disparities in childhood cancer survival.

Impact:
Improving health insurance coverage and access to care for children, especially those with low SES, may mitigate racial/ethnic survival disparities.
Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer
Authors: Peng Hui , James C. Alston , Cullinan Darren R. , Hogg Graham D. , Mudd Jacqueline L. , Zuo Chong , Takchi Rony , Caldwell Katharine E. , Liu Jingxia , DeNardo David G. , Fields Ryan C. , Gillanders William E. , Goedegebuure S. Peter , Hawkins William G. 
Published: September 2021

Abstract

Purpose:
FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system.

Experimental Design:
Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naïve (n = 20) and FOLFIRINOX-treated patients (n = 19) with primary PDAC tumors at the time of resection. PBMCs were characterized by 36 markers using mass cytometry by time of flight (CyTOF).

Results:
Compared with treatment-naïve patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX-treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27−Tbet+ effector/effector memory subsets of CD4 and CD8 T cells.

Conclusions:
Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in patients with PDAC.
Ovarian Cancer–Specific BRCA-like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial
Authors: Schouten Philip C. , Richters Lisa , Vis Daniel J. , Kommoss Stefan , van Dijk Ewald , Ernst Corinna , Kluin Roelof J.C. , Marmé Frederik , Lips Esther H. , Schmidt Sandra , Scheerman Esther , Prieske Katharina , van Deurzen Carolien H.M. , Burges Alexander , Ewing-Graham Patricia C. , Dietrich Dimo , Jager Agnes , de Gregorio Nikolaus , Hauke Jan , du Bois Andreas , Nederlof Petra M. , Wessels Lodewyk F. , Hahnen Eric , Harter Philipp , Linn Sabine C. , Schmutzler Rita K. 
Published: September 2021

Abstract

Purpose:
Previously, we developed breast cancer BRCA1-like and BRCA2-like copy-number profile shrunken centroid classifiers predictive for mutation status and response to therapy, targeting homologous recombination deficiency (HRD). Therefore, we investigated BRCA1- and BRCA2-like classification in ovarian cancer, aiming to acquire classifiers with similar properties as those in breast cancer.

Experimental Design: We analyzed DNA copy-number profiles of germline BRCA1- and BRCA2-mutant ovarian cancers and control tumors and observed that existing breast cancer classifiers did not sufficiently predict mutation status. Hence, we trained new shrunken centroid classifiers on this set and validated them in the independent The Cancer Genome Atlas dataset. Subsequently, we assessed BRCA1/2-like classification and obtained germline and tumor mutation and methylation status of cancer predisposition genes, among them several involved in HR repair, of 300 ovarian cancer samples derived from the consecutive cohort trial AGO-TR1 (NCT02222883).

Results:
The detection rate of the BRCA1-like classifier for BRCA1 mutations and promoter hypermethylation was 95.6%. The BRCA2-like classifier performed less accurately, likely due to a smaller training set. Furthermore, three quarters of the BRCA1/2-like tumors could be explained by (epi)genetic alterations in BRCA1/2, germline RAD51C mutations and alterations in other genes involved in HR. Around half of the non–BRCA-mutated ovarian cancer cases displayed a BRCA-like phenotype.

Conclusions:
The newly trained classifiers detected most BRCA-mutated and methylated cancers and all tumors harboring a RAD51C germline mutations. Beyond that, we found an additional substantial proportion of ovarian cancers to be BRCA-like.
HighFGFR1–4mRNA Expression Levels Correlate with Response to Selective FGFR Inhibitors in Breast Cancer
Authors: Sánchez-Guixé Mònica , Hierro Cinta , Jiménez José , Viaplana Cristina , Villacampa Guillermo , Monelli Erika , Brasó-Maristany Fara , Ogbah Zighereda , Parés Mireia , Guzmán Marta , Grueso Judit , Rodríguez Olga , Oliveira Mafalda , Azaro Analía , Garralda Elena , Tabernero Josep , Casanovas Oriol , Scaltriti Maurizio , Prat Aleix , Dienstmann Rodrigo , Nuciforo Paolo , Saura Cristina , Graupera Mariona , Vivancos Ana , Rodon Jordi , Serra Violeta 
Published: September 2021

AbstractPurpose:FGFR1 amplification (FGFR1amp) is recurrent in metastatic breast cancer (MBC) and is associated with resistance to endocrine therapy and CDK4/6 inhibitors (CDK4/6is). Multi-tyrosine kinase inhibitors (MTKIs) and selective pan-FGFR inhibitors (FGFRis) are being developed for FGFR1amp breast cancer. High-level FGFR amplification and protein expression by IHC have identified breast cancer responders to FGFRis or MTKIs, respectively.Experimental Design:Here, we used preclinical models and patient samples to identify predictive biomarkers to these drugs. We evaluated the antitumor activity of an FGFRi and an MTKI in a collection of 17 breast cancer patient–derived xenografts (PDXs) harboring amplification in FGFR1/2/3/4 and in 10 patients receiving either an FGFRi/MTKI. mRNA levels were measured on FFPE tumor samples using two commercial strategies. Proliferation and angiogenesis were evaluated by detecting Ki-67 and CD31 in viable areas by immunofluorescence.Results:High FGFR1–4 mRNA levels but not copy-number alteration (CNA) is associated with FGFRi response. Treatment with MTKIs showed higher response rates than with FGFRis (86% vs. 53%), regardless of the FGFR1–4 mRNA levels. FGFR-addicted PDXs exhibited an antiproliferative response to either FGFRis or MTKIs, and PDXs exclusively sensitive to MTKI exhibited an additional antiangiogenic response. Consistently, the clinical benefit of MTKIs was not associated with high FGFR1–4 mRNA levels and was observed in patients previously treated with antiangiogenic drugs.Conclusions:Tailored therapy with FGFRis in molecularly selected MBC based on high FGFR1–4 mRNA levels warrants prospective validation in patients with CDK4/6i-resistant luminal breast cancer and in patients with TNBC without targeted therapeutic options.
TAS-116 (Pimitespib), an Oral HSP90 Inhibitor, in Combination with Nivolumab in Patients with Colorectal Cancer and Other Solid Tumors: An Open-Label, Dose-Finding, and Expansion Phase Ib Trial (EPOC1704)
Authors: Kawazoe Akihito , Itahashi Kota , Yamamoto Noboru , Kotani Daisuke , Kuboki Yasutoshi , Taniguchi Hiroya , Harano Kenichi , Naito Yoichi , Suzuki Mitsuko , Fukutani Miki , Higuchi Tsukiko , Ikeno Takashi , Wakabayashi Masashi , Sato Akihiro , Koyama Shohei , Nishikawa Hiroyoshi , Shitara Kohei 
Published: September 2021

Abstract

Purpose:
This is a phase Ib trial of TAS-116, an oral HSP90 inhibitor, plus nivolumab for colorectal cancer and other solid tumors.

Patients and Methods:
Enrolled patients received TAS-116 plus nivolumab in a dose-finding part to estimate the recommended dose. Additional patients were enrolled in a dose-expansion part. TAS-116 monotherapy (orally once daily, 80–160 mg) was administered for 2 weeks followed by the combination with nivolumab (intravenously every 2 weeks, 3 mg/kg). The primary endpoint was dose-limiting toxicities (DLT). We also conducted biomarker research using paired samples from repeated blood collections and tumor biopsies.

Results:
A total of 44 patients with colorectal cancer (n = 29), gastric cancer (n = 8), sarcoma (n = 5), non–small cell lung cancer (n = 1), and melanoma (n = 1) were enrolled. Eleven patients had previously received immune-checkpoint inhibitors. No DLTs were observed at all dose levels, and TAS-116 160 mg was determined as recommended dose. The common grade 3 or worse treatment-related adverse events included liver transaminase increased (7%), creatinine increased (5%), and platelet count decreased (5%). Objective tumor response was observed in 6 patients, including 4 microsatellite stable (MSS) colorectal cancers, 1 microsatellite instability-high colorectal cancer, and 1 leiomyosarcoma, resulting in an objective response rate of 16% in MSS colorectal cancer without prior immune-checkpoint inhibitors. Biomarker analysis showed that TAS-116 inhibited the activity of regulatory T cells in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes.

Conclusions:
TAS-116 160 mg plus nivolumab had manageable safety profiles and antitumor activity, especially for MSS colorectal cancer patients.
Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT–Identified Oligometastatic Castration-Resistant Prostate Cancer
Authors: Zhang Henan , Orme Jacob J. , Abraha Feven , Stish B.J. , Lowe Val J. , Lucien Fabrice , Tryggestad Erik J. , Bold Michael S. , Pagliaro Lance C. , Choo C. Richard , Brinkmann Debra H. , Iott Matthew J. , Davis Brian J. , Quevedo J. Fernando , Harmsen William S. , Costello Brian A. , Johnson Geoffrey B. , Nathan Mark A. , Olivier Kenneth R. , Pisansky Thomas M. , Kwon Eugene D. , Dong Haidong , Park Sean S. 
Published: September 2021

Abstract

Purpose:
Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking.

Patients and Methods:
Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR.

Results:
128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7−CD45RA−) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS.

Conclusions:
This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.
A Novel Therapeutic Strategy Targeting the Mesenchymal Phenotype of Malignant Pleural Mesothelioma by Suppressing LSD1
Authors: Wirawan Aditya , Tajima Ken , Takahashi Fumiyuki , Mitsuishi Yoichiro , Winardi Wira , Hidayat Moulid , Hayakawa Daisuke , Matsumoto Naohisa , Izumi Kenta , Asao Tetsuhiko , Ko Ryo , Shimada Naoko , Takamochi Kazuya , Suzuki Kenji , Abe Masaaki , Hino Okio , Sekido Yoshitaka , Takahashi Kazuhisa 
Published: September 2021

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a low overall survival; however, no significant treatment advances have been made in the past 15 years. Large-scale molecular studies have identified a poor prognostic subset of MPM linked to the epithelial–mesenchymal transition (EMT) that may contribute toward resistance to chemotherapy, suggesting that EMT could be targeted to treat patients with MPM. Previously, we reported that histone modifiers regulating EMT could be therapeutic targets; therefore, in this study, we investigated whether targeting lysine-specific demethylase 1 (LSD1/KDM1), a histone-modifying enzyme responsible for demethylating histone H3 lysine 4 and lysine 9, could represent a novel therapeutic strategy for MPM. We suppressed LSD1 and investigated the EMT phenotype using EMT marker expression and wound-healing assay; and chemosensitivity using apoptosis assay. We found that suppressing LSD1 induces an epithelial phenotype in sarcomatoid MPM cells, while attenuating the mesenchymal phenotype sensitized MPM cells to cisplatin-induced apoptosis. Subsequent genome-wide identification, comprehensive microarray analysis, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to assess genome-wide changes in chromatin accessibility suggested that LSD1 directly regulates milk fat globulin protein E8 (MFGE8), an integrin ligand that is involved in the FAK pathway. Furthermore, we found that LSD1 regulates the mesenchymal phenotype and apoptosis by activating the FAK–AKT–GSK3β pathway via a positive feedback loop involving MFGE8 and Snail expression, thereby leading to cisplatin resistance.

Implications:
This study suggests that LSD1 regulates the mesenchymal phenotype and apoptosis, and that LSD1 inhibitors could be combined with the cisplatin as a novel therapy for patients with MPM.
Quantitative Longitudinal Imaging Reveals that Inhibiting Hedgehog Activity Alleviates the Hypoxic Tumor Landscape
Authors: Lama-Sherpa Tshering D. , Das Shamik , Hinshaw Dominique C. , Kammerud Sarah C. , Song Patrick N. , Alsheikh Heba A. , Sorace Anna G. , Samant Rajeev S. , Shevde Lalita A. 
Published: September 2021

Abstract
Metastases account for the majority of mortalities related to breast cancer. The onset and sustained presence of hypoxia strongly correlates with increased incidence of metastasis and unfavorable prognosis in patients with breast cancer. The Hedgehog (Hh) signaling pathway is dysregulated in breast cancer, and its abnormal activity enables tumor progression and metastasis. In addition to programming tumor cell behavior, Hh activity enables tumor cells to craft a metastasis-conducive microenvironment. Hypoxia is a prominent feature of growing tumors that impacts multiple signaling circuits that converge upon malignant progression. We investigated the role of Hh activity in crafting a hypoxic environment of breast cancer. We used radioactive tracer [18F]-fluoromisonidazole (FMISO) positron emission tomography (PET) to image tumor hypoxia. We show that tumors competent for Hh activity are able to establish a hypoxic milieu; pharmacologic inhibition of Hh signaling in a syngeneic mammary tumor model mitigates tumor hypoxia. Furthermore, in hypoxia, Hh activity is robustly activated in tumor cells and institutes increased HIF signaling in a VHL-dependent manner. The findings establish a novel perspective on Hh activity in crafting a hypoxic tumor landscape and molecularly navigating the tumor cells to adapt to hypoxic conditions.
Implications: Importantly, we present a translational strategy of utilizing longitudinal hypoxia imaging to measure the efficacy of vismodegib in a preclinical model of triple-negative breast cancer.