bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generating universal anti-CD19 CAR T cells with a defined memory phenotype by CRISPR/Cas9 editing and safety evaluation of the transcriptome
Authors: Pavlovic Kristina , Carmona-Luque MDolores , Corsi Giulia I. , Maldonado-Pérez Noelia , Molina-Estevez Francisco J. , Peralbo-Santaella Esther , Cortijo-Gutiérrez Marina , Justicia-Lirio Pedro , Tristán-Manzano María , Ronco-Díaz Víctor , Ballesteros-Ribelles Antonio , Millán-López Alejandro , Heredia-Velázquez Paula , Fuster-García Carla , Cathomen Toni , Seemann Stefan E. , Gorodkin Jan , Martin Francisco , Herrera Concha , Benabdellah Karim 
Published: May 2024

IntroductionChimeric antigen receptor-expressing T cells (CAR T cells) have revolutionized cancer treatment, particularly in B cell malignancies. However, the use of autologous T cells for CAR T therapy presents several limitations, including high costs, variable efficacy, and adverse effects linked to cell phenotype.MethodsTo overcome these challenges, we developed a strategy to generate universal and safe anti-CD19 CAR T cells with a defined memory phenotype. Our approach utilizes CRISPR/Cas9 technology to target and eliminate the B2M and TRAC genes, reducing graft-versus-host and host-versus-graft responses. Additionally, we selected less differentiated T cells to improve the stability and persistence of the universal CAR T cells. The safety of this method was assessed using our CRISPRroots transcriptome analysis pipeline, which ensures successful gene knockout and the absence of unintended off-target effects on gene expression or transcriptome sequence.ResultsIn vitro experiments demonstrated the successful generation of functional universal CAR T cells. These cells exhibited potent lytic activity against tumor cells and a reduced cytokine secretion profile. The CRISPRroots analysis confirmed effective gene knockout and no unintended off-target effects, validating it as a pioneering tool for on/off-target and transcriptome analysis in genome editing experiments.DiscussionOur findings establish a robust pipeline for manufacturing safe, universal CAR T cells with a favorable memory phenotype. This approach has the potential to address the current limitations of autologous CAR T cell therapy, offering a more stable and persistent treatment option with reduced adverse effects. The use of CRISPRroots enhances the reliability and safety of gene editing in the development of CAR T cell therapies.ConclusionWe have developed a potent and reliable method for producing universal CAR T cells with a defined memory phenotype, demonstrating both efficacy and safety in vitro. This innovative approach could significantly improve the therapeutic landscape for patients with B cell malignancies.
Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals
Authors: Sun Zewen , Yan Mingyue , Wang Junjie , Zhang Haoyun , Ji Xiaobin , Xiao Yujing , Wang Tianrui , Yu Tengbo 
Published: May 2024

BackgroundCartilage injury is the main pathological manifestation of osteoarthritis (OA). Healthy chondrocyte is a prerequisite for cartilage regeneration and repair. Differences between healthy and OA chondrocyte types and the role these types play in cartilage regeneration and OA progression are unclear.MethodThis study conducted single-cell RNA sequencing (scRNA-seq) on the cartilage from normal distal femur of the knee (NC group) and OA femur (OA group) cartilage, the chondrocyte atlas was constructed, and the differences of cell subtypes between the two groups were compared. Pseudo-time and RNA velocity analysis were both performed to verify the possible differentiation sequence of cell subtypes. GO and KEGG pathway enrichment analysis were used to explore the potential functional characteristics of each cell subtype, and to predict the functional changes during cell differentiation. Differences in transcriptional regulation in subtypes were explored by single-cell regulatory network inference and clustering (SCENIC). The distribution of each cell subtype in cartilage tissue was identified by immunohistochemical staining (IHC).ResultA total of 75,104 cells were included, they were divided into 19 clusters and annotated as 11 chondrocyte subtypes, including two new chondrocyte subtypes: METRNL+ and PRG4+ subtype. METRNL+ is in an early stage during chondrocyte differentiation, and RegC-B is in an intermediate state before chondrocyte dedifferentiation. With cell differentiation, cell subtypes shift from genetic expression to extracellular matrix adhesion and collagen remodeling, and signal pathways shift from HIF-1 to Hippo. The 11 subtypes were finally classified as intrinsic chondrocytes, effector chondrocytes, abnormally differentiated chondrocytes and dedifferentiated chondrocytes. IHC was used to verify the presence and distribution of each chondrocyte subtype.ConclusionThis study screened two new chondrocyte subtypes, and a novel classification of each subtype was proposed. METRNL+ subtype is in an early stage during chondrocyte differentiation, and its transcriptomic characteristics and specific pathways provide a foundation for cartilage regeneration. EC-B, PRG4+ RegC-B, and FC are typical subtypes in the OA group, and the HippO-Taz pathway enriched by these cell subtypes may play a role in cartilage repair and OA progression. RegC-B is in the intermediate state before chondrocyte dedifferentiation, and its transcriptomic characteristics may provide a theoretical basis for intervening chondrocyte dedifferentiation.
IRX5’s influence on macrophage polarization and outcome in papillary thyroid cancer
Authors: Qin Lu , Chen Cheng , Gui Zhengwei , Jiang Yun 
Published: May 2024

BackgroundWith a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the molecular level and the immune environment within tumors of various thyroid cancer subtypes in order to identify potential targets for therapy and provide precise treatment for patients with thyroid adenocarcinoma.MethodsFirst, we analyzed the expression of IRX5 in pan-cancer and papillary thyroid carcinoma by bioinformatics methods and collected paired samples from our center for validation. Subsequently, we analyzed the significance of IRX5 on the prognosis and diagnosis of PTC. Next, we explored the possible mechanisms by which IRX5 affects the prognosis of thyroid cancer patients by GO/KEGG enrichment analysis, and further investigated the effect of IRX5 on immune infiltration of thyroid cancer. Ultimately, by conducting experiments on cells and animals, we were able to show how IRX5 impacts the aggressive characteristics of thyroid cancer cells and its influence on macrophages within the immune system of thyroid cancer.ResultsIn 11 malignant tumors, including PTC, IRX5 is overexpressed and associated with a poor prognosis. IRX5 may affect the prognosis of PTC through embryonic organ development, ossification, mesenchyme development, etc. Increased IRX5 expression decreases the presence of cytotoxic and Th17 cells in papillary thyroid cancer. IRX5 was highly expressed in different PTC cell lines, such as K-1 and TPC-1. Silencing IRX5 effectively halted the growth and movement of PTC cells while also decreasing M2 polarization and enhancing M1 polarization in tumor-associated macrophages.ConclusionIRX5 could impact the outlook of individuals with PTC by stimulating the shift of macrophages to M2 in the immune surroundings of thyroid cancer growths, suggesting a potential new focus for treating thyroid cancer, particularly through immunotherapy.
Integrating GC-MS and comparative transcriptome analysis reveals that TsERF66 promotes the biosynthesis of caryophyllene in Toona sinensis tender leaves
Authors: Dai Jianhua , Wang Minyan , Yin Hengfu , Han Xiaojiao , Fan Yanru , Wei Yi , Lin Jie , Liu Jun 
Published: May 2024

IntroductionThe strong aromatic characteristics of the tender leaves of Toona sinensis determine their quality and economic value.Methods and resultsHere, GC-MS analysis revealed that caryophyllene is a key volatile compound in the tender leaves of two different T. sinensis varieties, however, the transcriptional mechanisms controlling its gene expression are unknown. Comparative transcriptome analysis revealed significant enrichment of terpenoid synthesis pathway genes, suggesting that the regulation of terpenoid synthesis-related gene expression is an important factor leading to differences in aroma between the two varieties. Further analysis of expression levels and genetic evolution revealed that TsTPS18 is a caryophyllene synthase, which was confirmed by transient overexpression in T. sinensis and Nicotiana benthamiana leaves. Furthermore, we screened an AP2/ERF transcriptional factor ERF-IX member, TsERF66, for the potential regulation of caryophyllene synthesis. The TsERF66 had a similar expression trend to that of TsTPS18 and was highly expressed in high-aroma varieties and tender leaves. Exogenous spraying of MeJA also induced the expression of TsERF66 and TsTPS18 and promoted the biosynthesis of caryophyllene. Transient overexpression of TsERF66 in T. sinensis significantly promoted TsTPS18 expression and caryophyllene biosynthesis.DiscussionOur results showed that TsERF66 promoted the expression of TsTPS18 and the biosynthesis of caryophyllene in T. sinensis leaves, providing a strategy for improving the aroma of tender leaves.
EFEKTIVITAS BROMELIN SEBAGAI DEPROTEINASI KUTIKULA PINJAL PADA PROSES PREPARAT PERMANEN
Authors: Nurhayati Dewi , Mulia Yuliansyah Sundara , Azhiima Amadda Fadhila 
Published: May 2024

Kitin yang merupakan salah satu komponen penyusun eksoskeleton arthropoda. Kitin merupakan polimer rantai panjang N-asetilglukosamin, turunan Amida dari glukosa. Ikatan peptide pada kitin dapat dipecah menggunakan larutan KOH yang berfungsi sebagai deproteinasi. Proses deproteinasi akan menyebabkan lapisan kitin eksoskleton menipis. Enzim dari buah nanas (Ananas comosus L. Merr) var. Subang yaitu Bromelin terbukti memiliki kemampuan untuk memecah ikatan peptida. Bromelin merupakan salah satu enzim yang banyak digunakan baik untuk industri pangan maupun non pangan. Bromelin akan digunakan pada proses deproteinase eksoskeleton pinjal yang mengandung kitin. Tujuan Penelitian adalah untuk menentukan kemampuan bromelin sebagai deproteinasi kutikula pinjal. Metode penelitian quasi eksperimen, pinjal kucing sebanyak 96 ekor terbagi menjadi tiga kelompok perlakukan kontak bromelin dan serangga dalam konsentrasi 15%, 20% dan 25% dibandingkan dengan satu kelompok kontrol kontak larutan KOH 10 % dan serangga, dengan waktu perendaman selama 24 jam dan 48 jam, serta dilakukan tiga kali pengulangan. Hasil penelitian yang sudah dilakukan dari tahapan penipisan dengan bromelin 15%, 20% dan 25% selama 24 jam dan 48 jam. Proses penipisan akan berakhir dengan pemberian entelan sebagai perekat preparat. Penelitian ini berlangsung selama 7 bulan dari bulan April sampai dengan Oktober 2020.Lokasi penelitian adalah Laboratorium Terpadu dan Laboratorium Parasitologi Jurusan Analis Kesehatan Poltekkes Bandung Hasil pemeriksaan secara mikroskopis dari preparat kemudian di analisis dengan uji Kruskal-Wallis dan Mann Whitney diperoleh hasil<0.05 menunjukkan terdapat perbedaan yang signifikan untuk semua perlakuan Hasil analisis data menghasilkan kualitas tertinggi deproteinasi pada perlakuan Bromelin 25% dan untuk waktu optimal yang menghasilkan kualitas deproteinasi tertinggi pada waktu 48 jam.
Highly Accurate and Efficient Deep Learning Paradigm for Full-Atom Protein Loop Modeling with KarmaLoop
Authors: Wang Tianyue , Zhang Xujun , Zhang Odin , Chen Guangyong , Pan Peichen , Wang Ercheng , Wang Jike , Wu Jialu , Zhou Donghao , Wang Langcheng , Jin Ruofan , Chen Shicheng , Shen Chao , Kang Yu , Hsieh Chang-Yu , Hou Tingjun 
Published: May 2024

Protein loop modeling is a challenging yet highly nontrivial task in protein structure prediction. Despite recent progress, existing methods including knowledge-based, ab initio, hybrid, and deep learning (DL) methods fall substantially short of either atomic accuracy or computational efficiency. To overcome these limitations, we present KarmaLoop, a novel paradigm that distinguishes itself as the first DL method centered on full-atom (encompassing both backbone and side-chain heavy atoms) protein loop modeling. Our results demonstrate that KarmaLoop considerably outperforms conventional and DL-based methods of loop modeling in terms of both accuracy and efficiency, with the average RMSDs of 1.77 and 1.95 Å for the CASP13+14 and CASP15 benchmark datasets, respectively, and manifests at least 2 orders of magnitude speedup in general compared with other methods. Consequently, our comprehensive evaluations indicate that KarmaLoop provides a state-of-the-art DL solution for protein loop modeling, with the potential to hasten the advancement of protein engineering, antibody–antigen recognition, and drug design.
Near-Term NASA Mars and Lunar In Situ Propellant Production: Complexity versus Simplicity
Authors: Rapp Donald 
Published: May 2024

Martian in situ propellant production (ISPP) has a fundamental advantage over lunar ISPP because it has much greater leverage. The value of Martian ISPP per liftoff far exceeds that for the lunar ISPP. This study analyzes the challenges and complexity of lunar ISPP versus Mars ISPP and finds that lunar ISPP is so challenging it might not even be feasible, and if it is feasible, the payoff appears to be limited, while the investment is likely to be great. By contrast, Mars ISPP based on atmosphere only is relatively simple with high payoff. NASA is heavily focused on lunar ISPP and seemingly has diminished interest in solid oxide electrolysis of Martian CO
2
to O
2
after an extremely successful demonstration on Mars by MOXIE. This might make sense at first glance, but when the 2 leading candidates for lunar ISPP are analyzed in detail, it is found that they are extremely difficult and challenging to implement, the effort and investment involved in developing and implementing them are high, and the potential payoff is limited. By contrast, Mars ISPP by solid oxide electrolysis cell (SOEC) of CO
2
is comparatively simple and reliable and has high payoff. A SOEC system is basically landed, and a switch is turned on. The only feedstock is the ubiquitous atmosphere. Lunar ISPP involves a seemingly endless number of complex dynamic steps including autonomous traverses of excavator/haulers to unearth (unmoon?) regolith and deliver it to and from a reactor.
CONTROL QUIMICO DE MALEZAS EN EL CULTIVO DE CACAHUATE EN SANTA MARIA DEL ORO, NAYARIT
Authors: Ríos-Torres Asunción 
Published: May 2024

Entre los factores que limitan la producción de cacahuate (Arachis hipogaea L.) en Nayarit, las malezas ocupan el primer lugar reduciendo el rendimiento hasta en 92%, por efectos de competencia. El objetivo de este trabajo fue determinar el tratamiento más eficaz para el control químico de malezas en este cultivo. El experimento se estableció en 1987 bajo condiciones de temporal,en San José de Mojarras, Municipio de Sta. María del Oro; se utilizó la variedad criolla de tres granos, en parcelas de 12 m2. Se estudiaron 10 tratamientos: Cinco con herbicidas preemergentes; tres postemergentes; deshierbes con azadón y el testigo (sin control de malezas). Se utilizó el diseño de bloques al azar con 4 repeticiones. El "Zacate Fresadilla" (Digitaria sp.) representó el 60% de la población total de malezas, la "Oreja de Ratón" (Ricardia scabra) el 30%, la "Aceitilla" (Bidens pilosa) el 4% y el "Gordolobo" (Heliamthus annuus) el 4%. Todos los tratamientos con herbicida mostraron buen control de las malezas; pero aquellos donde se aplicó Oxifluorfen, 1.0 l/ha; Oxifluorfen + Prometrina, 0.5 l+ 1 kg/ha, y Fomesafen + Fluazifop-b, 2 l + 2 1/ha causaron de 15 a 30% de fitotoxicidad en hojas, lo cual desapareció a los 10 días de su inicio. Los tratamientos que no causaron daño al cultivo fueron: Alaclor, 4 1/ha Alaclor + Prometrina, 2 l + 1 kg/ha; y Metolaclor + Prometrina, 2 l + 1 kg/ha. No obstante, el rendimiento fue estadísticamente igual en todos los tratamientos, excepto en el testigo. La fitotoxicidad observada nos reflejó en el rendimiento.
L’affaire Cotton au New York Times et ses répercussions dans la presse mainstream américaine
Authors: Laroche Loic 
Published: May 2024

Peu après le meurtre de George Floyd, la publication d’une tribune appelant à l’armée dans les pages opinions du New York Times entraîne une vive réaction d’une partie de la rédaction du journal qui s’étend à l’ensemble de la presse mainstream américaine. Elle provoqua la démission du directeur éditorial et de plusieurs de ses collègues ainsi que la remise en question par son directeur général de la politique éditoriale traditionnelle du journal, marquée jusque-là par l’ouverture au débat et à la controverse. Elle appelle à une évolution des normes journalistiques dans un paysage de guerres culturelles à l’heure de la cancel culture.
De la contestation par primaire au sein du Parti démocrate : la gauche états‑unienne face au défi du bipartisme
Authors: Jeangirard Thomas 
Published: May 2024

Les États‑Unis connaissent depuis quelques années un renouveau socialiste,qui s’est manifesté par les succès de diverses organisations, de journaux mais aussi d’hommes et de femmes politiques désormais médiatiques. Grâce à un succès dans ses actions militantes mais aussi dans les urnes, ce mouvement a modifié dans une certaine mesure la composition de l’échiquier politique états‑unien, et, à travers le mécanisme des primaires ouvertes, celle du Parti démocrate en elle‑même. Cet article revient sur cette stratégie socialiste de contestation par primaire en l’analysant comme réponse au contexte institutionnel particulier du pays. Il examine dans un second temps les différentes approches au sein du mouvement qui, loin d’être unifiées dans leur attitude vis-à-vis du Parti démocrate, parviennent toutefois à proposer un projet politique commun.
L’Arizona ou les raisons du tournant d’un bastion traditionnellement républicain devenu « violet »
Authors: Fortuné Cléa 
Published: May 2024

Cet article se propose d’aborder les élections présidentielles de 2020 sous l’angle des changements qui ont eu lieu ces dernières décennies en Arizona. Alors qu’il s’agit d’un État traditionnellement républicain, ses résidents ont voté démocrate pour la première fois depuis 1996. Nous nous interrogerons sur les raisons du passage d’un État rouge à violet, notamment à travers le changement démographique amorcé dans les années 2000, les mesures anti-migratoires comme SB 1070 en 2010, ainsi que la sécurité frontalière. Si le républicain Donald Trump avait promis de continuer une politique anti-migratoire stricte et de renforcer la sécurité à la frontière, Joseph Biden a quant à lui décidé d’annuler des décrets présidentiels de son prédécesseur, annonçant un revirement important pour l’État.
ANÁLISE DO TRANSTORNO DO ESPECTRO AUTISTA PELA PERSPECTIVA DA PELÍCULA “O RECEPCIONISTA”
Authors: Delgado Eserian Ana Luiza , Arantes Maia Glenia , Borges de Menezes Filho William , Silva Vaz Nathália , Soares Lorena Karine , Mesquita de Lima Netto Aristóteles 
Published: May 2024

Resumo: O artigo em questão analisa Transtorno do Espectro Autista (TEA) a partir da análise da película “O Recepcionista”. Para tal, foi utilizado a fundamentação teórica amparada no Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-V), como contribuições dos autores Dipietro (2019), Senju (2012), Oliveira (2009), dentre outras. Na contextualização teórica explicitamos o equívoco da película na utilização da terminologia Asperger, episódio que justifica a construção do diálogo proposto. A metodologia competiu revisão de literatura a partir da análise da película. E concluímos, que a utilização de recursos audiovisuais detém ampla pertinência para suporte a sujeitos com quadro diagnóstico de TEA.
Disforia toráxica en adolescentes y jóvenes trans masculinos y género diverso: revisión de la literatura
Authors: Retamal Parra Maria Dorca 
Published: May 2024

RESUMEN: Introducción: Un número cada vez mayor de adolescentes y jóvenes se identifican como transgénero y género diverso y con ello se han comenzado a visibilizar situaciones de salud, tal como la disforia toráxica presentada por un gran número de personas que se identifican dentro del espectro de la masculinidad, la cual se refiere a la angustia clínicamente significativa relacionada al desarrollo del tejido mamario irreversible, una vez que es iniciada la pubertad femenina, lo que puede generar consecuencias físicas y psicológicas graves a corto y largo plazo, de las que existe muy poca información. Este trabajo tiene como objetivo realizar una revisión de la literatura existente respecto de la disforia toráxica y así entregar información a profesionales, familia y adolescentes que les permita tener un autocuidado y tomar decisiones con información basada en evidencia. Métodos: El presente trabajo corresponde a una revisión teórica entre los años 2017-2024 de revistas científicas de habla inglesa e hispana indexadas en Google Académico y PUBMED.Resultados: De la revisión de los artículos en relación a la disforia toráxica, emergieron cuatro temas relevantes como (1) disforia toráxica y salud mental (2) uso de vendaje de tórax (3) cirugía de tórax (4) barreras en salud.Conclusiones: Para abordar la disforia toráxica se requiere una respuesta adecuada de prevención en la pubertad, de proyección a corto y largo plazo de las consecuencias físicas y psicológicas y de intervención centrada en el adolescente y su estado de salud más que en la edad cronológica.
Nuevos avances en cirugía hepática: Manejo de volumen hepático y nuevas terapias. (Parte 2)
Authors: Rojas Lizana Jesús , Muñoz Castro César 
Published: May 2024

El avance de la tecnología ha permitido el desarrollo de nuevas terapias y procedimientos en cirugía hepática dirigidos a disminuir la morbimortalidad perioperatoria y aumentar la resecabilidad. Un factor central en las resecciones hepáticas el Remanente Hepático Futuro (RHF) que se relaciona directamente con el riesgo de Falla Hépatica Postoperatoria, es por esto, que el desarrollo de técnicas como la Deprivación venosa o ALLPS tienen como objetivo incrementar el volumen hepático previo a la resección, usados en diferentes patologías con lesiones potencialmente irresecables en primera instancia. Por otro parte, técnicas como RAPID, DEBIRI o EX- SITU están dirigidas al tratamiento de paciente con tumores considerados irresecables, RAPID utiliza el concepto de trasplante hepático auxiliar previo a una hepatectomía mayor en segundo tiempo, utilizando bases fisiológicas del ALLPS. DEBIRI en tanto, mezcla el uso de terapias sistémicas combinadas con radiología intervencional para el control de tumores considerados irresecables y que no son candidatos a procedimientos mayores. Por último, la cirugía hepática Ex-situ permite resecar tumores de localización compleja en banco y luego reimplantar el hígado, asociado técnicas de perfusión de órganos y puentes venosos, todas estas técnicas aún en desarrollo, siendo necesario estandarizar las indicaciones de cada una.