bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S2. from High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models
Authors: Degagné Émilie , Donohoue Paul D. , Roy Suparna , Scherer Jessica , Fowler Tristan W. , Davis Ryan T. , Reyes Gustavo A. , Kwong George , Stanaway Morena , Larroca Vicena Vanina , Mutha Devin , Guo Raymond , Edwards Leslie , Schilling Benjamin , Shaw McKay , Smith Stephen C. , Kohrs Bryan , Kufeldt Heinrich J. , Churchward Glen , Ruan Finey , Nyer David B. , McSweeney Kyle , Irby Matthew J. , Fuller Christopher K. , Banh Lynda , Toh Mckenzi S. , Thompson Matthew , Owen Arthur L.G. , An Zili , Gradia Scott , Skoble Justin , Bryan Mara , Garner Elizabeth , Kanner Steven B.
Published: April 2024

In vitro serial rechallenge assay demonstrates long-term cytotoxicity activity of CB-011 against BCMA+ tumor cells.
Supplementary Figure S6 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells
Authors: Carnevale Silvia , Ponzetta Andrea , Rigatelli Anna , Carriero Roberta , Puccio Simone , Supino Domenico , Grieco Giovanna , Molisso Piera , Di Ceglie Irene , Scavello Francesco , Perucchini Chiara , Pasqualini Fabio , Recordati Camilla , Tripodo Claudio , Belmonte Beatrice , Mariancini Andrea , Kunderfranco Paolo , Sciumè Giuseppe , Lugli Enrico , Bonavita Eduardo , Magrini Elena , Garlanda Cecilia , Mantovani Alberto , Jaillon Sebastien
Published: April 2024

Figure S6. Neutrophil infiltration is associated with tissue repair gene signatures in patients with ulcerative colitis.
Related to Figure 6.
A-E) Enrichment plots for gene ontology term epithelial cell (GO:Epithelial Cell Proliferation (A, D); GO:Epithelial Cell Development (B, E); GO:Maintanance of Gastrointestinal Epithilium (C)) in CSF3Rhigh versus CSF3Rlow UC patients GSE109142 (A-C) GSE87473 (D-E). F-K) Enrichment plots for gene ontology term antimicrobial response (GO:Response to molecule of bacterial origin (F, I); GO:Defense response to bacterium; GO:Antimicrobial humoral immune response mediated by antimicrobial peptides) in CSF3Rhigh versus CSF3Rlow UC patients GSE109142 (F-H) and GSE87473 (I-K). CSF3R gene expression values were stratified by quartiles and patients belonging to the upper (GSE109142 n=51; GSE87473 n=21) and lower GSE109142 n=51; GSE97473 n=21) quartiles were considered for differential expression analysis. FDR, false discovery rate.
Supplementary Fig. S5 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S5: CTLA-4 blockade is critical for efficacy of combined chemotherapy with ICB in ICC by grafting 425 murine cells in C57Bl/6/FVB F1 mice.
Supplementary Fig. S3 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S3: ScRNAseq analysis of ICC TME after GC-based therapies in orthotopic murine 425-ICC model.
Supplementary Fig. S12 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S12: Effect of ICB treatment scheduling on efficacy and toxicity.
Supplementary Fig. S10 from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Supplementary Fig. S10: Schematic of the animal experiment design.
Data from Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Authors: Chen Jiang , Amoozgar Zohreh , Liu Xin , Aoki Shuichi , Liu Zelong , Shin Sarah M. , Matsui Aya , Hernandez Alexei , Pu Zhangya , Halvorsen Stefan , Lei Pin-Ji , Datta Meenal , Zhu Lingling , Ruan Zhiping , Shi Lei , Staiculescu Daniel , Inoue Koetsu , Munn Lance L. , Fukumura Dai , Huang Peigen , Sassi Slim , Bardeesy Nabeel , Ho Won Jin , Jain Rakesh K. , Duda Dan G.
Published: April 2024

Abstract
Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the anti–programmed cell death protein (PD)-1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti–cytotoxic T lymphocyte antigen (CTLA)-4 when combined with anti–PD-1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels and, when combined with dual CTLA-4/PD-1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+ T cells were necessary for the therapeutic benefit because the efficacy was compromised when CD8+ T cells were depleted. Expression of Cxcr3 on CD8+ T cells is necessary and sufficient because CD8+ T cells from Cxcr3+/+ but not Cxcr3–/– mice rescued efficacy in T cell‒deficient mice. Finally, rational scheduling of anti–CTLA-4 “priming” with chemotherapy followed by anti–PD-1 therapy achieved equivalent efficacy with reduced overall drug exposure. These data suggest that this combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.
Data from Dual Chimeric Antigen Receptor T Cells Targeting CD38 and SLAMF7 with Independent Signaling Demonstrate Preclinical Efficacy and Safety in Multiple Myeloma
Authors: Roders Nathalie , Nakid-Cordero Cecilia , Raineri Fabio , Fayon Maxime , Abecassis Audrey , Choisy Caroline , Nelson Elisabeth , Maillard Claire , Garrick David , Talbot Alexis , Fermand Jean-Paul , Arnulf Bertrand , Bories Jean-Christophe
Published: April 2024

Abstract
Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) induces high overall response rates. However, relapse still occurs and novel strategies for targeting multiple myeloma cells using CAR T-cell therapy are needed. SLAMF7 (also known as CS1) and CD38 on tumor plasma cells represent potential alternative targets for CAR T-cell therapy in multiple myeloma, but their expression on activated T cells and other hematopoietic cells raises concerns about the efficacy and safety of such treatments. Here, we used CRISPR/Cas9 deletion of the CD38 gene in T cells and developed DCAR, a double CAR system targeting CD38 and CS1 through activation and costimulation receptors, respectively. Inactivation of CD38 enhanced the anti–multiple myeloma activity of DCAR T in vitro. Edited DCAR T cells showed strong in vitro and in vivo responses specifically against target cells expressing both CD38 and CS1. Furthermore, we provide evidence that, unlike anti-CD38 CAR T-cell therapy, which elicited a rapid immune reaction against hematopoietic cells in a humanized mouse model, DCAR T cells showed no signs of toxicity. Thus, DCAR T cells could provide a safe and efficient alternative to anti-BCMA CAR T-cell therapy to treat patients with multiple myeloma.
Data from High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models
Authors: Degagné Émilie , Donohoue Paul D. , Roy Suparna , Scherer Jessica , Fowler Tristan W. , Davis Ryan T. , Reyes Gustavo A. , Kwong George , Stanaway Morena , Larroca Vicena Vanina , Mutha Devin , Guo Raymond , Edwards Leslie , Schilling Benjamin , Shaw McKay , Smith Stephen C. , Kohrs Bryan , Kufeldt Heinrich J. , Churchward Glen , Ruan Finey , Nyer David B. , McSweeney Kyle , Irby Matthew J. , Fuller Christopher K. , Banh Lynda , Toh Mckenzi S. , Thompson Matthew , Owen Arthur L.G. , An Zili , Gradia Scott , Skoble Justin , Bryan Mara , Garner Elizabeth , Kanner Steven B.
Published: April 2024

Abstract
Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti–B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor–derived T cells using a Cas12a CRISPR hybrid RNA–DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell–mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M–HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma.

See related Spotlight by Caimi and Melenhorst, p. 385
Figure S2 from Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen
Authors: Zhou Shiqi , Song Yiting , Luo Yuan , Quinn Breandan , Jiao Yang , Long Mark D. , Abrams Scott I. , Lovell Jonathan F.
Published: April 2024

CD8+ or CD4+ T cell depletion with murine anti-CD8 or anti-CD4 monoclonal antibodies
FIGURE 7 from Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen
Authors: Zhou Shiqi , Song Yiting , Luo Yuan , Quinn Breandan , Jiao Yang , Long Mark D. , Abrams Scott I. , Lovell Jonathan F.
Published: April 2024

p15E e-mimotope vaccines inhibit tumor growth after immunization. A, Schedule of vaccination and tumor inoculation for MC38 therapeutic challenge. Mice were inoculated with 1 × 105 MC38 cells subcutaneously followed with immunization with 2 µg peptide loaded liposomal vaccine on days 2 and 9. Tumor volume (B) and the percentage of mice with a tumor diameter <10 mm (C). Tumor volume of individual mice from the control group (D), wild-type group (E), 3M group (F), 3C group (G), and 3C2V group (H). I, Schedule of vaccination and tumor inoculation for B16-F10 prophylactic challenge. J, Tumor volume of all mice. K, Tumor volume on day 13 after tumor inoculation. L, The percentage of mice with a tumor diameter < 10 mm. Datapoints represent mean values of 5 mice from the same group for B and J or individual values of 5 mice from the same group in K. Statistical analysis of K applied one-way ANOVA followed by Tukey multiple comparisons tests. Statistical analysis of C and L applied log-rank (Mantel–Cox) test. * and ** indicating P < 0.05 and 0.01, respectively. Error bars show mean + or ± SD.
FIGURE 4 from Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen
Authors: Zhou Shiqi , Song Yiting , Luo Yuan , Quinn Breandan , Jiao Yang , Long Mark D. , Abrams Scott I. , Lovell Jonathan F.
Published: April 2024

Efficacy of p15E-3C and p15E-3M e-mimotope vaccines at submicrogram peptide doses in prophylactic and therapeutic MC38 tumor challenges. Mice were immunized intramuscularly with CPQ liposomes containing 0.8 µg PHAD, 0.8 µg QS-21, and 0.5 µg p15E wild-type, p15-3C, or p15-3M on days 0 and 7 and were challenged with 1 × 106 MC-38 cells subcutaneously on day 14 (n = 5 mice per group). Individual tumor volumes (A) and the percentage of mice with tumor length under 10 mm (B). For therapeutic challenge, mice were inoculated with 1 × 105 MC-38 cells on day 0 and immunized with 0.5 µg p15E wild-type or 3C or 3M liposomal vaccine on day 2 and 9 (n = 5 mice per group). Individual tumor volumes (C) and the percentage of mice with a tumor <10 mm in diameter (D). Statistical analysis by log-rank (Mantel–Cox) test. * and ** indicates P < 0.05 and 0.01, respectively.
Capecitabine-Related Fourth Nerve Palsy: A Case Report
Authors: Pastore Marco Rocco , Milan Serena , Cirigliano Gabriella , Tognetto Daniele
Published: April 2024

Introduction: Capecitabine has rarely been associated with neurotoxicity. Cerebellar ataxia, multifocal leukoencephalopathy, and sensorimotor peripheral neuropathy have been reported in the literature. A case of 6th nerve palsy associated with capecitabine has also been described. This article reports the first case of capecitabine-related 4th nerve palsy. Case Presentation: A 72-year-old Caucasian woman was referred by the Oncology Department because she had been complaining of binocular diplopia for 6 months. The symptoms started 1 month after the introduction of capecitabine. A diagnosis of right 4th nerve palsy was made using the Parks three-step test and the Hess test. Neuroimaging analysis was negative. A slow but progressive deterioration of function was confirmed during a year of follow-up. On suspicion of a chemotherapy-related palsy, capecitabine was discontinued and switched to vinorelbine. Subsequent improvement of the clinical picture was confirmed within 2 months. Conclusion: The recognition of chemotherapy-related neurotoxicity is of paramount importance in the management of oncology patients. Once secondary invasion of the brain or the orbit by the tumor itself is ruled out, it must be suspected to prevent further deterioration.
Novel Splice Site Pathogenic Variant in STXBP1 Gene in a Child with Intellectual Disability, Epilepsy, and Autism Spectrum Disorder: A Case Report
Authors: Amllal Nada , Lyahyai Jaber , Elalaoui Siham Chafai , El Kadiri Youssef , Sefiani Abdelaziz
Published: April 2024

Introduction: Pathogenic variants in the STXBP1 gene are associated to a large spectrum of severe early onset developmental and epileptic encephalopathies (OMIM #612164). They were also identified in various other neurodevelopmental disorders. This gene encodes for the syntaxin-binding protein 1, a member of the SEC-1 family of membrane-transport proteins that modulate the presynaptic vesicular fusion by interacting with soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). However, the physiopathology of STXBP1 pathogenic variants is not yet fully understood. Case Presentation: Herein, we report a patient presenting intellectual disability, early onset seizures, and autism. Clinical exome sequencing identified a novel monoallelic splice pathogenic variant STXBP1(NM_001032221.6):c.38–2A>G. Discussion: Splice-site pathogenic variants in the STXBP1 gene are mostly associated with West syndrome, early onset epilepsy and encephalopathy, and Ohtahara syndrome. Our findings extend clinical and molecular spectrum of STXBP1 gene variants by reporting the first splice-site variant associated with autism along with early onset epilepsy and, and intellectual disability in a patient.
A Right to Health-Based Approach to Dental Caries: Toward a Comprehensive Control Strategy
Authors: Mollet S. Dominique , Manton David John , Wollgast Jan , Toebes Brigit
Published: April 2024

Background: Health is a matter of human rights, and dental caries is the most common noncommunicable disease globally. Consequently, dental caries is a matter of human rights and its control, particularly prevention, must be a priority. Although largely preventable, this is too often neglected, both in the literature of human rights and health law, and in dental research. The right to oral health has recently been acknowledged by the World Health Organization (WHO), but it is insufficiently clear what this right entails. Summary: This article introduces a right to health-based narrative in the context of dental caries. The right to health is stipulated in human rights treaties, including the International Covenant on Economic, Social and Cultural Rights (ICESCR) and the Convention on the Rights of the Child (CRC). States that are parties to these treaties, which are virtually all States globally, are mandated to ensure the enjoyment of individuals’ right to the highest attainable standard of health, including oral health. Key Messages: Dental caries is a matter of human rights. States have binding obligations to address dental caries: they require the regulation of the healthcare system, i.e., the traditional focus on operative care, but also put the regulation of other risk factors on an equal footing, such as the regulation of the living environment and access to fluoride. A right to health-based approach to dental caries thus offers a comprehensive approach to dental caries control, particularly prevention.
PENGARUH KOMPETENSI SUMBER DAYA MANUSIA DAN AKUNTANSI AKRUAL TERHADAP KUALITAS LAPORAN KEUANGAN
Authors: Agus Agus , Yusuf Muhammad Yusfi , Jaya Andi Hadi Indra
Published: April 2024

Berdasarkan Standar Akuntansi Pemerintahan (SAP), laporan keuangan dapat dijadikan sebagai media informasi akuntabilitas sumber daya atau kinerja keuangan manajemen suatu pemerintahan kepada publik. Namun terdapat beberapa instansi yang masih belum memberikan informasi yang sesuai dengan aturan pemerintah dan terdapat penyimpangan serta kasus yang ditemukan oleh Badan Pemeriksaan Keuangan (BPK). Penelitian ini bertujuan untuk mengetahui serta menganalisis pengaruh kompetensi sumber daya manusia dan akuntansi akrual secara parsial dan simultan terhadap kualitas laporan keuangan pemerintah Provinsi Sulawesi Selatan. Penelitian ini diharapkan mampu memberikan kontribusi terhadap kelangsungan akuntansi pemerintahan, yang dapat digunakan sebagai bahan kajian untuk meningkatkan pengetahuan kapasitas sumber daya manusia pada mutu informasi laporan keuangan pemerintah Provinsi Sulawesi Selatan. Metode penelitian ini menggunakan penelitian kuantitatif dengan menggunakan uji statistik deskriptif, uji kualitas data, uji asumsi klasik serta pengujian hipotesis. Sampel pada penelitian ini sebanyak 82 responden yang berasal dari dua organisasi perangkat daerah yakni Badan Keuangan dan Aset Daerah (BKAD) dan Badan Pendapatan Daerah (BAPENDA) Provinsi Sulawesi Selatan. Data dianalisis dengan menggunakan software SPSS 23. Hasil Penelitian menunjukkan bahwa kompetensi sumber daya manusia dan akuntansi akrual berpengaruh positif dan signifikan secara parsial dan simultan terhadap kualitas laporan keuangan pemerintah Provinsi Sulawesi Selatan.
Nelson Rodrigues e o debate sobre a modernização teatral no Brasil
Authors: Faria João Roberto
Published: April 2024

O presente artigo tem por objetivo apresentar o debate sobre a modernização teatral no Brasil, no final da década de 1930 e início da seguinte. Por meio da pesquisa em jornais e revistas, o artigo traz à tona um conjunto de textos escritos por escritores, dramaturgos e críticos teatrais que se manifestaram sobre o surgimento do teatro amador, identificado com o teatro moderno, e sua oposição ao teatro profissional. Nesse contexto, a estreia de Vestido de noiva, de Nelson Rodrigues, em 1943, consolida a renovação teatral então em curso.
Entre Eros e Tânatos: A arquitetura de personagens com campo de ação coletivo no teatro de Nelson Rodrigues
Authors: Souto Carla Cristina Fernandes , Santos Carlos Vinicius Veneziani dos
Published: April 2024

Partindo das teorias de Pavis (2011) e Prado (1992) a respeito das origens e funções do coro no teatro, Costa (2021) e Greimas (2008) sobre actancialidade, e revendo estudos de Souto (2001 e 2007) sobre Nelson Rodrigues, este artigo tem como desígnio investigar a arquitetura das personagens coletivas (coro) presentes nas peças publicadas pelo dramaturgo entre 1943 e 1962, considerando sua diversidade de formas e promovendo comparações quando ocorre a apresentação ou reintrodução de grupos semelhantes. A proposição consiste em categorizar essas personagens em duas tipologias, ponderando a contribuição de cada agrupamento para a composição do mosaico que dialoga com a obsessão do autor por Eros e Tânatos. A primeira abarca grupos de profissionais, tais como médicos, jornalistas e coveiros. A segunda representa uma espécie de opinião pública julgadora, vinculada aos preconceitos, hipocrisias e ao senso comum da sociedade brasileira.
De retalhos e redes se faz um romance: a criação em Lima Barreto
Authors: Negreiros Carmem
Published: April 2024

The notebooks of Afonso Henriques de Lima Barreto (1881-1922), which he called Retalhos (Scrapbook), are made up of newspaper clippings pasted together without chronological sequence, quotations and sketches of works, handwritten notes. A place of storage and experimentation, the Retalhos suggest traces of the novelist's insertion in the literary life and how the complexity of the context also comes to integrate the work of writing. Destined for the trash, the notebooks unravel the networks that can illuminate the creative process of the Rio writer. In this work, we intend to approach the notebooks from a specific perspective: the production of the novel Triste fim de Policarpo Quaresma (Sad Ending of Policarpo Quaresma), considering the research, collection and storage of newspaper clippings about the cultural context that the work deals with; language exercises that suggest names of characters, scenes and plot themes; the long process of creation that contradicts biographers and critics who consider the production of the novel as a quick action, carried out in between the hustle and bustle of cafes and bars.
Blood Pressure Lowering in Patients With Central Hypertension: A randomized Clinical Trial
Authors: Sharman James E. , Otahal Petr , Stowasser Michael , Stanton Tony , Reid Christopher M. , Nolan Mark , Roberts-Thomson Philip , Negishi Kazuaki , Greenough Robert , Stewart Simon , Marwick Thomas H. , Abhayaratna Walter P.
Published: April 2024

BACKGROUND:

Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension.

METHODS:

This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs.

RESULTS:

At 24-months, there was a greater reduction in left ventricular mass index (−3.2 [95% CI, −5.0 to −1.3] g/m
2
;
P
=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, −6.16 [−9.60 to −2.72] mm Hg and clinic central systolic BP, −4.96 [−8.06 to −1.86] mm Hg;
P
≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, β, 0.17 [0.02–0.31] g/m
2
) or centrally (24-hour systolic BP, β, 0.16 [0.01–0.32] g/m
2
).

CONCLUSIONS:

Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP.

REGISTRATION:

URL:
https://www.anzctr.org.au/
; Unique identifier: ACTRN12613000053729
SIMÃO, I., REYES-BETANCORT, J.A., TALHINHAS, P., MORAIS-CECÍLIO, L. & SILVEIRA, P. (2024) Taxonomic revision of the genus Calendula (Asteraceae) in the Canary Islands. Phytotaxa 640 (2): 125–160.
Authors: SIMÃO INÊS , REYES-BETANCORT J. ALFREDO , TALHINHAS PEDRO , MORAIS-CECÍLIO LEONOR , SILVEIRA PAULO
Published: April 2024

Erratum
MOEIN, F., MAJIDI, R., KHAZAEI, Z. & ALIPOUR, S. (2023) Tulipa sarvestanica (Liliaceae), a new species from south-western Iran. Phytotaxa 630 (1): 87–92.
Authors: MOEIN FATEMEH , MAJIDI RAMIAR , KHAZAEI ZAHRA , ALIPOUR SAJAD
Published: April 2024

Erratum
Novelties in Brachystele Schltr. (Orchidaceae, Orchidoideae): a new synonym and a lectotype, including notes on geographic distribution, phenology, relationships and conservation status
Authors: DOS SANTOS IGOR SOARES , DA SILVA MARCOS JOSÉ
Published: April 2024

During taxonomic studies on the species of Brachystele Schlechter occurring in Brazil, we provide here the typification of B. subfiliformis (Cogniaux) Schlechter, a species endemic to Brazil, and we also propose B. bicrinita Szlachetko under its synonym. Therefore, we provide the updated geographic distribution of B. subfiliformis, its conservation status, images, and comments regarding its environmental preferences, phenology, and morphological relationships.
Lectotypification and a new name in Palicourea for the Brazilian Psychotria dusenii Standl. (Rubiaceae), with remarks on morphology and taxonomy
Authors: TORRES-LEITE FILIPE , CARMO JOÃO AFONSO MARTINS DO , BRUNIERA CARLA POLESELLI , CARRIJO TATIANA TAVARES , GOLDENBERG RENATO
Published: April 2024

Here we propose a lectotypification and a new name for the Brazilian Psychotria dusenii Standl. to be treated under Palicourea Aubl. The name Psychotria dusenii sensu Standley is illegitimate because it was previously assigned to an African Psychotria L. species described by K. Schumann. The new name proposed is Palicourea roseocalycina Torres-Leite.
Two New Taxa of Goniasteridae (Asteroidea, Echinodermata) and Noteworthy Observations of Deep-Sea Asteroidea by the NOAA Ship Okeanos Explorer in the North and Tropical Atlantic
Authors: MAH CHRISTOPHER L.
Published: April 2024

Two new species and one new genus, collected by NOAA ship Okeanos Explorer, Bathyceramaster kelliottae n. sp. and Rhianastra isosceles n. gen., n. sp. (Goniasteridae; Asteroidea) are described from deep-sea settings in the North Atlantic. Two potentially undescribed species are observed from imagery and new in situ observations further elucidate life modes and feeding behavior of several species from North Atlantic deep-sea habitats. New occurrences of Atlantic Neomorphaster are presented and Neomorphaster forcipatus is synonymized with Neomorphaster margaritaceus.
Two new species of Sarothrogammarus (Crustacea, Amphipoda) from Swat Valley, Pakistan
Authors: XIN WENPEI , ZHANG CHAO , ALI ABID , ZHANG XIAOQING , LI SHUQIANG , HOU ZHONGE
Published: April 2024

Two new species of the genus Sarothrogammarus Martynov, 1935 are described and illustrated from Pakistan. Sarothrogammarus miandamensis sp. nov. is characterized by the oval eyes; pereopod III having filtrative setae on merus, carpus and propodus; uropod III terminal article distinct and inner ramus scale-shaped; and having robust setae and slender setae on urosomites I–III. Sarothrogammarus kalamensis sp. nov. can be distinguished from the above species by pereopod III having filtrative setae on merus, but few on carpus and propodus. Detailed morphological characteristics, as well as comparisons with closely related species are provided. Molecular phylogenetic analyses suggest that S. miandamensis sp. nov. is clustered with S. kalamensis sp. nov., with a genetic distance of 19% for COI between the two species.
Morphological description and DNA barcoding of Ceratophysella gracilimucronata sp. nov. (Collembola: Hypogastruridae) from China, with a key to species of the C. armata group of the Sino–Japanese Region
Authors: JIA JUNLI , ZHAO XUEMENG , SKARŻYŃSKI DARIUSZ , WU RUIWEN , CHENG LIPING , AN JIANMEI
Published: April 2024

A new species, Ceratophysella gracilimucronata sp. nov. from Nan Ling Mountains (Guangdong Province, China), is described. It resembles C. ainu (Yosii, 1972), C. glancei Hammer, 1953 and C. falcifer Cassagnau, 1959 due to the B type chaeotataxy and short and slender mucro. Mitochondrial COI gene sequence of C. gracilimucronata sp. nov. is provided. A key to species of the C. armata group of the Sino–Japanese Region is given.
Sublimation of Snow
Authors: Lundquist Jessica D. , Vano Julie , Gutmann Ethan , Hogan Daniel , Schwat Eli , Haugeneder Michael , Mateo Emilio , Oncley Steve , Roden Chris , Osenga Elise , Carver Liz
Published: April 2024

Snow is a vital part of water resources, and sublimation may remove 10%–90% of snowfall from the system. To improve our understanding of the physics that govern sublimation rates, as well as how those rates might change with the climate, we deployed an array of four towers with over 100 instruments from NCAR’s Integrated Surface Flux System from November 2022 to June 2023 in the East River watershed, Colorado, in conjunction with the U.S. Department of Energy’s Surface Atmosphere Integrated Field Laboratory (SAIL) and the National Oceanic and Atmospheric Administration (NOAA)’s Study of Precipitation, the Lower Atmosphere and Surface for Hydrometeorology (SPLASH) campaigns. Mass balance observations, snow pits, particle flux sensors, and terrestrial lidar scans of the evolving snowfield demonstrated how blowing snow influences sublimation rates, which we quantified with latent heat fluxes measured by eddy-covariance systems at heights 1–20 m above the snow surface. Detailed temperature profiles at finer resolutions highlighted the role of the stable boundary layer. Four-stream radiometers indicated the important role of changing albedo in the energy balance and its relationship to water vapor losses. Collectively, these observations span scales from seconds to seasons, from boundary layer turbulence to valley circulation to mesoscale meteorology. We describe the field campaign, highlights in the observations, and outreach and education products we are creating to facilitate cross-disciplinary dialogue and convey relevant findings to those seeking to better understand Colorado River snow and streamflow.
The Impact on Simulated Bow Echoes of Changing Grid Spacing from 3 km to 1 km in the WRF Model
Authors: Dodson Dylan J. , Gallus William A.
Published: April 2024

Ten bow echo events were simulated using the Weather Research and Forecasting (WRF) Model with 3- and 1-km horizontal grid spacing with both the Morrison and Thompson microphysics schemes to determine the impact of refined grid spacing on this often poorly simulated mode of convection. Simulated and observed composite reflectivities were used to classify convective mode. Skill scores were computed to quantify model performance at predicting all modes, and a new bow echo score was created to evaluate specifically the accuracy of bow echo forecasts. The full morphology score for runs using the Thompson scheme was noticeably improved by refined grid spacing, while the skill of Morrison runs did not change appreciably. However, bow echo scores for runs using both schemes improved when grid spacing was refined, with Thompson runs improving most significantly. Additionally, near storm environments were analyzed to understand why the simulated bow echoes changed as grid spacing was changed. A relationship existed between bow echo production and cold pool strength, as well as with the magnitude of microphysical cooling rates. More numerous updrafts were present in 1-km runs, leading to longer intense lines of convection which were more likely to evolve into longer-lived bow echoes in more cases. Large-scale features, such as a low-level jet orientation more perpendicular to the convective line and surface boundaries, often had to be present for bow echoes to occur in the 3-km runs.
Exploring the Potential of Using a Text-Based Game to Inform Simulation Models of Risky Migration Decisions
Authors: Modirrousta-Galian Ariana , Prike Toby , Higham Philip A. , Hinsch Martin , Nurse Sarah , Belabbas Souhila , Bijak Jakub
Published: April 2024

Background

In this paper, we explore the potential of games to collect empirical data for informing agent-based simulation models of migration. To examine the usefulness of game-based approaches, we conducted a simple, yet carefully designed psychological experiment.

Methods

In a preregistered study, we used a novel, immersive experimental setting to investigate the risky migration decisions made by migrants and non-migrants. Participants (284 migrants and 284 non-migrants) played a choice-based interactive fiction game—a fully text-based game where players progress by selecting from a list of possible actions—that involved making three risky migration decisions. In one condition, participants were shown a non-linear progress bar and explicit acknowledgements of the choices they made to promote perceived agency: the feeling that one’s actions have a non-trivial impact on the game. In the other condition, the progress bar was linear, and the explicit acknowledgements were omitted.

Results

Our experimental manipulation was successful; participants in the former condition self-reported higher perceived agency than participants in the latter condition, as did migrants compared to non-migrants. Nevertheless, condition and migrant status did not meaningfully affect the risky migration decisions participants made in the game.

Conclusion

These findings indicate that the results of generic studies on risky migration decisions conducted on non-migrants can potentially inform simulation models of migration. However, these findings were obtained from a single experiment, and thus warrant replication and further research before definitive conclusions can be drawn. Furthermore, a simple text-based game may be too superficial to allow deep insights into the idiosyncrasies of migration decision-making. This suggests a possible trade-off between clear interpretability of the results and the usefulness for informing simulation models of complex social processes, such as migration.
Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A
Authors: Horling Frank M. , Reipert Birgit M. , Allacher Peter , Engl Werner , Pan Luying , Tangada Srilatha
Published: April 2024

Rurioctocog alfa pegol is an extended–half-life full-length recombinant factor VIII (FVIII) bound to 20-kDa polyethylene glycol (PEG) that has been shown to be well tolerated and efficacious in the treatment and prevention of bleeding events in previously treated patients with severe hemophilia A. Here, we present a comprehensive analysis of immunogenicity data collected during 6 clinical studies of rurioctocog alfa pegol, including a total of 360 unique previously treated patients with severe hemophilia A. The analysis included treatment-emerging FVIII-neutralizing antibodies (FVIII inhibitors); preexisting and treatment-emerging antibodies binding to FVIII, PEG-FVIII, or PEG; and treatment-emerging antibodies binding to Chinese hamster ovary host cell proteins. Moreover, the potential association between the presence of these binding antibodies and adverse events (AEs) observed in patients was investigated, and the potential impact of these antibodies on the incremental recovery of rurioctocog alfa pegol in patients was analyzed. Overall, the data indicate that rurioctocog alfa pegol is not associated with any unexpected immunogenicity characteristics. Of 360 patients, 1 patient developed a transient FVIII inhibitor with a titer of 0.6 Bethesda units per mL, which was not associated with any serious AEs. Antibodies binding to FVIII, PEG-FVIII, or PEG were not detected at the time when the inhibitor was present. Moreover, 54 of 360 patients either entered the clinical studies with preexisting binding antibodies or developed these antibodies after exposure to rurioctocog alfa pegol. These antibodies were transient in most patients and did not show any causal relationship to either AEs or spontaneous bleeding episodes.
Single intravenous dose ondansetron induces QT prolongation in adult emergency department patients: a prospective observational study
Authors: Rezaei Zadeh Rukerd Mohammad , Shahrbabaki Fatemeh Rafiei , Movahedi Mitra , Honarmand Amin , Pourzand Pouria , Mirafzal Amirhossein
Published: April 2024

Background

Ondansetron is one of the most commonly used drugs in the emergency department (ED) for treating nausea and vomiting, particularly in intravenous (IV) form. Nevertheless, it has been shown to prolong QT interval and increase the risk of ventricular dysrhythmias. This study evaluated the associations between single IV ondansetron dosage and subsequent QTc prolongation in the ED.

Methods

In this prospective observational study, a total number of 106 patients presenting to the ED in a 3-month period with nausea and vomiting treated with IV ondansetron were enrolled. QT and QTc intervals were measured at baseline (QT0 and QTc0), and 60 min (QT60 and QTc60) following a single-dose administration of ondansetron at 4 or 8 mg doses. To evaluate the predictive ability of these variables, we employed receiver operating characteristic (ROC) curve analyses.

Results

The predictive models for QTc prolongation 1-hour post-ondansetron administration showed the following: at baseline, the area under curve of 0.70 for QT, 0.71 for QTc, and 0.64 for dosage. Conversely, a QTc0 = 375 msec indicated a QTc60 > 480 msec with a specificity of 97%. Additionally, a QTc0 of 400 msec had a sensitivity of 100% in predicting a QTc60 < 480 msec, while a QTc0 > 460 msec predicted a QTc60 > 480 msec with a specificity of 98%. Moreover, 8 mg doses were associated with higher rates of QTc60 prolongation, while 4 mg doses favored maintaining QTc60 within normal limits.

Conclusions

Our study demonstrates the predictive capacity of QT0, QTc0, and ondansetron dosage in forecasting QTc60 prolongation (> 480 msec) post-ondansetron administration. These findings advocate for their incorporation into clinical protocols to enhance safety monitoring in adult ED patients.
Oil-based extraction as an efficient method for the quantification of microplastics in environmental samples
Authors: Lekše Nina , Žgajnar Gotvajn Andreja , Zupančič Marija , Griessler Bulc Tjaša
Published: April 2024

Background

Wastewater treatment plant outlets are a major source of microplastics, with more than 90% retained in sewage sludge. No standardised method for the extraction, quantification, and characterisation of microplastics in sewage sludge or soil exists, and direct comparison of studies is often impossible. Our aim was to validate oil extraction efficiency with and without pre-treatment with Fenton’s reagent of selected microplastics in various types of environmental samples (sewage sludge and organic-rich substrates).

Results

Oxidation with Fenton’s reagent removed up to 90% of organic material, which improves the recovery rate and made quantification and characterisation easier and more reliable, regardless of type, shape, size, or density of the selected microplastic particles used in this study. Pre-treatment, as a pre-step of the oil extraction method, was shown to be important in reducing organic matter in all environmental samples, including sewage sludge and organic-rich substrates. It also improved the reliability of the selected method, shortened its duration, and, by reducing organic matter, made extracted microplastics more visible. The recovery rate was better for particles 1–5 mm and lower for particles 0.1 < 1 mm.

Conclusions

By achieving up to a 100% recovery rate for certain types of microplastics (polypropylene and polystyrene), the selected method proved to be a promising extraction method. It was also shown to be efficient in the organic-rich substrates, for which the characterisation of microplastic particles was done by Fourier transform infrared spectroscopy. The most commonly detected types of microplastics in organic-rich substrates were polyethylene, polypropylene, polystyrene and polyester.
Genetic introgression from commercial European pigs to the indigenous Chinese Lijiang breed and associated changes in phenotypes
Authors: Yang Ruifei , Jin Siqi , Fang Suyun , Yan Dawei , Zhang Hao , Nie Jingru , Liu Jinqiao , Lv Minjuan , Zhang Bo , Dong Xinxing
Published: April 2024

Background

Gene flow is crucial for enhancing economic traits of livestock. In China, breeders have used hybridization strategies for decades to improve livestock performance. Here, we performed whole-genome sequencing of a native Chinese Lijiang pig (LJP) breed. By integrating previously published data, we explored the genetic structure and introgression of genetic components from commercial European pigs (EP) into the LJP, and examined the impact of this introgression on phenotypic traits.

Results

Our analysis revealed significant introgression of EP breeds into the LJP and other domestic pig breeds in China. Using a haplotype-based approach, we quantified introgression levels and compared EP to LJP and other Chinese domestic pigs. The results show that EP introgression is widely prevalent in Chinese domestic pigs, although there are significant differences between breeds. We propose that LJP could potentially act as a mediator for the transmission of EP haplotypes. We also examined the correlation between EP introgression and the number of thoracic vertebrae in LJP and identified VRTN and STUM as candidate genes for this trait.

Conclusions

Our study provides evidence of introgressed European haplotypes in the LJP breed and describes the potential role of EP introgression on phenotypic changes of this indigenous breed.
Microbiome composition as a potential predictor of longevity in rabbits
Authors: Biada Iliyass , Ibáñez-Escriche Noelia , Blasco Agustín , Casto-Rebollo Cristina , Santacreu Maria A.
Published: April 2024

Background

Longevity and resilience are two fundamental traits for more sustainable livestock production. These traits are closely related, as resilient animals tend to have longer lifespans. An interesting criterion for increasing longevity in rabbit could be based on the information provided by its gut microbiome. The gut microbiome is essential for regulating health and plays crucial roles in the development of the immune system. The aim of this research was to investigate if animals with different longevities have different microbial profiles. We sequenced the 16S rRNA gene from soft faeces from 95 does. First, we compared two maternal rabbit lines with different longevities; a standard longevity maternal line (A) and a maternal line (LP) that was founded based on longevity criteria: females with a minimum of 25 parities with an average prolificacy per parity of 9 or more. Second, we compared the gut microbiota of two groups of animals from line LP with different longevities: females that died/were culled with two parities or less (LLP) and females with more than 15 parities (HLP).

Results

Differences in alpha and beta diversity were observed between lines A and LP, and a partial least square discriminant analysis (PLS-DA) showed a high prediction accuracy (> 91%) of classification of animals to line A versus LP (146 amplicon sequence variants (ASV)). The PLS-DA also showed a high prediction accuracy (> 94%) to classify animals to the LLP and HLP groups (53 ASV). Interestingly, some of the most important taxa identified in the PLS-DA were common to both comparisons (Akkermansia, Christensenellaceae R-7, UnculturedEubacteriaceae, among others) and have been reported to be related to resilience and longevity.

Conclusions

Our results indicate that the first parity gut microbiome profile differs between the two rabbit maternal lines (A and LP) and, to a lesser extent, between animals of line LP with different longevities (LLP and HLP). Several genera were able to discriminate animals from the two lines and animals with different longevities, which shows that the gut microbiome could be used as a predictive factor for longevity, or as a selection criterion for these traits.
Predicting condensate formation of protein and RNA under various environmental conditions
Authors: Chin Ka Yin , Ishida Shoichi , Sasaki Yukio , Terayama Kei
Published: April 2024

Background

Liquid–liquid phase separation (LLPS) by biomolecules plays a central role in various biological phenomena and has garnered significant attention. The behavior of LLPS is strongly influenced by the characteristics of RNAs and environmental factors such as pH and temperature, as well as the properties of proteins. Recently, several databases recording LLPS-related biomolecules have been established, and prediction models of LLPS-related phenomena have been explored using these databases. However, a prediction model that concurrently considers proteins, RNAs, and experimental conditions has not been developed due to the limited information available from individual experiments in public databases.

Results

To address this challenge, we have constructed a new dataset, RNAPSEC, which serves each experiment as a data point. This dataset was accomplished by manually collecting data from public literature. Utilizing RNAPSEC, we developed two prediction models that consider a protein, RNA, and experimental conditions. The first model can predict the LLPS behavior of a protein and RNA under given experimental conditions. The second model can predict the required conditions for a given protein and RNA to undergo LLPS.

Conclusions

RNAPSEC and these prediction models are expected to accelerate our understanding of the roles of proteins, RNAs, and environmental factors in LLPS.