bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Tables from Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations
Authors: Bashi Azadeh C. , Coker Elizabeth A. , Bulusu Krishna C. , Jaaks Patricia , Crafter Claire , Lightfoot Howard , Milo Marta , McCarten Katrina , Jenkins David F. , van der Meer Dieudonne , Lynch James T. , Barthorpe Syd , Andersen Courtney L. , Barry Simon T. , Beck Alexandra , Cidado Justin , Gordon Jacob A. , Hall Caitlin , Hall James , Mali Iman , Mironenko Tatiana , Mongeon Kevin , Morris James , Richardson Laura , Smith Paul D. , Tavana Omid , Tolley Charlotte , Thomas Frances , Willis Brandon S. , Yang Wanjuan , O'Connor Mark J. , McDermott Ultan , Critchlow Susan E. , Drew Lisa , Fawell Stephen E. , Mettetal Jerome T. , Garnett Mathew J.
Published: May 2024

List of supplementary tables
Figure 4 from Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations
Authors: Bashi Azadeh C. , Coker Elizabeth A. , Bulusu Krishna C. , Jaaks Patricia , Crafter Claire , Lightfoot Howard , Milo Marta , McCarten Katrina , Jenkins David F. , van der Meer Dieudonne , Lynch James T. , Barthorpe Syd , Andersen Courtney L. , Barry Simon T. , Beck Alexandra , Cidado Justin , Gordon Jacob A. , Hall Caitlin , Hall James , Mali Iman , Mironenko Tatiana , Mongeon Kevin , Morris James , Richardson Laura , Smith Paul D. , Tavana Omid , Tolley Charlotte , Thomas Frances , Willis Brandon S. , Yang Wanjuan , O'Connor Mark J. , McDermott Ultan , Critchlow Susan E. , Drew Lisa , Fawell Stephen E. , Mettetal Jerome T. , Garnett Mathew J.
Published: May 2024

Combination activity of selumetinib plus venetoclax or AZD5991 in AML. A and B, Combo Emax versus HSA scores in 19 AML cell lines exposed to selumetinib combined with (a) venetoclax or (b) AZD5991. C and D, NOMO1 growth inhibition and HSA excess to the combination of selumetinib with (c) venetoclax or (d) AZD5991. E and F, Western blot analysis for apoptosis markers in NOMO1 cells following time course treatment with selumetinib (300 nmol/L) combined with (e) venetoclax (300 nmol/L) or (f) AZD5991 (100 nmol/L). G, Tumor growth in NOMO1 xenografts treated with selumetinib, AZD5991, or venetoclax alone or in combination for 28 days (n = 5 each arm). Control and monotherapy experimental arms were halted once the maximum permitted tumor volume (2,000 cm3) was reached. Data are plotted as mean tumor volume ± SEM.
Figure 1 from Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations
Authors: Bashi Azadeh C. , Coker Elizabeth A. , Bulusu Krishna C. , Jaaks Patricia , Crafter Claire , Lightfoot Howard , Milo Marta , McCarten Katrina , Jenkins David F. , van der Meer Dieudonne , Lynch James T. , Barthorpe Syd , Andersen Courtney L. , Barry Simon T. , Beck Alexandra , Cidado Justin , Gordon Jacob A. , Hall Caitlin , Hall James , Mali Iman , Mironenko Tatiana , Mongeon Kevin , Morris James , Richardson Laura , Smith Paul D. , Tavana Omid , Tolley Charlotte , Thomas Frances , Willis Brandon S. , Yang Wanjuan , O'Connor Mark J. , McDermott Ultan , Critchlow Susan E. , Drew Lisa , Fawell Stephen E. , Mettetal Jerome T. , Garnett Mathew J.
Published: May 2024

Dose response matrix combination screening landscape. A, Schematic of screen and analysis. Created with BioRender.com. B, Overview of cell line cancer types. C, Drug combinations screened grouped by drug target pathways. D, Combo Emax for 755 cell lines screened with 109 combinations. White represents combination/cell line pairs not screened.
Supplementary Table S3 from Cancer Mutations Converge on a Collection of Protein Assemblies to Predict Resistance to Replication Stress
Authors: Zhao Xiaoyu , Singhal Akshat , Park Sungjoon , Kong JungHo , Bachelder Robin , Ideker Trey
Published: May 2024

Table S3 Importance of assemblies in VNN models.xlsx
Figure S5 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: May 2024

Figure S5: PPARγ Antagonist GW9662 modulates induces tumor regression and modulates the TME.
Figure S2 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: May 2024

Figure S2: Innate immune cells are regulated by GM-CSF and contributes to tumorigenesis.
Data from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: May 2024

Abstract
The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression to fuel novel therapies. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation, which supports tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF–PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression. In the absence of TA-AM metabolic support, LUAD cells compensate by increasing cholesterol synthesis, and blocking PPARγ in TA-AMs simultaneous with statin therapy further suppresses tumor progression and increases proinflammatory immune responses. These results reveal new therapeutic combinations for immunotherapy-resistant EGFR-mutant LUADs and demonstrate how cancer cells can metabolically co-opt TA-AMs through GM-CSF–PPARγ signaling to provide nutrients that promote oncogenic signaling and growth.
Significance:
Alternate strategies harnessing anticancer innate immunity are required for lung cancers with poor response rates to T cell–based immunotherapies. This study identifies a targetable, mutually supportive, metabolic relationship between macrophages and transformed epithelium, which is exploited by tumors to obtain metabolic and immunologic support to sustain proliferation and oncogenic signaling.

This article is featured in Selected Articles from This Issue, p. 384
Data from Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms
Authors: Dunbar Andrew J. , Bowman Robert L. , Park Young C. , O'Connor Kavi , Izzo Franco , Myers Robert M. , Karzai Abdul , Zaroogian Zachary , Kim Won Jun , Fernández-Maestre Inés , Waarts Michael R. , Nazir Abbas , Xiao Wenbin , Codilupi Tamara , Brodsky Max , Farina Mirko , Cai Louise , Cai Sheng F. , Wang Benjamin , An Wenbin , Yang Julie L. , Mowla Shoron , Eisman Shira E. , Hanasoge Somasundara Amritha Varshini , Glass Jacob L. , Mishra Tanmay , Houston Remie , Guzzardi Emily , Martinez Benitez Anthony R. , Viny Aaron D. , Koche Richard P. , Meyer Sara C. , Landau Dan A. , Levine Ross L.
Published: May 2024

Abstract
Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic stem/progenitor cells, and extends overall survival to an extent not observed with pharmacologic JAK inhibition, including when cooccurring with somatic Tet2 loss. Our data suggest JAK2V617F represents the best therapeutic target in MPNs and demonstrate the therapeutic relevance of a dual-recombinase system to assess mutant-specific oncogenic dependencies in vivo.
Significance:
Current JAK inhibitors to treat myeloproliferative neoplasms are ineffective at eradicating mutant cells. We developed an endogenously expressed Jak2V617F dual-recombinase knock-in/knock-out model to investigate Jak2V617F oncogenic reversion in vivo. Jak2V617F deletion abrogates MPN features and depletes disease-sustaining MPN stem cells, suggesting improved Jak2V617F targeting offers the potential for greater therapeutic efficacy.

See related commentary by Celik and Challen, p. 701.

This article is featured in Selected Articles from This Issue, p. 695
Supplementary Table 2 from Spatial Mapping of Hematopoietic Clones in Human Bone Marrow
Authors: Young Andrew L. , Davis Hannah C. , Cox Maggie J. , Parsons Tyler M. , Burkart Samantha C. , Bender Diane E. , Sun Lulu , Oh Stephen T. , Challen Grant A.
Published: May 2024

Supplementary Table 2. Sequencing metrics for bulk bone marrow (BM), peripheral blood (PB), and femur head derived bone marrow fragments obtained from hip arthroplasty.
Supplementary Table 1 from Spatial Mapping of Hematopoietic Clones in Human Bone Marrow
Authors: Young Andrew L. , Davis Hannah C. , Cox Maggie J. , Parsons Tyler M. , Burkart Samantha C. , Bender Diane E. , Sun Lulu , Oh Stephen T. , Challen Grant A.
Published: May 2024

Supplementary Table 1. Panel of genes targeted by the Myeloseq assay.
Table S4 from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental Table 4 shows raw baseline BH3 profiling data on matched pre- and post-resistant AML PDX models.
Supplemental Table Legends from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental table legends 1-4.
Figure S7 from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental Figure 7 shows relapsed or primary refractory AML patients demonstrate reduced ex vivo drug sensitivity compared to diagnosis AML patients.
Figure S6 from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental Figure 6 shows drug response data in AML patient samples at diagnosis and relapse.
Figure S2 from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental Figure 2 shows RNA-seq signature of drug-resistant AML PDX models.
Figure S12 from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental Figure 12 shows targeted agents cluster by mechanism of action.
Figure S10 from Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Olesinski Elyse A. , Bhatia Karanpreet Singh , Wang Chuqi , Pioso Marissa S. , Lin Xiao Xian , Mamdouh Ahmed M. , Ng Shu Xuan , Sandhu Vedant , Jasdanwala Shaista Shabbir , Yilma Binyam , Bohl Stephan , Ryan Jeremy A. , Malani Disha , Luskin Marlise R. , Kallioniemi Olli , Porkka Kimmo , Adamia Sophia , Chng Wee Joo , Osato Motomi , Weinstock David M. , Garcia Jacqueline S. , Letai Anthony , Bhatt Shruti
Published: May 2024

Supplemental Figure 10 shows immunoblotting of FLT-3 signaling pathway in quizartinib-resistant AML PDX models.
Imobilizações de urgência em traumatologia
Authors: Fusco Enéas Brasiliense
Published: May 2024

O autor realizou uma exposição sistematizada das técnicas de imobilização de urgência em traumatologia, ilustrada com 51 figuras. Em face da pobreza de literatura, tanto nacional como estrangeira, sobre este assunto básico, o autor forneceu sua experiência de dez anos no Pronto Socorro do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.
Aspectos neurológicos da tuberculose
Authors: Assis José Lamartine de
Published: May 2024

Apôs ressaltar a importância do tema, a freqüência da neurotuberculose no País e as atuais possibilidades de tratamento, o autor sintetiza os principais tópicos referentes à etiopatogenia e à anatomia patológica.A seguir, descreve as características clínicas da neurotuberculose, considerando três formas principais: meningencefalite subaguda difusa, forma hipertensiva e forma tumoral. O diagnóstico é discutido sob os aspectos clínico, laboratorial e diferencial, ressaltando o valor do exame do líquido cefalorraquidiano no diagnóstico precoce da meningencefalite; referência especial é feita à progressiva baixa dos cloretos, como elemento dos mais sugestivos para o diagnóstico.Finalmente, o autor faz considerações sobre o tratamento, dividindo o assunto em duas partes: tratamento médico e tratamento cirúrgico. No primeiro, estuda as drogas standard, as de reserva e as adjuvantes; no segundo, aponta as técnicas mais usadas, destacando as derivações extracranianas.
Origem da hipercolesterolemia na síndrome nefrótica experimental
Authors: Editores Os
Published: May 2024

Foi efetuado o balanço contínuo de esteróides (15 a 20 dias) em 16 ratos nefróticos (N) e 8 controles (C). Em toda a experiência (duração de aproximadamente 2 meses), os animais ingeriram quantidades rigorosamente iguais de uma dieta balanceada e isenta de esteróides e, foi medida regularmente sua proteinúria para avaliação do grau de nefrose. Também foram medidos o colesterol e albumina no plasma.Após o período experimental, os ratos foram exsanguinados. Fígado, carcassa (excluídos o intestino e o sistema nervoso central) e fezes foram analisadas por cronatografia gás-líquido de esteróides após hidrólise alcalina, extração e cromatografia camada fina das amostras. As perdasde material foram corrigidas pela edição de colesterol e ácido eólico radioativos às amostras no início do processamento metodológico.Os resultados mostram que a excreção feudal em N permanecer igual a de C mas que houve um real acréscimo no conteúdo em colesterol de sangue, fígado e carcassa indicando ter havido uma síntese aumentada em N.A possível relação entre o metabolismo protêico e síntese hepática de colesterol na síndrome nefrótica é discutida.
Herpes vírus simples e carcinoma cérvico-uterino
Authors: Souen Jorge Saad , Pinheiro Walter , Sun Chen Rei , Yamada Terezinha , Salvatore Carlos Alberto
Published: May 2024

Nos últimos anos tem-se imputado relevante papel ao herpes vírus simples (HSV), como agente etiológico do carcinoma cérvico-uterino. Tal premissa baseia-se em dados epidemiológicos, similares em ambas as condições: a infecciosa e a neoplásica. Sabendo-se da possibilidade,comprovada experimentalmente e, às vezes clinicamente, de vírus constituirem-se em agentes neoplásicos, aventou-se a hipótese acima referida. No intuito de colaborar no esclarecimento de tão importante questão, procuramos, em nosso meio, pesquisar essa possibilidade. Efetuamos estudos clínico-anamnésticos, citológico, virológicos e sorológicos em portadoras de câncer comparando-as a mulheres de grupo controle. As três primeiras pesquisas objetivaram surpreender a presençamomentânea do vírus; e a última permitiu intuir uma possível infecção pregressa, que possivelmente possa ter induzido à oncogênese. A análise suscinta clínico-anamnéstica pesquisou sintomas e sinais de infecção presente e passada na mulher e no parceiro. O estudo citológico, demonstrando características celulares típicas de doença herpética, autorizou-nos, com certa precisão, detectar a presença do vírus. Igualmente o estudo virológico, através de efeitos indiretos citopáticos em culturas de células, acarretados pelo herpes, denunciou a presença de tal micro-organismo. O estudo sorológico procurou detectar no sangue periférico, anti-corpos anti-SHV, por meio de uma reação de fixação de complemento. Os nossos estudos não demonstraram que as cancerosas eram mais assíduamente suspeitas de infecção herpética atual ou passada.
Tratamento cirúrgico da insuficiência coronária
Authors: Stolf Noedir Antonio Groppo , Fernandes Paulo Manuel Pêgo
Published: May 2024

São revistas de maneira concisa vários espectos relacionados com o tratamento Cirúrgico da Insuficiência Coronária. Esses aspectos são abordados nos seguintes itens. 1. Incidência da doença coronária e histórico da Cirurgia de Coronárias. 2. Técnicas de revascularização do miocárdio. 3. Indicação da Cirurgia. 4. Os resultados da Cirurgia em relação a sobrevida dos pacientes, permeabilidade dos enxertos, morbidade da cirurgia, resultados funcionais.Baseados nesses dados são estabelecidas algumas conclusões.
Grafismos
Authors: Hansen José
Published: May 2024

Sem resumo.
Elementos da gênese da trilogia Wallenstein
Authors: Franceschini Pedro Augusto da Costa
Published: May 2024

A trilogia Wallenstein, de Schiller, cuja estreia nos palcos de Weimar se deu em 1798 e 1799, tem um longo período de gênese, acompanhando suas mais importantes discussões estéticas com Goethe durante a década de 1790. Nesse artigo, gostaríamos de delinear alguns elementos centrais desse processo, sobretudo a partir da correspondência entre ambos: o problema da forma trágica, a crítica ao drama então dominante, a recuperação dos princípios artístico da Antiguidade e uma releitura de Shakespeare. Desse modo, os desafios envolvidos na criação do Wallenstein, como uma tragédia moderna, testemunham a experimentação e a efetivação de temas importantes da profunda reflexão sobre a arte desenvolvida por Schiller e Goethe na virada do século.
Do padrão do gosto em Hume: a crítica e a racionalidade
Authors: Cachel Andrea
Published: May 2024

Hume shows, in the "Of the standard of taste" essay, how, despite the diversity inherent to taste, it is possible to establish an universal standard in thís matter, standing not on the object, but in human nature itself. He also poínts, however, that the finding of this standard is a result of experience, particularly, of that related to the practice of aesthetic criticism. He seems to establísh, therefore, the refinement as an essential item not only of the discovery of the standard of taste, but also as a component in the constitution of this standard. Our intention is, in this context, to investigate the role, in humean philosophy, of regulation in the processof establishing an universal principie for taste, as wellas pointing to, at last, some consequences of this subject to the analysis of the possibility of establishing a standard of rationality in a philosophy that separates experimental reason from demonstrative reason.
Counteracting Angiotensinogen Small-Interfering RNA-Mediated Antihypertensive Effects With REVERSIR
Authors: Ye Dien , Cruz-López Edwyn O. , Veghel Richard van , Garrelds Ingrid M. , Kasper Anne , Wassarman Kelly , Tu Ho-Chou , Zlatev Ivan , Danser A.H. Jan
Published: May 2024

BACKGROUND:

Small-interfering RNA (siRNA) targeting hepatic AGT (angiotensinogen) mRNA depletes AGT, lowering blood pressure for up to 6 months. However, certain situations may require a rapid angiotensin increase. The REVERSIR (RVR) - reverse siRNA silencing technology a potential approach to counteract siRNA effects.

METHODS:

Spontaneously hypertensive rats received 10 mg/kg AGT siRNA, and 3 weeks later were given AGT-RVR (1, 10, or 20 mg/kg). One week after AGT-RVR dosing, a redose of AGT siRNA assessed its post-AGT-RVR effectiveness for 2 weeks. Additionally, the impact of AGT-RVR after an equihypotensive dose of valsartan (4 mg/kg per day) was examined.

RESULTS:

Baseline mean arterial pressure (MAP) was 144±1 mm Hg. AGT siRNA reduced MAP by ≈16 mm Hg and AGT by >95%, while renin increased 25-fold. All AGT-RVR doses restored MAP to baseline within 4 to 7 days. Notably, 10 and 20 mg/kg restored AGT and renin to baseline, while 1 mg/kg allowed ≈50% AGT restoration, with renin remaining above baseline. A second AGT siRNA treatment, following 1 mg/kg AGT-RVR, reduced MAP to the same degree as the initial dose, while following 10 mg/kg AGT-RVR, it resulted in ≈50% of the first dose’s MAP effect at 2 weeks. The valsartan-induced MAP reduction was unaffected by AGT-RVR.

CONCLUSIONS:

In spontaneously hypertensive rats, angiotensinogen-RVR dose-dependently reversed AGT siRNA-induced AGT reduction, normalizing MAP. MAP normalization persisted even with 50% recovered AGT levels, likely due to upregulated renin maintaining adequate angiotensin generation. Post-AGT-RVR dosing, a second AGT siRNA dose lowered MAP again.
Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study
Authors: Shimbo Daichi , Cohen Morgan T. , McGoldrick Matthew , Ensari Ipek , Diaz Keith M. , Fu Jie , Duran Andrea T. , Zhao Shuqing , Suls Jerry M. , Burg Matthew M. , Chaplin William F.
Published: May 2024

Background

Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health.

Methods and Results

Apparently healthy adult participants (n=280) were randomized to an 8‐minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre−/post‐assessments of endothelial health including endothelium‐dependent vasodilation (reactive hyperemia index), circulating endothelial cell‐derived microparticles (CD62E+, CD31+/CD42−, and CD31+/Annexin V+) and circulating bone marrow‐derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (
P
=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (
P
=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (
P
=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell‐derived microparticles and endothelial progenitor cells from baseline to 40 minutes.

Conclusions

In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium‐dependent vasodilation.
Moyamoya Vasculopathy and Moyamoya-Related Systemic Vasculopathy: A Review With Histopathological and Genetic Viewpoints
Authors: Abumiya Takeo , Fujimura Miki
Published: May 2024

Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed.
Porphyry’s Account of Justice in On Abstinence
Authors: Tuominen Miira
Published: May 2024

In this essay, I argue for a new analysis of Porphyry’s argument for justice in On abstinence. I aim to show that (i) in addition to being an inner order of soul, justice is attributed to external actions and (ii) justice of actions consists in refraining from harming harmless living creatures, including animals and plants. The relevant harm, I argue, consists in taking the lives of living creatures and taking products from them by force or without care. I contend that Porphyry extends moral concern for others to all living creatures, but not merely on the basis of animal suffering. Finally, I argue that that the hierarchy of godlikeness in On abstinence does not support the subordination of moral concern for animals and plants to higher virtues of purity and theory.
Irish Liberty, Black Slavery, and the Green Atlantic
Authors: MacGiollabhuí Muiris
Published: May 2024

This article explores the relationship that the United Irishmen, Irish revolutionaries of the 1790s, had with slavery during the Revolutionary Period. The United Irishmen were exiled by the British Government as a result of a failed rebellion in 1798 and were exile throughout the Atlantic World. For the exiled United Irishmen, the United States became a primary destination for their exile, and here, slavery became an important source of disunity. In Ireland, resistance to slavery was assumed across the entire membership of the United Irishmen, but in exile, this unity diminished. In conversation with past histories, this scholarship focuses on the limitations of Jacobinism as a political ideology and the prominence of rhetoric in revolutionary ideologies of the period.
The Role of Institutional Networks in the Implementation of Innovative Collaborative Devices of Teacher Professional Development
Authors: Artigue Michèle , Masselin Blandine
Published: May 2024

This article aims to contribute to the body of knowledge developed by mathematics education research on the implementation of innovative TPD devices, i.e. organized systems of arrangements for professional development of mathematics teachers, that emphasize their collaborative work and have a strong bottom-up dimension, as well as to the development of analysis and modelling tools to guide and report on such research. More specifically, drawing on the systemic, institutional and ecological perspective of the anthropological theory of the didactic, we study the dynamics of implementation of such a device, which appeared in France in 2017, paying particular attention to the role played by institutional networks in its dynamics. To do this, we use concepts from the theory of hypergraphs and show their usefulness for modelling the dynamics at stake, a usefulness which, we assume, is not limited to this case study.

The impact sheet to this article can be accessed at 10.6084/m9.figshare.25507258.
The Tassels of Royal and Divine Sasanian Horses
Authors: Potts Daniel T.
Published: May 2024

While a great deal of time and effort has been spent on the identification of those human and divine actors featured on the Sasanian reliefs and silver vessels, much energy has also been expended on understanding the realia illustrated. Many interpretations of the so-called ‘tassels’ (Ger. Quasten, Pferdequasten, Puscheln, Troddeln; Fr. glands, houppes) shown suspended by chains, usually below, alongside or above a horse’s haunches, have been suggested. The purpose of this short note is to re-visit the topic and to suggest a viable interpretation which, although mooted in the past, has never been fully articulated.
New species of the plant bug genus Neolygus Knight from Japan, Taiwan and Thailand (Hemiptera: Heteroptera: Miridae: Mirini)
Authors: YASUNAGA TOMOHIDE
Published: May 2024

Ten new species of the Holarctic-Oriental mirine genus Neolygus Knight are documented, on the basis of specimens collected from eastern Asia and the Oriental Region: N. autumnus n. sp., N. chichibumontis n. sp., N. chikanoshima n. sp., N. hasegawai n. sp. and N. yonanus n. sp. (Japan); N. babai n. sp., N. formosaroseus n. sp., N. fuscovultus n. sp. and N. rufifemoratus n. sp. (Taiwan); and N. chaiyaphum n. sp. (Thailand). The generic characters are discussed, and a Japanese taxon, Neolygus tsugaruensis (Yasunaga, 1992), is herein proposed as a junior synonym of N. roseus (Yasunaga, 1991). Updated key to Japanese species and checklist of the Old World congeners are also provided.
Preparation of Reinforcement Coupler Grouting Material Based on the Orthogonal Design
Authors: Shen Hai-You , Zhang Xi-Wen , Zhao Peng , Liu Geng-Le , Hou Wei-Xing , Zhai Zi-Quan , Xiang Tai-Zhi
Published: May 2024

Due to escalating labor costs and the conclusion of the demographic dividend in China, prefabricated construction has rapidly advanced, with coupler grouting material playing a pivotal role in these structures. The optimal Ordinary Portland Cement (OPC) to Sulphoaluminate Cement (SAC)
mass ratio of 9:1 was established for the material of grouting by formulating the material of grouting through combined use of OPC and SAC in a mass ratio of 9:1 and assessing the composite’s strength, fluidity, and setting time. Subsequent controlled experiments determined the optimal
water-to-binder and binder-to-sand ratios to be 0.26 and 1:1, respectively. Using orthogonal experimental design, the ideal mix of mineral additives was identified. A detailed range and variance analysis determined the optimal mass ratios: 3% silica fume, 7% slag powder, and 5% fly ash. Further
experimentation with polycarboxylate water-reducer, organosilicon defoamer, and UEA expanding agent in single admixture trials led to the selection of the most effective dosages: water-reducer at 0.3%, defoamer at 0.05%, and UEA expanding agent between 0.03% and 0.05%, meeting the standard
requirements for grouting materials.
Advanced Lightweight Structural Materials for Automobiles: Properties, Manipulation, and Perspective
Authors: Guo Honghe , Zhou Xiaoguang , Liu Zhenyu
Published: May 2024

The key drivers for automotive manufacturers to develop vehicles with decreased weight are the growing requirements for improved fuel efficiency. This endeavor not only tackles the issues related to fuel efficiency but also aligns with the objectives of enhanced recyclability and overall
performance of the vehicle, encompassing factors like driving efficiency, braking characteristics, and collision safety. Herein, a successful strategy entails investigating and utilizing lightweight materials with superior performance as substitutes for conventional automotive materials such
as cast iron and steel. This article provides a thorough analysis of the lightweight materials that are currently being researched and available for use in the production of next-generation cars. These materials include composites, light alloys, high-strength steel, and other innovative materials.
The review covers all aspects of the life cycle of automotive materials, examining their mechanical and physical characteristics, production processes, characterization strategies, and their uses. Both the merits and limitations of these materials are analyzed, leading to a nuanced understanding
of suitable scenarios for their application. In anticipation of future challenges, the study suggests that advancements in versatile materials or enhancements in manufacturing and treatment techniques hold promise for overcoming potential obstacles, ultimately facilitating the creation of
more capable, safer, durable, and environmentally friendly vehicles.
Co-occurrence of patent foramen ovale and Chiari network in a diabetic patient
Authors: Abouzahir Hind , Belhouss Ahmed , Benyaich Hicham
Published: May 2024

Introduction

The coexistence of congenital cardiovascular anomalies provides valuable insights into the intricate nature of human cardiac anatomy and its potential interactions with underlying health conditions. This case report presents an autopsy analysis of a diabetic patient manifesting both a patent foramen ovale and a Chiari network.

Case presentation

A 26-year-old male with a history of type 2 diabetes mellitus was admitted with post cardiac arrest. He died despite resuscitative efforts. Autopsy revealed notable findings including a patent foramen ovale and a Chiari network. Post-mortem biochemical markers indicated elevated HbA1c level and hyperglycaemia. The absence of cryptogenic strokes or paradoxical embolism prompted exploration into potential relationships between these anomalies and metabolic disturbances, and prompts a discussion about whether the observed anatomical variations could potentially serve as risk factors contributing to the patient's death due to complications of diabetes.

Conclusion

The co-occurrence of a patent foramen ovale and a Chiari network within a diabetic patient, accompanied by elevated HbA1c level and hyperglycaemia, offers a unique perspective on the convergence of congenital cardiovascular variation and metabolic health. The juxtaposition of these anomalies with biochemical markers underscores the intricate interplay between cardiac morphology and metabolic conditions.
Undiagnosed rheumatic carditis causing sudden death in a young adult: A case report and review
Authors: Singh Bajrang K , Tomar Jitendra S , Jain Ravi , Prakash Surya , Narayan Suyasha
Published: May 2024

Acute rheumatic fever-related acquired heart disease in children and young adults is a worldwide issue, but it poses a serious public health threat in developing nations like India. We present a case report of a young adult who collapsed suddenly during a routine walk and was declared dead in an emergency ward on arrival. There was no significant past medical history. On autopsy, massive cardiomegaly and a “butter and bread” appearance of the pericardium, along with findings suggestive of mitral stenosis and aortic regurgitation, raised suspicion about rheumatic heart disease. Rheumatic carditis was confirmed by a microscopic examination that showed Aschoff bodies in the left ventricle, mitral valve and interventricular septum, in addition to uncommon Anitschkow cells in the left ventricle. A sudden death due to undiagnosed rheumatic carditis causing such massive cardiomegaly is rare. This case highlights the need to keep rheumatic carditis as a cause of sudden death.
A review of noteworthy progress and opportunities in swimsuit design
Authors: Li Shuyang , Zhao Fuwang , Li Li
Published: May 2024

Swimsuits represent an interdisciplinary research field of textiles and clothing, materials, bionics, fluid mechanics, and other disciplines. The aesthetic style, comfort design, speed performance, and additional functions of swimsuits have been studied extensively. However, due to the diversity of research topics, swimsuit-related research is scattered in various research branches. An overview of research progress and frontiers in this whole field is hard to find. Given that a comprehensive application of technologies is required to meet consumers’ increasing demands for more functional and professional sports products, it is necessary to have knowledge of the latest progress in each research area. This study covers the aesthetics, comfort, speed enhancement, and other additional functions of swimsuits, summarizes the research progress in each relevant area, and predicts potential hotspots based on analysis. It is predicted that smart textiles and technologies will be applied more widely to swimsuits for real-time monitoring and instruction, intelligent drag reduction, energy harvesting, etc. With the upgrade of each function, efforts will be needed to maintain the delicate balance between the multiple functions integrated into swimsuits, and a more refined classification will be required to meet the specialized demands of swimmers.
Measuring the impact of ginning stages on cotton fiber quality in the context of west and central Africa
Authors: Togola Mamadou , Gourlot Jean-Paul , Bachelier Bruno , Coulibaly Massa , Traoré Abdoul Karim , Gozé Eric
Published: May 2024

The ginning process has an effect on fiber quality. Avoiding fiber quality deterioration due to mistune or overspeed is crucial, especially in west and central Africa where value chains are highly dependent on prices paid for premium fiber quality. Indeed, fiber classification alone does not permit a reliable measurement of ginning impact, as it depends on many factors such as incoming seed cotton quality, equipment type, number, and settings within each ginning process stage. This study describes a sampling and analysis method precise enough to detect any commercial impact on fiber quality at each main ginning stage. It is based on fiber quality characteristic measurements before and after each main stage: seed cotton cleaning, ginning, and lint cleaning. The sampling and testing protocol was applied in Mali in seven industrial gins during the 2015–2016 ginning season. Seed cotton samples were taken before and after the seed cotton cleaning stage, and fiber samples before and after the lint cleaning stage. Seed cotton samples were ginned with a reference saw micro-gin. The precision of fiber characterization was measured by replicating twice each fiber sample characterization in a laboratory meeting the international standards. Based on the variability measured in Mali, we determined for each fiber characteristic the number of replicates required to detect any commercially harmful impact. Growing and ginning conditions in Mali are representative of those in west and central Africa. Based on this method, one needs to develop an on-line tool to measure fiber quality at every stage of industrial ginning.
Textile sorption and release of odorous volatile organic compounds from a synthetic sweat solution
Authors: McQueen Rachel H , Eyres Graham T , Laing Raechel M
Published: May 2024

Body odorants typically transfer to clothing fabrics by way of liquid sweat, yet investigations of odor retention in textiles often neglect this route of exposure in their test procedures. This paper describes a novel method for transferring selected odorous volatile organic compounds to six types of textile fibers in yarn bundle form by an aqueous sweat solution. Headspace volatile organic compounds varying by chemical class (ketones, aldehydes, carboxylic acids) were monitored at discrete time intervals (30 min, 3 h, 24 h) using proton transfer reaction mass spectrometry. Lower intensities of ketones and aldehydes were detected in the headspace above cellulosic fibers (cotton, mercerized cotton, viscose) than above wool, nylon, and polyester fibers at 30 min. A rapid decrease in ketones occurred for all fibers, but lower intensities of ketones were released after 3 h for cellulosic and wool fibers. Nylon fibers typically released the highest amounts of ketones and aldehydes at 30 min, but by 24 h higher intensities of these compounds were released from polyester. Carboxylic acids exhibited minimal differences in intensities between 30 min and 3 h, with few differences evident among fiber types. Understanding the preferential sorption of odorants when clothing is exposed to volatile organic compounds in aqueous solutions such as sweat is enhanced from the results of this investigation.
The impact of stroke on employment income: A cohort study using hospital and income tax data in Ontario, Canada
Authors: Duong Patrick , Egan Mary , Meyer Matthew , Morrison Tricia , Sauvé-Schenk Katrine
Published: May 2024

Objective

To document the impact of stroke on employment income among people employed at the time of stroke.

Design

Population-based cohort study.

Participants

People hospitalized for stroke in Ontario, Canada (2010–2014) and people without stroke matched on demographic characteristics.

Main measures

Robust Poisson regression to estimate the effects of stroke on the probability of reporting employment income on tax returns over 3 years. Quantile regression difference-in-differences to estimate the changes in annual employment income attributable to stroke.

Results

Stroke survivors were increasingly less likely to report any employment income poststroke, incidence rate ratios (IRR) 0.87 at 1 year (95% confidence intervals [CI]; 0.85–0.88), 0.82 at 2 years (95% CI; 0.81–0.84) and 0.81 at 3 years (95% CI; 0.79–0.82). IRR for reporting at least 50% of prestroke income levels were 0.76 at 1 year (95% CI; 0.75–0.78), 0.75 at 2 years (95% CI; 0.73–0.77) and 0.73 at 3 years (95% CI; 0.71–0.75). IRR for reporting at least 90% of prestroke income levels were 0.72 at 1 year (95% CI; 0.70–0.74), 0.66 at 2 years (95% CI; 0.64–0.68) and again 0.66 at 3 years (95% CI; 0.64–0.68). Relative changes in annual employment income attributable to stroke varied from a decrease of 13.8% (95% CI; 8.7–18.9) at the 75th income percentile to a decrease of 43.1% (95% CI; 18.7–67.6) at the 25th income percentile.

Conclusions

It is important for healthcare and service providers to recognize the impact of stroke on return to prestroke levels of employment income. Low-income stroke survivors experience a more drastic loss in employment income and may need additional social support.
Rural Botanical Knowledge in Urbanity: Restructurings and Resignifications in the Peripheries of a Patagonian City in Argentina
Authors: Molares S. , Ferreras I. , Hechem V.
Published: May 2024

The botanical knowledge of Mapuche people settled on the peripheries of Esquel city (Argentine Patagonia) was compared with that of urban residents in order to know their particularities, and to understand how rural–urban (rurban) hybridization resignifies their practices and medicinal plants richness for better adaptation to city life. Interviews were conducted with a sample of 79 patients attending primary health care centers (33 rurban Mapuches, 46 urban), and data were qualitative–quantitatively analyzed. Rurban residents cite similar plant richness to that of urban ones (∼69 species), though they are different in composition. Local medicinal flora provides responses to diseases with a similar incidence in both groups, but each group addresses them based on the resources it recognizes as most effective and accessible. The rurban system is flexible facing the challenge that life in the city implies, evidencing the incorporation and replacement of native resources by exotic ones as an expression of restructuring processes and cultural diversification. These changes allow for recreation of memory about the importance of medicinal plants, and adjustment of therapeutic practices to a present time, having different needs from those of rurality. Urban residents incorporate plants from Mapuche pharmacopoeia, some of which are on visualization, evidencing bidirectional resource and ethnobotanical knowledge transference between groups. As a conclusion, this case study points out the importance of recognizing rurbanity as a starting point for the establishment of public policies that improve governance and access to health for Mapuche migrants in the city.