bluuebunny/crossref_metadata_2025 huggingface dataset:
Duvelisib Eliminates CLL B Cells, Impairs CLL-Supporting Cells, and Overcomes Ibrutinib Resistance in a Xenograft Model
Authors: Chen Shih-Shih , Barrientos Jacqueline C. , Ferrer Gerardo , King-Richards Morgan , Chen Yu-Ju , Ravichandran Priyadarshini , Ibrahim Michael , Kieso Yasmine , Waters Sheila , Kutok Jeffery L. , Peluso Marisa , Sharma Sujata , Weaver David T. , Pachter Jonathan A. , Rai Kanti R. , Chiorazzi Nicholas
Published: April 2023

Purpose:

Inhibitors of Bruton's tyrosine kinase (BTKi) and PI3K (PI3Ki) have significantly improved therapy of chronic lymphocytic leukemia (CLL). However, the emergence of resistance to BTKi has introduced an unmet therapeutic need. Hence, we sought evidence for essential roles of PI3K-δi and PI3K-γi in treatment-naïve and BTKi-refractory CLL.

Experimental Design:

Responses to PI3K-δi, PI3K-γi, and the dual-inhibitor duvelisib in each B, T, and myeloid cell compartments of CLL were studied in vitro, and in a xenograft mouse model using primary cells from treatment-naïve and ibrutinib-resistant patients, and finally, in a patient with ibrutinib-resistant CLL treated with duvelisib.

Results:

We demonstrate the essential roles of PI3K-δ for CLL B-cell survival and migration, of PI3K-γ for T-cell migration and macrophage polarization, and of dual inhibition of PI3K-δ,γ for efficacious reduction of leukemia burden. We also show that samples from patients whose disease progressed on ibrutinib were responsive to duvelisib therapy in a xenograft model, irrespective of BTK mutations. In support of this, we report a patient with ibrutinib-resistant CLL, bearing a clone with BTK and PLCγ2 mutations, who responded immediately to single-agent duvelisib with redistribution lymphocytosis followed by a partial clinical remission associated with modulation of T and myeloid cells.

Conclusions:

Our data define the mechanism of action whereby dual inhibition of PI3K-δ,γ affects CLL B-cell numbers and T and myeloid cell pro-leukemia functions and support the use of duvelisib as a valuable approach for therapeutic interventions, including for patients refractory to BTKi.
FDA Oncology Center of Excellence Crowdsourcing Initiative: Outreach to the Scientific Community to Identify Research Questions for Pooled Analyses of Oncology Clinical Trial Data
Authors: Schneider Julie A. , Eckstein Julia , Goldberg Kirsten B. , Ascione Mark C. , Bailey Thamar , Taylor Kimberly , Coffey Aisha M. , Satchi Darshini , Philips Howard , Sridhara Rajeshwari , Nair Abhilasha , Pazdur Richard , Theoret Marc R.
Published: April 2023

The FDA Oncology Center of Excellence recently launched a crowdsourcing pilot to request ideas from the scientific community for research questions that FDA could address with pooled analyses of clinical trial data submitted to the agency for regulatory purposes. This effort builds on FDA's track record of publishing pooled analyses to explore scientific questions that cannot be addressed in a single trial due to limited sample size. The research crowdsourcing pilot tested a new approach for obtaining external input on regulatory science activities, because FDA is generally unable to share patient-level data outside of the agency due to federal disclosure laws and regulations protecting different types of data submitted in regulatory applications. We received 29 submissions over the 28-day crowdsourcing campaign, including one research idea that we are exploring for possible follow-up. Based on our experience with this pilot, we learned that crowdsourcing is a promising new approach to gather external input and feedback. We identified opportunities to build understanding in the external oncology community about the types of data typically included in regulatory applications and expand the dissemination of published FDA pooled analyses to help inform future drug development and clinical practice.
Data from Targeting RET Solvent-Front Mutants with Alkynyl Nicotinamide-Based Inhibitors
Authors: Khatri Ujjwol , Dayal Neetu , Hu Xueqing , Larocque Elizabeth , Naganna Nimishetti , Shen Tao , Liu Xuan , Holtsberg Frederick W. , Aman M. Javad , Sintim Herman O. , Wu Jie
Published: April 2023

Abstract
Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, RET mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation RET TKIs. While acquired RET G810C/R/S/V mutations were reported in selpercatinib-treated patients, it was unclear whether all of these and other potential G810 mutants are resistant to selpercatinib and pralsetinib. Here, we profiled selpercatinib and pralsetinib on all six possible G810 mutants derived from single nucleotide substitution and developed novel alkynyl nicotinamide-based RET TKIs to inhibit selpercatinib/pralsetinib-resistant RET G810 mutants. Surprisingly, the G810V mutant found in a clinical study was not resistant to selpercatinib or pralsetinib. Besides G810C/R/S, G810D also conferred selpercatinib/pralsetinib resistance. Alkynyl nicotinamide compounds such as HSN608, HSL476, and HSL468 have better drug-like properties than alkynyl benzamides. Six of these compounds inhibited all six G810 solvent-front mutants and the V804M gatekeeper mutant with IC50 < 50 nmol/L in cell culture. Oral administration of HSN608 at a well-tolerated dose (30 mg/kg) gave plasma level > 30x the IC50s of inhibiting all G810 mutants in cell culture. In cell-derived xenograft tumors driven by KIF5B-RET (G810C) that contains the most frequently observed solvent-front mutant in selpercatinib-treated patients, HSN608, HSL476, and HSL468 significantly suppressed and caused regression of the selpercatinib-resistant tumors. This study clarifies the sensitivities of different RET solvent-front mutants to selpercatinib and pralsetinib and identifies novel alkylnyl nicotinamide-based RET TKIs for inhibiting selpercatinib/pralsetinib-resistant G810 mutants.
Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation
Authors: Qiao Rui , Wei Mengmeng , Chen Hui , Zhang Xianhong , Zhang Jie , Gao Liyang , Ma Haijun , Wang Yujiong , Li Le
Published: April 2023

Cancer cells frequently alter their metabolism to support biogenesis and proliferation and survive specific metabolic stressors. The glucose-associated pentose phosphate pathway (PPP) is crucial for cancer cell proliferation. In particular, 6-phosphogluconate dehydrogenase (6PGD), the second dehydrogenase in the PPP, catalyzes the decarboxylation of 6-phosphogluconate into ribulose 5-phosphate (Ru5P). However, the mechanisms controlling 6PGD expression in cancer cells remain unclear. Herein, we show that TAp73 increases Ru5P and NADPH production through 6PGD activation to counteract reactive oxygen species and protects cells from apoptosis. Moreover, 6PGD overexpression rescues the proliferation and tumorigenic ability of TAp73-deficient cells. These findings further establish the critical role of TAp73 on glucose metabolism regulation, demonstrating that TAp73 can activate 6PGD expression to support oncogenic cell growth.

Implications:

By transcriptional upregulation of 6PGD, TAp73 promotes the generation of Ru5P and NADPH, and enhances tumor cell proliferation.
Data from Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma
Authors: Hoppe Michal Marek , Jaynes Patrick , Shuangyi Fan , Peng Yanfen , Sridhar Shruti , Hoang Phuong Mai , Liu Clementine Xin , De Mel Sanjay , Poon Limei , Chan Esther Hian Li , Lee Joanne , Ong Choon Kiat , Tang Tiffany , Lim Soon Thye , Nagarajan Chandramouli , Grigoropoulos Nicholas F. , Tan Soo-Yong , Hue Susan Swee-Shan , Chang Sheng-Tsung , Chuang Shih-Sung , Li Shaoying , Khoury Joseph D. , Choi Hyungwon , Harris Carl , Bottos Alessia , Gay Laura J. , Runge Hendrik F.P. , Moutsopoulos Ilias , Mohorianu Irina , Hodson Daniel J. , Farinha Pedro , Mottok Anja , Scott David W. , Pitt Jason J. , Chen Jinmiao , Kumar Gayatri , Kannan Kasthuri , Chng Wee Joo , Chee Yen Lin , Ng Siok-Bian , Tripodo Claudio , Jeyasekharan Anand D.
Published: April 2023

Abstract
Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6− (M+2+6−) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6− percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6− unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance.
Significance:
Using single-cell–resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer.

This article is highlighted in the In This Issue feature, p. 1027
Supplementary Tables from High Expression of MHC Class I Overcomes Cancer Immunotherapy Resistance Due to IFNγ Signaling Pathway Defects
Authors: Kawase Katsushige , Kawashima Shusuke , Nagasaki Joji , Inozume Takashi , Tanji Etsuko , Kawazu Masahito , Hanazawa Toyoyuki , Togashi Yosuke
Published: April 2023

Supplementary Table S1-S9
Table S1 from Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu
Published: April 2023

Clinical, pathological findings in the toxicity study in Cynomolgus Monkeys
Figure S8 from Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu
Published: April 2023

Mechanism of the TRK-950 antitumor effect in mouse model
Figure S7 from Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu
Published: April 2023

Properties of TRK-950
Figure S4 from Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu
Published: April 2023

CAPRIN-1 expression following EMT induction.
Supplementary File 7 from Integrative metatranscriptomic analysis reveals disease-specific microbiome-host interactions in oral squamous cell carcinoma
Authors: Jain Vinay , Baraniya Divyashri , Elhadedy Doaa E , Chen Tsute , Slifker Michael J. , Alakwaa Fadhl , Cai Kathy Q. , Chitrala Kumaraswamy Naidu , Fundakowski Christopher , Al-hebshi Nezar
Published: April 2023

Microbial enzyme classes (EC) and metabolic pathway profiles.
Supplementary File 3 from Integrative metatranscriptomic analysis reveals disease-specific microbiome-host interactions in oral squamous cell carcinoma
Authors: Jain Vinay , Baraniya Divyashri , Elhadedy Doaa E , Chen Tsute , Slifker Michael J. , Alakwaa Fadhl , Cai Kathy Q. , Chitrala Kumaraswamy Naidu , Fundakowski Christopher , Al-hebshi Nezar
Published: April 2023

Host differenntially expressed genes
Supplementary Table 8 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

ST_8 ATAC/ChIP-Seq to splicing
Supplementary Table 13 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

ST_13 BAZ1A and lineage plasticity
Supplementary Table 1 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

Supplementary Table_1 RIME
Supplementary Figure 9 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

SF_9 overlap miRNA
Supplementary Figure 7 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

SF_7 RNA-Seq volcanos
Supplementary Figure 3 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

SF_3 motifs in ATAC-Seq
Supplementary Figure 10 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

SF_10 cistrome-transcriptome
Data from Integrative metatranscriptomic analysis reveals disease-specific microbiome-host interactions in oral squamous cell carcinoma
Authors: Jain Vinay , Baraniya Divyashri , Elhadedy Doaa E , Chen Tsute , Slifker Michael J. , Alakwaa Fadhl , Cai Kathy Q. , Chitrala Kumaraswamy Naidu , Fundakowski Christopher , Al-hebshi Nezar
Published: April 2023

Abstract
Studies on the microbiome of oral squamous cell carcinoma (OSCC) have been limited to 16S rRNA gene sequencing. Here, laser microdissection coupled with brute-force, deep metatranscriptome sequencing was employed to simultaneously characterize the microbiome and host transcriptomes and predict their interaction in OSCC. The analysis involved 20 HPV16/18-negative OSCC tumor/adjacent normal tissue pairs (TT and ANT) along with deep tongue scrapings from 20 matched healthy controls (HC). Standard bioinformatic tools coupled with in-house algorithms were used to map, analyze, and integrate microbial and host data. Host transcriptome analysis identified enrichment of known cancer-related gene sets, not only in TT vs. the ANT and HC, but also in the ANT vs. HC contrast, consistent with field cancerization. Microbial analysis identified a low abundance yet transcriptionally active, unique multi-kingdom microbiome in OSCC tissues predominated by bacteria and bacteriophages. HC showed a different taxonomic profile yet shared major microbial enzyme classes and pathways with TT/ANT, consistent with functional redundancy. Key taxa enriched in TT/ANT compared to HC were Cutibacterium acnes, Malassezia restricta, Human Herpes Virus 6B, and bacteriophage Yuavirus. Functionally, hyaluronate lyase was overexpressed by C. acnes in TT/ANT. Microbiome-host data integration revealed that OSCC-enriched taxa were associated with upregulation of proliferation-related pathways. In a preliminary in vitro validation experiment, infection of SCC25 oral cancer cells with C. acnes resulted in upregulation of MYC expression. The study provides a new insight into potential mechanisms by which the microbiome can contribute to oral carcinogenesis, which can be validated in future experimental studies.
A content analysis of the language quality of thematic textbooks for elementary school students
Authors: Mardiyana Tina , Fauziati Endang , Prastiwi Yeny , Minsih Minsih
Published: April 2023

Primary school students rely heavily on textbooks for instruction. Using thevariety of textbooks, a description of the theme textbooks’ linguistic qualityis conspicuously absent, particularly for students in the fifth grade. Languagefit for students’ growth, communicative language, and coherence andcohesiveness were all included in this study’s analysis of textbooks’language quality. Qualitative content analysis was used in this study'smethodology. All texts from the heat and transfer-themed of fifth-gradetextbooks published by the Indonesian Ministry of Education and Culture,Yudhistira, and Erlangga publishers were included in the study.Documentation was utilized to collect the data. Sample, record, reduce,infer, and narrate were all data analysis approaches used. The findings of thisresearch indicated that the three publishers’ textbooks had excellentlanguage quality in terms of language compatibility for students’ growth andthe communicative language issued by the Indonesian Ministry of Educationand Culture and Erlangga was wonderful, but Yudhistira was awful. Therewere a lot of solid points made in the Ministry of Education and Culture’spublications. Both Yudhistira and Erlangga performed admirably. Thequality of textbook language was found to be satisfactory in this study.
Parental psychological control, autonomy frustration, and psychological well-being among boarding school adolescents
Authors: Manindjo Zahrah Aulianissa , Anindhita Vidya , Abidin Fitri Ariyanti
Published: April 2023

Psychological well-being is fundamental for adolescents to be adaptive and fully functioning in the environment. For adolescents who stay in boarding school, even though they are away from their parents due to boarding school rules, parents still have a role to provide support and direct their behavior through parental control. On the other hand, adolescence is a period where children learn to be detached from their parents and strive for autonomy. The present study aimed to investigate the role of autonomy need frustration as a mediating variable between parental psychological control and psychological well-being for adolescents who stayed in boarding school. A survey was completed by 318 Islamic boarding school adolescents with an age range from 12–18 years old. The findings showed that autonomy need frustration fully mediated the relationship between parental psychological control and psychological well-being. Parental psychological control causes a decline in boarding school adolescents’ psychological well-being through the feeling of autonomy need frustration. These results support further development of studies regarding the psychological well-being of adolescents, especially in the boarding school context.
Os Commonwealthmen a serviço da liberdade: a oposição a Guilherme III e ao “cânone republicano”
Authors: Herrmann Frédéric , Vargas Thiago
Published: April 2023

A historiografia neo-republicana de Cambridge estabeleceu uma franca distinção entre republicanismo e liberalismo que merece ser reexaminada. Este artigo busca contribuir para esse debate, propondo um estudo de caso dos commonwealthmen ou republicanos que apoiaram a revolução de 1688 na Inglaterra, mas que se opuseram à nova cultura política e à nova “economia de crédito” do reino de Guilherme III na década de 1690. Ao desviarmos nosso olhar do republicanismo enquanto linguagem para situá-lo sob o republicanismo enquanto cultura, bem como modo de ação política, é possível constatar uma porosidade entre direitos naturais e virtude cívica, mas também entre liberdade negativa e liberdade positiva.
O republicanismo e o pensamento político de Hume
Authors: Araujo Cicero
Published: April 2023

Este texto enfoca as percepções de Hume sobre os eventos políticos e político-econômicos de seu tempo. Ancorado na análise de J. G. A. Pocock, o artigo explora os modos pelos quais o pensamento político humeano pode ter sido influenciado pelo assim chamado “republicanismo britânico do século XVIII”, dado o contexto de difuso mal-estar com uma intrusão sem precedentes do poder econômico sobre a política. A despeito das muitas contribuições que a história social e a história do pensamento político já fizeram sobre esse tema e o respectivo período, a interpretação da perspectiva de Hume ainda deixa alguma perplexidade, à qual o artigo busca se endereçar.
Uma leitura do problema da divisão do trabalho em Smith
Authors: Gautier Claude , Vargas Thiago
Published: April 2023

Propondo uma releitura do problema da divisão do trabalho em Smith e partindo dos dois discursos sobre a questão desenvolvidos nos Livros I e V da Riqueza das nações, trata-se de analisar esta noção tanto sob o prisma das considerações naturalistas e epistemológicas de Smith quanto destacando o caráter relacional e interdependente presente na divisão do trabalho. Com isso, busca-se reconsiderar criticamente o “liberalismo” de Smith.
Uma entrevista inédita de Giannotti sobre Artigas
Authors: Giannotti José Arthur , Leite José Guilherme Pereira
Published: April 2023

Uma entrevista inédita de Giannotti sobre Artigas
Resenhas
Authors: Vargas Thiago , Lourenço Ciro
Published: April 2023

Resenhas de Paul Sagar. Adam Smith Reconsidered. History, Liberty, and the Foundations of Modern Politics. Princeton University Press, 2022, por Thiago Vargas (USP-FAPESP) e de Antoine Lilti. L’héritage des Lumières. Ambivalences de la modernité. Seuil ; Gallimard, 2019, por Ciro Lourenço (USP-Paris 1)
Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study
Authors: Xing Lucas Yixi , Diederichsen Søren Zöga , Højberg Søren , Krieger Derk W. , Graff Claus , Frikke-Schmidt Ruth , Olesen Morten S. , Brandes Axel , Køber Lars , Haugan Ketil Jørgen , Svendsen Jesper Hastrup
Published: April 2023

Background:

Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention.

Methods:

In the LOOP Study (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), 6004 AF-naïve individuals at least 70 years old and with additional stroke risk factors were randomized 1:3 to either screening with an implantable loop recorder (ILR) and initiation of anticoagulation upon detection of AF episodes lasting ≥6 minutes or usual care (control). This post hoc analysis included study participants with available NT-proBNP measurement at baseline.

Results:

A total of 5819 participants (96.9% of the trial population) were included. The mean age was 74.7 years (SD, 4.1 years) and 47.5% were female. The median NT-proBNP level was 15 pmol/L (interquartile range, 9–28 pmol/L) corresponding to 125 pg/mL (interquartile range, 76–233 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio, 1.84 [95% CI, 1.51–2.25]) and the control group (hazard ratio, 2.79 [95% CI, 2.30–3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (hazard ratio, 1.21 [95% CI, 0.96–1.54] for stroke or systemic embolism [SE], 1.60 [95% CI, 1.32–1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI, 1.61–2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (hazard ratio, 0.60 [95% CI, 0.40–0.90] and 0.70 [95% CI, 0.53–0.94], respectively) but not among those with lower levels (
P
interaction
=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus control (
P
interaction
=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings.

Conclusions:

In an older population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels but not among those with lower levels. These findings should be considered hypothesis generating and warrant further study before clinical implementation.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02036450.
Theorising in Educational Children’s Rights Research
Authors: Gillett-Swan Jenna , Quennerstedt Ann , Moody Zoe
Published: April 2023

Child rights research has increased since the adoption of the Convention on the Rights of the Child (crc) in 1989. Reviews of the research has indicated a lack of criticality and a reluctance to interrogate or challenge dominant views. Some scholars argue that this results from under theorisation, whereas other maintain that theorisation is abundant. The paradox suggesting that children’s rights research can be both abundant and deficient in theory calls for a thorough discussion about theorisation. This systematic review engages in this debate by exploring what is positioned as “theory” in educational children’s rights research, and what function theory has. Analysis determined that alignment with established theoretical approaches is uncommon. Previous research literature is instead often positioned as theory, mostly in combination with policy, law or an established theory. Main functions of theory are to construct the object of study and to provide analysis support. Some uses of theory appear to be more powerful than others.
Hickman, Buddhism, and Algorithmic Technology
Authors: Garrison Jim
Published: April 2023

This paper is a further reflection on my dialogue with Larry Hickman, director emeritus of the Center for Dewey Studies, and Daisaku Ikeda, president of the lay Buddhist organization Soka Gakkai International (sgi). One surprising outcome of this dialogue is how similar Deweyan pragmatism is to many forms of Mahayana Buddhism such as sgi. Here I survey some similarities between Hickman’s philosophy of technology and Buddhism by emphasizing value creation and criticism. (Soka Gakkai means value creating society.) I then explore Peter D. Herschock’s, Buddhism and Intelligent Technology relying on Hickman to rectify Herschock’s philosophy of technology before discussing how Herschock’s insightful application of Buddhist ethics to ai and the internet accord with Hickman.
A taxonomic overview of Orchis sect. Robustocalcare (Orchidaceae)
Authors: CALEVO JACOPO , CHRISTENHUSZ MAARTEN J. M. , FAY MICHAEL F.
Published: April 2023

Orchis patens has previously been considered to consist of three widely disjunct populations in northern Italy, Algeria/Tunisia and the Canary Islands. The last is already commonly treated as O. canariensis, but because the type of O. patens is from the Algerian populations, the name of the Italian taxon has been in doubt. We here review the taxonomic literature and provide a key to the species of O. section Robustocalcare supported by molecular data recently published for these three taxa. We conclude that Orchis patens subsp. brevicornis is the correct name for the Italian taxon.
Echeveria flammigera (Crassulaceae), a new name and status for E. pringlei var. parva
Authors: ROSALES-MARTÍNEZ C. SANTIAGO , HERNÁNDEZ-CAMPOS J. DANIEL
Published: April 2023

A revision of Echeveria pringlei var. parva was made based on morphological and biogeographical comparisons. The results show that this taxon should be raised to the species level and that it belongs to E. ser. Nudae. Since the epithet parva is unavailable for use due to the existence of E. parva, E. flammigera is proposed as a new replacement name. An updated description of the taxon is provided, as well as a distribution map.
Review of New Zealand Coastal Talitroids with description of three new genera (Crustacea, Amphipoda, Senticaudata)
Authors: HUGHES LAUREN E. , LOWRY JAMES K.
Published: April 2023

A generic revision is provided for the New Zealand coastal talitroids, which reports two families, seven genera and thirteen species. Three new genera are described: Aotearorchestia gen. nov.; Subantarctorchestia gen. nov.; and Tatahipeke gen. nov. to accommodate seven known species, A. chathamensis (Hurley, 1956) comb. nov.; A. telluris (Spence Bate, 1862) comb. nov.; S. aucklandiae (Spence Bate, 1862) comb. nov.; S. bollonsi (Chilton, 1909) comb. nov.; Tatahipeke cookii (Filhol, 1885) comb. nov.; T. kirki (Hurley, 1956) comb. nov.; and T. tumida (G.M. Thomson, 1885) comb. nov. The three genera, Bellorchestia Serejo & Lowry, 2008, Protorchestia Bousfield 1982 and Transorchestia Bousfield, 1982 are revised to include additional information on morphology, growth stages and distributions for three New Zealand species: Bellorchestia quoyana (Milne Edwards, 1840); Transorchestia miranda (Chilton, 1916); and Trans. serrulata (Dana, 1852a). Lastly, a small commentary is given on four species of coastal talitroids where additional museum collections could not be located for study, B. spadix (Hurley, 1956), Pictonorchestia dentata (Filhol, 1885), Protorchestia campbelliana (Bousfield, 1964), and T. kirki (Hurley, 1956) gen. et comb. nov. A dichotomous key and pictorial field guide are provided to all New Zealand coastal talitroids.
Temporal Variability of Global Surface Eddy Diffusivities: Estimates and Machine Learning Prediction
Authors: Zhang Guangchuang , Chen Ru , Li Xichen , Li Laifang , Wei Hao , Guan Wenting
Published: April 2023

Mesoscale eddies, ubiquitous in the global ocean, play a key role in the climate system by stirring and mixing key tracers. Estimating, understanding, and predicting eddy diffusivity is of great significance for designing suitable eddy parameterization schemes for coarse-resolution climate models. This is because climate model results are sensitive to the choice of eddy diffusivity magnitudes. Using 24-yr satellite altimeter data and a Lagrangian approach, we estimate time-dependent global surface cross-stream eddy diffusivities. We found that eddy diffusivity has nonnegligible temporal variability, and the regionally averaged eddy diffusivity is significantly correlated with the climate indices, including the North Pacific Gyre Oscillation, Atlantic multidecadal oscillation, El Niño–Southern Oscillation, Pacific decadal oscillation, and dipole mode index. We also found that, compared to the suppressed mixing length theory, random forest (RF) is more effective in capturing the temporal variability of regionally averaged eddy diffusivity. Our results indicate the need for using time-dependent eddy mixing coefficients in climate models and demonstrate the advantage of RF in predicting mixing temporal variability.

Significance Statement

Mixing induced by ocean eddies can greatly modulate the ocean circulation and climate variability. Steady eddy mixing coefficients are often specified in coarse-resolution climate models. However, using satellite observations, we show that the eddy mixing rate has significant temporal variability at the global ocean surface. The regional temporal variability of eddy mixing is linked with large-scale climate variability (e.g., North Pacific Gyre Oscillation and Atlantic multidecadal oscillation). We found that random forest, a user-friendly machine learning algorithm, is a better tool to predict the mixing temporal variability than the conventional mixing theory. This study suggests the possibility of improving climate model performance by using time-dependent eddy mixing coefficients inferred from machine learning methods.
Early impacts of the ‘National Suicide Prevention Trial’ on trends in suicide and hospital admissions for self-harm in Australia
Authors: Page Andrew , Pirkis Jane , Bandara Piumee , Oostermeijer Sanne , Hall Teresa , Burgess Philip M , Harris Meredith , Currier Dianne
Published: April 2023

Objectives:

The National Suicide Prevention Trial was announced by the Australian Government in 2016 and aimed to prevent suicidal behaviour in 12 trial sites (representing a population of ~8 million). This study investigated the early population-level impact of the National Suicide Prevention Trial activity on rates of suicide and hospital admissions for self-harm in comparison to control areas.

Methods:

Relative and absolute differences in monthly rates of suicide and hospital admissions for self-harm were compared in the period after the National Suicide Prevention Trial implementation (July 2017–November 2020) to the period prior to implementation (January 2010–June 2017) in (1) ‘National Suicide Prevention Trial areas’ and (2) ‘Control areas’, using a difference-in-difference method in a series of negative binomial models. Analyses also investigated whether associations for suicide and self-harm rates differed by key socio-demographic factors, namely sex, age group, area socio-economic status and urban–rural residence.

Results:

There were no substantial differences between ‘National Suicide Prevention Trial areas’ and ‘Control areas’ in rates of suicide (2% relative decrease, relative risk = 0.98, 95% confidence interval = [0.91, 1.06]) or self-harm (1% relative decrease, relative risk = 0.99, 95% confidence interval = [0.96, 1.02]), adjusting for sex, age group and socio-economic status. Stronger relative decreases in self-harm only were evident for those aged 50–64 years, high socio-economic status areas, metropolitan and remote geographic areas.

Conclusion:

There was limited evidence that the National Suicide Prevention Trial resulted in reductions in suicide or hospital admissions for self-harm during the first 4 years of implementation. Continued monitoring of trends with timely data is imperative over the next 2–3 years to ascertain whether there are any subsequent impacts of National Suicide Prevention Trial activities.
Usability of the Surprise Question by Nurses and Patients’ Families for Risk Stratification in Emergency Patients: A Prospective Cohort Study
Authors: Liu Yi , Li Dongze , Jia Yu , Yu Jing , Li Fanghui , Gao Yongli , Ma Yan , Wan Zhi , Zeng Zhi , Zhang Wei
Published: April 2023

The Surprise Question is an effective tool to identify patients in need of palliative care. But it is unknown whether the Surprise Question can effectively predict adverse outcomes in Emergency patients. Therefor this study is to determine the utility of the modified Surprise Question for risk stratification in emergency patients. And assessed if the modified Surprise Question could be used by different healthcare personnel. Nurses and patients’ families were asked to respond as “Yes” or “No” to the modified Surprise Question for each patient. The outcome was resuscitation unit admission. Logistic regression was used to determine covariant significantly associated with resuscitation unit admission. The area under the curve for the second Surprise Question response by nurses was 0.620, which improved to 0.704 when the responses of nurses and patients’ families were in agreement. The clinical impression of nurses is a valuable tool to predict altered conditions for medium-acuity patients, and the diagnostic accuracy improves when responses of patients’ families and nurses agreed. The clinical impression of nurses is a valuable tool to predict altered conditions for medium-acuity patients, and the diagnostic accuracy improves when responses of patients’ families and nurses agreed.
Aboriginal and Torres Strait Islander corporations: Time for a rethink?
Authors: Nehme Marina
Published: April 2023

The Corporations (Aboriginal and Torres Strait Islander) Act 2006 (Cth) is not currently equipped to empower Indigenous Australians to set up their for-profit businesses under its regime due to its rigidity and interventionist approach. This article argues the need for a change. A proposal is put forward to allow for the creation of a new type of corporation under the existing legislative framework for Indigenous entrepreneurs to run their for-profit businesses in a culturally appropriate way.
Circulating lncRNAs NONHSAT054669.2 and ENST00000525337 can be used as early biomarkers of gestational diabetes mellitus
Authors: Jiang Wen , Sun Xiubin , Liu Fangfei , Cheng Guanghui , Li Siyuan , Xu Mengru , Wu Yu , Wang Lina
Published: April 2023

Early diagnosis can help prevent and reduce the adverse effects of gestational diabetes mellitus (GDM). This study intended to investigate key circulating long non-coding RNAs (lncRNAs) as novel biomarkers for diagnosis of GDM at the early stages. First, lncRNA microarray analysis was conducted for plasma samples of GDM women before delivery and 48 h after delivery. The expression of differentially expressed lncRNAs in clinical samples at different trimesters was randomly validated by quantitative polymerase chain reaction (PCR). Moreover, the correlation between lncRNA expression and oral glucose tolerance test (OGTT) level in GDM women during the second trimester was analyzed, followed by evaluating the diagnostic value of key lncRNAs during different trimesters using receiver operating characteristic (ROC) curve. Higher NONHSAT054669.2 expression and lower ENST00000525337 expression were revealed in GDM women before delivery relative to 48 h after delivery ( P < 0.05). The expression of NONHSAT054669.2 and ENST00000525337 in GDM women during the first and second trimesters was dramatically higher than pregnant women ( P < 0.05) with normal glucose tolerance (NGT). During the second trimester, NONHSAT054669.2 expression was positively related to OGTT level at 1 h ( r = 0.41455, P < 0.001). Furthermore, ROC curve analysis revealed that ENST00000525337 alone, NONHSAT054669.2 alone, and their combination had high diagnostic value for GDM during the first (area under the ROC curve (AUC) = 0.979, 0.956, and 0.984, respectively) and second (AUC = 0.829, 0.809, and 0.838, respectively) trimesters (all P < 0.001). The plasma level of NONHSAT054669.2 and ENST00000525337 may be applied as novel diagnostic biomarkers for early diagnosis of GDM.
The processing mechanism of mixed prospective memory: Changes in internal and external attention
Authors: Gan Jiaqun , Guo Yunfei , Wang Enguo
Published: April 2023

While time-based prospective memory (TBPM) includes only time cues, mixed prospective memory (MPM) is a special form of prospective memory including both time and event cues. Depending on the classification of the clarity of time cues, MPM can be divided into time-period MPM and time-point MPM. While the time cue of the latter is a definite time point, the time cue of the former is a vague time period. As such, MPM and TBPM may have different processing mechanisms due to the additional event cue. This study aimed to investigate whether there are differences in the processing mechanisms between TBPM and the two types of MPM. A total of 240 college students were recruited to participate in the experiment. They were randomly assigned to a TBPM group, time-point MPM group, time-period MPM group, and baseline group. We adopted the performance of ongoing tasks to reflect internal attention indirectly and the frequency of time checks to measure external attention. The results showed that in terms of prospective memory, time-point MPM had the best performance, followed by time-period MPM, while TBPM had the worst performance. In relation to ongoing tasks, the two types of MPM had a better performance than TBPM in some stages, although worse than the baseline. In addition, the two MPMs evoked a lower time monitoring frequency than TBPM under different monitoring conditions. These results suggested that, compared with TBPM, MPM reduced both internal and external attention consumption and achieved better prospective memory performance. Internal attention consumption displayed dynamic changes for both types of MPM, and the time-point MPM had higher internal attention effectiveness than the time-period MPM. These results support the Dynamic Multiprocess Theory and the Attention to Delayed Intention model.
Evaluation of the toxicity of WS-5 in a 90-days nose-only exposure in sprague-dawley rats
Authors: Oldham Michael Jerome , Desai Rahat Wadhwa , Randazzo James , Lalonde Guy , Weil Roxana
Published: April 2023

Introduction

WS-5 is a flavor ingredient that provides a cooling sensation similar to that of menthol but without the characteristic menthol flavor. In the available toxicological evaluations of WS-5 there was no data specific to inhalation exposure.

Methods

A 90-days nose-only inhalation study was conducted using Sprague Dawley rats exposed to Filtered air, propylene glycol/glycerin (40/60 by weight; vehicle control), or one of three WS-5 concentrations (0.2, 0.4, or 0.8% by weight) to assess the inhalation toxicity of WS-5. The study design was consistent with the Organization for Economic Development and Cooperation test guideline 413 and included a 28-day and 6-week recovery sacrifices, in addition to the 13-week assessment.

Results

Food consumption and body weights were unaffected by WS-5 exposure compared to vehicle control or Filtered air. No WS-5 exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or bronchoalveolar lavage fluid cytology and clinical chemistry. Macroscopic examinations and terminal organ weights revealed no observations associated with exposure to WS-5.

Discussion

Histopathology findings of alveolar hemorrhage and mixed cell infiltration at the 28-day necropsy were either not present in the WS-5 exposed groups or were present at similar frequencies in the vehicle control and/or Filtered air groups at the 13-weeks necropsy and thus, were not considered to be vehicle control or WS-5 related.

Conclusion

Based on the absence of adverse effects, the no-observed-adverse effect concentration was considered to be 2.5 mg/L of aerosolized 0.8 w% WS-5 that achieved a mean measured exposure concentration of approximately 18 μg WS-5/L
Effects of Exercise Training and Physical Activity in Patients with Coronary Artery Disease
Authors: Vooturi Sudhindra , Anil Potharaju , Monica Yazala
Published: April 2023

Cardiovascular disease is a leading cause of mortality across the globe. More than one-third of these deaths are due to coronary artery disease (CAD). Importantly, 80% of CAD and atherosclerosis-related morbidity and mortality can be prevented by modifying behaviors like physical inactivity. However, exercise is often “under-prescribed” to CAD patients; among those referred, only 40% actually participate. Improved understanding of benefits and recent advances in cardiac rehabilitation by patients and physicians may help improve referral and compliance to exercise training in these patients. In the current review, we discuss how increasing physical activity over the long-term leads to improvement in coronary blood flow and consequently reduces morbidity and mortality in patients with CAD.
Narrow and Stripe Leaf 2 Regulates Leaf Width by Modulating Cell Cycle Progression in Rice
Authors: Shen Wenqiang , Sun Jiajie , Xiao Zan , Feng Ping , Zhang Ting , He Guanghua , Sang Xianchun
Published: April 2023

Background

Leaf morphology is an important component of the idea plant architecture that extensively influences photosynthesis, transpiration, and ultimately grain yield in crops. However, the genetic and molecular mechanisms regulating this morphology remain largely unclear.

Results

In this study, a mutant showing a narrow and stripe leaf phonotype, designated nsl2, was obtained. Histological analysis revealed defects in the vascular system and reduced epidermal cell number in the nsl2, while the cell size remained unchanged. Map-based cloning and genetic complementation experiments revealed that NSL2, which encodes a small subunit of ribonucleotide reductases (RNRs), is a null allelic with ST1 and SDL. The NSL2 was expressed in variety of tissues, with the highest levels detected in leaves, and its protein was localized in the nucleus and cytoplasm. The dNTPs level was altered in the nsl2 mutant, and thereby affecting the dNTPs pool balance. In addition, flow cytometric analysis and the altered transcript level of genes related to cell cycle indicated that NSL2 affects cell cycle progression.

Conclusions

Our findings here suggest that NSL2 function in the synthesis of dNTP, the deficient of which leads to DNA synthesis block and in turn affects cell cycle progression, and ultimately decreased cell number and narrow leaf in the nsl2 plant.