bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined transcriptomic and ChIPseq analyses of the
Bordetella pertussis
RisA regulon
Authors: Coutte Loïc , Antoine Rudy , Slupek Stephanie , Locht Camille 
Published: March 2024

ABSTRACT

The regulation of
Bordetella pertussis
virulence is mediated by the two-component system BvgA/S, which activates the transcription of virulence-activated genes (
vag
s). In the avirulent phase, the
vag
s are not expressed, but instead, virulence-repressed genes (
vrg
s) are expressed, under the control of another two-component system, RisA/K. Here, we combined transcriptomic and chromatin immunoprecipitation sequencing (ChIPseq) data to examine the RisA/K regulon. We performed RNAseq analyses of RisA-deficient and RisA-phosphoablative
B. pertussis
mutants cultivated in virulent and avirulent conditions. We confirmed that the expression of most
vrg
s is regulated by phosphorylated RisA. However, the expression of some, including those involved in flagellum biosynthesis and chemotaxis, requires RisA independently of phosphorylation. Many RisA-regulated genes encode proteins with regulatory functions, suggesting multiple RisA regulation cascades. By ChIPseq analyses, we identified 430 RisA-binding sites, 208 within promoter regions, 201 within open reading frames, and 21 in non-coding regions. RisA binding was demonstrated in the promoter regions of most
vrg
s and, surprisingly, of some
vag
s, as well as for other genes not identified as
vag
s or
vrg
s. Unexpectedly, many genes, including some
vag
s, like
prn
,
brpL
,
bipA,
and
cyaA
, contain a BvgA-binding site and a RisA-binding site, which increases the complexity of the RisAK/BvgAS network in
B. pertussis
virulence regulation.

IMPORTANCE

The expression of virulence-activated genes (
vag
s) of
Bordetella pertussis
, the etiological agent of whooping cough, is under the transcriptional control of the two-component system BvgA/S, which allows the bacterium to switch between virulent and avirulent phases. In addition, the more recently identified two-component system RisA/K is required for the expression of
B. pertussis
genes, collectively named
vrg
s, that are repressed during the virulent phase but activated during the avirulent phase. We have characterized the RisA/K regulon by combined transcriptomic and chromatin immunoprecipitation sequencing analyses. We identified more than 400 RisA-binding sites. Many of them are localized in promoter regions, especially
vrg
s, but some were found within open reading frames and in non-coding regions. Surprisingly, RisA-binding sites were also found in promoter regions of some
vag
s, illustrating the previously underappreciated complexity of virulence regulation in
B. pertussis
.
Nemertodermatida—Endosymbionts of Deep-Sea Acorn Worms (Hemichordata, Torquaratoridae)
Authors: Ezhova O. V. , Lukinykh A. I. , Malakhov V. V. 
Published: March 2024

Abstract
Worm-like endosymbionts were found in the hepatic region of the digestive tract of the deep-sea acorn worm Quatuoralisia malakhovi Ezhova et Lukinykh, 2022 (family Torquaratoridae) from the Bering Sea. The symbionts were assigned to the taxon Nemertodermatida on the basis of histological examination. Torquaratoridae are similar in feeding type to holothuroids, which have also been found to have Xenacoelomorpha endosymbionts.
Codesign of health technology interventions to support best-practice perioperative care and surgical waitlist management
Authors: Aitken Sarah Joy , James Sophie , Lawrence Amy , Glover Anthony , Pleass Henry , Thillianadesan Janani , Monaro Sue , Hitos Kerry , Naganathan Vasi 
Published: March 2024

ObjectivesThis project aimed to determine where health technology can support best-practice perioperative care for patients waiting for surgery.MethodsAn exploratory codesign process used personas and journey mapping in three interprofessional workshops to identify key challenges in perioperative care across four health districts in Sydney, Australia. Through participatory methodology, the research inquiry directly involved perioperative clinicians. In three facilitated workshops, clinician and patient participants codesigned potential digital interventions to support perioperative pathways. Workshop output was coded and thematically analysed, using design principles.ResultsCodesign workshops, involving 51 participants, were conducted October to November 2022. Participants designed seven patient personas, with consumer representatives confirming acceptability and diversity. Interprofessional team members and consumers mapped key clinical moments, feelings and barriers for each persona during a hypothetical perioperative journey. Six key themes were identified: ‘preventative care’, ‘personalised care’, ‘integrated communication’, ‘shared decision-making’, ‘care transitions’ and ‘partnership’. Twenty potential solutions were proposed, with top priorities a digital dashboard and virtual care coordination.DiscussionOur findings emphasise the importance of interprofessional collaboration, patient and family engagement and supporting health technology infrastructure. Through user-based codesign, participants identified potential opportunities where health technology could improve system efficiencies and enhance care quality for patients waiting for surgical procedures. The codesign approach embedded users in the development of locally-driven, contextually oriented policies to address current perioperative service challenges, such as prolonged waiting times and care fragmentation.ConclusionHealth technology innovation provides opportunities to improve perioperative care and integrate clinical information. Future research will prototype priority solutions for further implementation and evaluation.
High frequency dielectric study on the hydrogen bonding interaction on 1,5-pentanediol + 1,4-dioxane binary mixtures
Authors: Garad Nitin P. , Saknure Shankar H. , Dongre Daiwashala G. , Kumbharkhane Ashok C. 
Published: March 2024

The complex dielectric permittivity spectra (CPS) of a binary mixture of 1,5-pentanediol (1,5-PD) with 1,4-dioxane (1,4-DX) were determined using time-domain reflectometry in the frequency range of 10 MHz to 30 GHz. The experimental CPS data were fitted to the Cole–Davidson equation using a nonlinear least squares fit method to determine the dielectric relaxation parameters. The intermolecular interactions in the binary liquids were studied through the Kirkwood correlation factor, excess parameters, thermodynamic parameters, and Bruggeman’s factor.
Data from Metformin, Independent of AMPK, Induces mTOR Inhibition and Cell-Cycle Arrest through REDD1
Authors: Ben Sahra Isaam , Regazzetti Claire , Robert Guillaume , Laurent Kathiane , Le Marchand-Brustel Yannick , Auberger Patrick , Tanti Jean-François , Giorgetti-Peraldi Sophie , Bost Frédéric 
Published: March 2024

<div>Abstract<p>Metformin is a widely prescribed antidiabetic drug associated with a reduced risk of cancer. Many studies show that metformin inhibits cancer cell viability through the inhibition of mTOR. We recently showed that antiproliferative action of metformin in prostate cancer cell lines is not mediated by AMP-activated protein kinase (AMPK). We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin. We show that metformin increases REDD1 expression in a p53-dependent manner. REDD1 invalidation, using siRNA or REDD1<sup>−/−</sup> cells, abrogates metformin inhibition of mTOR. Importantly, inhibition of REDD1 reverses metformin-induced cell-cycle arrest and significantly protects from the deleterious effects of metformin on cell transformation. Finally, we show the contribution of p53 in mediating metformin action in prostate cancer cells. These results highlight the p53/REDD1 axis as a new molecular target in anticancer therapy in response to metformin treatment. <i>Cancer Res; 71(13);4366–72. ©2011 AACR</i>.</p></div>
Data from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer
Authors: Furman Craig , Puyang Xiaoling , Zhang Zhaojie , Wu Zhenhua J. , Banka Deepti , Aithal Kiran B. , Albacker Lee A. , Hao Ming-Hong , Irwin Sean , Kim Amy , Montesion Meagan , Moriarty Alyssa D. , Murugesan Karthikeyan , Nguyen Tuong-Vi , Rimkunas Victoria , Sahmoud Tarek , Wick Michael J. , Yao Shihua , Zhang Xun , Zeng Hao , Vaillancourt Frédéric H. , Bolduc David M. , Larsen Nicholas , Zheng Guo Zhu , Prajapati Sudeep , Zhu Ping , Korpal Manav 
Published: March 2024

<div>Abstract<p>Nearly 30% of patients with relapsed breast cancer present activating mutations in estrogen receptor alpha (ERα) that confer partial resistance to existing endocrine-based therapies. We previously reported the development of H3B-5942, a covalent ERα antagonist that engages cysteine-530 (C530) to achieve potency against both wild-type (ERα<sup>WT</sup>) and mutant ERα (ERα<sup>MUT</sup>). Anticipating that the emergence of C530 mutations could promote resistance to H3B-5942, we applied structure-based drug design to improve the potency of the core scaffold to further enhance the antagonistic activity in addition to covalent engagement. This effort led to the development of the clinical candidate H3B-6545, a covalent antagonist that is potent against both ERα<sup>WT/MUT</sup>, and maintains potency even in the context of ERα C530 mutations. H3B-6545 demonstrates significant activity and superiority over standard-of-care fulvestrant across a panel of ERα<sup>WT</sup> and ERα<sup>MUT</sup> palbociclib sensitive and resistant models. In summary, the compelling preclinical activity of H3B-6545 supports its further development for the potential treatment of endocrine therapy–resistant ERα<sup>+</sup> breast cancer harboring wild-type or mutant <i>ESR1</i>, as demonstrated by the ongoing clinical trials (NCT03250676, NCT04568902, NCT04288089).</p>Summary:<p>H3B-6545 is an ERα covalent antagonist that exhibits encouraging preclinical activity against CDK4/6i naïve and resistant ERα<sup>WT</sup> and ERα<sup>MUT</sup> tumors.</p></div>
A Prince, the Literati, and the Emperor: Two Faces of One Shuihu Play by Zhu Youdun
Authors: Chang Wenbo 
Published: March 2024

Abstract
Zhu Youdun, the prince of Zhou and the grandson of the Ming founding emperor, wrote and published thirty-one zaju plays. While Zhu Youdun’s plays have been well-researched in drama scholarship, their publication, circulation, and textual variations emerging from transmission among different audiences are rarely studied. Situating Zhu Youdun’s zaju writing and publishing activities as part of Ming princely publishing, this paper examines and compares two editions of Black Whirlwind Li Spurns Riches Out of Righteousness as a case study, one the printed edition circulating mainly among literati audience/readers and the other the heavily adapted manuscript edition based on inner palace performance for the imperial audience.
Collecting and Collectors in A Sea of Tales Past and Present
Authors: Zhang Jing 
Published: March 2024

Abstract
Printed in 1544, Gujin shuohai 古今說海 (A Sea of Tales from Past and Present; hereafter GJSH), was a distinct example of the genre of congshu 叢書 (collectanea). Thirteen collators are listed, nine of whom are also noted for their contribution of texts from their own collections. They were all connected in kinship or officialdom to Lu Shen 陸深 (zi Ziyuan 子淵; 1477–1544), a renowned official, calligrapher, poet, and bibliophile of Songjiang 松江 (today’s Shanghai) whose family owned the Yanshan Academy 儼山書院 that published GJSH. This congshu therefore presents an exemplary case to study how book-collecting and private publishing in early sixteenth-century Songjiang enabled its local literati community to perform their cultural authority – alternative to officialdom – in collecting and curating the narrative space of heteroglossia drawn from a miscellany of sources, social registers, and paratexts.
Late-Ming Book Culture and the Fujian Christian Community: a Case Study of Lixiu yijian 勵修一鑑 (A Mirror to Encourage Self-cultivation)
Authors: Xu Yunjing 
Published: March 2024

Abstract
This study demonstrates the importance of book culture in the building of a religious community and in the preservation and interpretation of local experiences, through the making of a book titled Lixiu yijian 勵修一鑑 (A mirror to encourage self-cultivation) around 1645. The main author, Li Jiugong 李久功, mobilized members of the Fujian Christian community to collaborate on this communal book project outside the Christian church. Both xylographic print culture and manuscript culture were involved in the process and in the final product of this project. Through genre affiliation, content categorization, and the addition of commentaries, Li and his associates transformed the diverse source materials into a cohesive guidebook for their fellow Christian readers. The book provided Chinese references or contexts to stories of Western origin. Meanwhile, it also portrayed a group image of devoted and resourceful local Chinese Christians among their Western peers, thus promoting Chinese Christians’ experience as an invaluable part of a universal religious system.
Subaltern-centred Pedagogy: Field Notes and Reflections from Tunisia
Authors: Fulco Carmen , Tatarević Dalila 
Published: March 2024

Abstract
This essay responds to the challenge of deconstructing the concept of democracy and decolonizing knowledge production. The authors, educators in secondary and higher education, grapple with the pedagogical dilemma of how to re-tell the stories of the marginalized and silenced ‘others’ in their classrooms. They explore the concept of ‘subalternity’ as a decolonial critique and a methodological perspective, with the aim of shifting the epistemic location of narratives about migration.
This essay proposes a radical change in educational approaches, urging practitioners to listen to the subaltern rather than speaking for them, and to adopt a ‘subaltern-centered pedagogy’ (Reed 2013) to counter hegemonic and dehumanizing narratives about migration. By doing so, this reflective essay emphasizes the role of educators in fostering critical thinking and awareness about positionality. Before concluding, the authors call for a bold epistemic intervention in education systems, aiming to leave a lasting impact on pedagogical practices. They propose a process of unlearning through critical reflexivity to deconstruct Eurocentric and nationalist narratives, ultimately empowering students to become global citizens in a globalized world.
Nowcasting of High-Intensity Rainfall for Urban Applications in the Netherlands
Authors: Lin Guo-Shiuan , Imhoff Ruben , Schleiss Marc , Uijlenhoet Remko 
Published: March 2024

Abstract
Radar rainfall nowcasting has mostly been applied to relatively large (often rural) domains (e.g., river basins), although rainfall nowcasting in small urban areas is expected to be more challenging. Here, we selected 80 events with high rainfall intensities (at least one 1-km2 grid cell experiences precipitation >15 mm h−1 for 1-h events or 30 mm day−1 for 24-h events) in five urban areas (Maastricht, Eindhoven, The Hague, Amsterdam, and Groningen) in the Netherlands. We evaluated the performance of 9060 probabilistic nowcasts with 20 ensemble members by applying the short-term ensemble prediction system (STEPS) from Pysteps to every 10-min issue time for the selected events. We found that nowcast errors increased with decreasing (urban) areas especially when below 100 km2. In addition, at 30-min lead time, the underestimation of nowcasts was 38% larger and the discrimination ability was 11% lower for 1-h events than for 24-h events. A set of gridded correction factors for the Netherlands, CARROTS (Climatology-based Adjustments for Radar Rainfall in an Operational Setting) could adjust the bias in real-time QPE and nowcasts by 70%. Yet, nowcasts were still found to underestimate rainfall more than 50% above 40-min lead time relative to the reference, which indicates that this error originates from the nowcasting model itself. Also, CARROTS did not adjust the rainfall spatial distribution in urban areas much. In summary, radar-based nowcasting for urban areas (between 67 and 213 km2) in the Netherlands exhibits a short skillful lead time of about 20 min, which can only be used for last-minute warning and preparation.
Prevalence of burnout among urologist and its risk factors in Indonesia
Authors: Rustandi Reginald , Rahman Fakhri , Manduaru Raga , Mochtar Chaidir Arif 
Published: March 2024

Abstract
Objective
To evaluate burnout syndrome among Indonesian urologists by describing its prevalence and risk factors.

Materials and methods
This is a cross-sectional study conducted from February to April 2020. A validated Indonesian version of the Maslach Burnout Inventory that consists of 22 questions addressing emotional exhaustion, depersonalization, and personal achievement was utilized. The questionnaire was constructed using Google Forms (Google, Inc.) and was distributed via e-mail and WhatsApp Messenger (Facebook, Inc.). Burnout was defined as either high score on emotional exhaustion, or high score on depersonalization, or low score on personal achievement. Several variables were analyzed as risk factors to burnout using multivariate analysis. All statistical analyses were carried out using Statistical Software for Social Science (SPSS) version 23.

Results
From 486 eligible members of IUA, 184 (37%) respondents completed the questionnaire. Burnout syndrome was detected in 43 respondents (23.4%). From the results, most of the respondents have low EE (54.9%), low DP (77.7%), and moderate PA (45.7%). Bivariate analysis showed that age of less than 44 years old and being single were associated with increased risk of burnout with OR 2.2 (1.0–5.1, 95% CI, p-value 0.04) while being married decreases risk of burnout with OR 0.2 (0.1–0.8, 95% CI, p-value < 0.01). Lower work load in COVID-19–19 era was related to protective results with OR 0.4 (0.2–0.9, 95% CI, p-value 0.03). Multivariate analysis showed that being married decreases risk of burnout with OR 0.3 (0.1–0.9, 95% CI, p-value 0.04). Multivariate analysis showed that being married was the only significantly protective factor from burnout.

Conclusion
Burnout syndrome among majority of urologists in Indonesia has a moderate degree of burnout, with being married the only significant factor influencing burnout in this study.
Chromatin profiling reveals TFAP4 as a critical transcriptional regulator of bovine satellite cell differentiation
Authors: Lyu Pengcheng , Jiang Honglin 
Published: March 2024

Abstract
Background
Satellite cells are myogenic precursor cells in adult skeletal muscle and play a crucial role in skeletal muscle regeneration, maintenance, and growth. Like embryonic myoblasts, satellite cells have the ability to proliferate, differentiate, and fuse to form multinucleated myofibers. In this study, we aimed to identify additional transcription factors that control gene expression during bovine satellite cell proliferation and differentiation.

Results
Using chromatin immunoprecipitation followed by sequencing, we identified 56,973 and 54,470 genomic regions marked with both the histone modifications H3K4me1 and H3K27ac, which were considered active enhancers, and 50,956 and 59,174 genomic regions marked with H3K27me3, which were considered repressed enhancers, in proliferating and differentiating bovine satellite cells, respectively. In addition, we identified 1,216 and 1,171 super-enhancers in proliferating and differentiating bovine satellite cells, respectively. Analyzing these enhancers showed that in proliferating bovine satellite cells, active enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation whereas repressed enhancers were associated with genes essential for myoblast differentiation, and that in differentiating satellite cells, active enhancers were associated with genes essential for myoblast differentiation or muscle contraction whereas repressed enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation. Active enhancers in proliferating bovine satellite cells were enriched with binding sites for many transcription factors such as MYF5 and the AP-1 family transcription factors; active enhancers in differentiating bovine satellite cells were enriched with binding sites for many transcription factors such as MYOG and TFAP4; and repressed enhancers in both proliferating and differentiating bovine satellite cells were enriched with binding sites for NF-kB, ZEB-1, and several other transcription factors. The role of TFAP4 in satellite cell or myoblast differentiation was previously unknown, and through gene knockdown and overexpression, we experimentally validated a critical role for TFAP4 in the differentiation and fusion of bovine satellite cells into myofibers.

Conclusions
Satellite cell proliferation and differentiation are controlled by many transcription factors such as AP-1, TFAP4, NF-kB, and ZEB-1 whose roles in these processes were previously unknown in addition to those transcription factors such as MYF5 and MYOG whose roles in these processes are widely known.
Serum interleukin-17 A and homocysteine levels in children with autism
Authors: Li Hui , Dang Yunhao , Yan Ying 
Published: March 2024

Abstract
Background
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) and the severity of ASD symptoms in children.

Methods
In this study, 50 children diagnosed with ASD comprised the observation group, while 50 healthy children constituted the control group. Serum levels of IL-17 A, Hcy, folate, and vitamin B12 were compared between the study group and control group, as well as among children with different degrees of ASD severity. The correlation between the Childhood Autism Rating Scale (CARS) score and serum levels of IL-17 A, Hcy, folate, and vitamin B12 was examined. Additionally, the relationship between serum IL-17 A and Hcy levels and their association with the severity ASD were explored.

Results
Compared to the control group, the observation group demonstrated elevated serum Hcy and IL-17 A levels alongside decreased folate and vitamin B12 levels. Individuals with severe ASD exhibited higher Hcy and IL-17 A levels but lower folate and vitamin B12 levels compared to those with mild to moderate ASD. The CARS score showed negative correlations with serum folate and vitamin B12 levels and positive correlations with serum IL-17 A and Hcy levels in ASD patients. Additionally, serum Hcy and IL-17 A levels were correlated with ASD severity.

Conclusion
Children diagnosed with ASD presented with reduced serum vitamin B12 levels and increased levels of Hcy, potentially contributing to the onset and severity of ASD.