bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auxin-inducible degron 2 system deciphers functions of CTCF domains in transcriptional regulation
Authors: Hyle Judith , Djekidel Mohamed Nadhir , Williams Justin , Wright Shaela , Shao Ying , Xu Beisi , Li Chunliang 
Published: January 2023

AbstractBackgroundCTCF is a well-established chromatin architectural protein that also plays various roles in transcriptional regulation. While CTCF biology has been extensively studied, how the domains of CTCF function to regulate transcription remains unknown. Additionally, the original auxin-inducible degron 1 (AID1) system has limitations in investigating the function of CTCF.ResultsWe employ an improved auxin-inducible degron technology, AID2, to facilitate the study of acute depletion of CTCF while overcoming the limitations of the previous AID system. As previously observed through the AID1 system and steady-state RNA analysis, the new AID2 system combined with SLAM-seq confirms that CTCF depletion leads to modest nascent and steady-state transcript changes. A CTCF domain sgRNA library screening identifies the zinc finger (ZF) domain as the region within CTCF with the most functional relevance, including ZFs 1 and 10. Removal of ZFs 1 and 10 reveals genomic regions that independently require these ZFs for DNA binding and transcriptional regulation. Notably, loci regulated by either ZF1 or ZF10 exhibit unique CTCF binding motifs specific to each ZF.ConclusionsBy extensively comparing the AID1 and AID2 systems for CTCF degradation in SEM cells, we confirm that AID2 degradation is superior for achieving miniAID-tagged protein degradation without the limitations of the AID1 system. The model we create that combines AID2 depletion of CTCF with exogenous overexpression of CTCF mutants allows us to demonstrate how peripheral ZFs intricately orchestrate transcriptional regulation in a cellular context for the first time.
Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD CAA prevention (KD-CAAP) trial protocol
Authors: Eleftheriou Despina , Moraes Yolanda Collaco , Purvis Cara , Pursell Molly , Morillas Marta Merida , Kahn Robin , Mossberg Maria , Kucera Filip , Tulloh Robert , Standing Joseph F. , Swallow Veronica , McCormack Rachael , Herberg Jethro , Levin Michael , Wan Mandy , Klein Nigel , Connon Roisin , Walker Ann Sarah , Brogan Paul 
Published: January 2023

Abstract
Background

Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe.

Methods
KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes.

Discussion
Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children.

Trial registration
ISRCTN71987471- March 31, 2020; Eudract 2019–004433-17.
Myeloid/lymphoid neoplasm with eosinophilia and BCR/FGFR1 rearrangement with transformation to cortical T-lymphoblastic lymphoma and erythroid precursors: a case report
Authors: Isaza Alejandro Pineda , Quintero Santiago Castaño , González Lisceth Paola Quintero , Córdoba Fabián Emiliano Ahumada , Olivar Andrés Felipe Arbeláez , Ocaña Juan Carlos Bravo 
Published: January 2023

Abstract
Background
Myeloproliferative neoplasms are a group of diseases with diverse biological and clinical characteristics. As a provisional separate entity, myeloid/lymphoid neoplasms with eosinophilia and genetic rearrangement have been described, which may present an initial clinical behavior of myeloproliferation and be characterized by varied genetic rearrangements. One of these entities is associated with FGFR1 rearrangements, characterized by its low prevalence and few treatment options.

Case presentation
We present the case of a 53-year-old Mestizo male patient of Hispanic origin who initially presented weight loss and fatigue, with a complete blood count showing leukocytosis and eosinophilia, with an initial diagnosis of nonspecific myeloproliferative disorder. In a next-generation sequencing study, BCR::FGFR1 rearrangement was documented, a diagnosis of myeloid/lymphoid neoplasia with eosinophilia and BCR::FGFR1 rearrangement was made, and hydroxyurea therapy was initiated. Subsequently, transformation to cortical T-lymphoblastic leukemia/lymphoma and erythroid precursors was documented, requiring management with chemotherapy.

Conclusions
Myeloid/lymphoid neoplasms with eosinophilia and genetic rearrangements constitute a group of deeply heterogeneous diseases with variable clinical and diagnostic characteristics and whose treatment is not clearly defined.
Effects of down-regulation of ackA expression by CRISPR-dCpf1 on succinic acid production in Actinobacillus succinogenes
Authors: Chen Chunmei , Zheng Pu 
Published: January 2023

AbstractSuccinic acid (SA), a key intermediate in the cellular tricarboxylic acid cycle (TCA), is a 4-carbon dicarboxylic acid of great industrial value. Actinobacillus succinogenes can ferment various carbon sources and accumulate relatively high concentrations of SA, but few reliable genetic engineering tools exist for A. succinogenes and this has hindered strain improvement to increase SA production for industrial application. Two different repressors, endonuclease-deactivated Cas9 (dCas9) from Streptococcus pyogenes and Cpf1 (dCpf1) from Francisella tularensis, were applied to construct a CRISPRi system in A. succinogenes. Codon-optimized Cas9 and native Cpf1 were successfully expressed in A. succinogenes, and the corresponding sgRNA and crRNA expression elements, promoted by the fumarate reductase promoter, frd, were introduced into the CRISPRi plasmid. The highest repression of the ackA gene (encoding acetate kinase) and thereby acetic acid production (~ eightfold) was achieved by the dCpf1-based CRISPRi system, in which the mutation site, E1006A acted at the start of the coding region of ackA, the gene which regulates acetic acid biosynthesis. Compared with the ackA gene knockout mutant, cell growth was moderately improved and SA production increased by 6.3%. Further, the SA titer and productivity in a 3 L fermenter reached 57.06 g/L and 1.87 g/L/h, and there was less acetic acid production. A dCpf1-based CRISPRi-mediated gene repression system was successfully established for the first time, providing a simple and effective tool for studying functional genomics in A. succinogenes and optimizing SA production.
Information embedding in DFRC networks through chirp waveform diversity
Authors: Chalise Batu K. , Amin Moeness G. , Fabrizio Giuseppe A. 
Published: January 2023

AbstractWe consider a dual function radar communications network and propose a waveform diversity-based approach to embed both target and scheduling data in the transmitter pulses. The scheduling data of radar signal bandwidth, carrier frequency, and waveform along with the information on target detection, range, and Doppler are shared among the network radar nodes without a need for designated communication links. Scheduling and target information are encoded to bits and transmitted over the radar coherent processing interval using up- and down-chirps. We derive exact expressions of probability of bit error and false alarm rate for sharing scheduling and target information data between two radar nodes. The effect of different parameters and data sharing on the radar performance is analyzed and validated by computer simulations. Using the cross-ambiguity function, we show the capability of the up- and down- chirp sequence transmission scheme in reducing range sidelobes compared to the conventional transmission of only the up- (or down-) chirps. To overcome the limited data rate associated with only using two chirp waveforms, we consider orthogonal chirp division multiplexing and derive its CAF. We demonstrate the suitability of OCDM for high data rate radar operations by examining the mainlobe width and sidelobe levels of the zero-Doppler and zero-delay cuts of the CAF.
Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
Authors: Yulug Burak , Altay Ozlem , Li Xiangyu , Hanoglu Lutfu , Cankaya Seyda , Lam Simon , Velioglu Halil Aziz , Yang Hong , Coskun Ebru , Idil Ezgi , Nogaylar Rahim , Ozsimsek Ahmet , Bayram Cemil , Bolat Ismail , Oner Sena , Tozlu Ozlem Ozdemir , Arslan Mehmet Enes , Hacimuftuoglu Ahmet , Yildirim Serkan , Arif Muhammad , Shoaie Saeed , Zhang Cheng , Nielsen Jens , Turkez Hasan , Borén Jan , Uhlén Mathias , Mardinoglu Adil 
Published: January 2023

Abstract
Background
Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.

Methods
Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.

Results
We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.

Conclusion
Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131
A framework towards resilient Mediterranean eco-solutions for small-scale farming systems
Authors: Lamonaca Emilia , Bouzid Amel , Caroprese Mariangela , Ciliberti Maria Giovanna , Cordovil Claudia M.d. S. , Karatzia Maria-Anastasia , Keskin Mahmut , Lazereg Messaoud , Lidga Christina , Panniello Umberto , Saratsis Anastasios , Tappi Marco , Valasi Irene , Yetişgin SezenOcak , Santeramo Fabio Gaetano 
Published: January 2023

Abstract
Background
The impacts of climate change on crop and livestock sectors are well-documented. Climate change and its related events (e.g., high temperatures, extreme events, disease outbreaks) affect livestock production in various ways (e.g., nutrition, housing, health, welfare), and tend to compromise the physical productivity and the economic performances. Understanding animal responses to climate change may help planning strategies to cope with the adverse climatic conditions and also to reduce polluting emissions. Through an interdisciplinary approach, we develop a conceptual framework to assess and develop new organisational models for Mediterranean small-scale farming systems so as to mitigate the impacts of climate change, to improve farm management and farming technologies, and to achieve an effective adaptation to the climate changes. The conceptual framework consists of four phases: (i) community engagement, (ii) strategies development, (iii) data collection and analysis, (iv) business model generation and sustainability assessment. We assess strengths, weaknesses, opportunities, and threats of the eco-solutions by mean of a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis technique.

Results
The proposed eco-solutions are expected to increase the sustainability of agriculture and food production systems by introducing new and efficient uses of natural resources. The proposed models are expected to have an impact not only on the environment (in terms of mitigation), but also on the economic and social performances, as they are expected to foster the responses of small-scale farms to the increasingly frequent effects of climate change (adaptation solutions). Among the positive impacts, we emphasise the importance of more stable revenues, a tendency that would help farmers to raise their revenues. Last but not least, we found that the proposed models are likely to increase the social resilience of the farming systems to the challenges imposed by the climate change.

Conclusions
The eco-solutions can support stakeholders involved in Mediterranean small-scale farming systems by suggesting novel land, crop, and livestock management approaches to optimise revenue flows, business models and climate change mitigation strategies thanks to the adoption of a systemic approach, that is not only focused on specific components of the system but instead based on the linkages between environmental, social, and economic aspects.
High-resolution metagenomic reconstruction of the freshwater spring bloom
Authors: Kavagutti Vinicius S. , Bulzu Paul-Adrian , Chiriac Cecilia M. , Salcher Michaela M. , Mukherjee Indranil , Shabarova Tanja , Grujčić Vesna , Mehrshad Maliheh , Kasalický Vojtěch , Andrei Adrian-Stefan , Jezberová Jitka , Seďa Jaromir , Rychtecký Pavel , Znachor Petr , Šimek Karel , Ghai Rohit 
Published: January 2023

Abstract
Background
The phytoplankton spring bloom in freshwater habitats is a complex, recurring, and dynamic ecological spectacle that unfolds at multiple biological scales. Although enormous taxonomic shifts in microbial assemblages during and after the bloom have been reported, genomic information on the microbial community of the spring bloom remains scarce.

Results
We performed a high-resolution spatio-temporal sampling of the spring bloom in a freshwater reservoir and describe a multitude of previously unknown taxa using metagenome-assembled genomes of eukaryotes, prokaryotes, and viruses in combination with a broad array of methodologies. The recovered genomes reveal multiple distributional dynamics for several bacterial groups with progressively increasing stratification. Analyses of abundances of metagenome-assembled genomes in concert with CARD-FISH revealed remarkably similar in situ doubling time estimates for dominant genome-streamlined microbial lineages. Discordance between quantitations of cryptophytes arising from sequence data and microscopic identification suggested the presence of hidden, yet extremely abundant aplastidic cryptophytes that were confirmed by CARD-FISH analyses. Aplastidic cryptophytes are prevalent throughout the water column but have never been considered in prior models of plankton dynamics. We also recovered the first metagenomic-assembled genomes of freshwater protists (a diatom and a haptophyte) along with thousands of giant viral genomic contigs, some of which appeared similar to viruses infecting haptophytes but owing to lack of known representatives, most remained without any indication of their hosts. The contrasting distribution of giant viruses that are present in the entire water column to that of parasitic perkinsids residing largely in deeper waters allows us to propose giant viruses as the biological agents of top-down control and bloom collapse, likely in combination with bottom-up factors like a nutrient limitation.

Conclusion
We reconstructed thousands of genomes of microbes and viruses from a freshwater spring bloom and show that such large-scale genome recovery allows tracking of planktonic succession in great detail. However, integration of metagenomic information with other methodologies (e.g., microscopy, CARD-FISH) remains critical to reveal diverse phenomena (e.g., distributional patterns, in situ doubling times) and novel participants (e.g., aplastidic cryptophytes) and to further refine existing ecological models (e.g., factors affecting bloom collapse). This work provides a genomic foundation for future approaches towards a fine-scale characterization of the organisms in relation to the rapidly changing environment during the course of the freshwater spring bloom.
Portuguese version of Bern Illegitimates Task Scale: adaptation and evidence of validity
Authors: Neves Paula C. , Andrade Cláudia , Paixão Rui , da Silva José Tomás 
Published: January 2023

Abstract
Background
A new element for job stress called Illegitimate Tasks has been investigated in recent years, along with stress as an offense to self-theory. Illegitimate tasks are those that are either needless or unrelated to the employee's role and can be categorized as unreasonable tasks and unnecessary tasks.

Methods
This study aimed to adapt the Bern Illegitimate Tasks Scale to Portuguese and provide evidence of its validity, through a confirmatory factor analysis with a sample of 472 workers from different sectors.

Results
The internal consistency, of the whole scale, measured by Cronbach’s alpha, was 0.923 and 0.902 and 0.928 for the unnecessary tasks and, for unreasonable tasks subscales respectively. The confirmatory analysis supported a two-factor model and showed good to very good indexes of fit (CFI = 0.985; TLI = 0.997; SRMR = 0.035; RMSEA = 0.171).

Discussion
The Portuguese version of the Bern Illegitimate Tasks Scale presents very good psychometric properties for the intended measurement goals and can now be used in research with Portuguese speaking samples.
Dual signal amplification coupling with DNA-templated silver nanoclusters for sensitive and label-free detection of thrombin
Authors: Zhang Baojun , Ma Weiwei , Guo Jun , Zhao Qiufeng , Zhang Chuangchuang , Zhu Shilong , Xu Haibo , Yin Yanyan 
Published: January 2023

AbstractSensitive and reliable determination of thrombin is relevant in the realms of medical and biological research as it serves as an essential biomarker of a number of blood-related illnesses. Herein, we integrate allosteric probe-based specific identification of thrombin and dual signal amplification to present an unique fluorescent technique for label-free and sensitive thrombin detection. Based on DNA polymerase and endonuclease-assisted signal amplification, the method exhibits a high sensitivity with a low limit of detection of 2.3 pM, while maintaining an excellent selectivity and stability. More importantly, the approach is successfully applied in analyzing the effect of nalbuphine on coagulation function of mice. Overall, this approach possesses the advantages of high specificity and sensitivity in label-free detection of thrombin, which is promising in the diagnosis of blood-related diseases.
The usefulness of laparoscopic surgery for inguinal endometriosis
Authors: Mushiake Shu , Kawaguchi Nao , Asakuma Mitsuhiro , Komeda Koji , Shimizu Tetsunosuke , Hirokawa Fumitoshi , Shimomura Tomoo , Lee Sang-Woong 
Published: January 2023

Abstract
Background
Inguinal endometriosis is a rare clinical disease with an unclear etiology and pathogenesis, and its diagnosis requires accurate medical history-taking and histological examination. However, surgical treatment for the condition has not yet been standardized. This report presents two cases of inguinal endometriosis.

Case presentation
The first patient was a 36-year-old woman who complained of pain and swelling in her right inguinal region. Physical examination revealed a soft, tender right inguinal mass. The size of the mass repeatedly increased and decreased during menstruation and did not show swelling with abdominal pressure. Magnetic resonance imaging showed a 3.5 × 2.5 cm mass with high intensity on T2-weighted imaging in the right inguinal canal, and no communication was found between the lesion site and the abdominal cavity. We diagnosed this case as inguinal endometriosis and managed it using an anterior approach and laparoscopic observation. The second patient was a 51-year-old woman who presented with an intermittently painful mass in her right inguinal region. The mass tended to increase in size, with worsening pain before menstruation. Abdominal computed tomography revealed a 2 × 2 cm cystic mass in the right inguinal region. We made a diagnosis of inguinal ectopic endometriosis and decided to operate via the totally extraperitoneal (TEP) method for excision plus transabdominal observation. The postoperative course in both cases was uneventful with no recurrence.

Conclusions
Inguinal endometriosis is a rare entity that should be suspected in patients with cyclical symptoms of inguinal pain and swelling that correlate with their menstrual cycle, which might otherwise be attributed to inguinal hernia. It is crucial to make a preoperative diagnosis based on a careful medical review, physical examination, and imaging studies, and to make an appropriate surgical plan. Particularly, in the case of ectopic inguinal endometriosis involving the canal of Nuck, laparoscopic observation is useful for the intraoperative diagnosis of inguinal endometriosis to help rule out the involvement of other abdominal sites. However, it is important to select and modify the surgical technique to avoid rupturing the endometrisis mass and prevent postoperative recurrence.