bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting C/EBPα overcomes primary resistance and improves the efficacy of FLT3 inhibitors in acute myeloid leukaemia
Authors: Wang Hanlin , Luo Guanghao , Hu Xiaobei , Xu Gaoya , Wang Tao , Liu Minmin , Qiu Xiaohui , Li Jianan , Fu Jingfeng , Feng Bo , Tu Yutong , Kan Weijuan , Wang Chang , Xu Ran , Zhou Yubo , Yang Jianmin , Li Jia 
Published: April 2023

AbstractThe outcomes of FLT3-ITD acute myeloid leukaemia (AML) have been improved since the approval of FLT3 inhibitors (FLT3i). However, approximately 30-50% of patients exhibit primary resistance (PR) to FLT3i with poorly defined mechanisms, posing a pressing clinical unmet need. Here, we identify C/EBPα activation as a top PR feature by analyzing data from primary AML patient samples in Vizome. C/EBPα activation limit FLT3i efficacy, while its inactivation synergistically enhances FLT3i action in cellular and female animal models. We then perform an in silico screen and identify that guanfacine, an antihypertensive medication, mimics C/EBPα inactivation. Furthermore, guanfacine exerts a synergistic effect with FLT3i in vitro and in vivo. Finally, we ascertain the role of C/EBPα activation in PR in an independent cohort of FLT3-ITD patients. These findings highlight C/EBPα activation as a targetable PR mechanism and support clinical studies aimed at testing the combination of guanfacine with FLT3i in overcoming PR and enhancing the efficacy of FLT3i therapy.
Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex
Authors: Jia Junqiao , Hilal Tarek , Bohnsack Katherine E. , Chernev Aleksandar , Tsao Ning , Bethmann Juliane , Arumugam Aruna , Parmely Lane , Holton Nicole , Loll Bernhard , Mosammaparast Nima , Bohnsack Markus T. , Urlaub Henning , Wahl Markus C. 
Published: April 2023

AbstractActivating signal co-integrator 1 complex (ASCC) subunit 3 (ASCC3) supports diverse genome maintenance and gene expression processes, and contains tandem Ski2-like NTPase/helicase cassettes crucial for these functions. Presently, the molecular mechanisms underlying ASCC3 helicase activity and regulation remain unresolved. We present cryogenic electron microscopy, DNA-protein cross-linking/mass spectrometry as well as in vitro and cellular functional analyses of the ASCC3-TRIP4 sub-module of ASCC. Unlike the related spliceosomal SNRNP200 RNA helicase, ASCC3 can thread substrates through both helicase cassettes. TRIP4 docks on ASCC3 via a zinc finger domain and stimulates the helicase by positioning an ASC-1 homology domain next to the C-terminal helicase cassette of ASCC3, likely supporting substrate engagement and assisting the DNA exit. TRIP4 binds ASCC3 mutually exclusively with the DNA/RNA dealkylase, ALKBH3, directing ASCC3 for specific processes. Our findings define ASCC3-TRIP4 as a tunable motor module of ASCC that encompasses two cooperating NTPase/helicase units functionally expanded by TRIP4.
Structure of the heterotrimeric membrane protein complex FtsB-FtsL-FtsQ of the bacterial divisome
Authors: Nguyen Hong Thuy Vy , Chen Xiaorui , Parada Claudia , Luo An-Chi , Shih Orion , Jeng U-Ser , Huang Chia-Ying , Shih Yu-Ling , Ma Che 
Published: April 2023

AbstractThe synthesis of the cell-wall peptidoglycan during bacterial cell division is mediated by a multiprotein machine, called the divisome. The essential membrane protein complex of FtsB, FtsL and FtsQ (FtsBLQ) is at the heart of the divisome assembly cascade in Escherichia coli. This complex regulates the transglycosylation and transpeptidation activities of the FtsW-FtsI complex and PBP1b via coordination with FtsN, the trigger for the onset of constriction. Yet the underlying mechanism of FtsBLQ-mediated regulation is largely unknown. Here, we report the full-length structure of the heterotrimeric FtsBLQ complex, which reveals a V-shaped architecture in a tilted orientation. Such a conformation could be strengthened by the transmembrane and the coiled-coil domains of the FtsBL heterodimer, as well as an extended β-sheet of the C-terminal interaction site involving all three proteins. This trimeric structure may also facilitate interactions with other divisome proteins in an allosteric manner. These results lead us to propose a structure-based model that delineates the mechanism of the regulation of peptidoglycan synthases by the FtsBLQ complex.
Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection
Authors: Pieren Daan K. J. , Kuguel Sebastián G. , Rosado Joel , Robles Alba G. , Rey-Cano Joan , Mancebo Cristina , Esperalba Juliana , Falcó Vicenç , Buzón María J. , Genescà Meritxell 
Published: April 2023

AbstractResident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Here we show that the frequency of CD4+ T cells secreting IFNγ in response to S-peptides is variable but overall similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses present less frequently a TRM phenotype compared to convalescent infected individuals and polyfunctional CD107a+ IFNγ+ TRM are virtually absent in vaccinated patients. These data indicate that mRNA vaccination induces specific T cell responses to SARS-CoV-2 in the lung parenchyma, although to a limited extend. It remains to be determined whether these vaccine-induced responses contribute to overall COVID-19 control.
Realizing high-capacity all-solid-state lithium-sulfur batteries using a low-density inorganic solid-state electrolyte
Authors: Wang Daiwei , Jhang Li-Ji , Kou Rong , Liao Meng , Zheng Shiyao , Jiang Heng , Shi Pei , Li Guo-Xing , Meng Kui , Wang Donghai 
Published: April 2023

AbstractLithium-sulfur all-solid-state batteries using inorganic solid-state electrolytes are considered promising electrochemical energy storage technologies. However, developing positive electrodes with high sulfur content, adequate sulfur utilization, and high mass loading is challenging. Here, to address these concerns, we propose using a liquid-phase-synthesized Li3PS4-2LiBH4 glass-ceramic solid electrolyte with a low density (1.491 g cm−3), small primary particle size (~500 nm) and bulk ionic conductivity of 6.0 mS cm−1 at 25 °C for fabricating lithium-sulfur all-solid-state batteries. When tested in a Swagelok cell configuration with a Li-In negative electrode and a 60 wt% S positive electrode applying an average stack pressure of ~55 MPa, the all-solid-state battery delivered a high discharge capacity of about 1144.6 mAh g−1 at 167.5 mA g−1 and 60 °C. We further demonstrate that the use of the low-density solid electrolyte increases the electrolyte volume ratio in the cathode, reduces inactive bulky sulfur, and improves the content uniformity of the sulfur-based positive electrode, thus providing sufficient ion conduction pathways for battery performance improvement.
Algal cell bionics as a step towards photosynthesis-independent hydrogen production
Authors: Xu Zhijun , Qi Jiarui , Wang Shengliang , Liu Xiaoman , Li Mei , Mann Stephen , Huang Xin 
Published: April 2023

AbstractThe engineering and modulation of living micro-organisms is a key challenge in green bio-manufacturing for the development of sustainable and carbon-neutral energy technologies. Here, we develop a cellular bionic approach in which living algal cells are interfaced with an ultra-thin shell of a conductive polymer along with a calcium carbonate exoskeleton to produce a discrete cellular micro-niche capable of sustained photosynthetic and photosynthetic-independent hydrogen production. The surface-augmented algal cells induce oxygen depletion, conduct photo-induced extracellular electrons, and provide structural and chemical stability that collectively give rise to localized hypoxic conditions and concomitant hydrogenase activity under daylight in air. We show that assembly of the living cellular micro-niche opens a direct extracellular photoelectron pathway to hydrogenase resulting in photosynthesis-independent hydrogen evolution for 200 d. In addition, surface-conductive dead algal cells continue to produce hydrogen for up to 8 d due to their structural stability and retention of functional hydrogenases. Overall, the integration of artificial biological hydrogen production pathways and natural photosynthesis in surface-augmented algal cells provides a cellular bionic approach to enhanced green hydrogen production under environmentally benign conditions and could pave the way to new opportunities in sustainable energy production.
Ruthenium-cobalt single atom alloy for CO photo-hydrogenation to liquid fuels at ambient pressures
Authors: Zhao Jiaqi , Liu Jinjia , Li Zhenhua , Wang Kaiwen , Shi Run , Wang Pu , Wang Qing , Waterhouse Geoffrey I. N. , Wen Xiaodong , Zhang Tierui 
Published: April 2023

AbstractPhotothermal Fischer-Tropsch synthesis represents a promising strategy for converting carbon monoxide into value-added chemicals. High pressures (2-5 MPa) are typically required for efficient C-C coupling reactions and the production of C5+ liquid fuels. Herein, we report a ruthenium-cobalt single atom alloy (Ru1Co-SAA) catalyst derived from a layered-double-hydroxide nanosheet precursor. Under UV-Vis irradiation (1.80 W cm−2), Ru1Co-SAA heats to 200 °C and photo-hydrogenates CO to C5+ liquid fuels at ambient pressures (0.1-0.5 MPa). Single atom Ru sites dramatically enhance the dissociative adsorption of CO, whilst promoting C-C coupling reactions and suppressing over-hydrogenation of CHx* intermediates, resulting in a CO photo-hydrogenation turnover frequency of 0.114 s−1 with 75.8% C5+ selectivity. Owing to the local Ru-Co coordination, highly unsaturated intermediates are generated during C-C coupling reactions, thereby improving the probability of carbon chain growth into C5+ liquid fuels. The findings open new vistas towards C5+ liquid fuels under sunlight at mild pressures.
An emerging generation of endocrine therapies in breast cancer: a clinical perspective
Authors: Patel Rima , Klein Paula , Tiersten Amy , Sparano Joseph A. 
Published: April 2023

AbstractAnti-estrogen therapy is a key component of the treatment of both early and advanced-stage hormone receptor (HR)-positive breast cancer. This review discusses the recent emergence of several anti-estrogen therapies, some of which were designed to overcome common mechanisms of endocrine resistance. The new generation of drugs includes selective estrogen receptor modulators (SERMs), orally administered selective estrogen receptor degraders (SERDs), as well as more unique agents such as complete estrogen receptor antagonists (CERANs), proteolysis targeting chimeric (PROTACs), and selective estrogen receptor covalent antagonists (SERCAs). These drugs are at various stages of development and are being evaluated in both early and metastatic settings. We discuss the efficacy, toxicity profile, and completed and ongoing clinical trials for each drug and highlight key differences in their activity and study population that have ultimately influenced their advancement.
A large-scale repository of spoken narratives in French, German and Spanish from Cantonese-speaking learners
Authors: Kang Xin , Yip Virginia , Matthews Stephen , Wong Patrick C. M. 
Published: April 2023

AbstractInterdisciplinary research on foreign language learning has important implications for learning and education. In this paper, we present the Repository of Third Language (L3) Spoken Narratives from Modern Language Learners in Hong Kong (L3HK Repository). This database contains 906 audio recordings and annotated transcripts of spoken narratives in French, German, and Spanish that were elicited from Cantonese-speaking (L1) young adults using a wordless picture book, “Frog, Where Are You?”. All participants spoke English as the second language (L2) and learned the target language as a third language (L3). We collected their demographic information, answers to a motivation questionnaire, parental socioeconomic status, and music background. Furthermore, for a subset of participants, we collected their L1 and L2 proficiency scores and additional experimental data on working memory and music perception. This database is valuable for examining cross-sectional changes in foreign language learning. The extensive data on phenotypes provide opportunities to explore learner-internal and learner-external factors in foreign language learning outcomes. These data may also be helpful for those who work on speech recognition.
Extensive 3D mapping of dislocation structures in bulk aluminum
Authors: Yildirim Can , Poulsen Henning F. , Winther Grethe , Detlefs Carsten , Huang Pin H. , Dresselhaus-Marais Leora E. 
Published: April 2023

AbstractThermomechanical processing such as annealing is one of the main methods to tailor the mechanical properties of materials, however, much is unknown about the reorganization of dislocation structures deep inside macroscopic crystals that give rise to those changes. Here, we demonstrate the self-organization of dislocation structures upon high-temperature annealing in a mm-sized single crystal of aluminum. We map a large embedded 3D volume ($$100\times 300\times 300$$

100
×
300
×
300

$$\upmu$$
μ
m$$^3$$

3

) of dislocation structures using dark field X-ray microscopy (DFXM), a diffraction-based imaging technique. Over the wide field of view, DFXM’s high angular resolution allows us to identify subgrains, separated by dislocation boundaries, which we identify and characterize down to the single-dislocation level using computer-vision methods. We demonstrate how even after long annealing times at high temperatures, the remaining low density of dislocations still pack into well-defined, straight dislocation boundaries (DBs) that lie on specific crystallographic planes. In contrast to conventional grain growth models, our results show that the dihedral angles at the triple junctions are not the predicted 120$$^{\circ }$$

∘

, suggesting additional complexities in the boundary stabilization mechanisms. Mapping the local misorientation and lattice strain around these boundaries shows that the observed strain is shear, imparting an average misorientation around the DB of $$\approx$$
≈
0.003 to 0.006$$^{\circ }$$

∘

.
The unconditioned fear response in dystrophin-deficient mice is associated with adrenal and vascular function
Authors: Lindsay Angus , Russell Aaron P. 
Published: April 2023

AbstractLoss of function mutations in the gene encoding dystrophin elicits a hypersensitive fear response in mice and humans. In the dystrophin-deficientmdxmouse, this behaviour is partially protected by oestrogen, but the mechanistic basis for this protection is unknown. Here, we show that femalemdxmice remain normotensive during restraint stress compared to a hypotensive and hypertensive response in malemdxand male/female wildtype mice, respectively. Partial dystrophin expression in femalemdxmice (heterozygous) also elicited a hypertensive response. Ovariectomized (OVX) femalemdxmice were used to explain the normotensive response to stress. OVX lowered skeletal muscle mass and lowered the adrenal mass and zona glomerulosa area (aldosterone synthesis) in femalemdxmice. During a restraint stress, OVX dampened aldosterone synthesis and lowered the corticosterone:11-dehydrocorticosterone. All OVX-induced changes were restored with replacement of oestradiol, except that oestradiol lowered the zona fasciculata area of the adrenal gland, dampened corticosterone synthesis but increased cortisol synthesis. These data suggest that oestrogen partially attenuates the unconditioned fear response inmdxmice via adrenal and vascular function. It also suggests that partial dystrophin restoration in a dystrophin-deficient vertebrate is an effective approach to develop an appropriate hypertensive response to stress.
Discrimination of the chemotherapy resistance status of human leukemia and glioblastoma cell lines by MALDI-TOF-MS profiling
Authors: Ledesma Martín , Poodts Daniela , Amoia Sofía , Hajos Silvia , Fundia Ariela , Vay Carlos , Pibuel Matías , Lompardía Silvina 
Published: April 2023

AbstractChemotherapy mistreatment is partially due to a lack of rapid and reliable tools to discriminate between sensitive and resistant phenotypes. In many cases, the resistance mechanism is not fully understood, contributing to the diagnostic tools' absence. This work aims to determine the capacity of MALDI-TOF-MS profiling to discriminate between chemotherapy-resistant and sensitive phenotypes in leukemia and glioblastoma cells. A multivariate analysis of two therapy-resistant leukemia cell lines (Ki562 and Kv562) and two TMZ-resistant glioblastoma cell lines (U251-R and LN229-R) and their sensitive counterparts was performed. In this work, we first show MALDI-TOF-MS patterns analysis ability to differentiate these cancer cell lines by their chemotherapy-resistant status. We present a rapid and inexpensive tool that would guide and complement the therapeutic decision.
A high step‐up DC–DC converter with switched‐capacitor and switched‐inductor using one coupled inductor
Authors: Luo Peng , Liang Tsorng‐Juu , Chen Shih‐Ming , Chen Kai‐Hui 
Published: April 2023

AbstractThis paper proposes a high step‐up DC–DC converter which integrates switched‐inductor and switched‐capacitor techniques with a four‐winding coupled‐inductor. With switched‐inductor technique, two primary windings of the coupled‐inductor are charged in parallel and discharged in series to obtain high voltage gain. Moreover, by adding two sets of diode‐capacitor circuits on both primary side windings, not only can recycle the energy causing the voltage spike on the power switches, but can also lift the conversion ratio. Then, the power switches with lower voltage stress are used to improve the efficiency of the proposed converter. The operating principle, steady state analyses, and key parameters design of the proposed converter are discussed and provided. Finally, a 400 W laboratory prototype with 24 V input voltage and 480 V output voltage is constructed and tested to validate the performance. The highest and full load efficiencies are 95.8% and 94.8%, respectively.
15 Erfolgsfaktoren für schlanke Materiallogistik im OP
Authors: Roß Claudia , Lütte Katharina 
Published: April 2023

ZusammenfassungGerade die letzten Jahre zeigen, dass sich das allgemeine Sicherheitsgefühl der vergangenen Jahrzehnte auch in Krankenhäusern und deren Logistik ausgebreitet hatte und die plötzliche
Konfrontation mit Materialknappheit und gestiegenen Materialkosten diese Selbstverständlichkeit empfindlich störten. Für diese Punkte mussten kurzfristig kreative Lösungen gefunden und
langfristige Konzepte für die Zukunft geschaffen werden, die viele, bisher kaum denkbare Eventualitäten berücksichtigen
Stereoselective Total Synthesis of Stereoisomers of Entecavir
Authors: Wang Chao , Pei Dong , Zhou Li , Sun Jian 
Published: April 2023

AbstractPractical methods for the synthesis of three stereoisomers of Entecavir have been developed. Starting from the reported intermediate (1S,2R)-2-((benzyloxy)methyl)cyclopent-3-en-1-ol and (1R,2S)-2-((benzyloxy)methyl)cyclopent-3-en-1-ol, respectively, three stereoisomers of Entecavir have been prepared with 17–20% overall yields. In principle, other stereoisomers could also be prepared by using the materials and reactions described in this article.
High quality colonoscopy: using textbook process as a composite quality measure
Authors: Nass Karlijn J. , van Doorn Sascha C. , Fockens Paul , Rees Colin J. , Pellisé Maria , van der Vlugt Manon , Dekker Evelien 
Published: April 2023

Abstract
Background High quality colonoscopy is fundamental to good patient outcomes. “Textbook outcome” has proven to be a feasible multidimensional measure for quality assurance between surgical centers. In this study, we sought to establish the “textbook process” (TP) as a new composite measure for the optimal colonoscopy process and assessed how frequently TP was attained in clinical practice and the variation in TP between endoscopists.
Methods To reach consensus on the definition of TP, international expert endoscopists completed a modified Delphi consensus process. The achievement of TP was then applied to clinical practice. Prospectively collected data in two endoscopy services were retrospectively evaluated. Data on colonoscopies performed for symptoms or surveillance between 1 January 2018 and 1 August 2021 were analyzed.
Results The Delphi consensus process was completed by 20 of 27 invited experts (74.1 %). TP was defined as a colonoscopy fulfilling the following items: explicit colonoscopy indication; successful cecal intubation; adequate bowel preparation; adequate withdrawal time; acceptable patient comfort score; provision of post-polypectomy surveillance recommendations in line with guidelines; and the absence of the use of reversal agents, early adverse events, readmission, and mortality. In the two endoscopy services studied, TP was achieved in 5962/8227 colonoscopies (72.5 %). Of 48 endoscopists performing colonoscopy, attainment of TP varied significantly, ranging per endoscopist from 41.0 % to 89.1 %.
Conclusion This study proposes a new composite measure for colonoscopy, namely “textbook process.” TP gives a comprehensive summary of performance and demonstrates significant variation between endoscopists, illustrating the potential benefit of TP as a measure in future quality assessment programs.
GAED Medal Lecture 2022: Challenging the Dogma in Diabetic Neuropathy and Beyond
Authors: Malik Rayaz A. 
Published: April 2023

AbstractDogma, according to the Britannica Dictionary, is ”a belief or set of beliefs that is accepted by the members of a group without being questioned or doubted.” Thus, in 2001, the heretical idea that corneal confocal microscopy (CCM)—an ophthalmic instrument—could be used to assess neurological disease truly challenged the dogma. The repurposing of CCM to study diabetic neuropathy and other neurodegenerative diseases is a wonderful illustration of being in the right time and place and having honest and open conversations between very different medical disciplines to 'challenge the dogma.' The Gulf Association of Diabetes and Endocrinology (GAED) Medal Lecture in 2022 and the European Association for the Study of Diabetes (EASD) Camillo Golgi Prize in 2019 have enabled me to tell my personal story in relation to the past, present, and future of CCM as a clinical tool to diagnose and predict neurodegeneration and identify nerve regeneration in clinical trials of new therapies for peripheral and central neurodegenerative diseases.