bluuebunny/crossref_metadata_2025_split huggingface dataset:
A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases
Authors: Ju Shuyun , Kuzelka Kaylee P. , Guo Rui , Krohn-Hansen Benjamin , Wu Jianping , Nair Satish K. , Yang Yang 
Published: September 2023

AbstractCatalytic asymmetric α-alkylation of carbonyl compounds represents a long-standing challenge in synthetic organic chemistry. Herein, we advance a dual biocatalytic platform for the efficient asymmetric alkylation of α-keto acids. First, guided by our recently obtained crystal structures, we develop SgvMVAV as a general biocatalyst for the enantioselective methylation, ethylation, allylation and propargylation of a range of α-keto acids with total turnover numbers (TTNs) up to 4,600. Second, we mine a family of bacterial HMTs from Pseudomonas species sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT from P. aeruginosa, PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvMVAV and PaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.
Real-space observation of ergodicity transitions in artificial spin ice
Authors: Saccone Michael , Caravelli Francesco , Hofhuis Kevin , Dhuey Scott , Scholl Andreas , Nisoli Cristiano , Farhan Alan 
Published: September 2023

AbstractEver since its introduction by Ludwig Boltzmann, the ergodic hypothesis became a cornerstone analytical concept of equilibrium thermodynamics and complex dynamic processes. Examples of its relevance range from modeling decision-making processes in brain science to economic predictions. In condensed matter physics, ergodicity remains a concept largely investigated via theoretical and computational models. Here, we demonstrate the direct real-space observation of ergodicity transitions in a vertex-frustrated artificial spin ice. Using synchrotron-based photoemission electron microscopy we record thermally-driven moment fluctuations as a function of temperature, allowing us to directly observe transitions between ergodicity-breaking dynamics to system freezing, standing in contrast to simple trends observed for the temperature-dependent vertex populations, all while the entropy features arise as a function of temperature. These results highlight how a geometrically frustrated system, with thermodynamics strictly adhering to local ice-rule constraints, runs back-and-forth through periods of ergodicity-breaking dynamics. Ergodicity breaking and the emergence of memory is important for emergent computation, particularly in physical reservoir computing. Our work serves as further evidence of how fundamental laws of thermodynamics can be experimentally explored via real-space imaging.
Estimating the burden of severe malarial anaemia and access to hospital care in East Africa
Authors: Winskill Peter , Dhabangi Aggrey , Kwambai Titus K. , Mori Amani Thomas , Mousa Andria , Okell Lucy C. 
Published: September 2023

AbstractSevere malarial anaemia can be fatal if not promptly treated. Hospital studies may under-represent the true burden because cases often occur in settings with poor access to healthcare. We estimate the relationship of community prevalence of malaria infection and severe malarial anaemia with the incidence of severe malarial anaemia cases in hospital, using survey data from 21 countries and hospital data from Kenya, Tanzania and Uganda. The estimated percentage of severe malarial anaemia cases that were hospitalised is low and consistent for Kenya (21% (95% CrI: 7%, 47%)), Tanzania (18% (95% CrI: 5%, 52%)) and Uganda (23% (95% CrI: 9%, 48%)). The majority of severe malarial anaemia cases remain in the community, with the consequent public health burden being contingent upon the severity of these cases. Alongside health system strengthening, research to better understand the spectrum of disease associated with severe malarial anaemia cases in the community is a priority.
A CO2 electrolyzer tandem cell system for CO2-CO co-feed valorization in a Ni-N-C/Cu-catalyzed reaction cascade
Authors: Möller Tim , Filippi Michael , Brückner Sven , Ju Wen , Strasser Peter 
Published: September 2023

AbstractCoupled tandem electrolyzer concepts have been predicted to offer kinetic benefits to sluggish catalytic reactions thanks to their flexibility of reaction environments in each cell. Here we design, assemble, test, and analyze the first complete low-temperature, neutral-pH, cathode precious metal-free tandem CO2 electrolyzer cell chain. The tandem system couples an Ag-free CO2-to-CO2/CO electrolyzer (cell-1) to a CO2/CO-to-C2+ product electrolyzer (cell-2). Cell-1 and cell-2 incorporate selective Ni-N-C-based and Cu-based Gas Diffusion Cathodes, respectively, and operate at sustainable neutral pH conditions. Using our tandem cell system, we report strongly enhanced rates for the production of ethylene (by 50%) and alcohols (by 100%) and a sharply increased C2+ energy efficiency (by 100%) at current densities of up to 700 mA cm−2 compared to the single CO2-to-C2+ electrolyzer cell system approach. This study demonstrates that coupled tandem electrolyzer cell systems can offer kinetic and practical energetic benefits over single-cell designs for the production of value-added C2+ chemicals and fuels directly from CO2 feeds without intermediate separation or purification.
Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis
Authors: Piña Jeremie Oliver , Raju Resmi , Roth Daniela M. , Winchester Emma Wentworth , Chattaraj Parna , Kidwai Fahad , Faucz Fabio R. , Iben James , Mitra Apratim , Campbell Kiersten , Fridell Gus , Esnault Caroline , Cotney Justin L. , Dale Ryan K. , D’Souza Rena N. 
Published: September 2023

AbstractThe terminal differentiation of osteoblasts and subsequent formation of bone marks an important phase in palate development that leads to the separation of the oral and nasal cavities. While the morphogenetic events preceding palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms driving the formation of this bony union of the fusing palate. Through bulk, single-nucleus, and spatially resolved RNA-sequencing analyses of the developing secondary palate, we identify a shift in transcriptional programming between embryonic days 14.5 and 15.5 pinpointing the onset of osteogenesis. We define spatially restricted expression patterns of key osteogenic marker genes that are differentially expressed between these developmental timepoints. Finally, we identify genes in the palate highly expressed by palate nasal epithelial cells, also enriched within palatal osteogenic mesenchymal cells. This investigation provides a relevant framework to advance palate-specific diagnostic and therapeutic biomarker discovery.
Chemical inhomogeneity–induced profuse nanotwinning and phase transformation in AuCu nanowires
Authors: Yang Chengpeng , Zhang Bozhao , Fu Libo , Wang Zhanxin , Teng Jiao , Shao Ruiwen , Wu Ziqi , Chang Xiaoxue , Ding Jun , Wang Lihua , Han Xiaodong 
Published: September 2023

AbstractNanosized metals usually exhibit ultrahigh strength but suffer from low homogeneous plasticity. The origin of a strength–ductility trade-off has been well studied for pure metals, but not for random solid solution (RSS) alloys. How RSS alloys accommodate plasticity and whether they can achieve synergy between high strength and superplasticity has remained unresolved. Here, we show that face-centered cubic (FCC) RSS AuCu alloy nanowires (NWs) exhibit superplasticity of ~260% and ultrahigh strength of ~6 GPa, overcoming the trade-off between strength and ductility. These excellent properties originate from profuse hexagonal close-packed (HCP) phase generation (2H and 4H phases), recurrence of reversible FCC-HCP phase transition, and zigzag-like nanotwin generation, which has rarely been reported before. Such a mechanism stems from the inherent chemical inhomogeneity, which leads to widely distributed and overlapping energy barriers for the concurrent activation of multiple plasticity mechanisms. This naturally implies a similar deformation behavior for other highly concentrated solid-solution alloys with multiple principal elements, such as high/medium-entropy alloys. Our findings shed light on the effect of chemical inhomogeneity on the plastic deformation mechanism of solid-solution alloys.
Interfacial friction enabling ≤ 20 μm thin free-standing lithium strips for lithium metal batteries
Authors: Huang Shaozhen , Wu Zhibin , Johannessen Bernt , Long Kecheng , Qing Piao , He Pan , Ji Xiaobo , Wei Weifeng , Chen Yuejiao , Chen Libao 
Published: September 2023

AbstractA practical high-specific-energy Li metal battery requires thin (≤20 μm) and free-standing Li metal anodes, but the low melting point and strong diffusion creep of lithium metal impede their scalable processing towards thin-thickness and free-standing architecture. In this paper, thin (5 to 50 μm) and free-standing lithium strips were achieved by mechanical rolling, which is determined by the in situ tribochemical reaction between lithium and zinc dialkyldithiophosphate (ZDDP). A friction-induced organic/inorganic hybrid interface (~450 nm) was formed on Li with an ultra-high hardness (0.84 GPa) and Young’s modulus (25.90 GPa), which not only enables the scalable process mechanics of thin lithium strips but also facilitates dendrite-free lithium metal anodes by inhibiting dendrite growth. The rolled lithium anode exhibits a prolonged cycle lifespan and high-rate cycle stability (in excess of more than 1700 cycles even at 18.0 mA cm−2 and 1.5 mA cm−2 at 25 °C). Meanwhile, the LiFePO4 (with single-sided load 10 mg/cm2) ||Li@ZDDP full cell can last over 350 cycles with a high-capacity retention of 82% after the formation cycles at 5 C (1 C = 170 mA/g) and 25 °C. This work provides a scalable approach concerning tribology design for producing practical thin free-standing lithium metal anodes.
A pan-sarcoma landscape of telomeric content shows that alterations in RAD51B and GID4 are associated with higher telomeric content
Authors: Sharaf Radwa , Jin Dexter X. , Grady John , Napier Christine , Ebot Ericka , Frampton Garrett M. , Albacker Lee A. , Thomas David M. , Montesion Meagan 
Published: September 2023

AbstractTumor cells need to activate a telomere maintenance mechanism, enabling limitless replication. The bulk of evidence supports that sarcomas predominantly use alternative lengthening of telomeres (ALT) mechanism, commonly associated with alterations in ATRX and DAXX. In our dataset, only 12.3% of sarcomas harbored alterations in these genes. Thus, we checked for the presence of other genomic determinants of high telomeric content in sarcomas. Our dataset consisted of 13555 sarcoma samples, sequenced as a part of routine clinical care on the FoundationOne®Heme platform. We observed a median telomeric content of 622.3 telomeric reads per GC-matched million reads (TRPM) across all samples. In agreement with previous studies, telomeric content was significantly higher in ATRX altered and POT1 altered sarcomas. We further observed that sarcomas with alterations in RAD51B or GID4 were enriched in samples with high telomeric content, specifically within uterus leiomyosarcoma for RAD51B and soft tissue sarcoma (not otherwise specified, nos) for GID4, Furthermore, RAD51B and POT1 alterations were mutually exclusive with ATRX and DAXX alterations, suggestive of functional redundancy. Our results propose a role played by RAD51B and GID4 in telomere elongation in sarcomas and open research opportunities for agents aimed at targeting this critical pathway in tumorigenesis.
Polyfunctional CD4 T-cells correlating with neutralising antibody is a hallmark of COVISHIELDTM and COVAXIN® induced immunity in COVID-19 exposed Indians
Authors: Rakshit Srabanti , Babji Sudhir , Parthiban Chaitra , Madhavan Ramya , Adiga Vasista , J Sharon Eveline , Chetan Kumar Nirutha , Ahmed Asma , Shivalingaiah Sudarshan , Shashikumar Nandini , V Mamatha , Johnson Avita Rose , Ramesh Naveen , B Ramkrishna Goud , Asokan Mangaiarkarasi , Mayor Satyajit , Kang Gagandeep , D’souza George , Dias Mary , Vyakarnam Annapurna 
Published: September 2023

AbstractDetailed characterisation of immune responses induced by COVID-19 vaccines rolled out in India: COVISHIELDTM (CS) and COVAXIN® (CO) in a pre-exposed population is only recently being discovered. We addressed this issue in subjects who received their primary series of vaccination between November 2021 and January 2022. Both vaccines are capable of strongly boosting Wuhan Spike-specific neutralising antibody, polyfunctional Th1 cytokine producing CD4+ T-cells and single IFN-γ + CD8+ T-cells. Consistent with inherent differences in vaccine platform, the vector-based CS vaccine-induced immunity was of greater magnitude, breadth, targeting Delta and Omicron variants compared to the whole-virion inactivated vaccine CO, with CS vaccinees showing persistent CD8+ T-cells responses until 3 months post primary vaccination. This study provides detailed evidence on the magnitude and quality of CS and CO vaccine induced responses in subjects with pre-existing SARS-CoV-2 immunity in India, thereby mitigating vaccine hesitancy arguments in such a population, which remains a global health challenge.
DMRT1 regulates human germline commitment
Authors: Irie Naoko , Lee Sun-Min , Lorenzi Valentina , Xu Haiqi , Chen Jinfeng , Inoue Masato , Kobayashi Toshihiro , Sancho-Serra Carmen , Drousioti Elena , Dietmann Sabine , Vento-Tormo Roser , Song Chun-Xiao , Surani M. Azim 
Published: September 2023

AbstractGermline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.
A lamprey neural cell type atlas illuminates the origins of the vertebrate brain
Authors: Lamanna Francesco , Hervas-Sotomayor Francisca , Oel A. Phillip , Jandzik David , Sobrido-Cameán Daniel , Santos-Durán Gabriel N. , Martik Megan L. , Stundl Jan , Green Stephen A. , Brüning Thoomke , Mößinger Katharina , Schmidt Julia , Schneider Celine , Sepp Mari , Murat Florent , Smith Jeramiah J. , Bronner Marianne E. , Rodicio María Celina , Barreiro-Iglesias Antón , Medeiros Daniel M. , Arendt Detlev , Kaessmann Henrik 
Published: September 2023

AbstractThe vertebrate brain emerged more than ~500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we established a spatially resolved cell type atlas of the entire brain of the sea lamprey—a jawless species whose phylogenetic position affords the reconstruction of ancestral vertebrate traits—based on extensive single-cell RNA-seq and in situ sequencing data. Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of cell types, tissue structures and gene expression programs of the ancestral vertebrate brain. However, our analyses also revealed key tissues and cell types that arose later in evolution. For example, the ancestral brain was probably devoid of cerebellar cell types and oligodendrocytes (myelinating cells); our data suggest that the latter emerged from astrocyte-like evolutionary precursors in the jawed vertebrate lineage. Altogether, our work illuminates the cellular and molecular architecture of the ancestral vertebrate brain and provides a foundation for exploring its diversification during evolution.
Optimized glycemic control of type 2 diabetes with reinforcement learning: a proof-of-concept trial
Authors: Wang Guangyu , Liu Xiaohong , Ying Zhen , Yang Guoxing , Chen Zhiwei , Liu Zhiwen , Zhang Min , Yan Hongmei , Lu Yuxing , Gao Yuanxu , Xue Kanmin , Li Xiaoying , Chen Ying 
Published: September 2023

AbstractThe personalized titration and optimization of insulin regimens for treatment of type 2 diabetes (T2D) are resource-demanding healthcare tasks. Here we propose a model-based reinforcement learning (RL) framework (called RL-DITR), which learns the optimal insulin regimen by analyzing glycemic state rewards through patient model interactions. When evaluated during the development phase for managing hospitalized patients with T2D, RL-DITR achieved superior insulin titration optimization (mean absolute error (MAE) of 1.10 ± 0.03 U) compared to other deep learning models and standard clinical methods. We performed a stepwise clinical validation of the artificial intelligence system from simulation to deployment, demonstrating better performance in glycemic control in inpatients compared to junior and intermediate-level physicians through quantitative (MAE of 1.18 ± 0.09 U) and qualitative metrics from a blinded review. Additionally, we conducted a single-arm, patient-blinded, proof-of-concept feasibility trial in 16 patients with T2D. The primary outcome was difference in mean daily capillary blood glucose during the trial, which decreased from 11.1 (±3.6) to 8.6 (±2.4) mmol L−1 (P < 0.01), meeting the pre-specified endpoint. No episodes of severe hypoglycemia or hyperglycemia with ketosis occurred. These preliminary results warrant further investigation in larger, more diverse clinical studies. ClinicalTrials.gov registration: NCT05409391.
Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial
Authors: Houot Roch , Bachy Emmanuel , Cartron Guillaume , Gros François-Xavier , Morschhauser Franck , Oberic Lucie , Gastinne Thomas , Feugier Pierre , Duléry Rémy , Thieblemont Catherine , Joris Magalie , Jardin Fabrice , Choquet Sylvain , Casasnovas Olivier , Brisou Gabriel , Cheminant Morgane , Bay Jacques-Olivier , Gutierrez Francisco Llamas , Menard Cédric , Tarte Karin , Delfau Marie-Hélène , Portugues Cédric , Itti Emmanuel , Palard-Novello Xavier , Blanc-Durand Paul , Al Tabaa Yassine , Bailly Clément , Laurent Camille , Lemonnier François 
Published: September 2023

AbstractAxicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT. The primary end point was investigator-assessed complete metabolic response at 3 months from the axi-cel infusion. Key secondary end points included progression-free survival, overall survival and safety. The study met its primary end point with a complete metabolic response of 71.0% (95% confidence interval, 58.1–81.8%) at 3 months. With a median follow-up of 12.0 months (range, 2.1–17.9), median progression-free survival was 11.8 months (95% confidence interval, 8.4–not reached) and overall survival was not reached. There was no unexpected toxicity. Grade 3–4 cytokine release syndrome and neurologic events occurred in 8.1% and 14.5% of patients, respectively. These results support axi-cel as second-line therapy in patients with R/R LBCL ineligible for ASCT. ClinicalTrials.gov Identifier: NCT04531046.
Best humans still outperform artificial intelligence in a creative divergent thinking task
Authors: Koivisto Mika , Grassini Simone 
Published: September 2023

AbstractCreativity has traditionally been considered an ability exclusive to human beings. However, the rapid development of artificial intelligence (AI) has resulted in generative AI chatbots that can produce high-quality artworks, raising questions about the differences between human and machine creativity. In this study, we compared the creativity of humans (n = 256) with that of three current AI chatbots using the alternate uses task (AUT), which is the most used divergent thinking task. Participants were asked to generate uncommon and creative uses for everyday objects. On average, the AI chatbots outperformed human participants. While human responses included poor-quality ideas, the chatbots generally produced more creative responses. However, the best human ideas still matched or exceed those of the chatbots. While this study highlights the potential of AI as a tool to enhance creativity, it also underscores the unique and complex nature of human creativity that may be difficult to fully replicate or surpass with AI technology. The study provides insights into the relationship between human and machine creativity, which is related to important questions about the future of creative work in the age of AI.
Purification and biological analysis of antimicrobial compound produced by an endophytic Streptomyces sp.
Authors: Devi Sapna , Sharma Manish , Manhas Rajesh Kumari 
Published: September 2023

AbstractFungal phytopathogens and drug-resistant bacteria are two significant challenges in agriculture and public health, respectively. As a result, new sources of antimicrobial compounds are urgently needed. Taking into consideration these aspects, the present study was carried out to explore the antimicrobial activity of Streptomyces sp. SP5 against drug-resistant bacteria, especially methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus and fungal phytopathogens. MRSA and VRE are both types of antibiotic-resistant bacteria that pose significant challenges to public health. In vitro analysis of the metabolites of Streptomyces sp. SP5 exhibited broad-spectrum antimicrobial activity against drug-resistant bacteria and phytopathogenic fungi. Further chemical investigation of the diethyl ether extract led to the isolation and purification of an antimicrobial compound. The structure of the purified compound was elucidated by performing detailed spectroscopic analysis including MS, IR, and NMR. The compound was identified as plicacetin. Plicacetin is a nucleoside antibiotic that has been reported for antibacterial activity against Gram-positive bacterium Mycobacterium tuberculosis. According to our knowledge, the present study is the first to demonstrate the antimicrobial properties of plicacetin against Fusarium oxysporum, Alternaria brassicicola, Fusarium solani, VRE and Bacillus subtilis. The outcome of the current study endorses that compound produced by Streptomyces sp. SP5 can be used as an antimicrobial agent against fungal phytopathogens and drug-resistant bacteria.