bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactoferrin in breast milk-based powders
Authors: Tsakali Efstathia , Aggarwal Rakesh , Houhoula Dimitra , Konteles Spiridon , Batrinou Athimia , Verheyen Davy , Van Impe Jan FM , Chatzilazarou Arhontoula
Published: January 2024

This study aimed to determine lactoferrin (LF) in breast milk-based powders and formulas. Lactoferrin is an important whey protein in all mammalian milks and is responsible in large part for the known antimicrobial effects of human milk in particular. As breast feeding is not always possible, formulas based on cows milk have been developed in order to meet the nutritional needs of the newborn, while more recently human breast milk-based powders have been introduced to offer the biological functionality of human milk to pre-term and critically ill babies. In the present work, the amount of LF in commercial breast milk-based powders was tested by a validated RF-HPLC method for the determination of LF in breast milk in order to examine both the applicability of the method but at a second level the amount of LF in these commercial products. The detection of LF was possible but the complexity of the matrix lead us to the use the standard addition methodology in order to achieve quantification. The results indicated that breast milk-based powders had higher amount of LF than cows milk-based formulas, both non-fortified and fortified.
Lightweight transformers for clinical natural language processing
Authors: Rohanian Omid , Nouriborji Mohammadmahdi , Jauncey Hannah , Kouchaki Samaneh , Nooralahzadeh Farhad ,   ISARIC Clinical Characterisation Group, Clifton Lei , Merson Laura , Clifton David A.
Published: January 2024

Specialised pre-trained language models are becoming more frequent in Natural language Processing (NLP) since they can potentially outperform models trained on generic texts. BioBERT (Sanh et al., Distilbert, a distilled version of bert: smaller, faster, cheaper and lighter. arXiv preprint arXiv: 1910.01108, 2019) and BioClinicalBERT (Alsentzer et al., Publicly available clinical bert embeddings. In Proceedings of the 2nd Clinical Natural Language Processing Workshop, pp. 72–78, 2019) are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like knowledge distillation, it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries, etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from
$15$
million to
$65$
million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including natural language inference, relation extraction, named entity recognition and sequence classification. To our knowledge, this is the first comprehensive study specifically focused on creating efficient and compact transformers for clinical NLP tasks. The models and code used in this study can be found on our Huggingface profile at https://huggingface.co/nlpie and Github page at https://github.com/nlpie-research/Lightweight-Clinical-Transformers, respectively, promoting reproducibility of our results.
Detection and Classification of Sporadic E Using Convolutional Neural Networks
Authors: Ellis J. A. , Emmons D. J. , Cohen M. B.
Published: January 2024

In this work, convolutional neural networks (CNN) are developed to detect and characterize sporadic E (Es), demonstrating an improvement over current methods. This includes a binary classification model to determine if Es is present, followed by a regression model to estimate the Es ordinary mode critical frequency (foEs), a proxy for the intensity, along with the height at which the Es layer occurs (hEs). Signal‐to‐noise ratio (SNR) and excess phase profiles from six Global Navigation Satellite System (GNSS) radio occultation (RO) missions during the years 2008–2022 are used as the inputs of the model. Intensity (foEs) and the height (hEs) values are obtained from the global network of ground‐based Digisonde ionosondes and are used as the “ground truth,” or target variables, during training. After corresponding the two data sets, a total of 36,521 samples are available for training and testing the models. The foEs CNN binary classification model achieved an accuracy of 74% and F1‐score of 0.70. Mean absolute errors (MAE) of 0.63 MHz and 5.81 km along with root‐mean squared errors (RMSE) of 0.95 MHz and 7.89 km were attained for estimating foEs and hEs, respectively, when it was known that Es was present. When combining the classification and regression models together for use in practical applications where it is unknown if Es is present, an foEs MAE and RMSE of 0.97 and 1.65 MHz, respectively, were realized. We implemented three other techniques for sporadic E characterization, and found that the CNN model appears to perform better.
Reducing the Environmental Impact of Sewer Network Overflows Using Model Predictive Control Strategy
Authors: Vasiliev I. , Luca L. , Barbu M. , Vilanova R. , Caraman S.
Published: January 2024

This paper proposes a method for reducing the environmental impact of sewer network (SN) overflows. The main objective of the paper is to minimize the wastewater quantity and the pollutant loads that overflow from the SN. The proposed algorithm to achieve this goal is Model Predictive Control using Particle Swarm Optimization as optimization method. It was tested in simulation using a simplified model of the network based on Benchmark Simulation Modelsewer as prediction model, and a forecasted influent. Three cases have been considered: (a) the fitness function is defined as the global yearly overflow volume calculated using equal weights for each tank; (b) the fitness function uses different weights for each tank depending on the medium loads and (c) integrating a penalty term related to the system state at the end of the prediction horizon in the previous fitness function. The simplified model determined a significant reduction of the integration time minimizing the optimization time.
SA‐RelayGANs: A Novel Framework for the Characterization of Complex Hydrological Structures Based on GANs and Self‐Attention Mechanism
Authors: Cui Zhesi , Chen Qiyu , Liu Gang , Xun Lei
Published: January 2024

Increased availability and quality of surface and subsurface observations provide the chance to improve the perception of hydrological phenomena. An important factor that hinders our understanding of hydrological structures is the characterization of heterogeneous patterns with continuous attributes inside the structures (e.g., porosity, permeability, fluid saturation, etc.). Unlike categorical attributes, continuous attributes convey more realistic characteristics but require more computational resources to characterize such complex earth systems. In this work, we propose a novel deep learning approach for the characterization of complex hydrological realism with continuous attributes based on generative adversarial networks (GANs) and self‐attention mechanism, named SA‐RelayGANs. To address the complexity of heterogeneous hydrological structures, we divide the modeling process into two stages: facies construction stage and property reconstruction stage. In the first stage, we employ an improved GAN with self‐attention mechanism to construct the heterogeneous structures while adhering to hard conditioning constraints. In the second stage, we utilize another GAN with an attribute enhancement term to reconstruct realizations based on the constructed structures and observations. SA‐RelayGANs can successfully predict the statistical distributions of heterogeneous structures with continuous attributes by using limited observations. This study highlights the effectiveness of using GANs to characterize the heterogeneous patterns of hydrological realism and the application over large geoscience fields.
Glaciers Rise and Fall—and Melt—with Tides
Authors: Sidik Saima
Published: January 2024

The effect of ocean water creeping beneath Greenland ice is stronger than scientists realized.
Observation of a single protein by ultrafast X-ray diffraction
Authors: Ekeberg Tomas , Assalauova Dameli , Bielecki Johan , Boll Rebecca , Daurer Benedikt J. , Eichacker Lutz A. , Franken Linda E. , Galli Davide E. , Gelisio Luca , Gumprecht Lars , Gunn Laura H. , Hajdu Janos , Hartmann Robert , Hasse Dirk , Ignatenko Alexandr , Koliyadu Jayanath , Kulyk Olena , Kurta Ruslan , Kuster Markus , Lugmayr Wolfgang , Lübke Jannik , Mancuso Adrian P. , Mazza Tommaso , Nettelblad Carl , Ovcharenko Yevheniy , Rivas Daniel E. , Rose Max , Samanta Amit K. , Schmidt Philipp , Sobolev Egor , Timneanu Nicusor , Usenko Sergey , Westphal Daniel , Wollweber Tamme , Worbs Lena , Xavier Paul Lourdu , Yousef Hazem , Ayyer Kartik , Chapman Henry N. , Sellberg Jonas A. , Seuring Carolin , Vartanyants Ivan A. , Küpper Jochen , Meyer Michael , Maia Filipe R. N. C.
Published: January 2024

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many. It was one of the arguments for building X-ray free-electron lasers. According to theory, the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier, and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes. This was first demonstrated on biological samples a decade ago on the giant mimivirus. Since then, a large collaboration has been pushing the limit of the smallest sample that can be imaged. The ability to capture snapshots on the timescale of atomic vibrations, while keeping the sample at room temperature, may allow probing the entire conformational phase space of macromolecules. Here we show the first observation of an X-ray diffraction pattern from a single protein, that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays, and demonstrate that the concept of diffraction before destruction extends to single proteins. From the pattern, it is possible to determine the approximate orientation of the protein. Our experiment demonstrates the feasibility of ultrafast imaging of single proteins, opening the way to single-molecule time-resolved studies on the femtosecond timescale.
Fc receptor-like 5 (FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma
Authors: Yu Zhengyu , Li Hexian , Lu Qizhong , Zhang Zongliang , Tong Aiping , Niu Ting
Published: January 2024

Multiple myeloma (MM) remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell (CAR-T) therapy. Current targets of CAR-T cells used in MM immunotherapy have limitations, with a subset of patients experiencing antigen loss resulting in relapse. Therefore, novel targets for enhancing CAR-T cell therapy in MM remain needed. Fc receptor-like 5 (FCRL5) is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions, offering an alternative treatment for MM. To further explore this option, we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models, specifically focusing on MM with gain of chromosome 1q21. Given the challenges in CAR-T therapies arising from limited T cell persistence, our approach incorporates interleukin-15 (IL-15), which enhances the functionality of central memory T (TCM) cells, into the design of FCRL5-directed CAR-T cells, to improve cytotoxicity and reduce T-cell dysfunction, thereby promoting greater CAR-T cell survival and efficacy. Both in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy, effectively inhibiting the proliferation of MM cells and leading to remarkable tumor suppression. Our results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency, suggesting a potential novel immunotherapeutic strategy for MM treatment.
Clinical applications of stem cell-derived exosomes
Authors: Tan Fei , Li Xuran , Wang Zhao , Li Jiaojiao , Shahzad Khawar , Zheng Jialin
Published: January 2024

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes with inescapable drawbacks that might limit its clinical translation. Compared to stem cells, stem cell-derived exosomes possess numerous advantages, such as non-immunogenicity, non-infusion toxicity, easy access, effortless preservation, and freedom from tumorigenic potential and ethical issues. Exosomes can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or multipotency. After a thorough search and meticulous dissection of relevant literature from the last five years, we present this comprehensive, up-to-date, specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived exosomes. Exosomes derived from stem cells (e.g., embryonic, induced pluripotent, hematopoietic, mesenchymal, neural, and endothelial stem cells) are capable of treating numerous diseases encountered in orthopedic surgery, neurosurgery, plastic surgery, general surgery, cardiothoracic surgery, urology, head and neck surgery, ophthalmology, and obstetrics and gynecology. The diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses, and cell-specific molecular signaling pathways. In this review, we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical conditions. We recommend that future research combines wisdoms from surgeons, nanomedicine practitioners, and stem cell researchers in this relevant and intriguing research area.
Cortical microinfarcts potentiate recurrent ischemic injury through NLRP3-dependent trained immunity
Authors: Feng Yiwei , Lin Lishan , Wu Tengteng , Feng Yukun , Liang Fengyin , Li Ge , Li Yongchao , Guan Yalun , Liu Shuhua , Zhang Yu , Xu Guangqing , Pei Zhong
Published: January 2024

Microinfarcts are common among the elderly and patients with microinfarcts are more vulnerable to another stroke. However, the impact of microinfarcts on recurrent stroke has yet to be fully understood. The purpose of this study was to explore the negative effects of microinfarcts on recurrent stroke. To achieve this, two-photon laser was used to induce microinfarcts, while photothrombotic stroke was induced on the opposite side. The results showed that microinfarcts led to trained immunity in microglia, which worsened the pro-inflammatory response and ischemic injury in the secondary photothrombotic stroke. Additionally, the study clarified the role of NLRP3 in microglial nuclei, indicating that it interacts with the MLL1 complex through NACHT domain and increases H3K4 methylation, which suggests that NLRP3 is critical in the formation of innate immune memory caused by microinfarcts. Furthermore, the knockout of NLRP3 in microglia alleviated the trained immunity and reduced the harmful effects of microinfarcts on recurrent stroke. This study emphasizes the detrimental effect of trained immunity on recurrent stroke and highlights the critical role of NLRP3 in mediating the formation of this memory, which may offer a potential therapeutic target for mitigating recurrent strokes.
TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma
Authors: Kang Donghee , Hwang Hyun Jung , Baek Yurim , Sung Jee Young , Kim KyeongJin , Park Heon Joo , Ko Young-Gyu , Kim Yong-Nyun , Lee Jae-Seon
Published: January 2024

The ubiquitin-proteasome system is a vital protein degradation system that is involved in various cellular processes, such as cell cycle progression, apoptosis, and differentiation. Dysregulation of this system has been implicated in numerous diseases, including cancer, vascular disease, and neurodegenerative disorders. Induction of cellular senescence in hepatocellular carcinoma (HCC) is a potential anticancer strategy, but the precise role of the ubiquitin-proteasome system in cellular senescence remains unclear. In this study, we show that the E3 ubiquitin ligase, TRIM22, plays a critical role in the cellular senescence of HCC cells. TRIM22 expression is transcriptionally upregulated by p53 in HCC cells experiencing ionizing radiation (IR)-induced senescence. Overexpression of TRIM22 triggers cellular senescence by targeting the AKT phosphatase, PHLPP2. Mechanistically, the SPRY domain of TRIM22 directly associates with the C-terminal domain of PHLPP2, which contains phosphorylation sites that are subject to IKKβ-mediated phosphorylation. The TRIM22-mediated PHLPP2 degradation leads to activation of AKT-p53-p21 signaling, ultimately resulting in cellular senescence. In both human HCC databases and patient specimens, the levels of TRIM22 and PHLPP2 show inverse correlations at the mRNA and protein levels. Collectively, our findings reveal that TRIM22 regulates cancer cell senescence by modulating the proteasomal degradation of PHLPP2 in HCC cells, suggesting that TRIM22 could potentially serve as a therapeutic target for treating cancer.
Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial
Authors: Galanis Evanthia , Dooley Katharine E. , Keith Anderson S. , Kurokawa Cheyne B. , Carrero Xiomara W. , Uhm Joon H. , Federspiel Mark J. , Leontovich Alexey A. , Aderca Ileana , Viker Kimberly B. , Hammack Julie E. , Marks Randolph S. , Robinson Steven I. , Johnson Derek R. , Kaufmann Timothy J. , Buckner Jan C. , Lachance Daniel H. , Burns Terry C. , Giannini Caterina , Raghunathan Aditya , Iankov Ianko D. , Parney Ian F.
Published: January 2024

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = −0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.
Vibronic effects on the quantum tunnelling of magnetisation in Kramers single-molecule magnets
Authors: Mattioni Andrea , Staab Jakob K. , Blackmore William J. A. , Reta Daniel , Iles-Smith Jake , Nazir Ahsan , Chilton Nicholas F.
Published: January 2024

Single-molecule magnets are among the most promising platforms for achieving molecular-scale data storage and processing. Their magnetisation dynamics are determined by the interplay between electronic and vibrational degrees of freedom, which can couple coherently, leading to complex vibronic dynamics. Building on an ab initio description of the electronic and vibrational Hamiltonians, we formulate a non-perturbative vibronic model of the low-energy magnetic degrees of freedom in monometallic single-molecule magnets. Describing their low-temperature magnetism in terms of magnetic polarons, we are able to quantify the vibronic contribution to the quantum tunnelling of the magnetisation, a process that is commonly assumed to be independent of spin-phonon coupling. We find that the formation of magnetic polarons lowers the tunnelling probability in both amorphous and crystalline systems by stabilising the low-lying spin states. This work, thus, shows that spin-phonon coupling subtly influences magnetic relaxation in single-molecule magnets even at extremely low temperatures where no vibrational excitations are present.
Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils
Authors: Sharma Kartikay , Stockert Fabian , Shenoy Jayakrishna , Berbon Mélanie , Abdul-Shukkoor Muhammed Bilal , Habenstein Birgit , Loquet Antoine , Schmidt Matthias , Fändrich Marcus
Published: January 2024

The transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, abnormal aggregation of TDP-43 has been linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration through the aggregation of its C-terminal domain. Here, we report a cryo-electron microscopy (cryo-EM)-based structural characterization of TDP-43 fibrils obtained from the full-length protein. We find that the fibrils are polymorphic and contain three different amyloid structures. The structures differ in the number and relative orientation of the protofilaments, although they share a similar fold containing an amyloid key motif. The observed fibril structures differ from previously described conformations of TDP-43 fibrils and help to better understand the structural landscape of the amyloid fibril structures derived from this protein.
A randomized trial looking at planning prompts to reduce opioid prescribing
Authors: Doctor Jason N. , Kelley Marcella A. , Goldstein Noah J. , Lucas Jonathan , Knight Tara , Stewart Emily P.
Published: January 2024

Prior work has demonstrated that personalized letters are effective at reducing opioid and benzodiazepine prescribing, but it is unclear whether If/when-then planning prompts would enhance this effect. We conducted a decedent-clustered trial which randomized 541 clinicians in Los Angeles County to receive a standard (n = 284), or comparator (n = 257) version of a letter with If/when-then prompts. We found a significant 12.85% (6.83%, 18.49%) and 8.32% (2.34%, 13.93%) decrease in the primary outcomes morphine (MME) and diazepam milligram equivalents (DME), respectively. This study confirms the benefit of planning prompts, and repeat letter exposure among clinicians with poor patient outcomes. Limitations include lack of generalizability and small sample size. Clinicaltrials.gov registration: NCT03856593.
Lithiated porous silicon nanowires stimulate periodontal regeneration
Authors: Kaasalainen Martti , Zhang Ran , Vashisth Priya , Birjandi Anahid Ahmadi , S’Ari Mark , Martella Davide Alessandro , Isaacs Mark , Mäkilä Ermei , Wang Cong , Moldenhauer Evelin , Clarke Paul , Pinna Alessandra , Zhang Xuechen , Mustfa Salman A. , Caprettini Valeria , Morrell Alexander P. , Gentleman Eileen , Brauer Delia S. , Addison Owen , Zhang Xuehui , Bergholt Mads , Al-Jamal Khuloud , Volponi Ana Angelova , Salonen Jarno , Hondow Nicole , Sharpe Paul , Chiappini Ciro
Published: January 2024

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/β-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/β-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.
Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance
Authors: Vasudevan Harish N. , Payne Emily , Delley Cyrille L. , John Liu S. , Mirchia Kanish , Sale Matthew J. , Lastella Sydney , Nunez Maria Sacconi , Lucas Calixto-Hope G. , Eaton Charlotte D. , Casey-Clyde Tim , Magill Stephen T. , Chen William C. , Braunstein Steve E. , Perry Arie , Jacques Line , Reddy Alyssa T. , Pekmezci Melike , Abate Adam R. , McCormick Frank , Raleigh David R.
Published: January 2024

Schwann cell tumors are the most common cancers of the peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or neurofibromatosis type-2 (NF-2). Functional interactions between NF1 and NF2 and broader mechanisms underlying malignant transformation of the Schwann lineage are unclear. Here we integrate bulk and single-cell genomics, biochemistry, and pharmacology across human samples, cell lines, and mouse allografts to identify cellular de-differentiation mechanisms driving malignant transformation and treatment resistance. We find DNA methylation groups of Schwann cell tumors can be distinguished by differentiation programs that correlate with response to the MEK inhibitor selumetinib. Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2.
Amide C–N bonds activation by A new variant of bifunctional N-heterocyclic carbene
Authors: Cai Yuxing , Zhao Yuxin , Tang Kai , Zhang Hong , Mo Xueling , Chen Jiean , Huang Yong
Published: January 2024

We report an organocatalyst that combines a triazolium N-heterocyclic carbene (NHC) with a squaramide as a hydrogen-bonding donor (HBD), which can effectively catalyze the atroposelective ring-opening of biaryl lactams via a unique amide C–N bond cleavage mode. The free carbene species attacks the amide carbonyl, forming an axially chiral acyl-azolium intermediate. Various axially chiral biaryl amines can be accessed by this methodology with up to 99% ee and 99% yield. By using mercaptan as a catalyst turnover agent, the resulting thioester synthon can be transformed into several interesting atropisomers. Both control experiments and theoretical calculations reveal the crucial role of the hybrid NHC-HBD skeleton, which activates the amide via H-bonding and brings it spatially close to the carbene centre. This discovery illustrates the potential of the NHC-HBD chimera and demonstrates a complementary strategy for amide bond activation and manipulation.
Accelerating the discovery of alkyl halide-derived natural products using halide depletion
Authors: Glasser Nathaniel R. , Cui Dongtao , Risser Douglas D. , Okafor C. Denise , Balskus Emily P.
Published: January 2024

Even in the genomic era, microbial natural product discovery workflows can be laborious and limited in their ability to target molecules with specific structural features. Here we leverage an understanding of biosynthesis to develop a workflow that targets the discovery of alkyl halide-derived natural products by depleting halide anions, a key biosynthetic substrate for enzymatic halogenation, from microbial growth media. By comparing the metabolomes of bacterial cultures grown in halide-replete and deficient media, we rapidly discovered the nostochlorosides, the products of an orphan halogenase-encoding gene cluster from Nostoc punctiforme ATCC 29133. We further found that these products, a family of unusual chlorinated glycolipids featuring the rare sugar gulose, are polymerized via an unprecedented enzymatic etherification reaction. Together, our results highlight the power of leveraging an understanding of biosynthetic logic to streamline natural product discovery.
Hagfish genome elucidates vertebrate whole-genome duplication events and their evolutionary consequences
Authors: Yu Daqi , Ren Yandong , Uesaka Masahiro , Beavan Alan J. S. , Muffato Matthieu , Shen Jieyu , Li Yongxin , Sato Iori , Wan Wenting , Clark James W. , Keating Joseph N. , Carlisle Emily M. , Dearden Richard P. , Giles Sam , Randle Emma , Sansom Robert S. , Feuda Roberto , Fleming James F. , Sugahara Fumiaki , Cummins Carla , Patricio Mateus , Akanni Wasiu , D’Aniello Salvatore , Bertolucci Cristiano , Irie Naoki , Alev Cantas , Sheng Guojun , de Mendoza Alex , Maeso Ignacio , Irimia Manuel , Fromm Bastian , Peterson Kevin J. , Das Sabyasachi , Hirano Masayuki , Rast Jonathan P. , Cooper Max D. , Paps Jordi , Pisani Davide , Kuratani Shigeru , Martin Fergal J. , Wang Wen , Donoghue Philip C. J. , Zhang Yong E. , Pascual-Anaya Juan
Published: January 2024

Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and 2R occurred in the gnathostome stem-lineage, maximally in the late Cambrian–earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced an additional independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only in the gnathostome but not in the cyclostome lineage, calling into question the general expectation that WGDs lead to leaps of bodyplan complexity.
Distress and its influencing factors among Chinese patients with incidental pulmonary nodules: a cross-sectional study
Authors: Yuan Jingmin , Xu Fenglin , Ren Hui , Chen Mingwei , Feng Sifang
Published: January 2024

The study aims to investigate the distress level and its influencing factors in Chinese pulmonary nodules patients. A total of 163 outpatients in a tertiary hospital in Xi'an, China, were recruited and investigated by using the Impact of Event Scale, Decision Conflict Scale, Consultation Care Measure, Lung Cancer Worry Scale and a demographic questionnaire. The logistic regression model was used to identify the factors of distress. The mean IES score was 37.35 ± 16.65, which was a moderate level. Patients aged 50–60 years, with higher decision conflicts scores, lower physician–patient communication quality score, and who are anxious about the results of future tests or treatments had higher distress score. Distress levels were moderate in patients with pulmonary nodules. Communication between medical staff and patients is extremely important for the management of pulmonary nodules, which affects the quality of the patient's decision-making and his level of distress.
Computational insights into shape effects and heat transport enhancement in MHD-free convection of polar ternary hybrid nanofluid around a radiant sphere
Authors: El-sayed Ehab A. , Alwawi Firas A. , Aljuaydi Fahad , Swalmeh Mohammed Z.
Published: January 2024

The control and management of energy and their associated issues are increasingly recognized as one of mankind’s greatest challenges in the coming years to keep pace with the surge in industrialization and technology. Free convection optimizes the heat transfer processes in energy systems like solar collectors and power plants, reducing energy consumption and increasing system effectiveness. Further, studying and analyzing critical factors like magnetic fields, thermal radiation, and the shape of nanoparticles can assist in the control of fluid motion and improve the efficiency of heat transfer processes in a wide range of real-world applications, such as the power sector, aerospace applications, molten metal, nuclear power, and aeronautical engineering. This study aims to scrutinize the thermal performance of a magneto tri-hybrid polar nanoliquid flowing over a radiative sphere, considering the nanosolids’ shape. The single-phase model is developed to acquire the problems governing equations, and the hybrid linearization spectral collection approach is utilized to approximate the solution. The present findings reveal that blade-shaped nanosolids exhibit the highest thermal conductivity ratio when incorporated into the base fluid, whereas spherical nanosolids exhibit the lowest ratio. Volume fraction and thermal radiation factors have an effective role in raising fluid velocity and thermal performance. The magnetic and microapolar factors significantly suppress fluid velocity and energy transfer. As the volume fraction factor increases, the average percentage improvement in convective heat transfer for Al2O3 + Cu + MWCNT/kerosene oil compared to Al2O3 + Cu + graphene/kerosene oil approximately ranges from 0.8 to 2.6%.
PIEZO2 expression is an independent biomarker prognostic for gastric cancer and represents a potential therapeutic target
Authors: Zhang Yun-Chao , Yang Min , Lu Cen-di , Li Quan-Yao , Shi Jin-na , Shi Jun
Published: January 2024

Gastric cancer (GC) is one of the most prevalent malignant tumors of the gastrointestinal system in the globe. The effect of PIEZO2 on the immune function and pathological features of gastric cancer remains to be explored. The Online database of cancer genes and GSE54129 have been used to analyze the clinical characteristics of PIEZO2 expression. We looked at the relationship between PIEZO2 and the immune systems of GC patients. The TIDE algorithm was used to explore the value of PIEZO2 in immunotherapy. Investigated the enrichment of PIEZO2 gene ontology and associated signal pathways using Online gene databases. The results show that overexpression of PIEZO2 was identified as an independent risk factor for patients with GC who had poor overall survival. Individuals may have a better prognosis if they had poorly differentiated GC and increased PIEZO2 expression (P < 0.05). We demonstrated a strong correlation between PIEZO2 and immune cells. The majority of immune checkpoint and immunological-related genes were associated with PIEZO2 expression. And PIEZO2 might be used as an immunotherapy target. Finally, the differential PIEZO2 genes in GC were mostly implicated in the processes of inflammation, immunological response, and tumor metastasis, according to functional analysis. PIEZO2 has a negative correlation with cell stemness and mutation levels in patients with GC and a positive correlation with immune cell infiltration and gene expression in the tumor microenvironment. These findings point to PIEZO2 as a potential new immunotherapy target of GC.
Exposure to worrisome topics can increase cognitive performance when incentivized by a performance goal
Authors: Demont Timothée , Horta-Sáenz Daniela , Raiber Eva
Published: January 2024

Worrisome topics, such as climate change, economic crises, or pandemics including Covid-19, are increasingly present and pervasive due to digital media and social networks. Do worries triggered by such topics affect the cognitive capacities of young adults? In an online experiment during the Covid-19 pandemic (N=1503), we test how the cognitive performance of university students responds when exposed to topics discussing (i) current adverse mental health consequences of social restrictions or (ii) future labor market hardships linked to the economic contraction. Moreover, we study how such a response is affected by a performance goal. We find that the labor market topic increases cognitive performance when it is motivated by a goal, consistent with a ‘tunneling effect’ of scarcity or a positive stress effect. However, we show that the positive reaction is mainly concentrated among students with larger financial and social resources, pointing to an inequality-widening mechanism. Conversely, we find limited support for a negative stress effect or a ‘cognitive load effect’ of scarcity, as the mental health topic has a negative but insignificant average effect on cognitive performance. Yet, there is a negative response among psychologically vulnerable individuals when the payout is not conditioned on reaching a goal.
Systematic study on the dependence of the warm-start quantum approximate optimization algorithm on approximate solutions
Authors: Okada Ken N. , Nishi Hirofumi , Kosugi Taichi , Matsushita Yu-ichiro
Published: January 2024

Quantum approximate optimization algorithm (QAOA) is a promising hybrid quantum-classical algorithm to solve combinatorial optimization problems in the era of noisy intermediate-scale quantum computers. Recently it has been revealed that warm-start approaches can improve the performance of QAOA, where approximate solutions are obtained by classical algorithms in advance and incorporated into the initial state and/or unitary ansatz. In this work, we study in detail how the accuracy of approximate solutions affects the performance of the warm-start QAOA (WS-QAOA). We numerically find that in typical MAX-CUT problems, WS-QAOA achieves higher fidelity (probability that exact solutions are observed) and approximation ratio than QAOA as the Hamming distance of approximate solutions to the exact ones becomes smaller. We reveal that this could be quantitatively attributed to the initial state of the ansatz. We also solve MAX-CUT problems by WS-QAOA with approximate solutions obtained via QAOA, having higher fidelity and approximation ratio than QAOA especially when the circuit is relatively shallow. We believe that our study may deepen understanding of the performance of WS-QAOA and also provide a guide as to the necessary quality of approximate solutions.
People punish defection, not failures to conform to the majority
Authors: Philippsen Ana , Mieth Laura , Buchner Axel , Bell Raoul
Published: January 2024

Do people punish others for defecting or for failing to conform to the majority? In two experiments, we manipulated whether the participants’ partners cooperated or defected in the majority of the trials of a Prisoner’s Dilemma game. The effects of this base-rate manipulation on cooperation and punishment were assessed using a multinomial processing tree model. High compared to low cooperation rates of the partners increased participants’ cooperation. When participants’ cooperation was not enforced through partner punishment, the participants’ cooperation was closely aligned to the cooperation rates of the partners. Moral punishment of defection increased when cooperation rates were high compared to when defection rates were high. However, antisocial punishment of cooperation when defection rates were high was much less likely than moral punishment of defection when cooperation rates were high. In addition, antisocial punishment was increased when cooperation rates were high compared to when defection rates were high. The latter two results contradict the assumption that people punish conformity-violating behavior regardless of whether the behavior supports or disrupts cooperation. Punishment is thus sensitive to the rates of cooperation and defection but, overall, the results are inconsistent with the idea that punishment primarily, let alone exclusively, serves to enforce conformity with the majority.
The effect of distant connections on node anonymity in complex networks
Authors: de Jong Rachel G. , van der Loo Mark P. J. , Takes Frank W.
Published: January 2024

Ensuring privacy of individuals is of paramount importance to social network analysis research. Previous work assessed anonymity in a network based on the non-uniqueness of a node’s ego network. In this work, we show that this approach does not adequately account for the strong de-anonymizing effect of distant connections. We first propose the use ofd-k-anonymity, a novel measure that takes knowledge up to distancedof a considered node into account. Second, we introduceanonymity-cascade, which exploits the so-called infectiousness of uniqueness: mere information about being connected to another unique node can make a given node uniquely identifiable. These two approaches, together with relevant “twin node” processing steps in the underlying graph structure, offer practitioners flexible solutions, tunable in precision and computation time. This enables the assessment of anonymity in large-scale networks with up to millions of nodes and edges. Experiments on graph models and a wide range of real-world networks show drastic decreases in anonymity when connections at distance 2 are considered. Moreover, extending the knowledge beyond the ego network with just one extra link often already decreases overall anonymity by over 50%. These findings have important implications for privacy-aware sharing of sensitive network data.
The importance of epistemic intentions in ascription of responsibility
Authors: Kovacevic Katarina M. , Bonalumi Francesca , Heintz Christophe
Published: January 2024

We investigate how people ascribe responsibility to an agent who caused a bad outcome but did not know he would. The psychological processes for making such judgments, we argue, involve finding a counterfactual in which some minimally benevolent intention initiates a course of events that leads to a better outcome than the actual one. We hypothesize that such counterfactuals can include, when relevant, epistemic intentions. With four vignette studies, we show that people consider epistemic intentions when ascribing responsibility for a bad outcome. We further investigate which epistemic intentions people are likely to consider when building counterfactuals for responsibility ascription. We find that, when an agent did not predict a bad outcome, people ascribe responsibility depending on the reasons behind the agents’ lack of knowledge. People judge agents responsible for the bad outcome they caused when they could have easily predicted the consequences of their actions but did not care to acquire the relevant information. However, when this information was hard to acquire, people are less likely to judge them responsible.
Static, refractive and monolithic Fourier transform spectrometer: development and prototyping
Authors: Frassetto Fabio , Cocola Lorenzo , Zuppella Paola , Da Deppo Vania , Poletto Luca
Published: January 2024

Static Fourier transform spectrometers are devices that can be realized as monolithic and compact assemblies. In the “grating-based” monolithic version, they are usually realized gluing together a beam-splitter with two reflective diffraction gratings using spacers as connecting elements. In this work we present the development and test of an alternative form of this kind of instrument in which the dispersive elements are Littrow’s prisms and are glued to the splitting element, forming in this way a robust and filled structure with no air gaps. The device can work in the visible/near infrared spectral region with a resolution power that varies across the spectral range due to the dispersion of the used glasses. The absence of hollow regions inside the monolithic block makes the device extremely robust and protects the optical surfaces inside the interferometer from possible contaminations. The device can be easily miniaturized, as it does not require spacers or structural elements other than just the optical parts. The tested instrument works in the 470–850 nm wavelength range with a variable resolution between 3000 and 300.
Electrical, optical, and electrochemical performances of phosphate-glasses-doped with ZnO and CuO and their composite with polyaniline
Authors: Mahani Ragab , Helmy A. Kh. , Fathi A. M.
Published: January 2024

Phosphate-based glasses (PBG) with appropriate doping agents have been used as solid electrolytes in solid-state ionic devices. Therefore, more light was shed on the electrical, optical, and electrochemical behavior of the phosphate-based glasses (PBG), containing ZnO or CuO in the absence and existence of conductive polyaniline (PANI), since no publications are available concerning this work. The glass samples were prepared by the rapid quenching method, then mixing phosphate glass and polyaniline (PANI) with metal oxide (ZnO, CuO). They were characterized by different techniques; diffuse reflectance spectrophotometer (DRS), broadband dielectric spectrometer (BDS), cyclic voltammetry (CV), and charge–discharge techniques. In the DRS study, the direct and indirect band gap were calculated from Tauc’s relationship where CuO-doped glasses have higher values than ZnO-doped glasses. In the BDS study, the permittivity of all glass compositions decreased while AC conductivity increased with increasing frequency. AC conductivity of PBG doped with metal oxides and mixed with PANI exhibited semiconducting features (6.8 × 10–4 S/cm). Further, these composites exhibited lower loss tangent (0.11), and giant permittivity (186,000) compared to the pure PBG. Also, the electrochemical study exhibited that the composite with 7% CuO content has the highest specific capacitance value (82.3 F/g at 1.0 A/g) which increased to about 113% of its first cycle and then decreased to about 55% after 2500 cycles and finally increased again to 77% after 4500 cycles, indicating its good stability. The combination of optical, electrical, and electrochemical features of these composites suggests their use for energy generation and storage devices.