bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractPrior 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

AbstractPeriodontal 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

AbstractSchwann 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

AbstractWe 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

AbstractEven 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

AbstractPolyploidy 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

AbstractThe 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

AbstractThe 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

AbstractGastric 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

AbstractWorrisome 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

AbstractQuantum 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

AbstractDo 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

AbstractEnsuring 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

AbstractWe 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.