bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Effects of Prunus Cerasus (Montmorency Tart Cherry) and Apocynum Venetum (Venetron®) On Sleep and Anxiety in Adults with Insomnia
Authors: Erfe Marie Crisel B. , Oliver Paige L. , Kazaryan Armenouhi , Grant Azure D. , Yoon Roy , Patel Ruchir P. , Tan Belinda , Craft Noah 
Published: April 2024

AbstractPurposeSleep aids derived from traditional plant medicines are strong candidates for safely improving insomnia but require wider validation in patient populations.MethodsWe conducted an open label trial of the impact of a compound, Sip2Sleep®, containing Montmorency tart cherry (prunus cerasus) extract and Venetron®(apocynum venetum) on subjective sleep quality, subjective daytime alertness, sleep duration, sleep latency, anxiety, and insomnia in 43 adults with moderate to severe insomnia. Participants collected data over four weeks, with the sleep aid consumed prior to bed during weeks two and four.ResultsThe Montmorency tart cherry and Venetron®mixture statistically improved subjective sleep quality, daytime alertness, insomnia symptoms, and anxiety without impacting sleep duration and latency. Subjective improvements in sleep quality exhibited a statistical upward trend across the entire study window, suggesting potential persistence of the compounds days after consumption and greater improvement with longer-term consumption.ConclusionsThe combination of Montmorency tart cherry and Venetron®in this commercially available tincture is a promising sleep aid warranting further investigation in larger trials.
Large Language Models Are Poor Clinical Decision-Makers: A Comprehensive Benchmark
Authors: Liu Fenglin , Li Zheng , Zhou Hongjian , Yin Qingyu , Yang Jingfeng , Tang Xianfeng , Luo Chen , Zeng Ming , Jiang Haoming , Gao Yifan , Nigam Priyanka , Nag Sreyashi , Yin Bing , Hua Yining , Zhou Xuan , Rohanian Omid , Thakur Anshul , Clifton Lei , Clifton David A. 
Published: April 2024

AbstractThe adoption of large language models (LLMs) to assist clinicians has attracted remarkable attention. Existing works mainly adopt the closeended question-answering (QA) task with answer options for evaluation. However, many clinical decisions involve answering open-ended questions without pre-set options. To better understand LLMs in the clinic, we construct a benchmarkClinicBench. We first collect eleven existing datasets covering diverse clinical language generation, understanding, and reasoning tasks. Furthermore, we construct six novel datasets and clinical tasks that are complex but common in real-world practice, e.g., open-ended decision-making, long document processing, and emerging drug analysis. We conduct an extensive evaluation of twenty-two LLMs under both zero-shot and few-shot settings. Finally, we invite medical experts to evaluate the clinical usefulness of LLMs1.
Peristromal niches protect lung cancers from targeted therapies through a combined effect of multiple molecular mediators
Authors: Desai Bina , Miti Tatiana , Prabhakaran Sandhya , Miroshnychenko Daria , Henry Menkara , Marusyk Viktoriya , Gatenbee Chandler , Bui Marylin , Scott Jacob , Altrock Philipp M. , Haura Eric , Anderson Alexander R.A. , Basanta David , Marusyk Andriy 
Published: April 2024

ABSTRACTTargeted therapies directed against oncogenic signaling addictions, such as inhibitors of ALK in ALK+ NSCLC often induce strong and durable clinical responses. However, they are not curative in metastatic cancers, as some tumor cells persist through therapy, eventually developing resistance. Therapy sensitivity can reflect not only cell-intrinsic mechanisms but also inputs from stromal microenvironment. Yet, the contribution of tumor stroma to therapeutic responsesin vivoremains poorly defined. To address this gap of knowledge, we assessed the contribution of stroma-mediated resistance to therapeutic responses to the frontline ALK inhibitor alectinib in xenograft models of ALK+ NSCLC. We found that stroma-proximal tumor cells are partially protected against cytostatic effects of alectinib. This effect is observed not only in remission, but also during relapse, indicating the strong contribution of stroma-mediated resistance to both persistence and resistance. This therapy-protective effect of the stromal niche reflects a combined action of multiple mechanisms, including growth factors and extracellular matrix components. Consequently, despite improving alectinib responses, suppression of any individual resistance mechanism was insufficient to fully overcome the protective effect of stroma. Focusing on shared collateral sensitivity of persisters offered a superior therapeutic benefit, especially when using an antibody-drug conjugate with bystander effect to limit therapeutic escape. These findings indicate that stroma-mediated resistance might be the major contributor to both residual and progressing disease and highlight the limitation of focusing on suppressing a single resistance mechanism at a time.
A look beyond the QR code of SNARE proteins
Authors: Yadav Deepak , Hacisuleyman Aysima , Dergai Mykola , Khalifeh Dany , Abriata Luciano A. , Dal Peraro Matteo , Fasshauer Dirk 
Published: April 2024

AbstractSoluble N-ethylmaleimide-sensitive factor Attachment protein REceptor (SNARE) proteins catalyze the fusion process of vesicles with target membranes in eukaryotic cells. To do this, they assemble in a zipper-like fashion into stable complexes between the membranes. Structural studies have shown that the complexes consist of four different helices, which we subdivide into Qa-, Qb-, Qc-, and R-helix on the basis of their sequence signatures. Using a combination of biochemistry, modeling and molecular dynamics, we investigated how the four different types are arranged in a complex. We found that there is a matching pattern in the core of the complex that dictates the position of the four fundamental SNARE types in the bundle, resulting in a QabcR complex. In the cell, several different cognate QabcR-SNARE complexes catalyze the different transport steps between the compartments of the endomembrane system. Each of these cognate QabcR complexes is compiled from a repertoire of about 20 SNARE subtypes. Our studies show that exchange within the four types is largely tolerated structurally, although some non-cognate exchanges lead to structural imbalances. This suggests that SNARE complexes have evolved for a catalytic mechanism, a mechanism that leaves little scope for selectivity beyond the QabcR rule.
Growth characteristics of natural microbial populations are skewed towards bacteria with low specific growth rates
Authors: Bulseco Ashley N , Yang Wenzhou , Huber Julie A , Vallino Joseph J 
Published: April 2024

AbstractMicrobes are often functionally characterized by traits that specify their optimum environmental conditions for growth, such as temperature or pH, as well as upper and lower bounds where growth is possible. While any given microbe will have a narrow environmental window where growth can occur, a diverse community can span a much larger range of conditions where growth is possible by at least some members of the community. One important trait of microbes is maximum specific growth rate, as this trait determines if a microbe can persist in environments with short residence times. In this study, we conducted a chemostat experiment with natural microbial communities and manipulated dilution rate to test how it would act as a selective force controlling community dynamics and microbial diversity. Using both experimental chemostats and trait-based modeling, we examine how the composition of a microbial community collected from a coastal meromictic pond changes as dilution rate increases from 0.1 to 10 d−1. We compare experimental results from 16S rRNA gene amplicon sequences to the output from two different simulations of the trait-based model, one in which maximum specific growth rate is initially evenly distributed across the community and another where maximum specific growth rate traits are pulled from a beta probability distribution that is skewed towards low specific growth rates. Our experimental results match the simulation where the initial natural population is dominated by slow-growing microbes. Our results also highlight the importance of initial trait distributions in modeling community response to environmental changes.ImportanceAll living organisms are constrained by environmental boundaries that govern where growth is possible, such as minimum and maximum temperature or pH. An organism’s maximum specific growth rate places a lower bound on the residence or turnover time of a system where an organism can persist without being removed from the system. While we have good bounds on the maximum specific growth rate of culturable organisms, such asEscherichiaorVibriospecies, information is lacking on how the maximum specific growth rate trait is distributed in natural microbial communities. This information is critical for understanding how a community will respond to changes in residence time. Using chemostats and trait-based modeling, this study assesses how maximum specific growth rate is distributed in a natural community collected from a coastal, salinity-stratified pond.
Harnessing Emergent Properties of Microbial Consortia: Assembly of the Xilonen SynCom
Authors: Gastélum Gabriela , Gómez-Gil Bruno , Olmedo-Álvarez Gabriela , Rocha Jorge 
Published: April 2024

AbstractSynthetic communities (SynComs) are valuable tools for addressing fundamental questions in microbial ecology regarding community assembly. They could also potentially aid in successfully manipulating microbial communities for clinical, biotechnological, and agricultural applications. SynCom design is complicated since interactions between microbes cannot be predicted based on their individual properties. Here, we aimed to assemble a higher-order SynCom from seed-endophytic bacteria isolated from native maize landraces. We screened co-cultures that included strains from the Bacilli class, and theBurkholderiaandPseudomonasgenera since these taxa have been previously shown to be important for the fertility of native maize landraces. We developed a combinatorial, bottom-up strategy aimed at the detection of a complex colony architecture as an emergent collective property. Using this simplified approach, we assembled a SynCom composed ofBacillus pumilusNME155,Burkholderia contaminansXM7 andPseudomonassp. GW6. The strains exhibited positive and negative interactions when evaluated in pairs, but their higher-order assembly results in a complex colony architecture, which is considered a proxy of biofilm formation. This SynCom was namedXilonenafter the Aztec goddess of young maize and fertility. TheXilonenSynCom will aid in studying the molecular and ecological basis mediating maize fertility.
Effect of glucose concentration in culture medium on the human preimplantation embryo methylome
Authors: Brison Daniel , McGrane Mollie , Kimber Sue 
Published: April 2024

AbstractStudy questionDoes glucose concentration in culture medium have an impact on the DNA methylome of the early human embryo?Summary answerGlucose concentration is associated with changes in gene expression, global DNA methylation, methylation levels at CpG islands and at key histone modifications in human blastocysts.What is known alreadyPreimplantation human embryos are highly sensitive to their local environment, and this may have long term implications for the health of the developing embryo, fetus and offspring. Glucose is a standard component of human embryo culture media, due to its importance as a nutrient. However, concentrations of glucose differ widely between different commercially available types. The present study was designed to determine whether changes in glucose concentration could influence global methylation and gene expression in the human preimplantation embryo.Study design, size, durationHuman embryos were cultured in clinically relevant concentrations of glucose and global DNA methylation analysis was performed. The effect of glucose concentration on the embryo epigenome, specifically DNA methylation, was analysed.Participants/materials, setting, methodsHuman embryos surplus to treatment requirements were donated with informed consent from several ART centres. Embryos were cultured to the blastocyst stage in Vitrolife G-TL™ medium, either at 0.9 mM or 3.5 mM glucose, separated via immunosurgery into Inner Cell Mass (ICM) and trophectoderm (TE) samples, and compared for both DNA methylation and gene expression. This allowed us to evaluate the association between DNA methylation and previously importantly identified biological pathways.Main results and the role of chanceThe concentration of glucose in human embryo culture medium was associated with changes in gene expression and global DNA methylation in both ICM and TE, and methylation levels at CpG islands and key histone modifications. These results are significant because glucose is a major nutrient metabolised by human embryos in culture, and yet we know relatively little of its downstream effects on the genome and epigenome.Wider implications of the findingsCommercially available embryo culture media with varying glucose levels have also been associated with altered fetal growth, birthweight and postnatal development of IVF offspring. Our findings may have important ramifications for potential clinical markers of embryo quality and pregnancy initiation, and improve understanding of the mechanisms underlying the impact of the early environment on the long term health of ART offspring.Study funding/competing interest(s)This work was funded by the National Council for Science and Technology of Mexico (CONACyT), an NIHR pre-doctoral fellowship (PCAF) to MM, the NIHR Local Comprehensive Research Network and NIHR Manchester Clinical Research Facility, the University of Manchester and Manchester University NHS Foundation Trust. None of the authors has any conflict of interest to declare.
A complete map of specificity encoding for a partially fuzzy protein interaction
Authors: Zarin Taraneh , Lehner Ben 
Published: April 2024

AbstractThousands of human proteins function by binding short linear motifs embedded in intrinsically disordered regions. How affinity and specificity are encoded in these binding domains and the motifs themselves is not well understood. The evolvability of binding specificity - how rapidly and extensively it can change upon mutation - is also largely unexplored, as is the contribution of ‘fuzzy’ dynamic residues to affinity and specificity in protein-protein interactions. Here we report the first complete map of specificity encoding for a globular protein domain. Quantifying >200,000 energetic interactions between a PDZ domain and its ligand identifies 20 major energetically coupled pairs of sites that control specificity. These are organized into six modules, with most mutations in each module reprogramming specificity for a single position in the ligand. Nine of the major energetic couplings controlling specificity are between structural contacts and 11 have an allosteric mechanism of action. The dynamic tail of the ligand is more robust to mutation than the structured residues but contributes additively to binding affinity and communicates with structured residues to enable changes in specificity. Our results quantify the binding specificities of >1,800 globular proteins to reveal how specificity is encoded and provide a direct comparison of the encoding of affinity and specificity in structured and dynamic molecular recognition.
Platform service decision and selling mode selection under different power structures
Authors: Wan Nana , Fan Jianchang 
Published: April 2024

PurposeThis paper forms an e-commerce supply chain that include a manufacturer providing products and an online platform providing service. The reselling platform mode and the agent platform mode are considered through an exploration of the manufacturer Stackelberg (MS), vertical Nash (VN), platform Stackelberg (PS) power structures. The purpose of this paper is to explore the pricing and platform service decisions under different platform selling modes and channel power structures.Design/methodology/approachBased on the game theory models, this paper investigates the interaction between the manufacturer and the online platform under four different scenarios. The optimal solutions of four models are provided. Through comparison analyses, this paper evaluates the impacts of platform selling mode and channel power structure on the pricing and platform service decisions and the members’ profits.FindingsThe manufacturer prefers the MS power structure in any platform mode. The online platform prefers the PS (MS) power structure under a low (high) service cost efficiency in the reselling platform mode, while prefers the PS and VN power structures in the agent platform mode. Moreover, the manufacturer prefers the agent (reselling) platform mode under a low (high) service cost efficiency in any power structure. The online platform prefers the reselling platform mode in the MS and PS power structures, while prefers the reselling (agent) platform mode under a low (high) service cost efficiency in the VN power structures.Originality/valueThe analysis result provides important managerial implications that help the supply chain members develop a better understanding of the selection of the platform selling mode and the effect of the channel power structure in the presence of platform service.
Impact of sub-national synchronization on the behavior of national business cycles in emerging economies with inflation targeting
Authors: Padilla Alcides J. , Quintero Otero Jorge David 
Published: April 2024

PurposeThe purpose of this paper is to assess sub-national business cycle (BC) synchronization's impact on national cycles in four emerging markets economies with inflation targeting (IT-EMEs): Brazil, Colombia, South Korea and Mexico.Design/methodology/approachThe authors use panel data models with fixed-effects and distributed lags.FindingsThe authors disclosed that sub-national synchronization increased national cycle amplitudes during expansion and recession phases. The authors also noticed that South Korea exhibited a more pronounced effect compared to Latin American countries, and this seemed to be associated with differences in the homogeneity of the production structures in the regions of these countries.Research limitations/implicationsThe authors cautioned that contrasting the findings with prior research on the effects of regional BC synchronization in IT-EMEs or with studies in different geographical contexts, is not possible due to the absence of prior research endeavors with this specific focus.Originality/valueThis study constitutes a first attempt to explain the impact of subnational cycle synchronization on the magnitude of national cycles in four IT-EMEs.
Does leader humor style matter employee knowledge sharing? From the lens of emotional contagion process
Authors: Xu Zhenting , Li Xianmiao , Sun Xiuming 
Published: April 2024

Purpose
This study aims to explore the enabling and suppressing effects of leader affiliative and aggressive humor on employee knowledge sharing form the lens of emotional contagion process, which provides theoretical reference for the applications of different leader humor style, thereby enhancing employee knowledge sharing.

Design/methodology/approach
This study collected three waves of data and surveyed 379 employees in China. Regression analysis, bootstrapping and latent moderation structural equation were adopted to test the hypotheses.

Findings
Leader affiliative humor has a positive impact on employee knowledge sharing, whereas leader aggressive humor has a negative impact on employee knowledge sharing. Positive emotion plays a mediating role between leader affiliative humor and employee knowledge sharing, and negative emotion plays a mediating role between leader aggressive humor and employee knowledge sharing. Moreover, supervisor–subordinate Guanxi moderates the relationship between leader affiliative humor and positive emotion, and between leader aggressive humor and negative emotion, respectively.

Originality/value
This study not only adds to the knowledge sharing literature calling for the exploration of antecedents and mechanism of employee knowledge sharing, but also contributes to our comprehensive understanding of the suppressing and enabling effects of leader humor style on employee knowledge sharing. Besides, this study also unpacks the dual-path mechanism and boundary condition between leader humor style and employee knowledge sharing and augments the theoretical explanations of emotional contagion theory between leader humor style and employee knowledge sharing.
An analysis of the geopolitical and economics influence on tourist arrivals in Russia using a nonlinear autoregressive distributed lag model
Authors: Georgescu Irina Alexandra , Oprea Simona Vasilica , Bâra Adela 
Published: April 2024

PurposeThe COVID-19 pandemic and the onset of the conflict in Ukraine led to a sustained downturn in tourist arrivals (TA) in Russia. This paper aims to explore the influence of geopolitical risk (GPR) and other indices on TA over 1995–2023.Design/methodology/approachWe employ a nonlinear autoregressive distributed lag (NARDL) model to analyze the effects, capturing both the positive and negative shocks of these variables on TA.FindingsOur research demonstrates that the NARDL model is more effective in elucidating the complex dynamics between macroeconomic factors and TA. Both an increase and a decrease in GPR lead to an increase in TA. A 1% negative shock in GPR leads to an increase in TA by 1.68%, whereas a 1% positive shock in GPR also leads to an increase in TA by 0.5%. In other words, despite the increase in GPR, the number of tourists coming to Russia increases by 0.5% for every 1% increase in that risk. Several explanations could account for this phenomenon: (1) risk-tolerant tourists: some tourists might be less sensitive to GPR or they might find the associated risks acceptable; (2) economic incentives: increased risk might lead to a depreciation in the local currency and lower costs, making travel to Russia more affordable for international tourists; (3) niche tourism: some tourists might be attracted to destinations experiencing turmoil, either for the thrill or to gain firsthand experience of the situation; (4) lagged effects: there might be a time lag between the increase in risk and the actual impact on tourist behavior, meaning the effects might be observed differently over a longer period.Originality/valueOur study, employing the NARDL model and utilizing a dataset spanning from 1995 to 2023, investigates the impact of GPR, gross domestic product (GDP), real effective exchange rate (REER) and economic policy uncertainty (EPU) on TA in Russia. This research is unique because the dataset was compiled by the authors. The results show a complex relationship between GPR and TA, indicating that factors influencing TA can be multifaceted and not always intuitive.