bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid-induced conformational switching of helical foldamers containing imidazole amide
Authors: Kimura Sakiko , Takeda Fumi , Ikeda Ayano , Tanimoto Asuka , Katagiri Kosuke , Kawahata Masatoshi , Okada Yusuke , Kobayashi Nagao , Kagechika Hiroyuki , Tanatani Aya 
Published: September 2024

Abstract
N-Alkylated oligo- and poly(p-benzamide)s exist as dynamic helical structures with all-cis amide conformation. Imidazole N-alkylated amides also show cis conformational preference, but their major conformer is changed from cis to trans by addition of acid. Here, based on those findings, we designed and synthesized aromatic triamides 3 and hexaamides 4 containing an imidazole ring as candidate foldamers anticipated to exhibit acid-induced conformational change. X-ray structure analysis of oligomer 3c showed that it takes all-cis conformation in the crystal. In solution, all the oligoamides examined existed as an equilibrium mixture of 4 conformers, among which the major conformer was the folded all-cis structure as judged from the low-temperature 1H NMR spectra. When trifluoroacetic acid-d was added to a solution of the oligoamides in methylene chloride-d2, only 2 conformers were observed in the low-temperature 1H NMR spectra, and the major conformer was the (trans,cis) form with respect to the amide bonds of the imidazole at the 4 and 2 positions. Experimental and theoretical analysis of the CD spectra indicated that the conformation of hexaamides 4 changes upon the addition of acid. Our results suggest that N-alkylated imidazole amide can serve as a key structural motif for the construction of foldamers with acid-switchable conformation.
Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy
Authors: Long Valérie , El Gebeily Gracia , Leblanc Élisabeth , Senhadji Marwa , Fiset Céline 
Published: September 2024

Abstract

Aims
Pregnant (P) women have a significantly elevated resting heart rate (HR), which makes cardiac arrhythmias more likely to occur. Although electrical remodelling of the sinoatrial node (SAN) has been documented, the underlying mechanism is not fully understood. The acetylcholine-activated potassium current (IKACh), one of the major repolarizing currents in the SAN, plays a critical role in HR control by hyperpolarizing the maximal diastolic potential (MDP) of the SAN action potential (AP), thereby reducing SAN automaticity and HR. Thus, considering its essential role in cardiac automaticity, this study aims to determine whether changes in IKACh are potentially involved in the increased HR associated with pregnancy.

Methods and results
Experiments were conducted on non-pregnant (NP) and pregnant (P; 17–18 days gestation) female CD-1 mice aged 2 to 4 months. IKACh was recorded on spontaneously beating SAN cells using the muscarinic agonist carbachol (CCh). Voltage-clamp data showed a reduction in IKACh density during pregnancy, which returned to control values shortly after delivery. The reduction in IKACh was explained by a decrease in protein expression of Kir3.1 channel subunit and the muscarinic type 2 receptor. In agreement with these findings, current-clamp data showed that the MDP of SAN cells from P mice were less hyperpolarized following CCh administration. Surface electrocardiograms (ECGs) recorded on anaesthetized mice revealed that the cholinergic antagonist atropine and the selective KACh channel blocker tertiapin-Q increased HR in NP mice and had only a minimal effect on P mice. AP and ECG data also showed that pregnancy is associated with a decrease in beating and HR variability, respectively.

Conclusion
IKACh function and expression are decreased in the mouse SAN during pregnancy, strongly suggesting that, in addition to other electrical remodelling of the SAN, reduced IKACh also plays an important role in the pregnancy-induced increased HR.
Combining the vasoactive-inotropic score with lactate levels to predict mortality in post-cardiotomy patients supported with venoarterial extracorporeal membrane oxygenation
Authors: Tian Xiaqiu , Wang Liangshan , Li Chenglong , Shao Juanjuan , Jia Ming , Wang Hong , Hou Xiaotong 
Published: September 2024

Abstract

OBJECTIVES
Our goal was to determine the predictive role of the combined assessment of the vasoactive-inotropic score (VIS) and lactate levels for the prognosis of patients with postcardiotomy cardiogenic shock (PCS) requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO).

METHODS
The data of adult patients with PCS requiring VA-ECMO between January 2015 and December 2018 at a tertiary hospital were analysed retrospectively. The incidence of in-hospital mortality and other clinical outcomes was analysed. The associations of the VIS and the lactate concentration and in-hospital mortality were assessed using logistic regression analysis.

RESULTS
A total of 222 patients were included and divided into 4 groups according to the cut-off points of the VIS (24.3) and the lactate level (6.85 mmol/L). The in-hospital mortality rates were 37.7%, 50.7%, 54.8% and 76.5% for the 4 groups (P &lt; 0.001), and the rates of successful weaning off VA-ECMO were 73.9%, 69%, 61.3% and 39.2%, respectively (P = 0.001). Groups 1 and 2 exhibited significant differences compared to group 4 in both in-hospital mortality and weaning rates (P &lt; 0.05). There was a statistically significant difference in the incidence of multiple organ dysfunction between group 1 and group 4 (P &lt; 0.05). Groups 1, 2 and 3 demonstrated significantly improved cumulative 30-day survival compared with group 4 (log-rank test, P &lt; 0.05). Logistic regression analysis revealed that age, a VIS &gt; 24.3 and lactate levels &gt; 6.85 mmol/L were independently predictive of in-hospital mortality.

CONCLUSIONS
Among patients with PCS requiring VA-ECMO, the initiation before reaching a VIS &gt; 24.3 and lactate levels &gt; 6.85 mmol/L was associated with improved in-hospital and 30-day outcomes, suggesting that the combined assessment of the VIS and lactate levels may be instructive for determining the initiation of VA-ECMO.
Supportive communication as a collective phenomenon: a dynamic systems account of emotional support provision and outcomes in online health communities
Authors: Rains Stephen A , Carter Shelby N 
Published: September 2024

Abstract
Developing a complete understanding of supportive communication requires learning more about how it unfolds among groups. We leveraged dynamic systems theory to document group-level emotional support provision practices in online health communities and examine their implications for discussion processes and the mood of support seekers. We evaluated sequences of person-centered feedback in the first three responses to threads started by community members seeking emotional support. Twelve different patterns of sequences were identified reflecting collective support provision behavior. Compared to the sequence containing only implicit recognition of a seeker’s feelings, sequences containing high person-centered feedback were more likely to foster high person-centered feedback in a later community response to the thread and more likely to be associated with an improvement in support seekers’ self-reported mood. The results of this project demonstrate how online communities collectively construct emotional support and the implications of those patterns for support seeking and provision.
Assessment of the public perception of the hospital pharmacist and their satisfaction level with the pharmacy services provided in a developing country: a cross-sectional survey in Malaysia
Authors: Kong Kian Keong , Ong Siew Chin 
Published: September 2024

Abstract

Objective
To assess the public perception of the role of hospital pharmacists, their satisfaction with the pharmacy service provided, and the factors associated with their perception and satisfaction.

Methods
A cross-sectional, questionnaire survey was conducted on adults older than 18 years who utilized public pharmacy services. A self-developed, validated questionnaire consisting of three parts was used, i.e., demographic data, perception, and satisfaction. The questionnaire was tested in a pilot study of 50 study participants and demonstrated good reliability results of 0.900 for the perception section and 0.836 for the satisfaction section. Therefore, all items were used in the final questionnaire.

Key findings
Four hundred and seventy-nine completed questionnaires were collected with a response rate of 91.6%. The Cronbach’s α for perception and satisfaction scores were 0.938 and 0.841, respectively. The median total score for public perception was 83 (interquartile range [IQR]: 15), whereas the median total score for public satisfaction was 38 (IQR: 33). The level of public perception was significantly associated with the age groups (P = .009), ethnic groups (P &lt; .001), respondents’ locality groups (P &lt; .001), the level of education achieved group (P = .017), and the income groups (P = .006). Satisfaction was not significantly associated with any sociodemographic factors.

Conclusions
This study has found that the general public had a favorable perception of the role of hospital pharmacists, and they were generally satisfied with the pharmacy service provided.
Cancer-associated SF3B1 mutations inhibit mRNA nuclear export by disrupting SF3B1–THOC5 interactions
Authors: Liu Gang , Zhao Bo , Shi Yueru , Wan Youzhong 
Published: September 2024

Abstract
Mutations in SF3B1 are common in many types of cancer, promoting cancer progression through aberrant RNA splicing. Recently, mRNA nuclear export has been reported to be defective in cells with the SF3B1 K700E mutation. However, the mechanism remains unclear. Our study reveals that the K700E mutation in SF3B1 attenuates its interaction with THOC5, an essential component of the mRNA nuclear export complex THO. Furthermore, the SF3B1 mutation caused reduced binding of THOC5 with some mRNA and inhibited the nuclear export of these mRNAs. Interestingly, overexpression of THOC5 restores the nuclear export of these mRNAs in cells with the SF3B1 K700E mutation. Importantly, other types of cancer-associated SF3B1 mutations also inhibited mRNA nuclear export similarly, suggesting that it is common for cancer-associated SF3B1 mutations to inhibit mRNA nuclear export. Our research highlights the critical role of the THOC5–SF3B1 interaction in the regulation of mRNA nuclear export and provides valuable insights into the impact of SF3B1 mutations on mRNA nuclear export.
Development of modular expression across phylogenetically distinct diazotrophs
Authors: Kulakowski Shawn , Rivier Alex , Kuo Rita , Mengel Sonya , Eng Thomas 
Published: September 2024

Abstract

Diazotrophic bacteria can reduce atmospheric nitrogen into ammonia enabling bioavailability of the essential element. Many diazotrophs closely associate with plant roots increasing nitrogen availability, acting as plant growth promoters. These associations have the potential to reduce the need for costly synthetic fertilizers if they could be engineered for agricultural applications. However, despite the importance of diazotrophic bacteria, genetic tools are poorly developed in a limited number of species, in turn narrowing the crops and root microbiomes that can be targeted. Here, we report optimized protocols and plasmids to manipulate phylogenetically diverse diazotrophs with the goal of enabling synthetic biology and genetic engineering. Three broad-host-range plasmids can be used across multiple diazotrophs, with the identification of one specific plasmid (containing origin of replication RK2 and a kanamycin resistance marker) showing the highest degree of compatibility across bacteria tested. We then demonstrated modular expression by testing seven promoters and eleven ribosomal binding sites using proxy fluorescent proteins. Finally, we tested four small molecule inducible systems to report expression in three diazotrophs and demonstrated genome editing in Klebsiella michiganensis M5al.

One-sentence summary
In this study, broad-host plasmids and synthetic genetic parts were leveraged to enable expression tools in a library of diazotrophic bacteria.
The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (&gt; 2 cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study
Authors: Miyoshi Tomohiro , Aokage Keiju , Watanabe Shun-ichi , Ito Hiroyuki , Sakakura Noriaki , Mun Mingyon , Yamashita Motohiro , Ohde Yasuhisa , Aoki Tadashi , Nishio Wataru , Taguri Masataka , Tsuboi Masahiro 
Published: September 2024

Abstract

Background
The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03).

Methods
Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1 &gt; 2 cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status.

Results
Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT−/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR− and UFT−/EGFR− patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT− group (P = 0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status.

Conclusion
In pathologic stage I (&gt;2 cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.
Direct numerical simulations of turbulent channel flow with wall transpiration using lattice Boltzmann method
Authors: Wu Chung-Ming , Lin Chao-An 
Published: September 2024

Abstract
Direct numerical simulations of turbulent channel flow with wall transpiration are conducted using the multi-relaxation time lattice Boltzmann method for the first time. Flows with two friction Reynolds numbers, $Re_\tau$ = 150 and 250, are investigated, and the explored transpiration rates based on the friction velocity range from 0.05 to 0.26. A successive block mesh-refinement strategy is adopted to resolve the near-wall structure, where the grid sizes are $\Delta ^+ \sim$1, 2, and 4. Under such resolution, the size of the maximum grid density employed is $775 \times 10^6$. At the low transpiration rate ($V^+=0.05$), the turbulence level at the suction side is damped relative to the less altered values along the injection side. However, at the high level of wall transpiration, i.e. $V^+=0.26$, turbulence levels are severely retarded on both the injection and suction sides. The predicted mean and turbulence quantities show good agreements with the available direct numerical simulation data, indicating the effectiveness of lattice Boltzmann method combined with mesh refinement in reproducing the correct physics of turbulent channel flows with different levels of wall transpiration.
The Current Regulation of Conflicts of Laws in International Commercial Arbitration
Authors: Hayward Benjamin 
Published: September 2024

Abstract
This chapter examines the current regulation of conflicts of laws in international commercial arbitration. It shows that diversity of approach is the regulatory status quo. It discusses the legal framework regulating conflicts questions, the categories of private international law provisions operating in international commercial arbitration, and ten conflict of laws rules arbitrators may draw upon. Arbitrators may apply the conflicts rules of: the arbitral seat; the State most closely connected to the dispute; the State which, absent the parties’ arbitration agreement, would have had jurisdiction over the dispute; the arbitrator’s home jurisdiction; the State of likely enforcement. They may also apply the substantive law of the seat of arbitration; the closest connection test; the cumulative approach; general principles of the conflict of laws; and they may also adopt conflicts rules found in a relevant international instrument.
Implementation and Conclusion
Authors: Hayward Benjamin 
Published: September 2024

Abstract
This chapter discusses the implementation of a (modified) Art 4 Rome Convention rule for arbitral conflicts through the reform of arbitration rules and the reform of arbitral laws. It argues that, on the current state of arbitral law and practice, there are significant difficulties with the regulatory status quo concerning conflicts of laws in international commercial arbitration. Nevertheless, these difficulties may give way to a test properly adapted to party expectation, party intention, and the appropriate prioritization of substantive certainty over procedural flexibility in arbitral conflicts of laws—should this book’s recommendations be adopted through reform to arbitration rules, the reform of arbitral laws, or through some other appropriate implementation methodology.
Synergistic effect of split DNA activators of Cas12a with exon-unwinding and induced targeting effect
Authors: Huang Shen , Lou Yongliang , Zheng Laibao 
Published: September 2024

Abstract
CRISPR-Cas12a, an RNA-guided nuclease, has been repurposed for genome editing and molecular diagnostics due to its capability of cis-cleavage on target DNA and trans-cleavage on non-target single-strand DNA (ssDNA). However, the mechanisms underlying the activation of trans-cleavage activity of Cas12a, particularly in the context of split DNA activators, remain poorly understood. We elucidate the synergistic effect of these activators and introduce the concepts of induced targeting effect and exon-unwinding to describe the phenomenon. We demonstrate that upon binding of split DNA activators adjacent to the Protospacer Adjacent Motif (PAM) to the Cas12a ribonucleoprotein (Cas12a–RNP), a ternary complex form that can capture and interact with distal split DNA activators to achieve synergistic effects. Notably, if the distal activator is double-strand DNA (dsDNA), the complex initiates exon-unwinding, facilitating the RNA-guide sequence's access. Our findings provide a mechanistic insight into action of Cas12a and propose a model that could significantly advance our understanding of its function.
DNA double-strand break movement in heterochromatin depends on the histone acetyltransferase dGcn5
Authors: Kendek Apfrida , Sandron Arianna , Lambooij Jan-Paul , Colmenares Serafin U , Pociunaite Severina M , Gooijers Iris , de Groot Lars , Karpen Gary H , Janssen Aniek 
Published: September 2024

Abstract
Cells employ diverse strategies to repair double-strand breaks (DSBs), a dangerous form of DNA damage that threatens genome integrity. Eukaryotic nuclei consist of different chromatin environments, each displaying distinct molecular and biophysical properties that can significantly influence the DSB-repair process. DSBs arising in the compact and silenced heterochromatin domains have been found to move to the heterochromatin periphery in mouse and Drosophila to prevent aberrant recombination events. However, it is poorly understood how chromatin components, such as histone post-translational modifications, contribute to these DSB movements within heterochromatin. Using irradiation as well as locus-specific DSB induction in Drosophila tissues and cultured cells, we find enrichment of histone H3 lysine 9 acetylation (H3K9ac) at DSBs in heterochromatin but not euchromatin. We find this increase is mediated by the histone acetyltransferase dGcn5, which rapidly localizes to heterochromatic DSBs. Moreover, we demonstrate that in the absence of dGcn5, heterochromatic DSBs display impaired recruitment of the SUMO E3 ligase Nse2/Qjt and fail to relocate to the heterochromatin periphery to complete repair. In summary, our results reveal a previously unidentified role for dGcn5 and H3K9ac in heterochromatic DSB repair and underscore the importance of differential chromatin responses at heterochromatic and euchromatic DSBs to promote safe repair.
The rice R2R3 MYB transcription factor FOUR LIPS connects brassinosteroid signaling to lignin deposition and leaf angle
Authors: Liu Huichao , Zhang Jie , Wang Junxue , Fan Zhibin , Qu Xiaoxiao , Yan Min , Zhang Chunxia , Yang Kezhen , Zou Junjie , Le Jie 
Published: September 2024

Abstract
Leaf angle is an important agronomic trait for crop architecture and yield. In rice (Oryza sativa), the lamina joint is a unique structure connecting the leaf blade and sheath that determines leaf angle. Brassinosteroid (BR) signaling involving GLYCOGEN SYNTHASE KINASE-3 (GSK3)/SHAGGY-like kinases and BRASSINAZOLE-RESISTANT1 (BZR1) has a central role in regulating leaf angle in rice. In this study, we identified the atypical R2R3-MYB transcription factor FOUR LIPS (OsFLP), the rice homolog of Arabidopsis (Arabidopsis thaliana) AtFLP, as a participant in BR-regulated leaf angle formation. The spatiotemporal specificity of OsFLP expression in the lamina joint was closely associated with lignin deposition in vascular bundles and sclerenchyma cells. OsFLP mutation caused loose plant architecture with droopy flag leaves and hypersensitivity to BRs. OsBZR1 directly targeted OsFLP, and OsFLP transduced BR signals to lignin deposition in the lamina joint. Moreover, OsFLP promoted the transcription of the phenylalanine ammonia-lyase family genes OsPAL4 and OsPAL6. Intriguingly, OsFLP feedback regulated OsGSK1 transcription and OsBZR1 phosphorylation status. In addition, an Ala-to-Thr substitution within the OsFLP R3 helix-turn-helix domain, an equivalent mutation to that in Osflp-1, affected the DNA-binding ability and transcriptional activity of OsFLP. Our results reveal that OsFLP functions with OsGSK1 and OsBZR1 in BR signaling to maintain optimal leaf angle by modulating the lignin deposition in mechanical tissues of the lamina joint.
How coat proteins shape autophagy in plant cells
Authors: Chung Taijoon , Choi Ye Eun , Song Kyoungjun , Jung Hyera 
Published: September 2024

Abstract
Autophagy is a membrane trafficking pathway through which eukaryotic cells target their own cytoplasmic constituents for degradation in the lytic compartment. Proper biogenesis of autophagic organelles requires a conserved set of autophagy-related (ATG) proteins and their interacting factors, such as signalling phospholipid phosphatidylinositol 3-phosphate (PI3P) and coat complex II (COPII). The COPII machinery, which was originally identified as a membrane coat involved in the formation of vesicles budding from the endoplasmic reticulum, contributes to the initiation of autophagic membrane formation in yeast, metazoan, and plant cells; however, the exact mechanisms remain elusive. Recent studies using the plant model species Arabidopsis thaliana have revealed that plant-specific PI3P effectors are involved in autophagy. The PI3P effector FYVE2 interacts with the conserved PI3P effector ATG18 and with COPII components, indicating an additional role for the COPII machinery in the later stages of autophagosome biogenesis. In this Update, we examined recent research on plant autophagosome biogenesis and proposed working models on the functions of the COPII machinery in autophagy, including its potential roles in stabilizing membrane curvature and sealing the phagophore.