bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels
Authors: Fu Xiaolong , Wan Peifeng , Lu Ling , Wan Yingcui , Liu Ziyi , Hong Guodong , Cao Shengda , Bi Xiuli , Zhou Jing , Qiao Ruifeng , Guo Siwei , Xiao Yu , Wang Bingzheng , Chang Miao , Li Wen , Li Peipei , Zhang Aizhen , Sun Jin , Chai Renjie , Gao Jiangang 
Published: May 2023

AbstractThe peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome‐deficient mouse models (Atoh1‐Pex5−/− and Pax2‐Pex5−/−) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency‐mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1‐Pex5−/‐ mice when compared to wild‐type (WT) mice. However, the expression of large‐conductance, voltage‐, and Ca2+‐activated K+ (BK) channels is less in Atoh1‐Pex5−/− mice as compared to the WT mice, and the administration of activators of BK channels (NS‐1619 and NS‐11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome‐related hearing diseases such as PBDs.
Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord‐Like Organoid (pSCO) with Dorsoventral Organization
Authors: Seo Kyubin , Cho Subin , Shin Hyogeun , Shin Aeri , Lee Ju‐Hyun , Kim June Hoan , Lee Boram , Jang Hwanseok , Kim Youngju , Cho Hyo Min , Park Yongdoo , Kim Hee Youn , Lee Taeseob , Park Woong‐Yang , Kim Yong Jun , Yang Esther , Geum Dongho , Kim Hyun , Cho Il‐Joo , Lee Sanghyuk , Ryu Jae Ryun , Sun Woong 
Published: May 2023

AbstractAxis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self‐organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord‐like organoids, which established self‐ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center‐edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.
Biomembrane‐inspired design of medical micro/nanorobots: From cytomembrane stealth cloaks to cellularized Trojan horses
Authors: Li Jinhua , Zhou Huaijuan , Liu Chun , Zhang Shuailong , Du Ran , Deng Yulin , Zou Xuenong 
Published: May 2023

AbstractMicro/nanorobots are promising for a wide range of biomedical applications (such as targeted tumor, thrombus, and infection therapies in hard‐to‐reach body sites) because of their tiny size and high maneuverability through the actuation of external fields (e.g., magnetic field, light, ultrasound, electric field, and/or heat). However, fully synthetic micro/nanorobots as foreign objects are susceptible to phagocytosis and clearance by diverse phagocytes. To address this issue, researchers have attempted to develop various cytomembrane‐camouflaged micro/nanorobots by two means: (1) direct coating of micro/nanorobots with cytomembranes derived from living cells and (2) the swallowing of micro/nanorobots by living immunocytes via phagocytosis. The camouflaging with cytomembranes or living immunocytes not only protects micro/nanorobots from phagocytosis, but also endows them with new characteristics or functionalities, such as prolonging propulsion in biofluids, targeting diseased areas, or neutralizing bacterial toxins. In this review, we comprehensively summarize the recent advances and developments of cytomembrane‐camouflaged medical micro/nanorobots. We first discuss how cytomembrane coating nanotechnology has been employed to engineer synthetic nanomaterials, and then we review in detail how cytomembrane camouflage tactic can be exploited to functionalize micro/nanorobots. We aim to bridge the gap between cytomembrane‐cloaked micro/nanorobots and nanomaterials and to provide design guidance for developing cytomembrane‐camouflaged micro/nanorobots.
Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial
Authors: O'Brien Kyra , Feng Rui , Sieber Frederick , Marcantonio Edward R. , Tierney Ann , Magaziner Jay , Carson Jeffrey L. , Dillane Derek , Sessler Daniel I. , Menio Diane , Ayad Sabry , Stone Trevor , Papp Steven , Schwenk Eric S. , Marshall Mitchell , Jaffe J. Douglas , Luke Charles , Sharma Balram , Azim Syed , Hymes Robert , Chin Ki‐Jinn , Sheppard Richard , Perlman Barry , Sappenfield Joshua , Hauck Ellen , Hoeft Mark A. , Karlawish Jason , Mehta Samir , Donegan Derek J. , Horan Annamarie , Ellenberg Susan S. , Neuman Mark D. ,   the REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) Investigators
Published: May 2023

AbstractINTRODUCTIONThe effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown.METHODSPost hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery.RESULTSAmong patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in‐hospital complications, and 60‐day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment.DISCUSSIONAnesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.
Macrocyclic β‐Sheets Stabilized by Hydrogen Bond Surrogates
Authors: Nazzaro Alex , Lu Brandon , Sawyer Nicholas , Watkins Andrew M. , Arora Paramjit S. 
Published: May 2023

AbstractMimics of protein secondary and tertiary structure offer rationally‐designed inhibitors of biomolecular interactions. β‐Sheet mimics have a storied history in bioorganic chemistry and are typically designed with synthetic or natural turn segments. We hypothesized that replacement of terminal inter‐β‐strand hydrogen bonds with hydrogen bond surrogates (HBS) may lead to conformationally‐defined macrocyclic β‐sheets without the requirement for natural or synthetic β‐turns, thereby providing a minimal mimic of a protein β‐sheet. To access turn‐less antiparallel β‐sheet mimics, we developed a facile solid phase synthesis protocol. We surveyed a dataset of protein β‐sheets for naturally observed interstrand side chain interactions. This bioinformatics survey highlighted an over‐abundance of aromatic–aromatic, cation‐π and ionic interactions in β‐sheets. In correspondence with natural β‐sheets, we find that minimal HBS mimics show robust β‐sheet formation when specific amino acid residue pairings are incorporated. In isolated β‐sheets, aromatic interactions endow superior conformational stability over ionic or cation‐π interactions. Circular dichroism and NMR spectroscopies, along with high‐resolution X‐ray crystallography, support our design principles.
Production of Pt decorated poly(3,4‐ethylenedioxythiophene)/ERGO/GCEas an efficient catalyst for methanol oxidation reaction
Authors: Doğru Mert Başak , Karazehir Tolga , Mert Mehmet Erman , Kardaş Gülfeza 
Published: May 2023

AbstractIn this study, Pt‐decorated poly(3,4‐ethylenedioxythiophene) (PEDOT) electrocatalyst was uniformly coated electrochemically reduced graphene oxide (ERGO) layer on glassy carbon electrode (GCE) has been created using appropriate procedures to facilitate the implementation of the methanol oxidation reaction (MOR). This multi‐layer catalyst was characterized in each production step via Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, field‐emission scanning electron microscopy and energy‐dispersive x‐ray analysis (FESEM‐EDX) morphological analysis beside the electrochemical tests. The favorable structures of both ERGO and PEDOT increase conductivity and electrocatalytic activity toward methanol oxidation, which may create a suitable matrix for Pt loading thanks to the formation of much more active centers for methanol electrooxidation. The results demonstrate that the electrochemical surface area (ECSA) of Pt/PEDOT/ERGO/GCE was 39.1 m2 g−1, and it has a convenient mass activity (MA with 467 mA mg Pt−1) compared to that of commercial Pt/C. According to chronoamperometric analysis, the current density of Pt/PEDOT/ERGO/GCE was stable during the 1200 s of operation. It demonstrated remarkable stability with a final current density of 4.36 mA cm−2.
Composition analysis of post‐consumer recycled blends of linear low‐ and low‐density polyethylene using a solution‐based technique
Authors: Hashemnejad Meysam 
Published: May 2023

AbstractBlends of linear low‐density polyethylene (LLDPE) and low‐density polyethylene (LDPE) are commonly used in film applications, including those made with post‐consumer recycled (PCR) film resins. The ratio of LLDPE/LDPE in PCR resins can vary based on the complexity of the waste stream, making it essential to determine their composition before incorporating them into virgin resins through mechanical recycling. In this study, we propose a quantitative analysis using a solution‐based crystallization elution fractionation (CEF) technique to determine the composition of PCR LLDPE/LDPE blends. The results were compared with those obtained by a standard differential scanning calorimetry (DSC) technique. A series of Ziegler–Natta catalyzed LLDPE resins were blended with LDPE to establish the CEF calibration curves. The CEF calibration curves were found to be similar for 1‐butene LLDPE/LDPE and 1‐hexene LLDPE/LDPE blends. Fourier transform infrared spectroscopy and nuclear magnetic resonance were used as needed to determine the type of comonomer in the LLDPE component for the DSC methodology, which varies the calibration curve. We found that the CEF and DSC techniques provide comparable results in terms of LDPE content for neat polymer blends, depending on the density of each component. However, the proposed CEF technique provides more accurate and reliable results than previously published techniques in estimating LDPE content in PCR LLDPE/LDPE blends that may contain inorganic compounds.
Animation generation for object transportation with a rope using deep reinforcement learning
Authors: Wong Sai‐Keung , Wei Xu‐Tao 
Published: May 2023

AbstractThis article presents a reinforcement learning‐based approach to generate animation in which two agents use a rope to collaboratively transport a block. The challenge is that the agents need to master several skills, including approaching the block, using the rope to wrap around it, and then moving the block to a predefined goal position. We propose several reward terms to learn the transportation policy and the adjustment policy that govern the skills of the agents. Experiment results showed that the proposed approach was able to generate various animations in different settings, including rope lengths, block sizes, and block shapes. An ablation test revealed the effects of the reward terms. We also investigated factors that affected the performance of the two policies.
Mild aortic insufficiency following transcatheter aortic valve replacement: A systematic review and meta‐analysis
Authors: Hameed Irbaz , Ahmed Adham , Kumar Ashish , Li Eric , Candelario Katherine , Khan Sumera , Kannan Amudhan , Latif Nida , Amabile Andrea , Geirsson Arnar , Williams Matthew L. 
Published: May 2023

AbstractBackgroundPost‐procedural aortic insufficiency (AI) continues to be prevalent following transcatheter aortic valve replacement (TAVR). While several studies have assessed the outcomes of moderate‐severe AI following TAVR, the incidence, predictors, and outcomes of mild AI remain unclear.MethodsA systematic literature review was performed to identify studies reporting on mild AI following TAVR. The primary outcome was pooled incidence of post‐TAVR mild AI. Secondary outcomes included pooled incidence of mild AI at 30 days and long term. The pooled incidence of midterm mortality in patients with post‐TAVR mild AI was also evaluated. The random effect generalized linear mixed‐effects model with logit‐transformed proportions and Hartung–Knapp adjustment was used to calculate pooled incidence rates. Meta‐regression was performed to identify predictors of mild AI.ResultsThe pooled analysis included 19,241 patients undergoing TAVR across 50 studies. The mean age of patients ranged from 73 to 85 years, and female patients ranged from 20.0% to 83.3%. The overall pooled incidence of post‐TAVR mild AI was 56.1% (95% confidence interval [CI] 0.31–0.64). The pooled incidence of mild AI at 30 days was 33.7% (95% CI 0.12–0.37). At mean follow‐up of 1.15 years, the pooled incidence of mild AI was 37.0% (95% CI 0.16–0.45). The overall pooled incidence of Midterm mortality (mean follow‐up 1.22 years) in patients with mild AI was 14.8% (95% CI 0.10–0.25). At meta‐regression, none of the explored variables correlated with a difference in mild AI incidence.ConclusionsIn published studies to date, 50% of patients undergoing TAVR develop mild AI postoperatively. In 37% of patients, this persists in long term. Though the incidence of AI is likely improving with newer generation TAVR valves, the prevalence and outcomes of mild AI should be closely monitored as TAVR volume and indications expand to younger patients with long life expectancy. The long‐term outcomes of mild AI remain unclear. Further dedicated studies on post‐TAVR mild AI are needed.
Mechanistic Aspects and Side Reactions during Reversible Mg Deposition and Oxygen Reduction on a Pt Film Electrode in BMP‐TFSI‐Based Electrolytes: A DEMS Study
Authors: Jusys Zenonas , Behm R. Jürgen 
Published: May 2023

AbstractReversible Mg deposition/stripping and O2 reduction/evolution on a Pt film electrode in neat and O2‐saturated 1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl) imide (BMP‐TFSI) electrolytes, containing Mg(TFSI)2 and/or Mg(BH4)2 as Mg source as well as Mg(BH4)2 and/or the crown ether 18‐c‐6 as additive, were investigated by online differential electrochemical mass spectrometry (DEMS) and by scanning electron microscopy/energy dispersed X‐ray spectroscopy. Combined cyclic voltammetry and DEMS measurements reveal a complex network of partial reactions, including borohydride electro‐oxidation by reaction with water or O2, chemical bulk reaction of these components, as well as electro‐oxidation of H2, and electrolyte decomposition, in addition to the primary reactions Mg deposition/stripping and ORR/OER. They provide detailed insights into the potential dependent reactions occurring under these conditions, demonstrating that also the additive 18‐c‐6 undergoes decomposition upon reduction of Mg2+. Contributions from chemical bulk reactions are resolved by DEMS measurements in borohydride containing solution without a Pt electrode. Electrocatalytic borohydride oxidation, explored by similar measurements with a Pt electrode, can lead to H2 or H+ formation. Under open circuit potential conditions, charge compensation by the ORR results in the formation of a mixed potential. Consequences of these findings for applications in Mg‐air batteries are discussed.
Iridium‐Catalyzed Site‐ and Enantioselective C(sp2)‐H Borylation of Benzhydryl Ethers: Enantioselectivity Amplification by Kinetic Resolution Relay
Authors: Jing Ke , Chen Lili , Zhang Panke , Xu Senmiao 
Published: May 2023

Comprehensive SummaryWe herein report a simple ether‐directed iridium‐catalyzed site‐ and enantioselective C(sp2)‐H borylation of benzhydryl ethers for the first time. Various chiral benzhydryl ethers were obtained with high enantioselectivities in the presence of a tailor‐made chiral bidentate boryl ligand. We found that the kinetic resolution relay significantly amplified the enantioselectivity. The synthetic utility of the current method was demonstrated by gram‐scale C—H borylation and C—B bond transformations.
Structure‐Activity Relationships of Flupirtine Analogues for Liver Esterase‐Mediated Cleavage of the 4‐Fluorobenzylamine Moiety and Its Possible Relevance to Liver Toxicity
Authors: Beirow Kristin , Jedamzik Julia , Schulig Lukas , Wurm Konrad W. , Lemmerhirt Christian J. , Hofstetter Robert K. , Link Andreas , Bednarski Patrick J. 
Published: May 2023

AbstractFlupirtine and retigabine were essential drugs to combat pain and epilepsy. However, the Kv7 potassium channel openers are fraught with hepatotoxicity and tissue discoloration, respectively, limiting their therapeutic value. Both adverse events are likely due to reactive metabolites arising from oxidative metabolism. Designing safer analogues lacking the structural elements leading to described side effects is an active area of current research. One of the main metabolites of flupirtine is the biologically inactive 4‐fluorohippuric acid. Hitherto unexplained, the proposed metabolic pathway leading to the formation of 4‐fluorohippuric acid from flupirtine is verified here. Through the use of eighteen flupirtine analogues, mechanistic details of this pathway could be elucidated. A possible connection with the in vitro hepatotoxicity of the flupirtine analogues and the levels of 4‐fluorobenzoic acid formed in enzyme incubations was examined by correlation analysis. These findings provide important information for the design of new flupirtine analogues as potential drug candidates.
The double‐edged sword effect of organizational resilience onESGperformance
Authors: Liang Lin , Li Yan 
Published: May 2023

AbstractBuilding on conservation of resources theory, we construct a dual‐pathway approach which aims to reveal the mixed effects of organizational resilience on environmental, social and corporate governance (ESG) performance. Specifically, this paper argues that organizational resilience will both stimulate innovation input, enhancing ESG performance (positive pathway) and promote strategic change, inhibiting ESG performance (negative pathway). Meanwhile, the indirect effect of organizational resilience on ESG performance via innovation input and strategic change is also moderated by industry concentration, and both indirect effects are stronger when industry concentration is low. Data of Chinese A‐share listed firms from 2010 to 2020 support the proposed theoretical framework. This study provides theoretical and managerial implications for organizational resilience research.
Large‐scale eDNA monitoring of multiple aquatic pathogens as a tool to provide risk maps for wildlife diseases
Authors: Sieber Natalie , King Alex , Krieg Raphael , Zenker Armin , Vorburger Christoph , Hartikainen Hanna 
Published: May 2023

AbstractMultiple parasites and pathogens cause disease in aquatic wildlife and in aquaculture species, generating a need for monitoring and management. Conventional disease monitoring methods involve laborious, costly, and invasive capture and examination of host species, and require specialized expertise for every host and pathogen of interest. Environmental DNA could provide simultaneous occurrence data for multiple pathogens across different host taxa, valuable for using parasite diversity as, for example, a bioindicator of ecosystem disturbance. Here, we tested the potential for simultaneous detection of four wildlife pathogens in water samples from 280, mainly riverine, sites across Switzerland. We targeted the crayfish pathogen Aphanomyces astaci, the amphibian pathogen Batrachochytrium dendrobatidis, and the fish pathogens Saprolegnia parasitica and Tetracapsuloides bryosalmonae. The eDNA detection showed a widespread distribution of A. astaci, S. parasitica, and T. bryosalmonae, although A. astaci and T. bryosalmonae were not detected in some alpine river catchments. B. dendrobatidis was detected only rarely, which was expected since the sampling did not target amphibian breeding sites. Co‐detection rates were higher in rivers than in lakes, likely reflecting the habitat preferences and distributions of the host species. We discuss the advantages and limitations of eDNA‐based pathogen monitoring and list a set of recommendations for managers. Our study illustrates how eDNA‐based techniques can monitor several pathogen species concurrently, thus facilitating more comprehensive disease monitoring schemes. Combined with metabarcoding approaches in the future, eDNA‐based sampling and detection can facilitate the incorporation of parasite and pathogen occurrence and diversity as an indicator for aquatic ecosystem health, and for revealing the hidden biodiversity and structure of parasite communities.
Bile acid‐activated receptors in innate and adaptive immunity: targeted drugs and biological agents
Authors: Cheung Kenneth C. P. , Ma Jiao , Loiola Rodrigo Azevedo , Chen Xingxuan , Jia Wei 
Published: May 2023

AbstractBile acid‐activated receptors (BARs) such as a G‐protein bile acid receptor 1 and the farnesol X receptor are activated by bile acids (BAs) and have been implicated in the regulation of microbiota‐host immunity in the intestine. The mechanistic roles of these receptors in immune signaling suggest that they may also influence the development of metabolic disorders. In this perspective, we provide a summary of recent literature describing the main regulatory pathways and mechanisms of BARs and how they affect both innate and adaptive immune system, cell proliferation, and signaling in the context of inflammatory diseases. We also discuss new approaches for therapy and summarize clinical projects on BAs for the treatment of diseases. In parallel, some drugs that are classically used for other therapeutic purposes and BAR activity have recently been proposed as regulators of immune cells phenotype. Another strategy consists of using specific strains of gut bacteria to regulate BA production in the intestine.