bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expiration analysis of the International Space Station formulary for exploration mission planning
Authors: Diaz Thomas E. , Ives Emma C. , Lazare Diana I. , Buckland Daniel M. 
Published: July 2024

AbstractEffective medications will be required to maintain human health for long-duration space operations. Previous studies have explored the stability and potency of several of the medications used on the International Space Station (ISS). This study is a comprehensive analysis of the expected terrestrial shelf-lives of the entire 2023 ISS formulary using 4 international registries. Of the 106 medications in the ISS formulary, shelf-life data was found in at least 1 of the registries for 91 (86%) medications. Of these 91 medications, 54 have an estimated terrestrial shelf-life of ≤36 months when stored in their original packaging. 14 will expire in less than 24 months. The results of this study provide operational insight to supplying a pharmacy for an exploration mission, optimize therapeutic outcomes, and prevent diseases associated with extended spaceflight operations. Ultimately, those responsible for the health of spaceflight crews will have to find ways to extend the expiration of medications to the complete mission duration or accept the elevated risk associated with administration of an expired medication.
High-depth whole-genome sequencing identifies structure variants, copy number variants and short tandem repeats associated with Parkinson’s disease
Authors: Wang Chaodong , Liu Hankui , Li Xu-Ying , Ma Jinghong , Gu Zhuqin , Feng Xiuli , Xie Shu , Tang Bei-Sha , Chen Shengdi , Wang Wei , Wang Jian , Zhang Jianguo , Chan Piu 
Published: July 2024

AbstractWhile numerous single nucleotide variants and small indels have been identified in Parkinson’s disease (PD), the contribution of structural variants (SVs), copy number variants (CNVs), and short tandem repeats (STRs) remains poorly understood. Here we investigated the association using the high-depth whole-genome sequencing data from 466 Chinese PD patients and 513 controls. Totally, we identified 29,561 SVs, 32,153 CNVs, and 174,905 STRs, and found that CNV deletions were significantly enriched in the end-proportion of autosomal chromosomes in PD. After genome-wide association analysis and replication in an external cohort of 352 cases and 547 controls, we validated that the 1.6 kb-deletion neighboring MUC19, 12.4kb-deletion near RXFP1 and GGGAAA repeats in SLC2A13 were significantly associated with PD. Moreover, the MUC19 deletion and the SLC2A13 5-copy repeat reduced the penetrance of the LRRK2 G2385R variant. Moreover, genes with these variants were dosage-sensitive. These data provided novel insights into the genetic architecture of PD.
Understanding mechanisms of generalization following locomotor adaptation
Authors: Rossi Cristina , Roemmich Ryan T. , Bastian Amy J. 
Published: July 2024

AbstractOur nervous system has the remarkable ability to adapt our gait to accommodate changes in our body or surroundings. However, our adapted walking patterns often generalize only partially (or not at all) between different contexts. Here, we sought to understand how the nervous system generalizes adapted gait patterns from one context to another. Through a series of split-belt treadmill walking experiments, we evaluated different mechanistic hypotheses to explain the partial generalization of adapted gait patterns from split-belt treadmill to overground walking. In support of the credit assignment hypothesis, our experiments revealed the central finding that adaptation involves recalibration of two distinct forward models. Recalibration of the first model generalizes to overground walking, suggesting that the model represents the general movement dynamics of our body. On the other hand, recalibration of the second model does not generalize to overground walking, suggesting the model represents dynamics specific to treadmill walking. These findings reveal that there is a predefined portion of forward model recalibration that generalizes across context, leading to overall partial generalization of walking adaptation.
Unravelling the UV/H2O2 process using bioelectrochemically synthesized H2O2 to reuse waste nutrient solution
Authors: Nam Joo-Youn , Eom Hyunji , Han Uijeong , Jwa Eunjin , Kim Hyojeon , Han SeungYeob , Kang Seoktae , Cho Si-Kyung 
Published: July 2024

AbstractIn this study, waste nutrient solution (WNS) was used as a catholyte in a bioelectrochemical cell to directly produce hydrogen peroxide (H2O2), after which the H2O2- containing WNS was integrated with the downstream UV oxidation process to meet quality standards for reuse. The generated current in the bioelectrochemical cell was successfully utilized at the cathode to produce H2O2 in WNS using a two-electron oxygen reduction reaction with different reaction times. The cathodic reaction time with the highest H2O2 production (504 ± 5.2 mg l−1) was 48 h, followed by that obtained from 24 h (368 ± 4.1 mg l−1), 12 h (158.8 ± 2.4 mg l−1), and 6 h (121.1 ± 4.1 mg l−1) reaction times. During H2O2 generation, calcium, magnesium, and phosphate in the WNS were recovered in the form of precipitates under alkaline conditions. The H2O2-containing WNS was further treated with different UV doses. After UV/H2O2 treatment, excitation-emission matrix and molecular weight distribution analyses demonstrated that aromatic compounds were reduced. Moreover, the gene expressions of sul1 (up to 95.65%), tetG (up to 93.88%), and aadA (up to 95.32%) were clearly downregulated compared with those of a control sample. Finally, a high disinfection efficiency was achieved with higher UV doses, resulting in successful seed germination. Thus, our results indicate that the developed method can be a promising process for reusing WNS in hydroponic systems.
Single-position oblique lumbar interbody fusion with navigation: improved efficiency and screw accuracy compared to dual-position with fluoroscopy
Authors: Park Hangeul , Son Hui , Kim Jun-Hoe , Kim Sum , Kim Young-Rak , Lee Chang-Hyun , Chung Chun Kee , Kim Chi Heon 
Published: July 2024

AbstractDual-position oblique lumbar interbody fusion with fluoroscopy (D-OLIF) requires repositioning the patient to a prone position for pedicle screw insertion. Recently, single-position surgery with navigation has been introduced. However, there are concerns regarding pedicle screw accuracy and achieving appropriate sagittal balance in single-position OLIF with navigation (S-OLIF). The purpose of this study is to evaluate the clinical and radiological outcomes of S-OLIF compared to D-OLIF. A retrospective analysis was conducted on 102 patients who underwent single-level OLIF at a single institution. The patients were divided into two groups: 55 in the S-OLIF group and 47 in the D-OLIF group. The numeric rating scale for back and leg, Oswestry disability index, and walking distance improvements showed no significant difference. However, the EuroQol 5-dimension 5-level index showed higher improvement in the S-OLIF (P = 0.029). The segmental lordosis, lumbar lordosis, and C7 sagittal vertical axis showed no significant difference. S-OLIF had significantly fewer cases of pedicle screw malposition (P = 0.045). Additionally, the surgery time was shorter in the S-OLIF (P = 0.002). In conclusion, S-OLIF exhibited clinical and radiological outcomes comparable to D-OLIF, with the added advantages of reduced surgery time and enhanced accuracy in pedicle screw placement.
Multi-kernel support vector regression with improved moth-flame optimization algorithm for software effort estimation
Authors: Li Jing , Sun Shengxiang , Xie Li , Zhu Chen , He Dubo 
Published: July 2024

AbstractIn this paper, a novel Moth-Flame Optimization (MFO) algorithm, namely MFO algorithm enhanced by Multiple Improvement Strategies (MISMFO) is proposed for solving parameter optimization in Multi-Kernel Support Vector Regressor (MKSVR), and the MISMFO-MKSVR model is further employed to deal with the software effort estimation problems. In MISMFO, the logistic chaotic mapping is applied to increase initial population diversity, while the mutation and flame number phased reduction mechanisms are carried out to improve the search efficiency, as well the adaptive weight adjustment mechanism is used to accelerate convergence and balance exploration and exploitation. The MISMFO model is verified on fifteen benchmark functions and CEC 2020 test set. The results show that the MISMFO has advantages over other meta-heuristic algorithms and MFO variants in terms of convergence speed and accuracy. Additionally, the MISMFO-MKSVR model is tested by simulations on five software effort datasets and the results demonstrate that the proposed model has better performance in software effort estimation problem. The Matlab code of MISMFO can be found athttps://github.com/loadstar1997/MISMFO.
A non-toxic equinatoxin-II reveals the dynamics and distribution of sphingomyelin in the cytosolic leaflet of the plasma membrane
Authors: Mori Toshiki , Niki Takahiro , Uchida Yasunori , Mukai Kojiro , Kuchitsu Yoshihiko , Kishimoto Takuma , Sakai Shota , Makino Asami , Kobayashi Toshihide , Arai Hiroyuki , Yokota Yasunari , Taguchi Tomohiko , Suzuki Kenichi G. N. 
Published: July 2024

AbstractSphingomyelin (SM) is a major sphingolipid in mammalian cells. SM is enriched in the extracellular leaflet of the plasma membrane (PM). Besides this localization, recent electron microscopic and biochemical studies suggest the presence of SM in the cytosolic leaflet of the PM. In the present study, we generated a non-toxic SM-binding variant (NT-EqtII) based on equinatoxin-II (EqtII) from the sea anemone Actinia equina, and examined the dynamics of SM in the cytosolic leaflet of living cell PMs. NT-EqtII with two point mutations (Leu26Ala and Pro81Ala) had essentially the same specificity and affinity to SM as wild-type EqtII. NT-EqtII expressed in the cytosol was recruited to the PM in various cell lines. Super-resolution microscopic observation revealed that NT-EqtII formed tiny domains that were significantly colocalized with cholesterol and N-terminal Lyn. Meanwhile, single molecule observation at high resolutions down to 1 ms revealed that all the examined lipid probes including NT-EqtII underwent apparent fast simple Brownian diffusion, exhibiting that SM and other lipids in the cytosolic leaflet rapidly moved in and out of domains. Thus, the novel SM-binding probe demonstrated the presence of the raft-like domain in the cytosolic leaflet of living cell PMs.
Multi-omics analysis unveils immunosuppressive microenvironment in the occurrence and development of multiple pulmonary lung cancers
Authors: Zhang Jiatao , Zhou Wenhao , Li Na , Li Huaming , Luo Haitao , Jiang Benyuan 
Published: July 2024

AbstractMultiple pulmonary lung cancers (MPLCs) are frequently encountered on computed tomography (CT) scanning of chest, yet their intrinsic characteristics associated with genomic features and radiological or pathological textures that may lead to distinct clinical outcomes remain largely unexplored. A total of 27 pulmonary nodules covering different radiological or pathological textures as well as matched adjacent normal tissues and blood samples were collected from patients diagnosed with MPLCs. Whole-exome sequencing (WES) and whole-transcriptome sequencing were performed. The molecular and immune features of MPLCs associated with distinct radiological or pathological textures were comprehensively investigated. Genomics analysis unveiled the distinct branches of pulmonary nodules originating independently within the same individual. EGFR and KRAS mutations were found to be prevalent in MPLCs, exhibiting mutual exclusivity. The group with KRAS mutations exhibited stronger immune signatures compared to the group with EGFR mutations. Additionally, MPLCs exhibited a pronounced immunosuppressive microenvironment, which was particularly distinct when compared with normal tissues. The expression of the FDSCP gene was specifically observed in MPLCs. When categorizing MPLCs based on radiological or pathological characteristics, a progressive increase in mutation accumulation was observed, accompanied by heightened chromatin-level instability as ground-glass opacity component declined or invasive progression occurred. A close association with the immunosuppressive microenvironment was also observed during the progression of pulmonary nodules. Notably, the upregulation of B cell and regulatory T cell marker genes occurred progressively. Immune cell abundance analysis further demonstrated a marked increase in exhausted cells and regulatory T cells during the progression of pulmonary nodules. These results were further validated by independent datasets including nCounter RNA profiling, single-cell RNA sequencing, and spatial transcriptomic datasets. Our study provided a comprehensive representation of the diverse landscape of MPLCs originating within the same individual and emphasized the significant influence of the immunosuppressive microenvironment in the occurrence and development of pulmonary nodules. These findings hold great potential for enhancing the clinical diagnosis and treatment strategies for MPLCs.
Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi
Authors: Choi Jae-Yeon , Gihaz Shalev , Munshi Muhammad , Singh Pallavi , Vydyam Pratap , Hamel Patrice , Adams Emily M. , Sun Xinghui , Khalimonchuk Oleh , Fuller Kevin , Ben Mamoun Choukri 
Published: July 2024

SummaryFungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa. The pathway regulates key cellular processes including metabolism of fatty acids, amino acids, sterols, and heme. In this study, we provide genetic evidence that disruption of the PCA pathway in Saccharomyces cerevisiae results in a significant alteration in the susceptibility of fungi to a wide range of xenobiotics, including clinically approved antifungal drugs through alteration of vacuolar morphology and drug detoxification. The drug potentiation mediated by genetic regulation of genes in the PCA pathway could be recapitulated using the pantazine analog PZ-2891 as well as the celecoxib derivative, AR-12 through inhibition of fungal AcCoA synthase activity. Collectively, the data validate the PCA pathway as a suitable target for enhancing the efficacy and safety of current antifungal therapies.
Synthesis of a highly thermostable insulin by phenylalanine conjugation at B29 Lysine
Authors: Sen Shantanu , Ali Rafat , Onkar Akanksha , Verma Shivani , Ahmad Quazi Taushif , Bhadauriya Pratibha , Sinha Pradip , Nair Nisanth N. , Ganesh Subramaniam , Verma Sandeep 
Published: July 2024

AbstractGlobally, millions of diabetic patients require daily life-saving insulin injections. Insulin heat-lability and fibrillation pose significant challenges, especially in parts of the world without ready access to uninterrupted refrigeration. Here, we have synthesized four human insulin analogs by conjugating ε-amine of B29 lysine of insulin with acetic acid, phenylacetic acid, alanine, and phenylalanine residues. Of these, phenylalanine-conjugated insulin, termed FHI, was the most stable under high temperature (65 °C), elevated salt stress (25 mM NaCl), and varying pH levels (ranging from highly acidic pH 1.6 to physiological pH 7.4). It resists fibrillation for a significantly longer duration with sustained biological activity in in vitro, ex vivo, and in vivo and displays prolonged stability over its native counterpart. We further unravel the critical interactions, such as additional aromatic π-π interactions and hydrogen bonding in FHI, that are notably absent in native insulin. These interactions confer enhanced structural stability of FHI and offer a promising solution to the challenges associated with insulin heat sensitivity.
Stabilization of P2 layered oxide electrodes in sodium-ion batteries through sodium evaporation
Authors: Zarrabeitia Maider , Salazar Iñigo , Acebedo Begoña , Muñoz-Márquez Miguel Ángel 
Published: July 2024

AbstractSodium-ion batteries are well positioned to become, in the near future, the energy storage system for stationary applications and light electromobility. However, two main drawbacks feed their underperformance, namely the irreversible sodium consumption during solid electrolyte interphase formation and the low sodiation degree of one of the most promising cathode materials: the P2-type layered oxides. Here, we show a scalable and low-cost sodiation process based on sodium thermal evaporation. This method tackles the poor sodiation degree of P2-type sodium layered oxides, thus overcoming the first irreversible capacity as demonstrated by manufacturing and testing all solid-state Na doped-Na~1Mn0.8Fe0.1Ti0.1O2 ǀǀ PEO-based polymer electrolyte ǀǀ Na full cells. The proposed sodium physical vapor deposition method opens the door for an easily scalable and low-cost strategy to incorporate any metal deficiency in the battery materials, further pushing the battery development.
Lead-sheathed telecom cables and historic leaded gasoline emissions substantially raise environmental lead levels in Portland, Oregon
Authors: Shiel Alyssa E. , Jovan Sarah , Murphy Christina J. 
Published: July 2024

AbstractWe conducted a high-resolution study of lead in an urban moss, Orthotrichum lyellii, to better understand lead distributions and sources in Portland, Oregon (United States). The outdoor lead landscape is found to be heterogenous, with lead concentrations varying with age of neighborhood: on average 8.3× and 19× the rural background in newer (≥1948) and older neighborhoods (≤1915), respectively. This study finds leaded gasoline to be a pervasive and persistent lead source, decades after the complete phase out of leaded gasoline use by on-road vehicles. The highest lead levels, up to 590× the rural background, are found in older residential neighborhoods where relic lead-sheathed telecommunication cables were identified. Leaching of lead from these cables is thought to be responsible for elevated lead in older residential neighborhoods in cities across the country. Targeted research is needed to quantify the impact of these cables on lead exposures in affected communities.
Distinct sources of uncertainty in simulations of the ocean biological carbon pump at different depths
Authors: Wang Bin , Fennel Katja 
Published: July 2024

AbstractModel uncertainty in simulating the biological carbon pump was quantified and partitioned using 14 models from the Coupled Model Intercomparison Project Phase 6. Uncertainty increases with depth. On the global scale, uncertainty in carbon export dominates above 900 m and uncertainty in transfer efficiency below. Reducing model uncertainty in carbon export and transfer efficiency offers similar benefits for understanding century-scale carbon sequestration and climate. These models produce three different qualitative patterns in transfer efficiency: one where it is globally homogenous and two opposite latitudinal patterns due to different model structures and parameters. The exponent b of the Martin curve, which has long been used to compare different representations of transfer efficiency, is shown here to underestimate uncertainty in transfer efficiency. This highlights the importance of using vertical profiles of carbon flux rather than the single exponent b in model validation and intercomparison exercises.
Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling
Authors: Domingues Neuza , Catarino Steve , Cristóvão Beatriz , Rodrigues Lisa , Carvalho Filomena A , Sarmento Maria João , Zuzarte Mónica , Almeida Jani , Ribeiro-Rodrigues Teresa , Correia-Rodrigues Ânia , Fernandes Fábio , Rodrigues-Santos Paulo , Aasen Trond , Santos Nuno C , Korolchuk Viktor I , Gonçalves Teresa , Milosevic Ira , Raimundo Nuno , Girão Henrique 
Published: July 2024

AbstractA robust and efficient cellular response to lysosomal membrane damage prevents leakage from the lysosome lumen into the cytoplasm. This response is understood to happen through either lysosomal membrane repair or lysophagy. Here we report exocytosis as a third response mechanism to lysosomal damage, which is further potentiated when membrane repair or lysosomal degradation mechanisms are impaired. We show that Connexin43 (Cx43), a protein canonically associated with gap junctions, is recruited from the plasma membrane to damaged lysosomes, promoting their secretion and accelerating cell recovery. The effects of Cx43 on lysosome exocytosis are mediated by a reorganization of the actin cytoskeleton that increases plasma membrane fluidity and decreases cell stiffness. Furthermore, we demonstrate that Cx43 interacts with the actin nucleator Arp2, the activity of which was shown to be necessary for Cx43-mediated actin rearrangement and lysosomal exocytosis following damage. These results define a novel mechanism of lysosomal quality control whereby Cx43-mediated actin remodelling potentiates the secretion of damaged lysosomes.
Unveiling the photophysical and excited state properties of multi-resonant OLED emitters using combined DFT and CCSD method
Authors: Sivasakthi Pandiyan , Samanta Pralok K. 
Published: July 2024

Multi-resonance thermally-activated delayed fluorescence is predominantly observed in organoboron heteroatom-embedded molecules, featuring enhanced performance in organic light-emitting diodes.