bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular features and race‐associated outcomes of SPOP‐mutant metastatic castration‐resistant prostate cancer
Authors: Stangl Andrew , Wilner Christopher , Li Pin , Maahs Lucas , Hwang Clara , Pilling Amanda 
Published: January 2023

AbstractBackgroundInactivating alterations in SPOP frequently occur in prostate cancer and promote increased dependency on androgen receptor (AR)‐mediated oncogenic signaling. The presence of SPOP mutation (SPOP‐mutant [SPOP‐mut]) may therefore impact therapeutic outcomes with AR‐directed therapies and docetaxel in metastatic castration‐resistant (mCRPC).MethodsThis was a retrospective study of mCRPC patients treated at an urban academic hospital (n = 103). Patients underwent tumor DNA sequencing to determine SPOP mutational status (SPOP‐mut). Outcomes measured were overall survival (OS) from diagnosis and treatment with second‐generation AR signaling inhibitor (ARSI) or docetaxel and time to PSA progression (prostate‐specific antigen‐progression‐free survival [PSA‐PFS]) compared by SPOP status using Kaplan–Meier curves and log‐rank test. The univariable and multivariable Cox proportional hazard model evaluated the association of SPOP mutation and outcomes adjusted for clinicopathologic features.ResultsSPOP‐mut was associated with longer PSA‐PFS in mCRPC (median 1.79 vs. 0.84 years; p = 0.06) and multivariate analysis (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.17–0.84; p = 0.02). SPOP‐mut demonstrated a higher median PSA decline compared to SPOP wild‐type (median decline 100% vs. 92%, p = 0.02). SPOP‐mut was not associated with OS from the start of ARSI or docetaxel (median OS not reached vs. 2.0 years) or PSA‐PFS on docetaxel (median PSA‐PFS 0.4 vs. 0.5 years) in mCRPC. The majority of SPOP mutations were identified in African American (AA) patients (69.2%) compared to Caucasian patients (30.8%). Race‐associated multivariate analysis revealed no significant differences in OS from the start of ARSI or the start of docetaxel and no differences in ARSI or docetaxel PSA‐PFS between AA and Caucasian patients. Molecular profiling demonstrated that AA patients had a higher frequency of SPOP mutations and greater heterogeneity of SPOP variants within the coding sequence. Analysis of concurrent genomic alterations revealed that SPOP mutations co‐occur with APC mutations (p = 0.001) and alterations in the Wnt pathway (p = 0.017).ConclusionsInactivating mutations in SPOP are associated with better response to ARSI treatment in mCRPC overall. Additional analysis with a larger cohort is needed to evaluate the association of SPOP status and outcomes with docetaxel. Race‐associated clinical outcomes and molecular features were observed, suggesting the benefit of biomarker‐directed therapy selection for individualized patient subsets in guiding treatment decisions for mCRPC patients.
The human ribosome‐associated complex suppresses prion formation in yeast
Authors: Kelly Christina , Ahmed Yusef , Elghawy Omar , Pachon Nikole Fandiño , Fontanese Matthew S. , Kim Seongchan , Kitterman Erica , Marley Amanda , Terrenzio Danielle , Wike Richard , Zeibekis Theodora , Cameron Dale M. 
Published: January 2023

AbstractMany human diseases are associated with the misfolding of amyloidogenic proteins. Understanding the mechanisms cells employ to ensure the integrity of the proteome is therefore a crucial step in the development of potential therapeutic interventions. Yeast cells possess numerous prion‐forming proteins capable of adopting amyloid conformations, possibly as an epigenetic mechanism to cope with changing environmental conditions. The ribosome‐associated complex (RAC), which docks near the ribosomal polypeptide exit tunnel and recruits the Hsp70 Ssb to chaperone nascent chains, can moderate the acquisition of these amyloid conformations in yeast. Here we examine the ability of the human RAC chaperone proteins Mpp11 and Hsp70L1 to function in place of their yeast RAC orthologues Zuo1 and Ssz1 in yeast lacking endogenous RAC and investigate the extent to which the human orthologues can perform RAC chaperone activities in yeast. We found that the Mpp11/Hsp70L1 complex can partially correct the growth defect seen in RAC‐deficient yeast cells, although yeast/human hetero species complexes were variable in this ability. The proportion of cells in which the Sup35 protein undergoes spontaneous conversion to a [PSI+] prion conformation, which is increased in the absence of RAC, was reduced by the presence of the human RAC complex. However, the toxicity in yeast from expression of a pathogenically expanded polyQ protein was unable to be countered by the human RAC chaperones. This yeast system can serve as a facile model for studying the extent to which the human RAC chaperones contribute to combating cotranslational misfolding of other mammalian disease‐associated proteins.
Molecular insight into cellulose degradation by the phototrophic green alga Scenedesmus
Authors: Velazquez María B. , Busi María V. , Gomez‐Casati Diego F. , Nag‐Dasgupta Chitralekha , Barchiesi Julieta 
Published: January 2023

AbstractLignocellulose is the most abundant natural biopolymer on earth and a potential raw material for the production of fuels and chemicals. However, only some organisms such as bacteria and fungi produce enzymes that metabolize this polymer. In this work we have demonstrated the presence of cellulolytic activity in the supernatant of Scenedesmus quadricauda cultures and we identified the presence of extracellular cellulases in the genome of five Scenedesmus species. Scenedesmus is a green alga which grows in both freshwater and saltwater regions as well as in soils, showing highly flexible metabolic properties. Sequence comparison of the different identified cellulases with hydrolytic enzymes from other organisms using multisequence alignments and phylogenetic trees showed that these proteins belong to the families of glycosyl hydrolases 1, 5, 9, and 10. In addition, most of the Scenedesmus cellulases showed greater sequence similarity with those from invertebrates, fungi, bacteria, and other microalgae than with the plant homologs. Furthermore, the data obtained from the three dimensional structure showed that both, their global structure and the main amino acid residues involved in catalysis and substrate binding are well conserved. Based on our results, we propose that different species of Scenedesmus could act as biocatalysts for the hydrolysis of cellulosic biomass produced from sunlight.
Molecular characterization of hexokinase (HK) in Haemaphysalis longicornis and evaluation of HK protein‐ and DNA‐based vaccines against adult ticks
Authors: Wang Duo , Li Ru , Wu Ya‐Xue , Fan Xiang‐Yuan , Liu Xiao‐Ya , Yang Feng , Zhang Tian‐Tian , Ma Jing‐Yi , Hu Yong‐Hong 
Published: January 2023

AbstractBackgroundHaemaphysalis longicornis is an obligate hematophagous ectoparasite, which transmits various pathogens to humans, livestock and wild animals. Hexokinase (HK) is a key regulatory enzyme of the glycolytic pathway in the organisms. However, little is known about hexokinase and its functions in ticks.ResultsThe open reading frame of the H. longicornis HK (HlHK) gene was 1425 bp and encoded a protein of 474 amino acids, containing conserved domains for glucose, glucose 6‐phosphate, and adenosine triphosphate. The expression of HlHK gene was detected at different developmental stages and in different tissues of unfed female ticks. Enzyme‐linked immunosorbent assay revealed that both HK protein‐ and DNA‐based vaccines increased the antibody levels of the immunized animals. A vaccination trail on rabbits against H. longicornis infestation indicated that the rHlHK protein and HlHK DNA vaccines reduced the number of attached female ticks by 9% and 12%, egg mass weight by 36% and 34%, and egg hatching rate by 41% and 17%, respectively. Overall, protein vaccination conferred 65.6% protection against adult female ticks, whereas the DNA vaccine conferred 51.8% protection.ConclusionThis is the first report of the molecular characterization of the HK protein and sequencing of the HK gene from H. longicornis. Positive results from vaccination trials on rabbits of the recombinant HK protein and HK DNA suggest that these novel anti‐tick vaccines potentially can be used as viable tick control tools for the management of the Asian longhorned tick. Additionally, inhibition of glucose metabolism may be a new strategy for tick control. © 2023 Society of Chemical Industry.
Vaccine clinical trials with dynamic borrowing of historical controls: Two retrospective studies
Authors: Callegaro Andrea , Karkada Naveen , Aris Emmanuel , Zahaf Toufik 
Published: January 2023

AbstractTraditional vaccine efficacy trials usually use fixed designs with fairly large sample sizes. Recruiting a large number of subjects requires longer time and higher costs. Furthermore, vaccine developers are more than ever facing the need to accelerate vaccine development to fulfill the public's medical needs. A possible approach to accelerate development is to use the method of dynamic borrowing of historical controls in clinical trials. In this paper, we evaluate the feasibility and the performance of this approach in vaccine development by retrospectively analyzing two real vaccine studies: a relatively small immunological trial (typical early phase study) and a large vaccine efficacy trial (typical Phase 3 study) assessing prophylactic human papillomavirus vaccine. Results are promising, particularly for early development immunological studies, where the adaptive design is feasible, and control of type I error is less relevant.
Tenuifolin ameliorates the sleep deprivation‐induced cognitive deficits
Authors: Jiang Ning , Zhang Yiwen , Yao Caihong , Liu Yupei , Chen Yuzhen , Chen Fang , Wang Yan , Choudhary Muhammad Iqbal , Liu Xinmin 
Published: January 2023

AbstractTenuifolin (TEN), a natural neuroprotective compound obtained from the Polygala tenuifolia Willd plant, has improved cognitive symptoms. However, the impact of TEN on memory impairments caused by sleep deprivation (SD) is unclear. Accordingly, the objective of this study was to investigate the mechanisms behind the preventative benefits of TEN on cognitive impairment caused by SD. TEN (10 and 20 mg/kg) and Huperzine A (0.1 mg/kg) were given to mice through oral gavage for 28 days during the SD process. The results indicate that TEN administrations improve short‐ and long‐term memory impairments caused by SD in the Y‐maze, object identification, and step‐through tests. Moreover, TEN stimulated the generation of anti‐inflammatory cytokines (interleukin‐10), lowered the production of pro‐inflammatory cytokines (interleukin‐1β, interleukin‐6, and interleukin‐18), and activated microglia, improving antioxidant status in the hippocampus. TEN treatments significantly boosted the expression of nuclear factor erythroid 2‐related factor 2 and heme oxygenase‐1 while considerably decreasing the expression of NOD‐like receptor thermal protein domain associated protein 3 and caspase‐1 p20. Additionally, TEN restored the downregulation of the brain‐derived neurotrophic factor signaling cascade and the impaired hippocampal neurogenesis induced by SD. When considered collectively, our data suggest that TEN is a potentially effective neuroprotective agent for cognition dysfunction.
Time to diagnosis of pulmonary hypertension and diagnostic burden: A retrospective analysis of nationwide US healthcare data
Authors: Didden Eva‐Maria , Lee Eileen , Wyckmans Julie , Quinn Deborah , Perchenet Loïc 
Published: January 2023

AbstractThe main aim of this analysis was to investigate time from symptom onset (chronic unexplained dyspnoea [CUD]) to diagnosis of Group 1 pulmonary hypertension (PH)—pulmonary arterial hypertension (PAH)—and to characterize healthcare resource utilization leading up to diagnosis using a nationwide US claims and an electronic health record (EHR) database from Optum©. Eligible patients were ≥18 years old at first CUD diagnosis (index event) and had a PAH diagnosis on or after index date. Based on administrative codes, PAH was defined as right heart catheterization (RHC), ≥ 2 PAH diagnoses (1 within a year of RHC), and ≥1 post‐RHC prescription for PAH treatment. All values are median (1st quartile–3rd quartile) unless otherwise stated. Of 854,722 patients with CUD in the claims database, 582 (0.1%) had PAH. Time from CUD to PAH diagnosis was 2.26 (0.73–4.22) years. PAH patients experienced 3 (2–4) transthoracic echocardiograms (TTEs), 6 (3–12) specialist visits, and 2 (1–4) hospitalizations during the diagnostic interval. Almost one‐third of patients (29%) waited 10 months or more to have a TTE. Findings from the EHR database were broadly similar. Resource utilization during the diagnostic interval was also analyzed in an overall PH cohort: findings were generally similar to the PAH cohort (2 [1–3] TTEs, 4 [2–9] specialist visits and 2 [1–4] hospitalizations). These data indicate a delay in the diagnostic pathway for PAH, and illustrate the burden associated with PAH diagnosis.
Revisiting the generalized pseudospectral method: Energy degeneracies, radial expectation values, and Schwarz‐like inequalities of the shell‐confined atom
Authors: Zhou Zhi Ling , Zheng Ruo Yu , Jiao Li Guang , Liu Aihua , Montgomery Henry E. , Ho Yew Kam 
Published: January 2023

AbstractWe revisit the generalized pseudospectral (GPS) method to investigate the physical properties of shell‐confined atoms. Based on a general mapping function, the GPS method is developed for obtaining highly accurate bound state energies, wave functions, and radial quantities for the shell‐confined hydrogen atom. Besides the incidental and simultaneous degeneracies in the energy spectrum, we find that energy degeneracy appears very commonly in the shell‐confined system. The contour maps of the eigenenergies for some low‐lying bound states are obtained and the corresponding wave functions are analyzed. Radial expectation values with both positive and negative powers are calculated with high accuracy. By analyzing the Schwarz‐like inequalities, we show that the ground state density function for the outer‐confined hydrogen atom is second‐order monotonic, while for the shell‐confined hydrogen atom the radial densities for all bound states are zeroth‐order monotonic. In the extreme situation when the inner radius coalesces with the outer radius, the electron becomes a classical particle.
Terminal and bridging ligand effects on M(I)M(I) multiple bonding: ADFTinvestigation of the coordination in (X)[M2Cl]L2complexes (M = Cr,Fe,L = CO,PEt3,X = Cl, allyl,Cp, and indenyl)
Authors: Mecheri Sabri , Zouchoune Bachir 
Published: January 2023

AbstractA theoretical DFT investigation has been achieved on (X)[M2Cl]L2(M = Cr, Fe, L = CO, PEt3, and X = allyl, cyclopentadienyl, and indenyl) complexes by means of BP86 and B3LYP* functionals. The geometry optimizations showed an η3‐coordination for the allyl, while Cp and indenyl ligands adopt the same η5‐coordination mode and the chloride acts as bridging ligand. The metal–metal bond distances are very sensitive to the replacement of the CO with PEt3(triethylphosphine) with regard to the electron‐donation and electron π‐backdonation properties for the former and only to the electron‐donation for the later. This replacement impacts drastically the metal–metal bonding. Changing the metal from Cr to Fe increases the metal–metal bond distance, decreases the bond order and the oxidation sate of Fe, in agreement with the decrease of Wiberg bond indices (WBI) and Mayer bond order values (MBO). The findings showed that the Cl−and allyl−behave as 4‐electron donors, while Cp−and Ind−behave as 6–electron donors leading to outstanding electron properties stemming from different coordination, which are clarified by the σ‐donation and π‐backdonation properties, which are highlighted by the orbitals' populations and the energy decomposition analysis (EDA). Based on the aforementioned information, the chromium and iron complexes of Cl−and allyl−are of 22‐ and 24‐metal valence electrons (MVE), where those of Cp−and Ind−are of 26‐ and 28‐MVE, respectively. It is well noted that the metal–metal multiple bonding overcomes the electrons' deficiency.
Nonsingular fixed‐time fault‐tolerant attitude control for tailless flying wing aircraft with time‐varying flight envelope constraints
Authors: Yu Zhilong , Li Yinghui , Pei Binbin , Lv Maolong , Xu Wenfeng 
Published: January 2023

AbstractThis article investigates the fault‐tolerant attitude control problem for the tailless flying wing aircraft subject to time‐varying flight envelope constraints in the presence of the matched/mismatched disturbance, uncertain parameters, and time‐varying actuator failures. To handle these problems and improve the convergence rate of the attitude control system, a nonsingular fixed‐time convergent robust fault‐tolerant control methodology is proposed. First, the time‐varying barrier Lyapunov functions is introduced to confine the flight envelope within the predefined time‐varying compact set while ensuring the transient performance of the attitude tracking error. Subsequently, the fixed‐time sliding mode observer is designed to compensate for the matched/mismatched disturbance, uncertainties, and time‐varying actuator failures, meanwhile, by introducing an intermediate control law in the attitude controller, the singularity problem is avoided without utilizing any filters or continuous and differentiable piecewise functions. Further, it has been analytically proved that all signals of the closed‐loop system are bounded and converge to the residual set around the origin in a fixed time. Finally, simulations are conducted to illustrate the superiorities of the proposed scheme.
Assessing the occurrence of egg stranding for trout and salmon in a regulated river
Authors: Skoglund Helge , Vollset Knut Wiik , Wiers Tore , Barlaup Bjørn Torgeir 
Published: January 2023

AbstractA key challenge in many regulated rivers is to define adequate flow levels to protect aquatic organisms. Provisioning of suitable flow can be pivotal bottlenecks for fishes such as salmon and trout that use the riverbed as an incubation habitat. Additionally, the locations where females spawn will define the probability that embryos will be dewatered during the incubation period in a regulated flow regime. We investigated the water flow, dewatering, and incubation mortality in Atlantic salmon and brown trout in natural nests over 19 years in the regulated Bjoreio River in western Norway. During the study period, different flow strategies were applied to mitigate the dewatering of incubating salmon and trout embryos. Average survival in nests sampled in late winter ranged from 54% to 92% among years and was significantly correlated with the minimum water flow occurring during the incubation period. Mortality was significantly higher in nests in shallow areas, reflecting nests exposed to dewatering. The results demonstrate a strong link between incubation mortality and managed flow regimes for river spawning salmonids. Using detailed information on the nest location and incubation mortality, we estimate minimum flow requirements for this river and demonstrate an approach to effectively mitigate the impact of river regulations on embryo survival in Atlantic salmon and brown trout.
Zeolitic Imidazolate Framework‐8 Triggers the Inhibition of Arginine Biosynthesis to Combat Methicillin‐Resistant Staphylococcus Aureus
Authors: Liu Bo , Yang Yue , Wu Haiyan , Wang Sihan , Tian Jijing , Dai Chongshan , Liu Tianlong 
Published: January 2023

AbstractThe self‐preservation and intelligent survival abilities of methicillin‐resistant Staphylococcus aureus (MRSA) result in the ineffective treatment of many antibiotics. Nano‐drug delivery systems have emerged as a new strategy to overcome MRSA infection. ZIF‐8 nanoparticles (ZIF‐8 NPs) exhibit good antibacterial activities, while its molecular mechanisms are largely elusive. In this study, the ZIF‐8 NPs are prepared using the room temperature solution reaction method. The values of minimum inhibitory concentration of ZIF‐8 NPs against Escherichia coli and MRSA isolates are 25 and 12.5 µg mL−1, respectively. Transcriptome and metabonomic analyses reveal that ZIF‐8 NPs could trigger the inhibition of arginine biosynthesis pathway and the production of ROS, which lead to dysfunctional tricarboxylic acid cycle and disruption of cell membrane integrity, eventually killing MRSA isolates. Moreover, ZIF‐8 NPs show desirable treatment and repair effects on mice model of MRSA isolates wound infected‐model. The results, for the first time, reveal that the inhibition of arginine biosynthesis mediates the production of ROS and energy metabolism dysfunction contributes to the antibacterial ability of ZIF‐8 NPs against MRSA. This study offers a new insight into ZIF‐8 NPs combating MRSA isolates.
Nanosecond Laser “Pulling” Patterning of Micro–Nano Structures on Zr‐Based Metallic Glass
Authors: Cui Mingming , Huang Hu , Zhang Lin , Yan Jiwang 
Published: January 2023

AbstractFlexible and controllable fabrication of micro–nano structures on metallic glasses (MGs) endow them with more functional applications, but it is still challenging due to the unique mechanical, physical, and chemical properties of MGs. In this study, inspired by a new physical phenomenon observed in the nanosecond laser–MG interaction (i.e., the surface structure is transformed from the normally observed microgroove into the micro–nano bulge at a critical peak laser power intensity), a nanosecond laser “pulling” method is proposed to pattern the MG surface. The formation mechanism and evolution of the micro–nano bulge are investigated in detail, and accordingly, various micro–nano structures including the unidirectional stripe, pillar, cross‐hatch patterns, “JLU”, circle, triangle, and square, are derived and created on the MG surface, which affects the surface optical diffraction. Overall, this study provides a highly flexible and controllable method to fabricate micro–nano structures on MGs.
Recent Progress in Metal Phosphorous Chalcogenides: Potential High‐Performance Electrocatalysts
Authors: Zhang Hao , Wei Tianran , Qiu Yuan , Zhang Shusheng , Liu Qian , Hu Guangzhi , Luo Jun , Liu Xijun 
Published: January 2023

AbstractSince the discovery of graphene, research on the family of 2D materials has been a thriving field. Metal phosphorous chalcogenides (MPX3) have attracted renewed attention due to their distinctive physical and chemical properties. The advantages of MPX3, such as tunable layered structures, unique electronic properties, thermodynamically appropriate band alignments and abundant catalytic active sites on the surface, make MPX3 material great potential in electrocatalysis. In this review, the applications of MPX3 electrocatalysts in recent years, including hydrogen evolution reaction, oxygen evolution reaction, and oxygen reduction reaction, are summarized. Structural regulation, chemical doping and multi‐material composite that are often effective and practical research methods to further optimize the catalytic properties of these materials, are introduced. Finally, the challenges and opportunities for electrocatalytic applications of MPX3 materials are discussed. This report aims to advance future efforts to develop MPX3 and related materials for electrocatalysis.