bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Advances in RNA‐Targeted Cancer Therapy
Authors: Li Miao , Zhu Jinfeng , Lv Zhengzhong , Qin Hongni , Wang Xiaoyan , Shi Haibin 
Published: November 2023

AbstractRibonucleic acid (RNA) plays a pivotal role in gene regulation and protein biosynthesis. Interfering the physiological function of key RNAs to induce cell apoptosis holds great promise for cancer treatment. Many RNA‐targeted anti‐cancer strategies have emerged continuously. Among them, RNA interference (RNAi) has been recognized as a promising therapeutic modality for various disease treatments. Nevertheless, the primary obstacle in siRNA delivery‐escaping the endosome and crossing the plasma membrane severely impedes its therapeutic potential. Thus far, a variety of nanosystems as well as carrier‐free bioconjugation for siRNA delivery have been developed and employed to enhance the drug delivery and anti‐tumor efficiency. Besides, the use of small molecules to target specific RNA structures and disrupt their function, along with the covalent modification of RNA, has also drawn tremendous attention recently owing to high therapeutic efficacy. In this review, we will provide an overview of recent progress in RNA‐targeted cancer therapy including various siRNA delivery strategies, RNA‐targeting small molecules, and newly emerged covalent RNA modification. Finally, challenges and future perspectives faced in this research field will be discussed.
Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study
Authors: Rajdev Lakshmi , Jackie Wang Chia‐Ching , Joshi Himanshu , Lensing Shelly , Lee Jeannette , Ramos Juan Carlos , Baiocchi Robert , Ratner Lee , Rubinstein Paul G. , Ambinder Richard , Henry David , Streicher Howard , Little Richard F. , Chiao Elizabeth , Dittmer Dirk P. , Einstein Mark H. , Cesarman Ethel , Mitsuyasu Ronald , Sparano Joseph A. ,   for the AIDS Malignancy Consortium
Published: November 2023

AbstractBackgroundAlthough immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer.MethodsPLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100–199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled.ResultsA total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose‐limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3–64.7). The median duration of response was 9.0 months overall and 12.5 months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load.ConclusionsNivolumab has a safety profile in PLWH similar to HIV‐negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function.Trial RegistrationClinicalTrials.gov Identifier: NCT02408861.
Generation of synthetic aortic valve stenosis geometries for in silico trials
Authors: Verstraeten Sabine , Hoeijmakers Martijn , Tonino Pim , Brüning Jan , Capelli Claudio , van de Vosse Frans , Huberts Wouter 
Published: November 2023

AbstractIn silico trials are a promising way to increase the efficiency of the development, and the time to market of cardiovascular implantable devices. The development of transcatheter aortic valve implantation (TAVI) devices, could benefit from in silico trials to overcome frequently occurring complications such as paravalvular leakage and conduction problems. To be able to perform in silico TAVI trials virtual cohorts of TAVI patients are required. In a virtual cohort, individual patients are represented by computer models that usually require patient‐specific aortic valve geometries. This study aimed to develop a virtual cohort generator that generates anatomically plausible, synthetic aortic valve stenosis geometries for in silico TAVI trials and allows for the selection of specific anatomical features that influence the occurrence of complications. To build the generator, a combination of non‐parametrical statistical shape modeling and sampling from a copula distribution was used. The developed virtual cohort generator successfully generated synthetic aortic valve stenosis geometries that are comparable with a real cohort, and therefore, are considered as being anatomically plausible. Furthermore, we were able to select specific anatomical features with a sensitivity of around 90%. The virtual cohort generator has the potential to be used by TAVI manufacturers to test their devices. Future work will involve including calcifications to the synthetic geometries, and applying high‐fidelity fluid–structure‐interaction models to perform in silico trials.
Heat Capacity Function, Enthalpy of Formation and Absolute Entropy of Mg(AlH4)2
Authors: Habermann Franziska , Wirth Anneliese , Burkmann Konrad , Störr Bianca , Seidel Jürgen , Gumeniuk Roman , Bohmhammel Klaus , Mertens Florian 
Published: November 2023

AbstractIn this investigation, we set out first to characterize the thermodynamics of Mg(AlH4)2 and secondly to use the determined data to reevaluate and update existing estimation procedures for heat capacity functions, enthalpies of formation and absolute entropies of alanates. Within this study, we report the heat capacity function of Mg(AlH4)2 in the temperature range from 2 K to 370 K and its enthalpy of formation and absolute entropy at 298.15 K, being
kJ mol−1 and 133.06 J (K mol)−1, respectively. Using these values, we updated and expanded methods for the estimation of thermodynamic data of alanates.
First Principle Investigations on Structural, Mechanical, Electronic, And Thermoelectric Properties of XCoP (XTi, Zr, Hf) Half Heusler Alloys for Energy Recovery Application
Authors: Klinton Brito K. , Shobana Priyanka D. , Srinivasan M. , Ramasamy P. 
Published: November 2023

AbstractXCoP (XTi, Zr, Hf) half Heusler alloys are investigated through density functional theory in stable non‐magnetic phase. The exchange‐correlation functional Generalized Gradient Approximation (GGA) is used to study these alloys. The equilibrium lattice constants and corresponding ground state energies of the studied alloys are calculated in stable γ‐phase. All these three reported alloys exhibit semiconducting behavior with corresponding bandgap values of 1.40, 1.29, and 1.38 eV for TiCoP, ZrCoP, and HfCoP, respectively. The studied alloys are mechanically stable and ductile in nature. The obtained thermoelectric figure of merit for p‐type TiCoP, ZrCoP and HfCoP are 0.5, 0.6, and 0.7 at 1200 K. Similarly, the figure of merit obtained for n‐type TiCoP, ZrCoP, HfCoP are 0.54, 0.37, and 0.31, respectively, at the same temperature. The investigated favorable transport properties of these alloys show that they are the potential candidates for waste heat energy harvesting application.
Dominance of the coral Pocillopora acuta around Phuket Island in the Andaman Sea, Thailand
Authors: Fiesinger Anna , Held Christoph , Schmidt Andrea L. , Putchim Lalita , Melzner Frank , Wall Marlene 
Published: November 2023

AbstractPocillopora damicornis (Linnaeus, 1758), a species complex, consists of several genetic lineages, some of which likely represent reproductively isolated species, including the species Pocillopora acuta Lamarck, 1816. Pocillopora acuta can exhibit similar morphological characteristics as P. damicornis, thus making it difficult to identify species‐level taxonomic units. To determine whether the P. damicornis‐like colonies on the reefs in the Andaman Sea (previously often identified as P. damicornis) consist of different species, we sampled individual colonies at five sites along a 50 km coastal stretch at Phuket Island and four island sites towards Krabi Province, Thailand. We sequenced 210 coral samples for the mitochondrial open reading frame and identified six distinct haplotypes, all belonging to P. acuta according to the literature. Recently, P. acuta was observed to efficiently recolonize heat‐damaged reefs in Thailand as well as globally, making it a potentially important coral species in future reefs. Specifically in the light of global change, this study underscores the importance of high‐resolution molecular species recognition, since taxonomic units are important factors for population genetic studies, and the latter are crucial for management and conservation efforts.
Ivabradine could not decrease mitral regurgitation triggered atrial fibrosis and fibrillation compared with carvedilol
Authors: Lee Wei‐Chieh , Lin Yu‐Wen , Shih Jhih‐Yuan , Chen Zhih‐Cherng , Wu Nan‐Chun , Chang Wei‐Ting 
Published: November 2023

AbstractBackgroundIvabradine, a medical treatment for heart failure (HF), reduces heart rate (HR) and prolongs diastolic perfusion time. It is frequently prescribed to patients with HF who have a suboptimal response or intolerance to beta‐blockers. Degenerative mitral regurgitation (MR) is a valvular heart disease often associated with the development of HF and atrial fibrillation (AF). However, studies comparing the effects of ivabradine and beta‐blockers on MR are lacking. Therefore, this study aimed to explore the potential therapeutic effects of ivabradine and carvedilol on MR using a rat model.Methods and resultsUsing a novel echo‐guided mini‐invasive surgery, MR was created in 12‐weeks‐old Sprague–Dawley rats. After 2 weeks, the rats were randomized to receive either ivabradine or carvedilol for 4 weeks. Echocardiography was performed at baseline and at two‐week intervals. Following haemodynamic studies, postmortem tissues were analysed. Notably, the MR‐induced myocardial dysfunction did not improve considerably after treatment with ivabradine or carvedilol. However, in haemodynamic studies, pharmacological therapies, particularly carvedilol, mitigated MR‐induced chamber dilatation (end‐systolic volume and end‐diastolic volume; MR vs. MR + Carvedilol; P < 0.05) and decreased compliance (end‐systolic pressure–volume relationship; MR vs. MR + Carvedilol; P < 0.05). Compared with ivabradine, a shorter duration (MR vs. MR + Carvedilol; P < 0.05) and reduced inducibility (MR vs. MR + Carvedilol and MR vs. MR + Ivabradine; P < 0.05) of AF were observed in MR rats treated with carvedilol. Similarly, reduced cardiac fibrosis and apoptosis were observed in the MR rat model in the treatment groups, especially in those treated with carvedilol (MR vs. MR + Carvedilol; P < 0.01).ConclusionsAlthough both ivabradine and carvedilol, at least in part, mitigated MR‐induced chamber dilatation and decreased compliance, carvedilol had a better effect on reversing MR‐induced cardiac fibrosis, apoptosis, and arrhythmogenesis than ivabradine. When compared with Ivabradine, MR rats treated with carvedilol exhibited a shorter duration and reduced inducibility of AF, thus providing more effective suppression of HCN4. Further investigations are required to validate our findings.
Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N‐ethyl‐N‐nitrosourea
Authors: Judice Stephen A. , Sussman Hillary E. , Walker Dale M. , O'Neill J. Patrick , Albertini Richard J. , Walker Vernon E. 
Published: November 2023

AbstractMutations in T lymphocytes (T‐cells) are informative quantitative markers for environmental mutagen exposures, but risk extrapolations from rodent models to humans also require an understanding of how T‐cell development and proliferation kinetics impact mutagenic outcomes. Rodent studies have shown that patterns in chemical‐induced mutations in the hypoxanthine‐guanine phosphoribosyltransferase (Hprt) gene of T‐cells differ between lymphoid organs. The current work was performed to obtain knowledge of the relationships between maturation events during T‐cell development and changes in chemical‐induced mutant frequencies over time in differing immune compartments of a mouse model. A novel reverse transcriptase‐polymerase chain reaction based method was developed to determine the specific T‐cell receptor beta (Tcrb) gene mRNA expressed in mouse T‐cell isolates, enabling sequence analysis of the PCR product that then identifies the specific hypervariable CDR3 junctional region of the expressed Tcrb gene for individual isolates. Characterization of spontaneous Hprt mutant isolates from the thymus, spleen, and lymph nodes of control mice for their Tcrb gene expression found evidence of in vivo clonal amplifications of Hprt mutants and their trafficking between tissues in the same animal. Concurrent analyses of Hprt mutations and Tcrb gene rearrangements in different lymphoid tissues of control versus N‐ethyl‐N‐nitrosourea‐exposed mice permitted elucidation of the localization and timing of mutational events in T‐cells, establishing that mutagenesis occurs primarily in the pre‐rearrangement replicative period in pre‐thymic/thymic populations. These findings demonstrate that chemical‐induced mutagenic burden is determined by the combination of mutagenesis and T‐cell clonal expansion, processes with roles in immune function and in the pathogenesis of autoimmune disease and cancer.
Late Quaternary tectono‐geomorphological investigations of Zanskar Basin, NW Himalaya, India, using geospatial techniques
Authors: Irfan Mohammad , Bali Bikram Singh , Afzal Ahsan 
Published: November 2023

AbstractGeospatial techniques play a crucial role in geomorphic studies, particularly in the challenging terrains like mountainous regions, inaccessible areas and densely vegetated landscapes, where geomorphic features cannot be recorded easily. Tectono‐geomorphologic observations provide important clues regarding the landscape evolution, morpho‐dynamics and ongoing tectonism of the region. The present study has been carried out in the Zanskar Basin (ZB), located to the south of the Indus Tsangpo Suture Zone (ITSZ), in the hinterland of the NW Himalaya. This study has been carried out to assess and evaluate active tectonics by employing tectono‐geomorphic analysis, dynamics in drainage networks, geomorphological field observations and the Geographic Information System (GIS) environment. High‐resolution satellite images, topographic maps and the Shuttle Radar Topography Mission (SRTM) Digital Elevation Model (DEM) were used to generate primary data sets, which were corroborated with field investigations for valid inferences. The geometry of the ZB suggests that continuous tectonic activity exerts first‐order control on the overall shape, size and structure of the ZB. This first‐order response is clearly reflected in the landforms modified by tectonic processes, namely, linear mountain fronts, elongated shape and tilting of the basin, braided and meandering river courses and lower stream length gradient index values in hard rock terrain. The ZB exhibits several eye‐catching geomorphic features, such as well‐defined triangular facets with wide base lengths and wine‐glass valleys with small outlets along the footwall block of the Zanskar Shear Zone/South Tibetan Detachment System (ZSZ/STDS), as well as the presence of wind gaps, water gaps, bedrock incision, incised and entrenched valleys, narrow gorges and a high incision rate inferring active tectonics and recent uplift in the region. In addition, the existence of uplifted river terraces, as well as the stepped morphology of fans and strath terraces, suggests that the region is experiencing recent activity and ongoing tectonic uplift. These modified geomorphic characteristics suggest that the hinterland, which is part of the NW Himalaya, is tectonically quite active and has experienced a differential rate of tectonics during its evolution. The quantified geomorphic indices and their relations with the tectonics, climate and erosion activity infer that the basin geometry is mostly controlled by the ZSZ/STDS that dips 20°–70° NE, the south‐dipping Zanskar Counter Thrust (ZCT) and other local tectonic elements like the Choksti Thrust (CT), Stondgey Thrust, Zangla Thrust and tectonic structures. The synergised results of quantified geomorphic indices and tectono‐geomorphic evidence in the ZB strongly indicate that both the past and ongoing tectonism have significantly shaped and modified geomorphology of the ZB.
Punctuated equilibrium at 50: Anything there for evolutionary anthropology? Yes; definitely
Authors: O'Brien Michael J. , Valverde Sergi , Duran‐Nebreda Salva , Vidiella Blai , Bentley R. Alexander 
Published: November 2023

AbstractThe theory of punctuated equilibrium (PE) was developed a little over 50 years ago to explain long‐term, large‐scale appearance and disappearance of species in the fossil record. A theory designed specifically for that purpose cannot be expected, out of the box, to be directly applicable to biocultural evolution, but in revised form, PE offers a promising approach to incorporating not only a wealth of recent empirical research on genetic, linguistic, and technological evolution but also large databases that document human biological and cultural diversity across time and space. Here we isolate the fundamental components of PE and propose which pieces, when reassembled or renamed, can be highly useful in evolutionary anthropology, especially as humanity faces abrupt ecological challenges on an increasingly larger scale.
Understanding the improvement mechanism of plasma etching treatment on oxygen reduction reaction catalysts
Authors: Rao Peng , Yu Yanhui , Wang Shaolei , Zhou Yu , Wu Xiao , Li Ke , Qi Anyuan , Deng Peilin , Cheng Yonggang , Li Jing , Miao Zhengpei , Tian Xinlong 
Published: November 2023

AbstractPlasma etching treatment is an effective strategy to improve the electrocatalytic activity, but the improvement mechanism is still unclear. In this work, a nitrogen‐doped carbon nanotube‐encased iron nanoparticles (Fe@NCNT) catalyst is synthesized as the model catalyst, followed by plasma etching treatment with different parameters. The electrocatalytic activity improvement mechanism of the plasma etching treatment is revealed by combining the physicochemical characterizations and electrochemical results. As a result, highly active metal–nitrogen species introduced by nitrogen plasma etching treatment are recognized as the main contribution to the improved electrocatalytic activity, and the defects induced by plasma etching treatment also contribute to the improvement of the electrocatalytic activity. In addition, the prepared catalyst also demonstrates superior ORR activity and stability than the commercial Pt/C catalyst.
An immersed boundary method‐discrete unified gas kinetic scheme simulation of particle‐laden turbulent channel flow on a nonuniform orthogonal mesh
Authors: Karzhaubayev Kairzhan , Wang Lian‐Ping , Peng Cheng , Zhakebayev Dauren 
Published: November 2023

AbstractParticle‐resolved simulations of turbulent particle‐laden flows provide a powerful research tool to explore detailed flow physics at all scales. However, efficient particle‐resolved simulations for wall‐bounded turbulent particle‐laden flows remain a challenging task. In this article, we develop a simulation approach for a turbulent channel flow laden with finite‐size particles on a nonuniform mesh by combining the discrete unified gas kinetic scheme (DUGKS) and the immersed boundary method (IBM). The standard discrete delta function was modified according to reproducible kernel particle method to take into account mesh non‐uniformity and correctly conserve force moments. Simulation results based on uniform and nonuniform meshes are compared to validate and examine the accuracy of the nonuniform mesh DUGKS‐IBM. Finally, the computational performance of the nonuniform mesh DUGKS‐IBM is discussed.
Business applications and state‐level stock market realized volatility: A forecasting experiment
Authors: Bonato Matteo , Cepni Oguzhan , Gupta Rangan , Pierdzioch Christian 
Published: November 2023

AbstractWe analyze the predictive value of (the surprise component of) state‐level business applications, as a proxy of local investor sentiment, for the state‐level realized US stock‐market volatility. We use high‐frequency data for the period from September 2011 to October 2021 to compute realized volatility. Using an extended version of the popular heterogeneous autoregressive realized volatility model and accounting for the possibility that users of forecasts have an asymmetric loss function, we show that business applications tend to have predictive value for realized state‐level stock‐market volatility, as well as for upside (“good”) and downside (“bad”) realized volatility, for users of forecasts who suffer a larger loss from an underprediction of realized volatility than from an overprediction of the same (absolute) seize, after controlling for realized moments (realized skewness, realized kurtosis, realized jumps, and realized tail risks). We also highlight that the COVID‐19 period is a major driver of our empirical results.
Alterations in the gut microbiota of toddlers with cow milk protein allergy treated with a partially hydrolyzed formula containing synbiotics: A nonrandomized controlled interventional study
Authors: Qian Mengyao , Liu Wei , Feng Xueying , Yang Zhaochuan , Liu Xiaomei , Ma Liang , Shan Yanchun , Ran Ni , Yi Mingji , Wei Changlong , Lu Chenyang , Wang Yanxia 
Published: November 2023

AbstractFormulas containing intact cow milk protein are appropriate alternatives when human milk (HM) is not feasible. However, for babies with a physician‐diagnosed cow milk protein allergy (CMPA), hydrolyzed formulas are needed. We conducted a 3‐month, open‐label, nonrandomized concurrent controlled trial (ChiCTR2100046909) between June 2021 and October 2022 in Qingdao City, China. In this study, CMPA toddlers were fed with a partially hydrolyzed formula containing synbiotics (pHF, n = 43) and compared with healthy toddlers fed a regular intact protein formula (IF, n = 45) or HM (n = 21). The primary endpoint was weight gain; the secondary endpoints were changes in body length and head circumference of both CMPA and healthy toddlers after 3‐month feeding; and the exploratory outcomes were changes in gut microbiota composition. After 3 months, there were no significant group differences for length‐for‐age, weight‐for‐age, or head circumference‐for‐age Z scores. In the gut microbiota, pHF feeding increased its richness and diversity, similar to those of IF‐fed and HM‐fed healthy toddlers. Compared with healthy toddlers, the toddlers with CMPA showed an increased abundance of phylum Bacteroidota, Firmicutes, class Clostridia, and Bacteroidia, and a decreased abundance of class Negativicutes, while pHF feeding partly eliminated these original differences. Moreover, pHF feeding increased the abundance of short‐chain fatty acid producers. Our data suggested that this pHF partly simulated the beneficial effects of HM and shifted the gut microbiota of toddlers with CMPA toward that of healthy individuals. In conclusion, this synbiotic‐containing pHF might be an appropriate alternative for toddlers with CMPA.