bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical exchange saturation transfer MRI detects myelin changes in cuprizone mouse model at 3T
Authors: Chen Zilin , Huang Jianpan , Lai Joseph H. C. , Tse Kai‐Hei , Xu Jiadi , Chan Kannie W. Y.
Published: March 2023

Chemical exchange saturation transfer (CEST) sensitively detects molecular alterations in the brain, such as relayed nuclear Overhauser effect (rNOE) CEST contrast at −3.5 ppm representing aliphatic protons in both lipids and proteins, and CEST contrast at 3.5 ppm correlating with amide proton in proteins. Myelin is rich in lipids and proteins, and therefore CEST can be explored as a biomarker for myelin pathology, which could contribute to the diagnosis and prognosis of multiple sclerosis (MS). In the current study, we investigate the specificity of aliphatic rNOE and the amide pool in myelin detection using the cuprizone (CPZ) mouse model, which recapitulates the demyelination and remyelination of MS. In this study, preclinical 3T MRI was performed in 19 male C57BL/6 mice. Mice in the normal control (NC) group (n = 9) were fed a normal diet for the whole course, while mice in the CPZ group (n = 10) were fed with CPZ for 10 weeks, followed by 4 weeks with a normal diet. The CEST contrast of rNOE (−3.5 ppm) and amide (3.5 ppm) in brain regions of the corpus callosum (CC) and the caudate putamen were compared. Statistical differences between the groups were calculated using two‐way ANOVA. We observed significantly decreased rNOE (NC: 4.85% ± 0.09%/s vs. CPZ: 3.88% ± 0.18%/s, p = 0.007) and amide pool (NC: 3.20% ± 0.10%/s vs. CPZ: 2.46% ± 0.16%/s, p = 0.02) in the CC after 8 weeks on CPZ diet (p < 0.05). Moreover, the rNOE in the CPZ group recovered to a level comparable with the NC group at week 14 (p = 0.39), while amide remained at a level as low as that for the NC group (p = 0.051). Significant rNOE and amide changes, validated by immunohistochemistry results for demyelination and remyelination, demonstrate the huge potential of CEST for revealing myelin pathology, which has implications for MS identification at the clinical field strength of 3T.
Correction of B0 and linear eddy currents: Impact on morphological and quantitative ultrashort echo time double echo steady state (UTE‐DESS) imaging
Authors: Jang Hyungseok , Athertya Jiyo S. , Jerban Saeed , Ma Yajun , Lombardi Alecio F. , Chung Christine B. , Chang Eric Y. , Du Jiang
Published: March 2023

The purpose of the current study was to investigate the effects of B0 and linear eddy currents on ultrashort echo time double echo steady state (UTE‐DESS) imaging and to determine whether eddy current correction (ECC) effectively resolves imaging artifacts caused by eddy currents. 3D UTE‐DESS sequences based on either projection radial or spiral cones trajectories were implemented on a 3‐T clinical MR scanner. An off‐isocentered thin‐slice excitation approach was used to measure eddy currents. The measurements were repeated four times using two sets of tested gradient waveforms with opposite polarities and two different slice locations to measure B0 and linear eddy currents simultaneously. Computer simulation was performed to investigate the eddy current effect. Finally, a phantom experiment, an ex vivo experiment with human synovium and ankle samples, and an in vivo experiment with human knee joints, were performed to demonstrate the effects of eddy currents and ECC in UTE‐DESS imaging. In a computer simulation, the two echoes (S+ and S‐) in UTE‐DESS imaging exhibited strong distortion at different orientations in the presence of B0 and linear eddy currents, resulting in both image degradation as well as misalignment of pixel location between the two echoes. The same phenomenon was observed in the phantom, ex vivo, and in vivo experiments, where the presence of eddy currents degraded S+, S‐, echo subtraction images, and T2 maps. The implementation of ECC dramatically improved both the image quality and image registration between the S+ and S‐ echoes. It was concluded that ECC is crucial for reliable morphological and quantitative UTE‐DESS imaging.
Impact of transformational leadership on the person–organization fit of Chinese nurses: The moderating effect of emotional intelligence
Authors: Liu Nan , Wang Lin , Yin Jiemei
Published: March 2023

Aims

To explore the relationships between transformational leadership and person–organization fit, as well as to test the moderating effects of emotional intelligence.

Design

A descriptive cross‐sectional study design was used to conduct an online questionnaire survey among 326 nurses in Chinese hospitals between March and June 2022.

Methods

Transformational leadership, person–organization fit and emotional intelligence were measured using the Person–Organization Fit Scale, Transformational Leadership Questionnaire and Emotional Intelligence Scale. Hierarchical multiple linear regression models and simple slope analyses were used.

Results

Transformational leadership had a significant positive impact on person–organization fit. Furthermore, emotional intelligence had a conditional moderating effect on the relationship between transformational leadership and nurses’ person–organization fit. Under a high level of emotional intelligence, transformational leadership had a stronger positive effect on person–organization fit, while under a low level of emotional intelligence, the relationship between the two was not significant.

Conclusion

Transformational leadership has a positive predictive effect on person–organization fit, but this positive predictive effect is driven by conditional effect. The emotional intelligence of nurses plays a moderating role between them.
Saliva interleukin‐17 levels are decreased in patients with severe oral candidiasis
Authors: Ohga Noritaka , Sakata Ken‐ichiro , Hato Hiroyuki , Asaka Takuya , Sato Jun , Kitagawa Yoshimasa
Published: March 2023

Aim

Oral candidiasis is often complicated by other oral diseases, and long‐term follow‐up is essential because oral candidiasis often recurs. Failure to provide appropriate treatment for oral candidiasis will lead to persistence of the fungal cell in the oral cavity and increase the risk of severe oral candidiasis and recurrence of infection. We hypothesized that various inflammatory cytokines are involved in the pathogenesis and progression of oral candidiasis.

Methods

We measured cytokine levels in the saliva samples of candida‐negative and candida‐positive patients.

Results

Saliva interleukin (IL)‐17 concentrations were significantly lower in patients with oral candidiasis than in healthy individuals. Saliva IL‐17A concentrations were significantly lower in candida‐positive patients than in candida‐negative patients. However, the levels of tumor necrosis factor‐α, IL‐2, IL‐4, IL‐5, and IL‐6 showed no significant differences between the two groups of patients.

Conclusion

Saliva IL‐17A levels were significantly lower in patients with severe oral candidiasis, providing a potentially highly useful indicator for the pathogenesis and progression of severe oral candidiasis.
Lead(II) sulfide micro‐crystals doped graphene nanosheets dispersed thermoplastic and multifunctional poly(benzoxazines) cured epoxy resin nanocomposites for medium temperature proton exchange membrane fuel cell applications
Authors: Kesava Munusamy , Saravanan Velautham , Krishnan Srinivasan , Dinakaran Kannaiyan
Published: March 2023

The amphiphilic polybenzoxazines‐co‐epoxy membrane (POPBOs/PTGP) was created by thermally cross‐linking the multi‐functional octylamine‐based benzoxazine monomer (OPBOs) with synthesized 1,3,5‐tris(oxiran‐2‐yl methoxy)benzene epoxy monomer (TGP). Fourier transform infrared spectroscopy, powder x‐ray diffraction, scanning electron microscopy, and high‐resolution transmission electron microscopy were used to investigate the functionality, crystallinity, and morphology of microcrystal lead(II) sulfide (PbS)/graphene nanosheets (mPbS/GNs). The bare POPBOs/PTGP and different amounts of mPbS/GNs dispersed polymer nanocomposites (PNCs) were obtained from the thermal curing process. Following that, these PNCs were used in medium‐temperature proton exchange membrane fuel cells. The water uptake, ion exchange capacity (IEC), swelling ratio, oxidative stability, and proton conductivity (PC) of bare and loaded mPbS/GNs hybrid nanostructures on POPBOs/PTGP composite membranes were determined. 3 wt% mPbS/GNs distributed with POPBOs/PTGP PNCs exhibit the highest IEC value of 3.61 mmol/g−1 at room temperature, and a PC value of around 6.33 × 10−2 S/cm−1 at 120°C was obtained for the POPBOs/PTGP PNCs. In addition, the single‐cell electrode analysis of the 3 wt% mPbS/GNs‐filled POPBOs/PTGP amphiphilic PNCs showed excellent peak power density and open circuit voltage values of 0.897 W cm−2 and 0.97 V at 120°C.
Targeted muscle reinnervation and regenerative peripheral nerve interfaces for pain prophylaxis and treatment: A systematic review
Authors: Mauch Jaclyn T. , Kao Dennis S. , Friedly Janna L. , Liu Yusha
Published: March 2023

Objective

Nerve pain frequently develops following amputations and peripheral nerve injuries. Two innovative surgical techniques, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI), are rapidly gaining popularity as alternatives to traditional nerve management, but their effectiveness is unclear.

Literature Survey

A review of literature pertaining to TMR and RPNI pain results was conducted. PubMed and MEDLINE electronic databases were queried.

Methodology

Studies were included if pain outcomes were assessed after TMR or RPNI in the upper or lower extremity, both for prophylaxis performed at the time of amputation and for treatment of postamputation pain. Data were extracted for evaluation.

Synthesis

Seventeen studies were included, with 14 evaluating TMR (366 patients) and three evaluating RPNI (75 patients). Of these, one study was a randomized controlled trial. Nine studies had a mean follow‐up time of at least 1 year (range 4–27.6 months). For pain treatment, TMR and RPNI improved neuroma pain in 75%–100% of patients and phantom limb pain in 45%–80% of patients, averaging a 2.4–6.2‐point reduction in pain scores on the numeric rating scale postoperatively. When TMR or RPNI was performed prophylactically, many patients reported no neuroma pain (48%–100%) or phantom limb pain (45%–87%) at time of follow‐up. Six TMR studies reported Patient‐Reported Outcomes Measurement Information System (PROMIS) scores assessing pain intensity, behavior, and interference, which consistently showed a benefit for all measures. Complication rates ranged from 13% to 31%, most frequently delayed wound healing.

Conclusions

Both TMR and RPNI may be beneficial for preventing and treating pain originating from peripheral nerve dysfunction compared to traditional techniques. Randomized trials with longer term follow‐up are needed to directly compare the effectiveness of TMR and RPNI with traditional nerve management techniques.
Water activated by the atmospheric air streamer‐to‐spark transition discharge over its surface
Authors: Zhao Zhiguo , Liu Guoqiang , Li Guofeng , Ni Weiyuan , Liu Dongping
Published: March 2023

Here, we report on the optimized design for the needle‐to‐plane electrode geometry to generate the atmospheric air streamer‐to‐spark transition discharge over the surface of the water at the pulsed voltage of ±30 kV. This design contributes to an increase in the electric field at the head of air surface streamers during their propagation, which eventually evolves into a spark over water. The length of streamer‐to‐spark transition discharge is up to 150 mm, which is affected by the conductivity of water, the electrode polarity, and the horizontal distance between the high‐voltage pin electrode and the grounded plane electrode. Water is quickly activated by the streamer‐to‐spark transition discharge, which can be attributed to the dissolution of plasma‐generated species including long‐lived and short‐lived reactive species in the gas phase. Compared to the negative streamer‐to‐spark transition discharge, the positive one is more effective in increasing the biological reactivity of water. Analysis indicates that the positive ions in the positive surface streamers can dissolve in water, which contributes to the formation of reactive species in water, thus an increase in the biological reactivity of water.
Plasma activation mechanisms governed by specific energy input: Potential and perspectives
Authors: Hegemann Dirk
Published: March 2023

In a low‐temperature plasma, the electrons pick up energy from the electric field in collisions with atoms and molecules, gaining high kinetic energy that must be sufficient for ionizing reactions to sustain the plasma. For molecular gases, an average energy per heavy gas particle is thus available in the plasma, the specific energy input, yielding plasma activation by inelastic collisions. Following a distribution law, the probability for the activation mechanism can be described by an Arrhenius‐like equation. The potential of this approach is demonstrated on the basis of plasma polymerization and plasma CO2conversion. For perspective, energy efficiencies are discussed as a function of conversion indicating the optimum that can be achieved by electron impact activation compared with additional ways of energy transfer, probably depending on certain constraints.
Controllable Preparation of Nanosized LiMnPO4/C with Rod‐Like Morphology by Hydrothermal Method with Excellent Electrochemical Performance
Authors: Zhang Da‐Jun , Luo Shao‐Hua , Zhang Jun
Published: March 2023

The nanosized rod‐like LiMnPO4/C cathode materials have successfully in situ synthesized on the surface of flaky structure MnPO4·H2O self‐sacrificing template by the hydrothermal method. The crystal microstructure, micro shape, and electrochemical parameters of LiMnPO4/C are comprehensively studied by XRD, SEM, TEM, and electrochemical measurement methods. The physical and chemical properties analysis confirms that the vinyl acetate solution (VAc‐H2O) with a proper molar ratio is beneficial to generate orthorhombic olivine structure LiMnPO4 with microporous structure and nanorod‐shaped morphology. The electrochemical measurement results indicate that LMP‐X1‐AA sample delivers an initial discharge capacity of 148.1 mAh g−1 at 0.05 C, the capacity retention rate still maintains at 89.2% after 200 cycles. As the discharge rate increases to 1 C, the discharge capacity still remains at 133.4 mAh g−1. The results indicate that the synergistic effect of nanosized rod‐like morphology and conductive carbon coating is beneficial to improving the lithium ions diffusivity and electrochemical properties of LiMnPO4 materials.
Ca2+ ions facilitate the organization of the Annexin A2/S100A10 heterotetramer
Authors: Lindsay Samuel , Bartolotti Libero , Li Yumin
Published: March 2023

Annexin A2 (A2) is a member of the Annexin family, which contains Ca2+‐regulated phospholipid‐binding proteins. Annexins associate with S100 proteins to form heterotetramers. The A2/S100A10 heterotetramer (A2t) is the most extensively studied of these heterotetramers. It induces membrane microdomain formation, causes membrane budding, and facilitates proliferation of some cancers. In this work, the first molecular dynamics (MD) study on the complete A2t of 868 amino acids was performed. MD trajectories of more than 600 ns each were generated for complete A2t complexes with and without Ca2+ ions. The outward extension of membrane‐binding residues A2‐K279 and A2‐K281 was shown to be inhibited in the absence of Ca2+ as they were captured by Ca2+‐binding residue D322. F‐actin binding residue A2‐D339 was observed to occupy either an exposed or buried state in the absence of Ca2+, while it only occupied the buried state in the presence of Ca2+. The observed motions of the A2t subunits are highly organized with a strongly correlated central region which is negatively correlated with the periphery of the complex. The central region contains the S100A10 (p11) dimer, A2‐N, and A2‐I, while the periphery contains A2‐II, A2‐III, and A2‐IV. Novel interactions between A2 and p11 were identified. A2 residues outside of A2‐N (K80, R77, E82, and R145) had strong interactions with p11. Residue R145 of A2 may have a significant effect on the dynamics of the system, with its interaction resulting in asymmetric motions of A2. The presented results provide novel insights to inform future experimental studies.
Coevolutionary analysis of Forkhead box protein P3 and its physical binary interactors E3 ubiquitin‐protein ligase CHIP, Zfp‐90, and nuclear receptor ROR‐α
Authors: D'Amico Fabio , Skarmoutsou Evangelia , Libra Massimo
Published: March 2023

Forkhead box protein P3 (FOXP3) is known to orchestrate the development and maintenance of T regulatory cells, a cell population specialized in immune suppression and peripheral immune tolerance. FOXP3 activity is fine‐tuned through its interaction with several protein‐binding partners. By using IntAct database, we retrieved three physical binary interactors: E3 ubiquitin‐protein ligase CHIP, Zfp‐90, and nuclear receptor ROR‐α. Coevolution clusters between FOXP3 and its interactors were identified with the use of iBIS2 algorithm, the iterative version of BIS/BIS2. Most of the coevolving pairs came from some species of monotremes and marsupials, as well as from a group of bats, thus suggesting that protein interactions of FOXP3 with its partners may be changed and/or modulated during mammalian speciation. Furthermore, our analysis would suggest the occurrence of a determinant role of FOXP3 in suppressing pregnancy alloreactions in placental mammals. Similarly, FOXP3, through its interaction with different protein interaction mechanisms, would explain the unique control of inflammatory response to infections in bats. By identifying several inter‐protein clusters between the different protein pairs, our findings may provide a guide for new therapeutic approaches to modulate T regulatory suppression and/or enhance immune tolerance.
Relationship between factor VIII levels and bleeding for rFVIII‐SingleChain in severe hemophilia A: A repeated time‐to‐event analysis
Authors: Bukkems Laura H. , Jönsson Siv , Cnossen Marjon H. , Karlsson Mats O. , Mathôt Ron A. A. ,   the OPTI‐CLOT studies and the SYMPHONY consortium
Published: March 2023

Publications on the exposure‐effect relationships of factor concentrates for hemophilia treatment are limited, whereas such analyses give insight on treatment efficacy. Our objective was to examine the relationship between the dose, factor VIII (FVIII) levels and bleeding for rFVIII‐SingleChain (lonoctocog alfa, Afstyla). Data from persons with severe hemophilia A on rFVIII‐SingleChain prophylaxis from three clinical trials were combined. The published rFVIII‐SingleChain population pharmacokinetic (PK) model was evaluated and expanded. The probability of bleeding was described with a parametric repeated time‐to‐event (RTTE) model. Data included 2080 bleeds, 2545 chromogenic stage assay, and 3052 one‐stage assay FVIII levels from 241 persons (median age 19 years) followed for median 1090 days. The majority of the bleeds occurred in joints (65%) and the main bleeding reason was trauma (44%). The probability of bleeding decreased during follow‐up and a FVIII level of 8.9 IU/dL (95% confidence interval: 6.9–10.9) decreased the bleeding hazard by 50% compared to a situation without FVIII in plasma. Variability in bleeding hazard between persons with similar FVIII levels was large, and the pre‐study annual bleeding rate explained part of this variability. When a FVIII trough level of 1 or 3 IU/dL is targeted during prophylaxis, simulations predicted two (90% prediction interval [PI]: 0–17) or one (90% PI: 0–11) bleeds per year, respectively. In conclusion, the developed PK‐RTTE model adequately described the relationship between dose, FVIII levels and bleeds for rFVIII‐SingleChain. The obtained estimates were in agreement with those published for the FVIII concentrates BAY 81‐8973 (octocog alfa) and BAY 94‐9027 (damoctocog alfa pegol), indicating similar efficacy to reduce bleeding.
An intelligent indicator for warning of short‐term high CO2 damage to garlic scapes
Authors: Hu Hanyan , Bai Yahui , Li Haichuan , Li Keyi , Hu Yunfeng , Chen Junran
Published: March 2023

A pH‐sensitive indicator film based on CO2 change was prepared by mixing a water‐soluble indicator (bromocresol green and chlorophenol red sodium) with a film‐forming carrier (methyl cellulose (MC), polyvinyl alcohol (PVA) and glycerin). The innovation is not only to analyse the response characteristics of the colorimetric indicator to CO2, but also to optimise the preparation parameters of the film. The response experiment showed that CO2 dissolved rapidly in water and the pH value remained unchanged after reaching equilibrium, with a one‐to‐one relationship between pH and CO2 concentration. As the CO2 concentration rose from 18% to 20%, the colour of the indicator film changed from blue–purple to yellow–green in a different colour space, allowing the change to be easily distinguished by the naked eye. The optimum parameters (13 g‧L−1 MC, 5 g‧L−1 PVA, 10 g‧L−1 glycerin, 15 ml‧L−1 indicator and a casting amount of 0.2 ml‧cm−2) for preparing the intelligent film were optimised based on puncture strength (PS), water vapour permeability (WVP), water solubility (WS), casting time (CT) and colour performance. Evaluating this application using garlic scapes stored at 15°C revealed that the total colour difference was 34.23 as the CO2 concentration increased from 18.7% to 20.4%, and the colour of the indicator film changed from blue–purple to yellow–green. Therefore, the intelligent packaging film was able to effectively provide a warning when garlic scapes were exposed to damage from a short‐term high CO2 level.
Analog ensemble data assimilation in a quasigeostrophic coupled model
Authors: Grooms Ian , Renaud Camille , Stanley Zofia , Yang L. Minah
Published: March 2023

The ensemble forecast dominates the computational cost of many data assimilation methods, especially for high‐resolution and coupled models. In situations where the cost is prohibitive, one can either use a lower‐cost model or a lower‐cost data assimilation method, or both. Ensemble optimal interpolation (EnOI) is a classical example of a lower‐cost ensemble data assimilation method that replaces the ensemble forecast with a single forecast and then constructs an ensemble about this single forecast by adding perturbations drawn from climatology. This research develops lower‐cost ensemble data assimilation methods that add perturbations to a single forecast, where the perturbations are obtained from analogs of the single model forecast. These analogs can either be found from a catalog of model states, constructed using linear combinations of model states from a catalog, or constructed using generative machine‐learning methods. Four analog ensemble data assimilation methods, including two new ones, are compared with EnOI in the context of a coupled model of intermediate complexity: Q‐GCM. Depending on the method and on the physical variable, analog methods can be up to 40% more accurate than EnOI.
Supervised machine learning to estimate instabilities in chaotic systems: Estimation of local Lyapunov exponents
Authors: Ayers Daniel , Lau Jack , Amezcua Javier , Carrassi Alberto , Ojha Varun
Published: March 2023

In chaotic dynamical systems such as the weather, prediction errors grow faster in some situations than in others. Real‐time knowledge about the error growth could enable strategies to adjust the modelling and forecasting infrastructure on the fly to increase accuracy and/or reduce computation time. For example, one could change the ensemble size, the distribution and type of target observations, and so forth. Local Lyapunov exponents are known indicators of the rate at which very small prediction errors grow over a finite time interval. However, their computation is very expensive: it requires maintaining and evolving a tangent linear model, orthogonalisation algorithms and storing large matrices. In this feasibility study, we investigate the accuracy of supervised machine learning in estimating the current local Lyapunov exponents, from input of current and recent time steps of the system trajectory, as an alternative to the classical method. Thus machine learning is not used here to emulate a physical model or some of its components, but “nonintrusively” as a complementary tool. We test four popular supervised learning algorithms: regression trees, multilayer perceptrons, convolutional neural networks, and long short‐term memory networks. Experiments are conducted on two low‐dimensional chaotic systems of ordinary differential equations, the Rössler and Lorenz 63 models. We find that on average the machine learning algorithms predict the stable local Lyapunov exponent accurately, the unstable exponent reasonably accurately, and the neutral exponent only somewhat accurately. We show that greater prediction accuracy is associated with local homogeneity of the local Lyapunov exponents on the system attractor. Importantly, the situations in which (forecast) errors grow fastest are not necessarily the same as those in which it is more difficult to predict local Lyapunov exponents with machine learning.
The rare case of Hurricane Catarina (2004) over the South Atlantic Ocean: The origin of its precipitation through a Lagrangian approach
Authors: Pérez‐Alarcón Albenis , Coll‐Hidalgo Patricia , Fernández‐Alvarez José C. , Trigo Ricardo M. , Nieto Raquel , Gimeno Luis
Published: March 2023

Tropical cyclones (TCs) are extremely rare over the South Atlantic Ocean (SATL) due to predominantly unfavourable conditions, that is, cool sea‐surface temperature and strong vertical wind shear. Nevertheless, unusual conditions over SATL associated with a blocking system promoted the formation of Hurricane Catarina from an extratropical precursor in late March 2004, which produced heavy rainfall over the states of Santa Catarina and the Rio Grande do Sul in south Brazil. This work identifies the moisture sources for the precipitation produced by Catarina along its 6‐hourly trajectory, through a Lagrangian moisture‐tracking method. We extracted the pathways of precipitating air parcels within the cyclone's outer radius from the global outputs of the FLEXPART model forced with the ERA‐Interim reanalysis. Our findings revealed the terrestrial source in south‐southeastern Brazil (SEB) and the oceanic source limited by the box between 20‐40°S and 30–50°W over SATL (WSATL) as the principal moisture sources, with the overall support of ∼27% and ∼66%, respectively. However, their contribution varied according to the development phase of Catarina. While the moisture uptake from SEB decreased from ∼75% during the extratropical phase to ∼8% during the hybrid stage, the moisture contribution from WSATL notable increased from ∼20% to 87%, respectively. Likewise, the contributions from SEB and WSATL during the tropical phase of the cyclone accounted for ∼13% and ∼85%, respectively. The tracked air parcels achieved the high water content in a short period before the precipitation, leading to a reduction of the mean water vapour residence time to ∼3.1 days. Additionally, the precipitating moisture uptake along the Catarina trajectory was noticeably higher than the climatological value.
Penalized maximum likelihood inference under the mixture cure model in sparse data
Authors: Xu Changchang , Bull Shelley B.
Published: March 2023

Introduction

When a study sample includes a large proportion of long‐term survivors, mixture cure (MC) models that separately assess biomarker associations with long‐term recurrence‐free survival and time to disease recurrence are preferred to proportional‐hazards models. However, in samples with few recurrences, standard maximum likelihood can be biased.

Objective and Methods

We extend Firth‐type penalized likelihood (FT‐PL) developed for bias reduction in the exponential family to the Weibull‐logistic MC, using the Jeffreys invariant prior. Via simulation studies based on a motivating cohort study, we compare parameter estimates of the FT‐PL method to those by ML, as well as type 1 error (T1E) and power obtained using likelihood ratio statistics.

Results

In samples with relatively few events, the Firth‐type penalized likelihood estimates (FT‐PLEs) have mean bias closer to zero and smaller mean squared error than maximum likelihood estimates (MLEs), and can be obtained in samples where the MLEs are infinite. Under similar T1E rates, FT‐PL consistently exhibits higher statistical power than ML in samples with few events. In addition, we compare FT‐PL estimation with two other penalization methods (a log‐F prior method and a modified Firth‐type method) based on the same simulations.

Discussion

Consistent with findings for logistic and Cox regressions, FT‐PL under MC regression yields finite estimates under stringent conditions, and better bias‐and‐variance balance than the other two penalizations. The practicality and strength of FT‐PL for MC analysis is illustrated in a cohort study of breast cancer prognosis with long‐term follow‐up for recurrence‐free survival.
Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars
Authors: Wen Xiaona , Ou Luping , Cutshaw Gabriel , Uthaman Saji , Ou Yu‐Chuan , Zhu Tian , Szakas Sarah , Carney Brandon , Houghton Jacob , Gundlach‐Graham Alexander , Rafat Marjan , Yang Kai , Bardhan Rizia
Published: March 2023

The in vivo dynamics of nanoparticles requires a mechanistic understanding of multiple factors. Here, for the first time, the surprising breakdown of functionalized gold nanostars (F‐AuNSs) conjugated with antibodies and 64Cu radiolabels in vivo and in artificial lysosomal fluid ex vivo, is shown. The short‐term biodistribution of F‐AuNSs is driven by the route of systemic delivery (intravenous vs intraperitoneal) and long‐term fate is controlled by the tissue type in vivo. In vitro studies including endocytosis pathways, intracellular trafficking, and opsonization, are combined with in vivo studies integrating a milieu of spectroscopy and microcopy techniques that show F‐AuNSs dynamics is driven by their physicochemical properties and route of delivery. F‐AuNSs break down into sub‐20 nm broken nanoparticles as early as 7 days postinjection. Martini coarse‐grained simulations are performed to support the in vivo findings. Simulations suggest that shape, size, and charge of the broken nanoparticles, and composition of the lipid membrane depicting various tissues govern the interaction of the nanoparticles with the membrane, and the rate of translocation across the membrane to ultimately enable tissue clearance. The fundamental study addresses critical gaps in the knowledge regarding the fate of nanoparticles in vivo that remain a bottleneck in their clinical translation.
Glycol‐Split Heparin‐Linked Prodrug Nanoparticles Target the Mitochondrion Apparatus for Cancer Metastasis Treatment
Authors: Sun Feng , Hou Huiwen , Li Yan , Tang Wen , Wang Jie , Lu Lu , Fu Jiaai , Liu Zengmei , Gao Didi , Zhao Feiyan , Gao Xinqing , Ling Peixue , Wang Fengshan , Tan Haining
Published: March 2023

The progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX‐GSHP‐CYS‐ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor‐targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis‐related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor‐bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti‐angiogenesis properties. This multi‐targeted nanoparticle system potentially enhances the antitumor and anti‐metastatic effects of combination chemotherapy and antiangiogenic drugs.
Specific Chemiluminescence Imaging and Enhanced Photodynamic Therapy of Bacterial Infections by Hemin‐Modified Carbon Dots
Authors: Cheng Ke , Wang Henggang , Sun Shan , Wu Mingyu , Shen Hongzhe , Chen Ke , Zhang Zhiyuan , Li Si , Lin Hengwei
Published: March 2023

Antibacterial photodynamic therapy (aPDT) is a promising antibiotics‐alternative strategy for bacterial infectious diseases, which features broad‐spectrum antibacterial activity with a low risk of inducing bacterial resistance. However, clinical applications of aPDT are still hindered by the hydrophobicity‐caused inadequate photodynamic activity of conventional photosensitizers and the hypoxic microenvironment of bacterial infections. To address these problems, herein, a promising strategy is developed to achieve specific chemiluminescence (CL) imaging and enhanced PDT of bacterial infections using hemin‐modified carbon dots (H‐CDs). The H‐CDs can be facilely prepared and exhibit favorable water solubility, augmented photodynamic activity, and unique peroxidase‐mimicking capacity. Compared with the free CDs, the photodynamic efficacy of H‐CDs is significantly augmented due to the increased electron–hole separation efficiency. Moreover, the peroxidase catalytic performance of H‐CDs enables not only infection identification via bacterial infection microenvironment‐responsive CL imaging but also oxygen self‐supplied aPDT with hypoxia‐relief‐enhanced bacteria inactivation effects. Finally, the enhanced aPDT efficiencies of H‐CDs are validated in both in vivo abscess and infected wound models. This work may provide an effective antibacterial platform for the selective imaging‐guided treatment of bacterial infections.
Decreasing Interfacial Pitfalls with Self‐Grown Sheet‐Like Li2S Artificial Solid‐Electrolyte Interphase for Enhanced Cycling Performance of Lithium Metal Anode
Authors: Zhang Rui , Chen Biao , Shi Chunsheng , Sha Junwei , Ma Liying , Liu Enzuo , Zhao Naiqin
Published: March 2023

Constructing a 3D composite Li metal anode (LMA) along with the engineering of artificial solid electrolyte interphase (SEI) is a promising strategy for achieving dendrite‐free Li deposition and high cycling stability. The nanostructure of artificial SEI is closely related to the performance of the LMA. Herein, the self‐grown process and morphology of in situ formed Li2S during lithiation of CuxS is studied systematically, and a large‐sized sheet‐like Li2S layer as an artificial SEI is in situ generated on the inner surface of a 3D continuous porous Cu skeleton (3DCu@Li2S‐S). The sheet‐like Li2S layer with few interfacial pitfalls (Cu/Li2S heterogeneous interface) possesses enhanced diffusion of Li ions. And the continuous porous structure provides transport channels for lithium‐ion transport. As a result, the 3DCu@Li2S‐S presents a high Coulombic efficiency (99.3%), long cycle life (500 cycles), and high‐rate performance (10 mA cm−2). Furthermore, Li/3DCu@Li2S anode fabricated by thermal infusion method inherits the synergistic advantages of sheet‐like Li2S and continuous porous structure. The Li/3DCu@Li2S anode shows significantly enhanced cycling life in both liquid and solid electrolytes. This work provides a new concept to design artificial SEI for LMA with high safe and high performance.
Regulating π‐Conjugation in sp2‐Carbon‐Linked Covalent Organic Frameworks for Efficient Metal‐Free CO2 Photoreduction with H2O
Authors: Yang Lan , Yan Wenkai , Yang Na , Wang Guofeng , Bi Yingpu , Tian Chengcheng , Liu Honglai , Zhu Xiang
Published: March 2023

The development of sp2‐carbon‐linked covalent organic frameworks (sp2c‐COFs) as artificial photocatalysts for solar‐driven conversion of CO2 into chemical feedstock has captured growing attention, but catalytic performance has been significantly limited by their intrinsic organic linkages. Here, a simple, yet efficient approach is reported to improve the CO2 photoreduction on metal‐free sp2c‐COFs by rationally regulating their intrinsic π‐conjugation. The incorporation of ethynyl groups into conjugated skeletons affords a significant improvement in π‐conjugation and facilitates the photogenerated charge separation and transfer, thereby boosting the CO2 photoreduction in a solid‐gas mode with only water vapor and CO2. The resultant CO production rate reaches as high as 382.0 µmol g−1 h−1, ranking at the top among all additive‐free CO2 photoreduction catalysts. The simple modulation approach not only enables to achieve enhanced CO2 reduction performance but also simultaneously gives a rise to extend the understanding of structure‐property relationship and offer new possibilities for the development of new π‐conjugated COF‐based artificial photocatalysts.
A Mesoporous Tungsten Oxynitride Nanofibers/Graphite Felt Composite Electrode with High Catalytic Activity for the Cathode in Zn‐Br Flow Battery
Authors: Jung HyunJin , Lee JaeHyuk , Park JaeYun , Shin Kyungjae , Kim Hee‐Tak , Cho EunAe
Published: March 2023

High electrochemical polarization during a redox reaction in the electrode of aqueous zinc–bromine flow batteries largely limits its practical implementation as an effective energy storage system. This study demonstrates a rationally‐designed composite electrode that exhibits a lower electrochemical polarization by providing a higher number of catalytically‐active sites for faster bromine reaction, compared to a conventional graphite felt cathode. The composite electrode is composed of electrically‐conductive graphite felt (GF) and highly active mesoporous tungsten oxynitride nanofibers (mWONNFs) that are prepared by electrospinning and simple heat treatments. Addition of the 1D mWONNFs to porous GF produces a web‐like structure that significantly facilitates the reaction kinetics and ion diffusion. The cell performance achieves in this study demonstrated high energy efficiencies of 89% and 80% at current densities of 20 and 80 mA cm−2, respectively. Furthermore, the cell can also be operated at a very high current density of 160 mA cm−2, demonstrating an energy efficiency of 62%. These results demonstrate the effectiveness of the mWONNF/GF composite as the electrode material in zinc–bromine flow batteries.
Effect of Functional Group Modifications on the Photocatalytic Performance of g‐C3N4
Authors: Wang Na , Cheng Lei , Liao Yulong , Xiang Quanjun
Published: March 2023

In recent years, photocatalysis has received increasing attention in alleviating energy scarcity and environmental treatment, and graphite carbon nitride (g‐C3N4) is used as an ideal photocatalyst. However, it still remains numerous challenges to obtain the desirable photocatalytic performance of intrinsic g‐C3N4. Functional group functionalization, formed by introducing functional groups into the bulk structure, is one of the common modification techniques to modulate the carrier dynamics and increases the number of active sites, offering new opportunities to break the limits for structure‐to‐performance relationship of g‐C3N4. Nevertheless, the general overview of the advance of functional group modification of g‐C3N4 is less reported yet. In order to better understand the structure‐to‐performance relationship at the molecular level, a review of the latest development of functional group modification is urgently needed. In this review, the functional group modification of g‐C3N4 in terms of structures, properties, and photocatalytic activity is mainly focused, as well as their mechanism of reaction from the molecular level insights is explained. Second, the recent progress of the application of introducing functional groups in g‐C3N4 is introduced and examples are given. Finally, the difficulties and challenges are presented, and based on this, an outlook on the future research development direction is shown.
A Cascade‐Targeted Enzyme‐Instructed Peptide Self‐Assembly Strategy for Cancer Immunotherapy through Boosting Immunogenic Cell Death
Authors: Xie Limin , Ding Yinghao , Zhang Xiangyang , Zhang Zhenghao , Zeng Sheng , Wang Ling , Yang Zhimou , Liu Qian , Hu Zhi‐Wen
Published: March 2023

Immunogenic cell death (ICD) approaches by encumbering mitochondrial functions provide great promise for the treatment of malignant tumors, but these kinds of ICD strategies are still in their infancy. Here, one multifunctional drug‐loaded, cascade‐targeted, and enzyme‐instructed self‐assembling peptide nanomedicine (Comp. 4) for ICD‐based cancer therapy is constructed. Comp. 4 consists of 1) lonidamine (LND) that specifically interferes with mitochondrial functions; 2) a programmed death ligand 1 (PD‐L1) binding peptide sequence (NTYYEDQG) and a mitochondria‐specific motif (triphenylphosphonium, TPP) that can sequentially control the cell membrane and mitochondria targeting capacities, respectively; and 3) a ‐GDFDFpDY‐ assembly core to in situ organize peptide assemblies responsive to alkaline phosphatase (ALP). Comp. 4 demonstrates noticeable structural and morphological transformations in the presence of ALP and produces peptide assemblies in mouse colon cancer cells (CT26) with high expressions of both ALP and PD‐L1. Moreover, the presence of PD‐L1‐ and mitochondria‐specific motifs can assist Comp. 4 for effective endocytosis and endosomal escape, forming peptide assemblies and delivering LND into mitochondria. Consequently, Comp. 4 shows superior capacities to in vivo induce abundant mitochondrial oxidative stress, provoke robust ICD responses, and produce an immunogenic tumor microenvironment, successfully inhibiting CT26 tumor growth by eliciting a systemic ICD‐based antitumor immunity.
Strong and Tough Nanostructured Hydrogels and Organogels Prepared by Polymerization‐Induced Self‐Assembly
Authors: Zeng Zhong , Li Ziyun , Li Qili , Song Guangjie , Huo Meng
Published: March 2023

In nature, the hierarchical structure of biological tissues endows them with outstanding mechanics and elaborated functions. However, it remains a great challenge to construct biomimetic hydrogels with well‐defined nanostructures and good mechanical properties. Herein, polymerization‐induced self‐assembly (PISA) is for the first time exploited as a general strategy for nanostructured hydrogels and organogels with tailored nanodomains and outstanding mechanical properties. As a proof‐of‐concept, PISA of BAB triblock copolymer is used to fabricate hydrogels with precisely regulated spherical nanodomains. These nanostructured hydrogels are strong, tough, stretchable, and recoverable, with mechanical properties correlating to their nanostructure. The outstanding mechanical properties are ascribed to the unique network architecture, where the entanglements of the hydrophilic chains act as slip links that transmit the tension to the micellar crosslinkers, while the micellar crosslinkers dissipate the energy via reversible deformation and irreversible detachment of the constituting polymers. The general feasibility of the PISA strategy toward nanostructured gels is confirmed by the successful fabrication of nanostructured hydrogels, alcogels, poly(ethylene glycol) gels, and ionogels with various PISA formulations. This work has provided a general platform for the design and fabrication of biomimetic hydrogels and organogels with tailorable nanostructures and mechanics and will inspire the design of functional nanostructured gels.
Effect of Polymer Additives on the Crystal Habit of Metformin HCl
Authors: Bellucci Michael A. , Marx Anke , Wang Bing , Fang Liwen , Zhou Yunfei , Greenwell Chandler , Li Zhuhong , Becker Axel , Sun GuangXu , Brandenburg Jan Gerit , Sekharan Sivakumar
Published: March 2023

The crystal habit can have a profound influence on the physical properties of crystalline materials, and thus controlling the crystal morphology is of great practical relevance across many industries. Herein, this work investigates the effect of polymer additives on the crystal habit of metformin HCl with both experiments and computational methods with the aim of developing a combined screening approach for crystal morphology engineering. Crystallization experiments of metformin HCl are conducted in methanol and in an isopropanol‐water mixture (8:2 V/V). Polyethylene glycol, polyvinylpyrrolidone, Tween80, and hydroxypropyl methylcellulose polymer additives are used in low concentrations (1–2% w/w) in the experiments to study the effect they have on modifying the crystal habit. Additionally, this work has developed computational methods to characterize the morphology “landscape” and quantifies the overall effect of solvent and additives on the predicted crystal habits. Further analysis of the molecular dynamics simulations is used to rationalize the effect of additives on specific crystal faces. This work demonstrates that the effects of additives on the crystal habit are a result of their absorption and interactions with the slow growing {100} and {020} faces.
A Top‐Down Strategy for Reforming the Characteristics of NiO Hole Transport Layer in Inverted Perovskite Solar Cells
Authors: Ko Seonkyung , Yong Taeyeong , Kim Soo-Kwan , Park Jin Young , Lee Gyudong , You Hyung Ryul , Han Sanghun , Lee Duck Hoon , Choi Seongmin , Choi Yong Chan , Kim Younghoon , Lee Nam-Suk , Song Seulki , Choi Jongmin
Published: March 2023

The hole transport layer (HTL) plays a key role in inverted perovskite solar cells (PSCs), and nickel oxide has been widely adopted for HTL. However, a conventional solution‐processed bottom‐up approach for NiOx (S‐NiO) HTL fabrication shows several drawbacks, such as poor coverage, irregular film thickness, numerous defect sites, and inefficient hole extraction from the perovskite layer. To address these issues, herein, a novel NiOx HTL top‐down synthesis route via electrochemical anodization is developed. The basicity of the electrolyte used in anodization considerably influences electrochemical reactions and results in the structure of the anodized NiOx (A‐NiO). The optimized A‐NiO provides outstanding optoelectrical properties, including uniform film thickness, enhanced transmittance, deep‐lying valance band, low trap density, and better hole extraction ability from the perovskite. Owing to these advantages, the A‐NiO‐based inverted PSC exhibits an improved power conversion efficiency of 21.9% compared with 19.1% for the S‐NiO‐based device. In addition, the A‐NiO device shows a higher inlet and long‐term ambient stability than the S‐NiO device due to the superior hole transfer ability of A‐NiO, which suppresses charge accumulation between NiOx and the perovskite interface.
Role of Ionic Liquids in Perovskite Solar Cells
Authors: Zhang Kai , Zhang Xianfu , Brooks Keith G. , Ding Bin , Kinge Sachin , Ding Yong , Dai Songyuan , Nazeeruddin Mohammad Khaja
Published: March 2023

Although the power conversion efficiency of perovskite solar cells (PSCs) has reached 25.7%, there is still great potential for improvement in their performance and stability. In the past few years, ionic liquids (ILs) have been extensively investigated and demonstrated to enhance the efficiency and stability of devices substantially. Herein, the role of ILs in PSCs as additives, solvents, interface engineering, and charge transport layer is reviewed. Also, this review will guide the researchers in understanding bulk doping and interface engineering for efficient and stable PSCs.