bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of low‐molecular‐weight heparin on placenta‐mediated fetal growth restriction in a tertiary referral hospital: A 7‐year retrospective cohort study
Authors: Xu Jinfeng , Tang Yuxin , Peng Bing , Zhang Wei‐Hong , Wang Xiaodong
Published: September 2023

Objective

To investigate the effect of low‐molecular‐weight heparin (LMWH) on placenta‐mediated fetal growth restriction (FGR).

Methods

A cohort of 570 pregnant women diagnosed with placenta‐mediated FGR were enrolled from January 1, 2015 through to December 31, 2021. A birth database, including demographic data, antenatal complications, and detailed delivery and newborn data, was created to collect variables from the Hospital Information System (HIS) Database. The unique personal registration number, assigned to each patient on first registration with HIS in the West China Second University Hospital, was used to link these patients. LMWH use was defined as at least 1‐week prescription from diagnosis of placenta‐mediated FGR. Pregnant women received LMWH (Enoxaparin 4000 IU/day) by self‐administered subcutaneous injection only when they agreed and signed informed consent. Primary outcome was intrauterine fetal death after 20 weeks of pregnancy. Secondary outcomes included preterm birth (PB), Apgar score less than 7 at 1 min, admission to neonatal intensive care unit (NICU), and birth weight. Logistic regression analysis was conducted to compute adjusted odds ratio (aOR) with 95% confidence intervals (CI) for outcomes.

Results

After controlling for confounders, LMWH use was associated with a decreased risk of intrauterine fetal death (aOR 2.49, 95% CI 1.35–4.57, P = 0.003), PB before 37 weeks of pregnancy (aOR 3.35, 95% CI 2.14–5.23, P < 0.001), PB before 34 weeks of pregnancy (aOR 2.25, 95% CI 1.36–3.74, P = 0.002), Apgar score less than 7 at 1 min (aOR 2.25, 95% CI 1.36–3.74, P = 0.002), NICU admission (aOR 2.29, 95% CI 1.48–3.55, P < 0.001). Using LMWH increased the mean birth weight in PB before 32 weeks of pregnancy (mean ± standard deviation [SD] 1126.4 ± 520.0 g, P = 0.020), PB before 37 weeks of pregnancy (mean ± SD 1563.9 ± 502.7 g, P = 0.019), early‐onset FGR (mean ± SD 2125.2 ± 665.7 g, P < 0.001), late‐onset FGR (mean ± SD 2343.4 ± 507.9, P < 0.001), and non‐severe FGR (mean ± SD 2231.1 ± 607.2 g, P < 0.001).

Conclusion

Use of LMWH can significantly improve the fetal and neonatal outcomes among pregnant women with placenta‐mediated FGR, particularly reducing the risk of intrauterine fetal death.
Cytocompatibility, antibacterial, and corrosion properties of chitosan/polymethacrylates and chitosan/poly(4‐vinylpyridine) smart coatings, electrophoretically deposited on nanosilver‐decorated titania nanotubes
Authors: Pawłowski Łukasz , Bartmański Michał , Ronowska Anna , Banach‐Kopeć Adrianna , Mania Szymon , Cieślik Bartłomiej Michał , Mielewczyk‐Gryń Aleksandra , Karczewski Jakub , Zieliński Andrzej
Published: September 2023

The development of novel implants subjected to surface modification to achieve high osteointegration properties at simultaneous antimicrobial activity is a highly current problem. This study involved different surface treatments of titanium surface, mainly by electrochemical oxidation to produce a nanotubular oxide layer (TNTs), a subsequent electrochemical reduction of silver nitrate and decoration of a nanotubular surface with silver nanoparticles (AgNPs), and finally electrophoretic deposition (EPD) of a composite of chitosan (CS) and either polymethacrylate‐based copolymer Eudragit E 100 (EE100) or poly(4‐vinylpyridine) (P4VP) coating. The effects of each stage of this multi‐step modification were examined in terms of morphology, roughness, wettability, corrosion resistance, coating‐substrate adhesion, antibacterial properties, and osteoblast cell adhesion and proliferation. The results showed that the titanium surface formed nanotubes (inner diameter of 97 ± 12 nm, length of 342 ± 36 nm) subsequently covered with silver nanoparticles (with a diameter of 88 ± 8 nm). Further, the silver‐decorated nanotubes were tightly coated with biopolymer films. Most of the applied modifications increased both the roughness and the surface contact angle of the samples. The deposition of biopolymer coatings resulted in reduced burst release of silver. The coated samples revealed potent antimicrobial activity against both Gram‐positive and Gram‐negative bacteria. Total elimination (99.9%) of E. coli was recorded for a sample with CS/P4VP coating. Cytotoxicity results using hFOB 1.19, a human osteoblast cell line, showed that after 3 days the tested modifications did not affect the cellular growth according to the titanium control. The proposed innovative multilayer antibacterial coatings can be successful for titanium implants as effective postoperative anti‐inflammation protection.
Beta vulgaris‐derived exosome‐like nanovesicles alleviate chronic doxorubicin‐induced cardiotoxicity by inhibiting ferroptosis
Authors: Cai Jiejie , Pan Jingye
Published: September 2023

Dose‐dependent heart failure is a major complication of the clinical use of doxorubicin (Dox), one of the most potent chemotherapeutic agents. Effective adjuvant therapy is required to prevent Dox‐induced cardiotoxicity. Currently, plant‐derived exosome‐like nanovesicle (PELNV) has revealed their salubrious antioxidant and immunological regulating actions in various disease models. In this study, we isolated, purified and characterized Beta vulgaris‐derived exosome‐like nanovesicle (BELNV). Dox or normal saline was given to HL‐1 cells (3 μM) and 8‐week C57BL/6N mice (5 mg/kg bodyweight per week for 4 weeks) to establish the in vitro and in vivo model of Dox‐induced cardiotoxicity. Administration of BELNV significantly alleviated chronic Dox‐induced cardiotoxicity in terms of echocardiographic and histological results. A reduced malondialdehyde (MDA), increased ratio of glutathione (GSH) to oxidized glutathione (GSSG) and levels of system xc− and glutathione peroxidase 4 were observed, indicating that DOX‐stimulated ferroptosis was reversed by BELNV. Besides, the safety of BELNV was also validated since no liver, spleen, and kidney toxicity induced by BELNV was observed. These findings provide evidence that BELNV may act as a novel therapeutic biomaterial for patients undergoing adverse effects of Dox, at least partly mediated by inhibiting Dox‐induced ferroptosis.
Mass production of morin‐stabilized silver nanoparticles: Characterization, antioxidant, and antimicrobial activities
Authors: Zayed Mervat F. , Abdel‐Monem Yasser K. , Arafa Abeer A. , Eisa Wael H.
Published: September 2023

Phytochemical‐conjugated silver nanoparticles (AgNPs) are believed to act as a bridge between nanotechnology and therapy. There is a significant need for green and mass production of such materials due to their extensive applications, especially in the biomedical sector. In this study, morin‐stabilized silver nanoparticles (morin/AgNPs) were synthesized on a massive scale using a one‐pot solid‐state technique. The reaction is achieved by ball milling of morin and silver nitrate powders at ambient temperature without any solvent or toxic reagent. The prepared morin/AgNPs exhibited a semi‐hexagonal shape and ranged in size from 21 to 43 nm. The x‐ray diffraction results elucidated the formation of highly crystalline AgNPs. Fourier transform infrared and x‐ray photoelectron spectroscopic analyses prove that the hydroxyl, carbonyl, and aromatic functionalities in morin are playing major roles in the reduction and stabilization of AgNPs. The antioxidant potential of morin/AgNPs was evaluated utilizing 2,2‐Diphenyl‐1‐picryl‐hydrazyl (DPPH) assay. Morin/AgNPs exhibited better free radical scavenging activity (IC50 = 11.7 μg/mL) than morin (IC50 = 14.8 μg/mL). Furthermore, the synthesized AgNPs showed promising antimicrobial activity against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, and Candida albicans. The largest inhibition zones were observed against S. aureus (21.2 ± 0.6 mm) and K. pneumonia (20.3 ± 0.5 mm) bacteria. The foregoing results highlighted the prospective application of morin/AgNPs as a promising antioxidant and antimicrobial material for safe medical applications.

Research Highlights

A simple green route for the large‐scale production of AgNPs was developed.

Morin acts as reducing/stabilizing agent in solid‐state synthesis of AgNPs.

Morin/AgNPs exhibited promising antimicrobial and antioxidant activity.
Composting post‐anaerobic digestion for emerging contaminant biodegradation: Impacts of operating conditions
Authors: Larson Victoria J. , Rico Jorge L. , Wolfe Lisa M. , Sharvelle Sybil , Prenni Jessica , De Long Susan K.
Published: September 2023

Sustainable manure management technologies are needed, and combining anaerobic digestion (AD) for energy generation and aerobic composting (AC) to stabilize digestate and remove emerging contaminants (ECs), including veterinary pharmaceuticals and steroid hormones, is promising. This study identified post‐AD, AC operating conditions that maximized degradation of study ECs, expected to be present in cattle manure digested using treated municipal wastewater as the water source. Study ECs included sulfamethoxazole (SMX), chlortetracycline (CTC), oxytetracycline (OTC), estrone (E1), and naproxen (NPX). Composting conditions were simulated in bench‐scale reactors, with microorganisms from digestate produced in an AD system (25L scale), by varying temperatures, pH, and carbon source compositions (representing food waste/manure co‐digestion with different residence times). Results indicate maximum SMX biodegradation occurred at 35°C, pH 7, and with high levels of easily degradable carbon (≥99%, 99%, and 98%), and maximum E1 biodegradation occurred at 35°C, and with low levels of easily degradable carbon (≥97% and 99%). Abiotic degradation was responsible for the nearly complete removal of tetracyclines under all conditions and for partial degradation of NPX (between 20% and 48%). Microorganisms originating from the AD system putatively capable of SMX and E1 biodegradation, or of contributing to biodegradation during the AC phase, were identified, including phylotypes previously shown to biodegrade SMX (Brevundimonas and Alcaligenes).
Downregulated expression of plakophilin‐2 gene in patients with colon adenocarcinoma predicts an unfavorable prognosis and immune infiltrate
Authors: Dai Meng , Su Yuantao , Wu Zhixiong
Published: September 2023

Background

Plakophilin 2 gene (PKP2) has been revealed to be differentially expressed in various cancer types and is correlated with prognosis. However, the role of PKP2 in colon adenocarcinoma remains indistinct.

Methods

Differences in transcriptional expression of PKP2 between colon adenocarcinoma tissues and normal adjacent tissues were acquired from the publicly available dataset—the Cancer Genome Atlas. A receiver operating curve (ROC) was constructed to differentiate colon adenocarcinoma tissues from adjacent normal tissues. The Kaplan–Meier plot method was performed to evaluate the effect of PKP2 on survival. The correlation between mRNA expression of PKP2 and immune infiltrating was determined by the Tumor Immune Estimation Resource and Tumor–Immune System Interaction databases.

Results

The expression of PKP2 in colon adenocarcinoma tissues was significantly downregulated compared with corresponding adjacent normal tissues. Decreased PKP2 mRNA expression was associated with lymph node metastases and advanced pathological stage. The ROC curve analysis indicated that with a cutoff value of 6.034, the sensitivity and specificity for PKP2 differentiating the colon adenocarcinoma tissues from the adjacent normal tissues were 90.2 and 66.5% respectively. Kaplan–Meier plot survival analysis revealed that colon adenocarcinoma patients with low‐PKP2 had a worse prognosis than those with high‐PKP2 (68.2 vs. 101.4 months, p = 0.028). Correlation analysis showed that mRNA expression of PKP2 was correlative with immune infiltrates.

Conclusions

Downregulated PKP2 is significantly correlated with unfavorable immune infiltrating and survival in colon adenocarcinoma. This research indicates that PKP2 can be selected as a novel biomarker of potential immunotherapy targets and unfavorable prognosis in colon adenocarcinoma.
Stable isotope synthesis of glycine transporter 1 inhibitor Iclepertin (BI 425809) and its major metabolites
Authors: Latli Bachir , Hrapchak Matt J. , Chevliakov Maxim , Samankumara Lalith P. , Frutos Rogelio P. , Lee Heewon
Published: September 2023

Stable isotope labeled Iclepertin (BI 425809, 1) and its major metabolites are needed as internal standards in bioanalytical studies. BI 425809 consists of two main building blocks, 5‐methylsulfonyl‐2‐[(1R)‐2,2,2‐trifluoro‐1‐methyl‐ethoxy]benzoic acid (2) and 3‐[(1R,5R)‐3‐azabicyclo[3.1.0]hexan‐5‐yl]‐5‐(trifluoromethyl)isoxazole (3) linked to each other via an amide bond. We used fluoro[13C6]benzene as the starting material in the preparation of [13C6]‐2. This intermediate was then employed to access carbon 13 labeled Iclepertin ([13C6]‐1) and other metabolites. The major metabolite BI 761036 (6), which resulted from cytochrome P450 oxidation and amide hydrolysis of BI 425809, was prepared labeled with carbon 13 and nitrogen 15 via two synthetic routes. In the first route, diethyl [13C3]malonate, [13C]methyl iodide, and hydroxyl[15N]amine were used to provide [13C4,15N]‐BI 761036 ([13C4,15N]‐6a) in 13 steps in 6% overall yield, whereas in the second route, [13C3]propargyl alcohol, potassium [13C]cyanide, and [15N]ammonia were used to furnish [13C4,15N]‐BI 761036 ([13C4,15N]‐6b) in 11 steps in 1% overall yield. The detailed stable isotope synthesis of 1 and its major metabolites is described.
Adsorption Dynamics of Uremic Toxins to Novel Modified Magnetic Nanoparticles
Authors: Li Shuhui , Sharaf Mehdi Ghaffari , Zhang Lun , Wishart David S. , Tonelli Marcello , Unsworth Larry D.
Published: September 2023

Kidney dysfunction leads to the retention of metabolites in the blood compartment, some of which reach toxic levels. Uremic toxins are associated with the progression of kidney disease and other symptoms of kidney failure (i.e., nausea, itchiness, and hypertension). Toxin removal ameliorates symptoms and reduces further organ damage, but membrane‐based methods are inadequate for this purpose. Engineered adsorbents may facilitate enhanced removal of retained toxins, especially those bound strongly by proteins. Poly 2‐(methacryloyloxy)ethyl phosphorylcholine‐co‐β‐cyclodextrin (p(MPC‐co‐PMβCD)) coated magnetic nanoparticles are synthesized, characterized for their physicochemical properties (Fourier‐transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), thermogravimetric analysis(TGA), gel permeation chromatography (GPC), and transmission electron microscope (TEM), and evaluated toxin adsorption from a complex solution for the first time to quantify the effects of film chemistry and incubation time on the adsorbed toxinome (the collection of toxins). Uremic toxins are bound by even “low‐fouling” polymer films themselves; providing further insight into how small molecule interactions with “low‐fouling” films may affect protein‐surface interactions. These results suggest a dynamic interaction between toxins and surfaces that is not driven by solution concentration alone. This knowledge will help advance the design of novel adsorbent films for clearing uremic toxins.
Existence of the solution for a class of the semilinear degenerate elliptic equation involving the Grushin operator in R2$\mathbb {R}^2$: The interaction between Grushin's critical exponent and exponential growth
Authors: Alves Claudianor Oliveira , de Holanda Angelo Roncalli Furtado
Published: September 2023

In this work, we study the existence of the solution for a class of semilinear degenerate elliptic equations in the whole space involving the Grushin operator and a nonlinearity that involves the Grushin's critical growth and the exponential growth. The existence of at least one nontrivial weak solution is done by combining the mountain‐pass theorem, Trudinger–Moser inequality, and a version of a result due to Lions for the exponential growth in in the corresponding weighted Sobolev space.
Projection of future precipitation change using CMIP6 multimodel ensemble based on fusion of multiple machine learning algorithms: A case in Hanjiang River Basin, China
Authors: Wang Dong , Liu Jiahong , Luan Qinghua , Shao Weiwei , Fu Xiaoran , Wang Hao , Gu Yanling
Published: September 2023

Projecting precipitation changes is essential for researchers to understand climate change impacts on hydrological cycle. This study projected future precipitation over the Hanjiang River Basin (HRB) based on the multimodel ensemble (ME) of six global climate models from Phase 6 of the Coupled Model Intercomparison Project (CMIP6). An ME method using the fusion of four machine learning (ML) algorithms (random forest [RF], K‐nearest neighbors [KNN], extra tree [ET], and gradient boosting decision tree [GBDT]) was proposed in this study. The future precipitation changes were investigated during 2023–2042 (Near‐term), 2043–2062 (Mid‐term), and 2081–2100 (Long‐term) periods, with reference to the base period 1995–2014, under three integrated scenarios (SSP1‐2.6, SSP2‐4.5, and SSP5‐8.5) of the Shared Socioeconomic Pathways (SSPs) and the representative concentration pathways (RCPs). The results show that: (1) the proposed ME method performs better than the ME mean and individual ML algorithms, with a correlation coefficient value reaching 0.88 and Taylor skill score reaching 0.764. (2) The precipitation under SSP5‐8.5 has the largest upward trend with the annual precipitation variation range of −9.27% to 112.84% from 2023 to 2100, followed by SSP2‐4.5 with −30.48% to 44.67%, and the smallest under SSP1‐2.6 with −37.19% to 37.78%, which show a significant trend of humidification over the HRB in the future. (3) The precipitation changes over the HRB are projected to increase over time, with the largest in the Long‐term, followed by Mid‐term, and the smallest in the Near‐term. (4) The northeastern parts of the HRB are projected to experience a large precipitation in the future, and the southeastern parts are smaller. (5) Uncertainties in the projected precipitation over the HRB still exist, which can be reduced by ME. The findings obtained in this study have important implications for hydrological policymakers to make adaptive strategies to reduce the risks of climate change.
Optical ridge waveguides in Nd3+‐doped fluorophosphate glasses fabricated by carbon ion implantation and femtosecond laser ablation
Authors: Liu Chun‐Xiao , Lu Yan , Sun Xiu‐Jun , Chen Hong‐Yu
Published: September 2023

In this work, the ridge waveguide was formed by the femtosecond laser ablation with a central wavelength of 0.808 μm and a speed of 50 μm/s on the planar Nd3+‐doped fluorophosphate glass waveguide that was fabricated by the C3+ ion implantation with an energy of 6.0 MeV and a fluence of 1.0×1012 C3+s/mm2. The mechanism of the ion‐implanted waveguide was discussed by the Stopping and Range of Ions in Matter 2013. The cross‐section morphology of the ridge waveguide was captured by an optical microscope. Its mode characteristics were analyzed by the end‐face coupling method. The ridge Nd3+‐doped fluorophosphate glass waveguides have potential as fundamental structures for many optoelectronic devices including waveguide amplifiers and lasers.
Prevalence, stability, and predictive utility of the Multidimensional Assessment of Preschoolers Scales clinically optimized irritability score: Pragmatic early assessment of mental disorder risk
Authors: Wiggins Jillian Lee , Ureña Rosario Ana , MacNeill Leigha A. , Krogh‐Jespersen Sheila , Briggs‐Gowan Margaret , Smith Justin D. , Wakschlag Lauren S.
Published: September 2023

Objectives

Characterizing the scope and import of early childhood irritability is essential for real‐world actualization of this reliable indicator of transdiagnostic mental health risk. Thus, we utilize pragmatic assessment to establish prevalence, stability, and predictive utility of clinically significant early childhood irritability.

Methods

Data included two independent, diverse community samples of preschool age children (N = 1857; N = 1490), with a subset enriched for risk (N = 425) assessed longitudinally from early childhood through preadolescence (∼4–9 years old). A validated, brief (2‐item) scale pragmatically assessed clinically significant irritability. In the longitudinal subsample, clinical interviews assessed internalizing/externalizing disorders.

Results

One in five preschool‐age children had clinically significant irritability, which was independently replicated. Irritability was highly stable through preadolescence. Children with versus without clinically significant early childhood irritability had greater odds of early onset, persistent internalizing/externalizing disorders. The pragmatic assessment effectively screened out low‐risk children and identified 2/3 of children with early‐onset, persistent psychopathology.

Conclusions

Clinically significant early childhood irritability prevalence is akin to the pediatric obesity epidemic and may warrant similar universal screening/intervention. Also, irritability's stability demonstrates the common guidance “they'll grow out of it” to be false. Finally, pragmatic irritability assessment has transdiagnostic predictive power and addresses a need for feasible measures to flag risk.
Adding realistic noise models to synthetic ground‐penetrating radar data
Authors: Stephan Sophie Marie , Allroggen Niklas , Tronicke Jens
Published: September 2023

Cost‐effective computing capabilities have paved the road for the use of numerical modelling to develop advanced methods and applications of ground‐penetrating radar (GPR). Realistic synthetic data and the corresponding modelling techniques, respectively, should consider all subsurface and above‐ground aspects that influence GPR wave propagation and the characteristics of recorded signals. Critical aspects that can be realized in modern GPR modelling tools include heterogeneous and frequency‐dependent material properties, complex structures and interface geometries as well as three‐dimensional antenna models, including the interaction between the antenna and the subsurface. However, realistic noise related to the electronic components of a GPR system or ambient electromagnetic noise is often not considered, or simplified by assuming a white Gaussian noise model which is added to the modelled data. We present an approach to include realistic noise scenarios as typically observed in GPR field data into the flow of modelling synthetic GPR data. In our approach, we extract the noise from recorded GPR traces and add it to the modelled GPR data via a convolution‐based process. We illustrate our methodology using a modelling exercise, where we contaminate a synthetic two‐dimensional GPR dataset with frequency‐dependent noise recorded in an urban environment. Comparing our noise‐contaminated synthetic data with field data recorded in a similar environment illustrates that our method allows the generation of synthetic GPR with realistic noise characteristics and further highlights the limitations of assuming pure white Gaussian noise models.
Lipid accumulation product and visceral adiposity index for incidence of cardiovascular diseases and mortality; results from 13 years follow‐up in Isfahan cohort study
Authors: Fakhrolmobasheri Mohammad , Abhari Amir Parsa , Heidarpour Maryam , Paymannejad Saina , Pourmahdi‐Boroujeni Mahsa , Saffari Amir Sepehr , Okhovat Paria , Roohafza Hamidreza , Sadeghi Masoumeh , Rabanipour Najmeh , Shafie Davood , Sarrafzadehgan Nizal
Published: September 2023

Background

/Aims: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are novel anthropometric indices that have shown an association with metabolic syndrome; however, limited data are available regarding the predictive performance of these indices for the incidence of cardiovascular diseases (CVD) and mortality.

Methods

This study was performed on the data retrieved from Isfahan Cohort Study (ICS). ICS is an ongoing population‐based cohort study conducted in 3 counties in central Iran. Pearson correlation analysis was performed between LAP, VAI, and metabolic parameters. Cox regression analysis and receiver operative characteristics (ROC) curve analysis were performed in order to evaluate the ability of VAI and LAP for the incidence of CVD, CVD‐associated mortality, and all‐cause mortality. We further compared the predictive performance of VAI and LAP with body mass index (BMI).

Results

LAP and VAI were significantly correlated with all metabolic variables, including blood pressure, fasting blood glucose, and lipid profile components. Univariate regression analysis indicated a significant association between LAP and VAI and CVD incidence. In multivariate analysis, only VAI was significantly associated with CVD incidence. Regarding CVD mortality, only VAI in the multivariate analysis revealed a significant association. Interestingly, Both VAI and LAP were negatively associated with all‐cause mortality. ROC curve analysis indicated the superior performance of LAP and VAI for predicting CVD incidence compared to BMI; however, BMI was better in predicting all‐cause mortality.

Conclusion

Compared to BMI, LAP and VAI have better predictive performance for the incidence of CVD. In contrast, BMI was superior to VAI and LAP in the prediction of all‐cause mortality.
Model reduction for ‐induced vesicle fusion dynamics
Authors: Ernst Ariane , Falkenhagen Undine , Winkelmann Stefanie
Published: September 2023

In this work, we adapt an established model for the ‐induced fusion dynamics of synaptic vesicles and employ a lumping method to reduce its complexity. In the reduced system, sequential ‐binding steps are merged to a single releasable state, while keeping the important dependence of the reaction rates on the local concentration. We examine the feasibility of this model reduction for a representative stimulus train over the physiologically relevant site‐channel distances. Our findings show that the approximation error is generally small and exhibits an interesting nonlinear and non‐monotonic behavior where it vanishes for very low distances and is insignificant at intermediary distances. Furthermore, we give expressions for the reduced model's reaction rates and suggest that our approach may be used to directly compute effective fusion rates for assessing the validity of a fusion model, thereby circumventing expensive simulations.
Parental experiences of the informed consent process in randomized clinical trials—A Nordic study
Authors: Mogensen Nina , Kreicbergs Ulrika , Albertsen Birgitte Klug , Lähteenmäki Päivi , Heyman Mats , Harila Arja
Published: September 2023

Background

Randomized clinical trials (RCTs) are an essential part of improving acute lymphoblastic leukemia (ALL) treatment. This population‐based questionnaire study investigated parents’ experiences of the informed consent process in the RCTs within the Nordic NOPHO (Nordic Society of Paediatric Haematology and Oncology) ALL2008 trial.

Procedure

Parents in Sweden, Denmark, and Finland whose child was alive and in first remission after end of therapy and who were asked to participate in any RCT in the ALL2008 protocol, were asked to complete 15 questions/items regarding their experience of the RCT consent process.

Results

A total of 483 parents of 279 children met the inclusion criteria and answered the study questionnaire. Most (91%) agreed/strongly agreed to having received sufficient information to make a well‐informed decision, felt confidence in the study design (86%), and thought that the process was satisfactory (86%). Those who did not consent reported a generally more negative experience of the process. More than a third of all parents and over half of parents who had refused participation felt that it was burdensome to decide. Most parents (66%) in general, and one‐third of those with children 8 years or older, reported that their child was not involved in the process.

Conclusions

Parents were in general satisfied with the informed consent process, although many parents, particularly those who refused participation, reported it as burdensome to make the decision concerning RCT. Fewer than expected of the school‐aged children were involved in the decision process, which calls for attention on how children are included in the consent procedure in clinical trials.
Prescribing for people with a learning disability
Authors: Adams Danielle , Jubraj Barry
Published: September 2023

There are many factors that can impact the safety and effectiveness of medicines in people with a learning disability. As part of our series on medicines optimisation in people with additional needs, this article discusses the important issues to consider when prescribing for people with a learning disability.
Update on the National Clinical Guideline for Stroke
Authors: Chaplin Steve
Published: September 2023

The National Clinical Guideline for Stroke provides evidence‐based guidance to improve the quality of care for stroke patients in the UK and Ireland. This article summarises the main changes that have been made in the 2023 update of the guideline.
Advances in MRI: Peptide and peptidomimetic‐based contrast agents
Authors: Pierri Giovanni , Schettini Rosaria
Published: September 2023

Magnetic resonance imaging (MRI) is a common medical imaging technique that provides three‐dimensional body images. MRI contrast agents improve image contrast by raising the rate of water proton relaxation in specific tissues. Peptides and peptidomimetics act as scaffolds for MRI imaging agents because of their increased size and offer the possibility to engine a higher hydration value within the design. The design of a new Gd‐based contrast agent must take into account high stability constants to avoid free Gd(III), with the subsequent nephrotoxicity, and high relaxivity values. This review analyzes various synthetic approaches, reports studies of relaxometric parameters, and focuses on the description and application of Gd(III)‐chelates based on peptide and peptidomimetic scaffolds. In addition, the X‐ray molecular structures of three DOTA complexes will be reported to emphasize the necessity of using the X‐ray diffraction analysis to identify the coordination sphere of the metals and the mechanism of action of the compounds.
Dimensional optimisation and an inverse kinematic solution method of a safety‐enhanced remote centre of motion manipulator
Authors: Huang Fang , Sang Hongqiang , Liu Fen , Han Rui
Published: September 2023

Background

With the expansion of minimally invasive surgery (MIS) applications in surgery, the remote centre of motion (RCM) manipulator requires a more flexible workspace to meet different operation requirements. Thus, the mechanical structure and motion control of the RCM manipulator play important roles.

Methods

A multi‐objective genetic algorithm was exploited to maximise the kinematic performance and obtain a compact structure of the RCM manipulator. An inverse kinematic solution method is proposed to meet task accuracy and kinematic singularity avoidance constraints for safety motion control.

Results

Simulation results demonstrate that there are significant improvements in the reachable workspace inside the abdominal cavity, the flexibility of the workspace, kinematic performance, and compactness of the RCM manipulator. Experiments verify the feasibility of the prototype and the validity of the proposed inverse kinematic solution method.

Conclusions

This enhances the adaptability and safety of the RCM manipulator and provides potential prospects for MIS application.
Discovery of a New Dihydropyrimidinone Derivative as a Potential Haspin Kinase Inhibitor: Structure‐Guided Insights, In‐Vitro and Molecular Dynamics‐Based Validation
Authors: Sharma Omprakash , Srivastava Shubham , Sharma Manish , Malik Ruchi
Published: September 2023

Structure‐based virtual screening is efficient method for finding novel scaffolds/molecules for biological targets. Due to the accessibility of the Haspin crystal structure and its prevalence in various diseases; we sought exploring novel Haspin kinase inhibitors. We used the commercially available Chembridge library for virtual screening which had nearly 7,00,000 compounds. We employed variety of computational tools such as molecular docking, molecular dynamics simulations, in silico pharmacokinetics analysis to identify novel inhibitors targeting Haspin kinase. Based on chemical features, docking score, and MMGB/SA binding strength, 10 ligands were chosen. On in vitro determination, one chemical entity was found to inhibit Haspin's enzyme function at 72 % at 10 μM. Compound 16503395 had higher selectivity over Haspin kinase activity than the other kinases. The IC50 value for the compound 16503395 that inhibits Haspin kinase significantly was determined and was found to be 2.6 μM. After subjecting to molecular dynamics simulation analysis for compound 16503395 Haspin protein complex, we found that the Haspin kinase binding site amino acid unique residues Gly608, Glu492, Lys511, Asn654, Asp687, Ala503, Leu656 and Phe605 play important role in binding kinetics. We claim 5‐(hydroxymethyl)‐N‐[cis‐3‐(6‐oxo‐2‐pyrrolidin‐1‐yl‐1,6‐dihydropyrimidin‐4‐yl)cyclobutyl]‐2‐furamide (16503395) as a selective and potential Haspin kinase inhibitor.
KCl/MgO Composite Templates for Achieving Hierarchical Porous Carbons with High Performance in Supercapacitor
Authors: Hu Renjie , Li Ruiyang , Tan Shengnan , Song Rongjun
Published: September 2023

Simple and convenient protocols for fabricating hierarchical porous carbons (HPCs) are highly imperative owing to their superior electrochemical performance. This work prepared a kind of KCl/MgO composite templates for synthesizing HPCs from polyethylene glycol‐200 carbon precursor with one‐step pyrolysis. The results show that the ratio of KCl and MgO can profoundly influence the morphology and microstructure of HPCs. At 50 wt % of KCl, the HPC‐5 displays the largest specific surface area and contains the best pore‐size distribution. When used as the supercapacitor electrodes without conductive additives, the HPC‐5 has a maximum capacitance (321.82 F g−1 at 0.5 A g−1), excellent rate performance (68.9 % of capacitance retention at the high current density of 10 A g−1), as well as remarkable cyclic stability (98 % capacitance retention after 5000 cycles) in aqueous electrolyte of 6 M KOH. When assembled into a symmetrical double‐electrode system, the HPC‐5 provides a high energy density of 11.20 Wh kg−1 at 390.66 W kg−1 power density in 1 M Na2SO4. The composite template methods are proposed as a promising route for the controllable synthesis of HPCs with high electrochemical properties.
Interlayer Coupling in Anisotropic/Isotropic Van der Waals Heterostructures of ReS2 and WS2
Authors: You Bingying , Xu Zheyuan , Yang Junqiang , Jiang Xingxing , Li Yanfang , Shao Gonglei , Jin Yuanyuan , Xiang Haiyan , Jiang Huili , Liu Xiaochi , Sun Jian , Feng Yexing , Jiang Ying , Pan Anlian , Liu Song
Published: September 2023

Van der Waals (vdW) heterostructures are composed of atomically thin layers assembled through weak (vdW) force, which have opened a new era for integrating materials with distinct properties and specific applications. However, few studies have focused on whether and how anisotropic materials affect heterostructure system. The study introduces anisotropic and isotropic materials in a heterojunction system to change the in‐plane symmetry, offering a new degree of freedom for modulating its properties. The sample is fabricated by manually stacking ReS2 and WS2 flakes prepared by mechanical exfoliation. Raman spectra and photoluminescence measurements confirm the formation of an effective heterojunction, indicating interlayer coupling of the system. The anisotropy and asymmetry of the WS2‐ReS2 heterostructure system can be adjusted by the introduction of isotropic WS2 and anisotropic ReS2, which can be proved by the change of the polarized Raman pattern. In the transient absorption measurement, the transient absorption spectra of WS2‐ReS2 heterostructure are red‐shifted compared to those of WS2 monolayer, and the charge transfer is observed in the heterostructure. These results show the potential of anisotropic 2D materials in anisotropy modulation of heterostructures, which may promote future electronic or photonic application.
Orally‐Delivered, Cytokine‐Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease
Authors: Liu Jingang , Ren He , Zhang Chen , Li Jiexin , Qiu Qian , Zhang Nan , Jiang Ning , Lovell Jonathan F. , Zhang Yumiao
Published: September 2023

The use of orally‐administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal‐IL10‐EVs (C/A) that protects interleukin 10 (IL‐10) from degradation in the stomach and enables targeted delivery of IL‐10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL‐10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL‐10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal‐IL10‐EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal‐IL10‐EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal‐IL10‐EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal‐IL10‐EVs (C/A) features biocompatibility, pH‐responsive drug release, and macrophage‐targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.
Controlling 1D Nanostructures and Handedness by Polar Residue Chirality of Amphiphilic Peptides
Authors: Xu Hai , Qi Kai , Zong Cheng , Deng Jing , Zhou Peng , Hu Xuzhi , Ma Xiaoyue , Wang Dong , Wang Muhan , Zhang Jun , King Stephen M. , Rogers Sarah E. , Lu Jian Ren , Yang Jun , Wang Jiqian
Published: September 2023

Peptide assemblies are promising nanomaterials, with their properties and technological applications being highly hinged on their supramolecular architectures. Here, how changing the chirality of the terminal charged residues of an amphiphilic hexapeptide sequence Ac‐I4K2‐NH2 gives rise to distinct nanostructures and supramolecular handedness is reported. Microscopic imaging and neutron scattering measurements show thin nanofibrils, thick nanofibrils, and wide nanotubes self‐assembled from four stereoisomers. Spectroscopic and solid‐state nuclear magnetic resonance (NMR) analyses reveal that these isomeric peptides adopt similar anti‐parallel β‐sheet secondary structures. Further theoretical calculations demonstrate that the chiral alterations of the two C‐terminal lysine residues cause the formation of diverse single β‐strand conformations, and the final self‐assembled nanostructures and handedness are determined by the twisting direction and degree of single β‐strands. This work not only lays a useful foundation for the fabrication of diverse peptide nanostructures by manipulating the chirality of specific residues but also provides a framework for predicting the supramolecular structures and handedness of peptide assemblies from single molecule conformations.
High‐Performance Pressure Sensors Based on Shaped Gel Droplet Arrays
Authors: Wang Zhenwu , Cai Qianyu , Lu Lutong , Levkin Pavel A.
Published: September 2023

Polymer gel‐based pressure sensors offer numerous advantages over traditional sensing technologies, including excellent conformability and integration into wearable devices. However, challenges persist in terms of their performance and manufacturing technology. In this study, a method for fabricating gel pressure sensors using a hydrophobic/hydrophilic patterned surface is introduced. By shaping and fine‐tuning the droplets of the polymer gel prepolymerization solution on the patterned surface, remarkable sensitivity improvements compared to unshaped hydrogels have been achieved. This also showcased the potential for tailoring gel pressure sensors to different applications. By optimizing the configuration of the sensor array, an uneven conductive gel array is fabricated, which exhibited a high sensitivity of 0.29 kPa−1 in the pressure range of 0–30 kPa, while maintaining a sensitivity of 0.13 kPa−1 from 30 kPa up to 100 kPa. Furthermore, the feasibility of using these sensors for human motion monitoring is explored and a conductive gel array for 2D force detection is successfully developed. This efficient and scalable fabrication method holds promise for advancing pressure sensor technology and offers exciting prospects for various industries and research fields.
Ligand‐Directed Shape Reconfiguration in Inorganic Materials
Authors: Paul Nishat , Zhang Lecheng , Lei Shijun , Huang Dali , Wang Ling , Cheng Zhengdong , Zeng Minxiang
Published: September 2023

Polymer elastomers with reversible shape‐changing capability have led to significant development of artificial muscles, functional devices, and soft robots. By contrast, reversible shape transformation of inorganic nanoparticles is notoriously challenging due to their relatively rigid lattice structure. Here, the authors demonstrate the synthesis of shape‐changing nanoparticles via an asymmetrical surface functionalization process. Various ligands are investigated, revealing the essential role of steric hindrance from the functional groups. By controlling the unbalanced structural hindrance on the surface, the as‐prepared clay nanoparticles can transform their shape in a fast, facile, and reversible manner. In addition, such flexible morphology‐controlled mechanism provides a platform for developing self‐propelled shape‐shifting nanocollectors. Owing to the ion‐exchanging capability of clay, these self‐propelled nanoswimmers (NS) are able to autonomously adsorb rare earth elements with ultralow concentration, indicating the feasibility of using naturally occurring materials for self‐powered nanomachine.
Configurational Entropy Strategy Enhanced Structure Stability Achieves Robust Cathode for Aluminum Batteries
Authors: Kang Rongkai , Zhang Dongmei , Du Yiqun , Sun Chenyi , Zhou Wei , Wang Han , Wan Jiaqi , Chen Guowen , Zhang Jianxin
Published: September 2023

Rechargeable aluminum batteries (RABs) are an emerging energy storage device owing to the vast Al resources, low cost, and high safety. However, the poor cyclability and inferior reversible capacity of cathode materials have limited the enhancement of RABs performance. Herein, a high configurational entropy strategy is presented to improve the electrochemical properties of RABs for the first time. The high‐entropy (Fe, Mn, Ni, Zn, Mg)3O4 cathode exhibits an ultra‐stable cycling ability (109 mAh g−1 after 3000 cycles), high specific capacity (268 mAh g−1 at 0.5 A g−1), and rapid ion diffusion. Ex situ characterizations indicate that the operational mechanism of (Fe, Mn, Ni, Zn, Mg)3O4 cathode is mainly based on the redox process of Fe, Mn, and Ni. Theoretical calculations demonstrate that the oxygen vacancies make a positive contribution to adjusting the distribution of electronic states, which is crucial for enhancing the reaction kinetics at the electrolyte and cathode interface. These findings not only propose a promising cathode material for RABs, but also provide the first elucidation of the operational mechanism and intrinsic information of high‐entropy electrodes in multivalent ion batteries.
ATSM: A coverage‐based framework and a tool for test suite minimization
Authors: Alekseev Yaroslav , Onischuck Mikhail , Zorin Arseniy , Chernyi Vitaliy , Iliyn Evgeniy , Itsykson Vladimir
Published: September 2023

Software projects grow larger every year, which, in turn, makes the testing process harder. One of the most useful methods for testing large projects is unit‐test generation. However, some tests can repeatedly cover the same parts of the code, making it difficult to maintain a growing test codebase. In software testing, test suite minimization plays a crucial role in reducing the cost of testing and improving the efficiency of the testing process. In this paper, we provide an extensible minimization engine that detects redundant tests using one of the supported minimization algorithms without changing the coverage metrics. We also performed a comprehensive analysis of existing approaches and techniques, developed an engine structure, and implemented multiple algorithms of different kinds. Finally, we evaluated our tool on various open‐source projects to demonstrate its effectiveness and efficiency.
Construction of Cation‐Sieving Function Layers Enabling Dendrite‐Free Zinc Metal Anodes for Durable Aqueous Systems
Authors: Dong Wenju , Liu Chenxu , Ji Xu , Yao Huan , Li Juan , Du Heliang , Cheng Shuang
Published: September 2023

Rechargeable aqueous zinc‐ion batteries are considered as promising candidates for safe and green energy storage. Yet, Zn anodes still suffer from serious challenges. Herein, an effective cation‐sieve of polyethersulfone‐modified sulfonated polyether ether ketone is developed as protective coating layer of the Zn anodes. Cation‐only transmission and dense property of the layer can protect the Zn from active water and anions, inhibiting corrosion, hydrogen evolution reaction (HER), and passivation. Zincophilic property of the layer can homogenize Zn2+ flow, and promote uniform plating of Zn. Therefore, protected symmetric Zn||Zn cell can maintain as long as 5600 h with a low polarization at 1.0 mA cm−2 and 0.5 mAh cm−2, and still long as 800 h at 5.0 mA cm−2 and 5.0 mAh cm−2. It is found that not only the dendrites but also the popular existed passivation product of Zn4SO4(OH)6·5H2O can be inhibited effectively. In asymmetric Zn||Ti cells, average Coulombic efficiency can reach 98.2%, suggesting corrosion and HER are restrained effectively. Matched with MnO2 cathode, full cells using coated Zn exhibit much better cycling performance than that using bare Zn. Moreover, Zn4O3(SO4)·7H2O (ZSH)‐assisted reversible conversion mechanism between the ZSH and ZnxHyMnO2 is revealed through operando Raman.
AACSB accreditation and student demand
Authors: Cameron Marisa , McCannon Bryan C. , Starr Katherine
Published: September 2023

We ask whether Association to Advance Collegiate Schools of Business (AACSB) accreditation has a meaningful impact on higher education admissions. To do this, we use the Synthetic control Method to explore 19 U.S. institutions which first achieved this certification recently. We, first, restrict attention to business school enrollment. While initial evidence suggests that the accreditation is associated with a decrease in enrollments, we show that this is complicated by non‐parallel trends prior to accreditation. Compared to their peers, institutions who seek out accreditation were experiencing flatter business enrollments. Correcting for the non‐parallel trends, we fail to find evidence that AACSB accreditation halts this negative undergraduate enrollment trend. We do find potential benefits to graduate business enrollment. Second, considering institution‐wide effects, we fail to find an impact on undergraduate applications, first‐year enrollment, price, or quality of the incoming student body.