bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of the effective thermal conductivity of iron oxide‐coated hexagonal boron nitride/polyimide composite sheets using samarium–cobalt magnets
Authors: Itaoka Takuro , Matsubayashi Ryohei , Haruki Masashi
Published: July 2023

The orientation and distribution of the filler in hexagonal boron nitride (hBN) coated with iron oxide (Fe3O4@hBN)/polyimide (PI) composite sheets were controlled via magnetic field treatment (MFT) to enhance the effective thermal conductivity (TC) in the out‐of‐plane direction. Filler chain structures gradually formed in the direction of the magnetic field in the precursor solution. The effective TC of the Fe3O4@hBN/PI sheet after MFT was much higher than that of pristine hBN/PI. The effective TC of the composites was preferably improved by placing the sample near a one‐sided magnet instead of in the middle of a pair of magnets. The effective TC of 10, 20, and 30 vol% Fe3O4@hBN/PI composites improved by 59%, 53%, and 35%, respectively, compared to that of pristine hBN/PI for a magnet distance of 10 mm and with the sample placed 2 mm from the bottom magnet. These values are in good agreement with those reported in the literature using MFT. The tensile strengths of the 10, 20, and 30 vol% Fe3O4@hBN/PI composites prepared using MFT were 33%, 33%, and 22% lower, respectively, than those of the composites prepared without MFT.
ReaxFF reactive force field model enables accurate prediction of physiochemical and mechanical properties of crystalline and amorphous shape‐memory polyurethane
Authors: Afroz Mohammad M. , Shin Yun Kyung , van Duin Adri C. T. , Li‐Oakey Katie D.
Published: July 2023

We investigate reactive force field (ReaxFF) prediction of physiochemical and mechanical properties, and stimuli response behavior of a shape‐memory polyurethane (SMPU) rigid segment. We used SMPUs as a platform to link the rigid/hard segment domain crystallinity with properties that can also be experimentally measured. Specifically, we developed models for crystalline and amorphous forms of a common rigid segment of SMPUs, for example, 4,4′‐diphenylmethane diisocyanate (MDI) with n‐butanediol (BDO), denoted as MDI‐BDO. ReaxFF molecular dynamics simulations with equilibrium dynamics are performed by controlling mass, temperature, and pressure or volume to predict the structural and physiochemical properties of crystalline and amorphous rigid segments of SMPU systems, followed by simulating their XRD and FTIR patterns, respectively. Non‐equilibrium ReaxFF simulations are implemented by using uniaxial box deformation technique to study response‐behavior of crystalline SMPU under tensile loading and during stress‐relaxation. The model and simulation scheme presented in this study demonstrates a robust theoretical pathway toward application‐dictated, on‐demand design of high‐performance SMPUs in applications such as soft robotics.
Femtosecond Laser‐Induced Periodic Surface Structuring of the Topological Insulator Bismuth Telluride
Authors: Hu Meilin , JJ Nivas Jijil , Salvatore Marcella , Oscurato Stefano L. , Guarino Anita , Fittipaldi Rosalba , Amoruso Salvatore , Vecchione Antonio
Published: July 2023

Surface structuring of topological insulator Bi2Te3 single crystals with femtosecond laser by varying pulses N and energy E is reported. Interesting effects related to laser‐induced periodic surface structures formation in this class of materials are evidenced. At low pulse energy, a clear formation of periodic, subwavelength ripples oriented orthogonally to the laser polarization is observed; those are restricted to an annular region surrounding a featureless central disk as the laser energy progressively increases. The structural analysis shows that some degree of crystallinity is preserved in the rippled area, but the central disk is amorphous resembling what is observed for germanium (Ge) and is associated with the hindering of surface structure formation due to a thick melted surface layer. Interestingly, at larger fluence or number of pulses, a transition to suprawavelength grooves occurs within the annular region covered by surface structures. The findings demonstrate a clear incubation behavior, suggesting that the formation of laser‐induced periodic surface structures is coherent with the general features of the process already reported for other materials. However, the disappearance of these structures in the central area, possibly resulting from the influence of the depth of the melt layer, indicates a mixed behavior for Bi2Te3.
Dual‐mode security authentication of SrAl2O4:Eu,Dy phosphor encapsulated in electrospun cellulose acetate nanofibrous films
Authors: El‐Newehy Mohamed , El‐Hamshary Hany , Abdul Hameed Meera Moydeen
Published: July 2023

Photochromic inks have been an attractive authentication strategy to improve the anti‐counterfeiting efficiency of commercial products. However, recent reports have shown significant disadvantages with photochromic inks, including poor durability and high cost. In this context, we developed novel photochromic nanofibres for advanced anti‐counterfeiting applications. Lanthanide‐doped strontium aluminate (LdSA) nanoparticles (NPs) were prepared and immobilized into electrospun cellulose acetate nanofibres (CANF). Authentication materials immobilized with inorganic photochromic agents can warranty durability and photostability. Therefore, the ultraviolet‐stimulated photochromism of LdSA‐encapsulated cellulose acetate nanofibres (LdSA@CANF) demonstrated high reversibility and photostability. A broad range of cellulose acetate nanofibres with unique emission characteristics was developed when applying different ratios of LdSA NPs. LdSA@CANF appeared colourless under visible daylight, whereas a green emission was monitored under ultraviolet‐light illumination. The shape and chemical content of the photochromic fibrous films were examined using various analytical techniques. The mechanical characteristics of LdSA@CANF‐coated paper were investigated. The emission wavelength was detected at 514 nm to designate green colour, whereas the excitation wavelength was detected at 369 nm to indicate transparency. The prepared cellulose acetate nanofibrous film can be described as an efficient strategy for the anti‐counterfeiting of commercialized items.
Induction chemotherapy‐based organ‐preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer—Results of a matched‐pair analysis
Authors: Yang Yifan , Feng Ling , Zhong Qi , Zhang Yang , Huang Zhigang , Zhang Shurong , Li Shuling , Gao Junmao , Hou Lizhen , Ma Hongzhi , He Shizhi , Shi Qian , Lian Meng , Zhao Yanming , Shen Xixi , Chen Jiaming , Wang Lingwa , Li Haiyang , Chen Shaoshi , Xu Jiaqi , Wang Ru , Fang Jugao
Published: July 2023

Background

We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy‐based organ‐preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy.

Methods

351 patients who were treated with organ‐preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression‐free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS).

Results

No statistical difference was observed for 3‐, 5‐, and 10‐year PFS and OS in two groups. In the organ‐preservation group, the 3‐, 5‐, and 10‐year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05).

Conclusions

Survival outcomes did not significantly differ between the two groups. The organ‐preservation approach allowed more than 70% of the survivors to retain their larynx function.
An unusual no‐reflow phenomenon due to neointimal tissue embolization during drug eluting balloon intervention in stent restenosis: A case report
Authors: Kim Sung Eun , Choi Ki Hong , Song Young Bin
Published: July 2023

Acute coronary syndrome is one of the leading causes of death worldwide. Percutaneous coronary intervention (PCI), along with various devices, have been technically developed to dramatically improve mortality risk in patients with acute myocardial infarction. However, no‐reflow phenomenon still remains a problematic complication during a PCI, even in the era of drug eluting stents. There are various hypotheses and mechanisms for no‐reflow phenomenon, but none have been confirmed. Treatment for no‐reflow phenomenon also depends on various underlying conditions, but have not yet shown effective improvement. We presented a case of no‐reflow phenomenon caused by an unusual cause.
Substrate Selectivity Imparted by Self‐Assembled Molecular Containers and Catalysts
Authors: Lorenzetto Tommaso , Bordignon Francesca , Munarin Luca , Mancin Fabrizio , Fabris Fabrizio , Scarso Alessandro
Published: July 2023

Recent trends in catalysis are devoted to mimicking some peculiar features of enzymes like site selectivity, through functional group recognition, and substrate selectivity, through recognition of the entire surface of the substrate. The latter is a specific feature of enzymes that is seldomly present in homogeneous catalysis. Supramolecular catalysis, thanks to the self‐assembly of simple subunits, enables the creation of cavities and surfaces whose confinement effects drive the preferential binding of a substrate among others with consequent substrate selectivity. The topic is an emerging field that exploits recognition phenomena to discriminate the reagents based on their size and shape. This review deals this cutting‐edge field of research covering examples of supramolecular self‐assembled molecular containers and catalysts operating in organic as well as aqueous media, with special emphasis for catalytic systems dealing with direct competitive experiments involving two or more substrates.
Cobalt‐Catalyzed Decarboxylative Allylations: Development and Mechanistic Studies
Authors: Joseph Ebbin , Hernandez Rafael D. , Tunge Jon A.
Published: July 2023

In recent years, there has been a concerted drive to develop methods that are greener and more sustainable. Being an earth‐abundant transition metal, cobalt offers an attractive substitute for commonly employed precious metal catalysts, though reactions engaging cobalt are still less developed. Herein, we report a method to achieve the decarboxylative allylation of nitrophenyl alkanes, nitroalkanes, and ketones employing cobalt. The reaction allows for the formation of various substituted allylated products in moderate‐excellent yields with a broad scope. Additionally, the synthetic potential of the methodology is demonstrated by the transformation of products into versatile heterocyclic motifs. Mechanistic studies revealed an in situ activation of the Co(II)/dppBz precatalyst by the carboxylate salt to generate a Co(I)‐species, which is presumed to be the active catalyst.
Synthesis and Structure of the Inclusion Compound COF300‐ALA
Authors: Hong Yuexian , Zhang Mingxuan , Zhou Zhipeng , Zhu Zhenyu , Lu Jiaxing , Sun Junliang , Zheng Zhikun
Published: July 2023

Comprehensive Summary

Finding a new multimolecular lattice inclusion host is still challenging. We report the synthesis and the crystal structure of the first example of an inclusion compound COF300‐ALA by using three‐dimensional covalent organic frameworks (3D‐COFs) as the multimolecular host lattice. The guest‐host dynamics upon inclusion and exclusion of the gust molecule are uncovered in a 3D covalent organic framework.
Patients hospitalized with acute heart failure, worsening renal function, and persistent congestion are at high risk for adverse outcomes despite current medical therapy
Authors: Cooper Lauren , DeVore Adam , Cowger Jennifer , Pinney Sean , Baran David , DeWald Tracy A. , Burt Tara , Pietzsch Jan B. , Walton Antony , Aaronson Keith , Shah Palak
Published: July 2023

Introduction

Approximately 1/3 of patients with acute decompensated heart failure (ADHF) are discharged with persistent congestion. Worsening renal function (WRF) occurs in approximately 50% of patients hospitalized for ADHF and the combination of WRF and persistent congestion are associated with higher risk of mortality and HF readmissions.

Methods

We designed a multicenter, prospective registry to describe current treatments and outcomes for patients hospitalized with ADHF complicated by WRF (defined as a creatinine increase ≥0.3 mg/dL) and persistent congestion at 96 h. Study participants were followed during the hospitalization and through 90‐day post‐discharge. Hospitalization costs were analyzed in an economic substudy.

Results

We enrolled 237 patients hospitalized with ADHF, who also had WRF and persistent congestion. Among these, the average age was 66 ± 13 years and 61% had a left ventricular ejection fraction (LVEF) ≤ 40%. Mean baseline creatinine was 1.7 ± 0.7 mg/dL. Patients with persistent congestion had a high burden of clinical events during the index hospitalization (7.6% intensive care unit transfer, 2.1% intubation, 1.7% left ventricular assist device implantation, and 0.8% dialysis). At 90‐day follow‐up, 33% of patients were readmitted for ADHF or died. Outcomes and costs were similar between patients with reduced and preserved LVEF.

Conclusions

Many patients admitted with ADHF have WRF and persistent congestion despite diuresis and are at high risk for adverse events during hospitalization and early follow‐up. Novel treatment strategies are urgently needed for this high‐risk population.
Angiotensin I‐converting enzyme type 2 expression is increased in pancreatic islets of type 2 diabetic donors
Authors: Fignani Daniela , Pedace Erika , Licata Giada , Grieco Giuseppina Emanuela , Aiello Elena , de Luca Carmela , Marselli Lorella , Marchetti Piero , Sebastiani Guido , Dotta Francesco
Published: July 2023

Aims

Angiotensin I‐converting enzyme type 2 (ACE2), a pivotal SARS‐CoV‐2 receptor, has been shown to be expressed in multiple cells, including human pancreatic beta‐cells. A putative bidirectional relationship between SARS‐CoV‐2 infection and diabetes has been suggested, confirming the hypothesis that viral infection in beta‐cells may lead to new‐onset diabetes or worse glycometabolic control in diabetic patients. However, whether ACE2 expression levels are altered in beta‐cells of diabetic patients has not yet been investigated. Here, we aimed to elucidate the in situ expression pattern of ACE2 in Type 2 diabetes (T2D) with respect to non‐diabetic donors which may account for a higher susceptibility to SARS‐CoV‐2 infection in beta‐cells.

Material and Methods

Angiotensin I‐converting enzyme type 2 immunofluorescence analysis using two antibodies alongside insulin staining was performed on formalin‐fixed paraffin embedded pancreatic sections obtained from n = 20 T2D and n = 20 non‐diabetic (ND) multiorgan donors. Intensity and colocalisation analyses were performed on a total of 1082 pancreatic islets. Macrophage detection was performed using anti‐CD68 immunohistochemistry on serial sections from the same donors.

Results

Using two different antibodies, ACE2 expression was confirmed in beta‐cells and in pancreas microvasculature. Angiotensin I‐converting enzyme type 2 expression was increased in pancreatic islets of T2D donors in comparison to ND controls alongside with a higher colocalisation rate between ACE2 and insulin using both anti‐ACE2 antibodies. CD68+ cells tended to be increased in T2D pancreata, in line with higher ACE2 expression observed in serial sections.

Conclusions

Higher ACE2 expression in T2D islets might increase their susceptibility to SARS‐CoV‐2 infection during COVID‐19 in T2D patients, thus worsening glycometabolic outcomes and disease severity.
Accounting for temporal variability in functional magnetic resonance imaging improves prediction of intelligence
Authors: Li Yang , Ma Xin , Sunderraman Raj , Ji Shihao , Kundu Suprateek
Published: July 2023

Neuroimaging‐based prediction methods for intelligence have seen a rapid development. Among different neuroimaging modalities, prediction using functional connectivity (FC) has shown great promise. Most literature has focused on prediction using static FC, with limited investigations on the merits of such analysis compared to prediction using dynamic FC or region‐level functional magnetic resonance imaging (fMRI) times series that encode temporal variability. To account for the temporal dynamics in fMRI, we propose a bi‐directional long short‐term memory (bi‐LSTM) approach that incorporates feature selection mechanism. The proposed pipeline is implemented via an efficient algorithm and applied for predicting intelligence using region‐level time series and dynamic FC. We compare the prediction performance using different fMRI features acquired from the Adolescent Brain Cognitive Development (ABCD) study involving nearly 7000 individuals. Our detailed analysis illustrates the consistently inferior performance of static FC compared to region‐level time series or dynamic FC for single and combined rest and task fMRI experiments. The joint analysis of task and rest fMRI leads to improved intelligence prediction under all models compared to using fMRI from only one experiment. In addition, the proposed bi‐LSTM pipeline based on region‐level time series identifies several shared and differential important brain regions across fMRI experiments that drive intelligence prediction. A test–retest analysis of the selected regions shows strong reliability across cross‐validation folds. Given the large sample size of ABCD study, our results provide strong evidence that superior prediction of intelligence can be achieved by accounting for temporal variations in fMRI.
Data‐driven electrical conductivity brain imaging using 3 T MRI
Authors: Jung Kyu‐Jin , Mandija Stefano , Cui Chuanjiang , Kim Jun‐Hyeong , Al‐masni Mohammed A. , Meerbothe Thierry G. , Park Mina , van den Berg Cornelis A. T. , Kim Dong‐Hyun
Published: July 2023

Magnetic resonance electrical properties tomography (MR‐EPT) is a non‐invasive measurement technique that derives the electrical properties (EPs, e.g., conductivity or permittivity) of tissues in the radiofrequency range (64 MHz for 1.5 T and 128 MHz for 3 T MR systems). Clinical studies have shown the potential of tissue conductivity as a biomarker. To date, model‐based conductivity reconstructions rely on numerical assumptions and approximations, leading to inaccuracies in the reconstructed maps. To address such limitations, we propose an artificial neural network (ANN)‐based non‐linear conductivity estimator trained on simulated data for conductivity brain imaging. Network training was performed on 201 synthesized T2‐weighted spin‐echo (SE) data obtained from the finite‐difference time‐domain (FDTD) electromagnetic (EM) simulation. The dataset was composed of an approximated T2‐w SE magnitude and transceive phase information. The proposed method was tested three in‐silico and in‐vivo on two volunteers and three patients' data. For comparison purposes, various conventional phase‐based EPT reconstruction methods were used that ignore magnitude information, such as Savitzky–Golay kernel combined with Gaussian filter (S‐G Kernel), phase‐based convection‐reaction EPT (cr‐EPT), magnitude‐weighted polynomial‐fitting phase‐based EPT (Poly‐Fit), and integral‐based phase‐based EPT (Integral‐based). From the in‐silico experiments, quantitative analysis showed that the proposed method provides more accurate and improved quality (e.g., high structural preservation) conductivity maps compared to conventional reconstruction methods. Representatively, in the healthy brain in‐silico phantom experiment, the proposed method yielded mean conductivity values of 1.97 ± 0.20 S/m for CSF, 0.33 ± 0.04 S/m for WM, and 0.52 ± 0.08 S/m for GM, which were closer to the ground‐truth conductivity (2.00, 0.30, 0.50 S/m) than the integral‐based method (2.56 ± 2.31, 0.39 ± 0.12, 0.68 ± 0.33 S/m). In‐vivo ANN‐based conductivity reconstructions were also of improved quality compared to conventional reconstructions and demonstrated network generalizability and robustness to in‐vivo data and pathologies. The reported in‐vivo brain conductivity values were in agreement with literatures. In addition, the proposed method was observed for various SNR levels (SNR levels = 10, 20, 40, and 58) and repeatability conditions (the eight acquisitions with the number of signal averages = 1). The preliminary investigations on brain tumor patient datasets suggest that the network trained on simulated dataset can generalize to unforeseen in‐vivo pathologies, thus demonstrating its potential for clinical applications.
In vitro biological responses of plasma nanocoatings for coronary stent applications
Authors: Phan ThiThuHa , Jones John E. , Chen Meng , Strawn T. L. , Khoukaz Hekmat B. , Ji Yan , Kumar Arun , Bowles Douglas K. , Fay William P. , Yu Qingsong
Published: July 2023

In‐stent restenosis and thrombosis remain to be long‐term challenges in coronary stenting procedures. The objective of this study was to evaluate the in vitro biological responses of trimethylsilane (TMS) plasma nanocoatings modified with NH3/O2 (2:1 molar ratio) plasma post‐treatment (TMS + NH3/O2 nanocoatings) on cobalt chromium (CoCr) alloy L605 coupons, L605 stents, and 316L stainless steel (SS) stents. Surface properties of the plasma nanocoatings with up to 2‐year aging time were characterized by wettability assessment and x‐ray photoelectron spectroscopy (XPS). It was found that TMS + NH3/O2 nanocoatings had a surface composition of 41.21 ± 1.06 at% oxygen, 31.90 ± 1.08 at% silicon, and 24.12 ± 1.7 at% carbon, and very small but essential amount of 2.77 ± 0.18 at% nitrogen. Surface chemical stability of the plasma coatings was noted with persistent O/Si atomic ratio of 1.292–1.413 and N/Si atomic ratio of ~0.087 through 2 years. The in vitro biological responses of plasma nanocoatings were studied by evaluating the cell proliferation and migration of porcine coronary artery endothelial cells (PCAECs) and smooth muscle cells (PCASMCs). 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium (MTT) assay results revealed that, after 7‐day incubation, TMS + NH3/O2 nanocoatings maintained a similar level of PCAEC proliferation while showing a decrease in the viability of PCASMCs by 73 ± 19% as compared with uncoated L605 surfaces. Cell co‐culture of PCAECs and PCASMCs results showed that, the cell ratio of PCAEC/PCASMC on TMS + NH3/O2 nanocoating surfaces was 1.5‐fold higher than that on uncoated L605 surfaces, indicating enhanced selectivity for promoting PCAEC growth. Migration test showed comparable PCAEC migration distance for uncoated L605 and TMS + NH3/O2 nanocoatings. In contrast, PCASMC migration distance was reduced nearly 8.5‐fold on TMS + NH3/O2 nanocoating surfaces as compared to the uncoated L605 surfaces. Platelet adhesion test using porcine whole blood showed lower adhered platelets distribution (by 70 ± 16%), reduced clotting attachment (by 54 ± 12%), and less platelet activation on TMS + NH3/O2 nanocoating surfaces as compared with the uncoated L605 controls. It was further found that, under shear stress conditions of simulated blood flow, TMS + NH3/O2 nanocoating significantly inhibited platelet adhesion compared to the uncoated 316L SS stents and TMS nanocoated 316L SS stents. These results indicate that TMS + NH3/O2 nanocoatings are very promising in preventing both restenosis and thrombosis for coronary stent applications.
Daboxin P, a phospholipase A2 of Indian Daboia russelii venom, modulates thrombin‐mediated platelet aggregation
Authors: Yasmin Rafika , Chanchal Shankar , Ashraf Mohammad Zahid , Doley Robin
Published: July 2023

Daboxin P, reported earlier from the venom of Daboia russellii, disturbs the blood coagulation cascade by targeting factor X and factor Xa. The present study exhibits that Daboxin P also inhibits platelet aggregation induced by various agonists. The thrombin‐induced platelet aggregation was inhibited maximum whereas inhibition of collagen‐induced platelet aggregation was found to be 50% and no inhibition of adenosine diphosphate (ADP) and arachidonic acid‐induced aggregation was observed. Daboxin P dose‐dependently inhibited the thrombin‐induced platelet aggregation with Anti‐Aggregation 50 (AD50) dose of 55.166 nM and also reduced the thrombin‐mediated calcium influx. In‐silico interaction studies suggested that Daboxin P binds to thrombin and blocks its interaction with its receptor on the platelet surface. Quenching of thrombin's emission spectrum by Daboxin P and electrophoretic profiles of pull‐down assay further reveals the binding between Daboxin P and thrombin. Thus, the present study demonstrates that Daboxin P inhibits thrombin‐induced platelet aggregation by binding to thrombin.
Targeting peptide‐mediated interaction between the N‐protein and P‐protein of human pediatric respiratory syncytial virus by molecular design of chemically stapled helical peptides
Authors: Yan Tingting , Zhang Yixian , Liu Lu , Shi Zhuo , Sun Tao , Yang Juan , Xue Liang , Shi Xiangxiang , Sha Ning
Published: July 2023

Background

Human respiratory syncytial virus (hRSV) is a leading viral etiologic agent of pediatric lower respiratory infection in infants, young children, and immunocompromised elderly individuals.

Objective

Targeting the intermolecular interaction between the viral nucleocapsid protein (N‐protein) and phosphoprotein (P‐protein) has been recognized as a promising therapeutic strategy against hRSV infection, which is a so‐called peptide‐mediated protein/protein interaction (PmPPI) by binding the short C‐terminal tail of P‐protein to the globular domain of N‐protein.

Methods

The PmPPI dynamics behavior and thermodynamics property were investigated systematically by integrating computational simulations and experimental assays.

Results

It is revealed that the C‐terminal tail of P‐protein is intrinsically disordered in free state but would fold into a structured helix when binding to N‐protein, known as coupled folding‐upon‐binding, thus incurring a considerable entropy penalty upon the binding. Several flexible P‐peptide segments with different lengths were derived from the C‐terminus of P‐protein and then stapled chemically by using an all‐hydrocarbon bridge, which effectively constrained the peptide disordered conformation into an ordered helical form in free state, thus considerably improving their affinity to N‐protein by minimizing the unfavorable entropy penalty.

Conclusions

Electrostatic contribution is primarily responsible for N/P complex stability, while other noncovalent factors such as hydrogen bond and aromatic stacking confer specificity to the complex recognition. The Phe241 residue at the C‐terminal end of P‐protein plays a crucial role that anchors the flexible C‐terminal tail of P‐protein to a druggable pocket on N‐protein surface.
A modelling framework for translating discrete choice experiment results into cost‐effectiveness estimates: an application to designing tailored and scalable HIV and contraceptive services for adolescents in Gauteng, South Africa
Authors: Govathson Caroline , Long Lawrence C. , Russell Colin A. , Moolla Aneesa , Pascoe Sophie , Nichols Brooke E.
Published: July 2023

Introduction

South African youth and adolescents face a high burden of (Sexually Transmitted Infections) STIs, HIV and unintended pregnancies, but uptake of services remains low. To address this, tailored and scalable interventions are urgently needed. We developed a framework to fill the gap and translate the impact of facility‐level attributes into a cost‐effectiveness analysis for increasing HIV/contraceptive service uptake in adolescents using a discrete choice experiment (DCE).

Methods

We used a DCE (n = 805) conducted in Gauteng, South Africa, which found that staff attitude, confidentiality, Wi‐Fi, subsidized food, afternoon hours and youth‐only services were preferred attributes of health services. Based on this, we simulated the uptake of services adapted for these preferences. We divided preferences into modifiable attributes that could readily be adapted (e.g. Wi‐Fi), and challenging to modify (more nuanced attributes that are more challenging to cost and evaluate): staff attitude and estimated the incremental change in the uptake of services using adapted services. Costs for modifiable preferences were estimated using data from two clinics in South Africa (2019 US$). We determined the incremental cost‐effectiveness ratio (ICER) for additional adolescents using services of 15 intervention combinations, and report the results of interventions on the cost‐effectiveness frontier.

Results

Greatest projected impact on uptake was from friendly and confidential services, both of which were considered challenging to modify (18.5% 95% CI: 13.0%−24.0%; 8.4% 95% CI: 3.0%−14.0%, respectively). Modifiable factors on their own resulted in only small increases in expected uptake. (Food: 2.3% 95% CI: 4.0%−9.00%; Wi‐Fi: 3.0% 95% CI: −4.0% to 10.0%; Youth‐only services: 0.3% 95% CI: −6.0% to 7.0%; Afternoon services: 0.8% 95% CI: −6.0% to 7.0%). The order of interventions on the cost‐effectiveness frontier are Wi‐Fi and youth‐only services (ICER US$7.01−US$9.78 per additional adolescent utilizing HIV and contraceptive services), Wi‐Fi, youth‐only services and food (ICER US$9.32−US$10.45), followed by Wi‐Fi, youth‐only services and extended afternoon hours (ICER US$14.46–US$43.63).

Conclusions

Combining DCE results and costing analyses within a modelling framework provides an innovative way to inform decisions on effective resource utilization. Modifiable preferences, such as Wi‐Fi provision, youth‐only services and subsidized food, have the potential to cost‐effectively increase the proportion of adolescents accessing HIV and contraceptive services.
Magnetic Resonance Imaging of Lung Perfusion
Authors: Triphan Simon M.F. , Bauman Grzegorz , Konietzke Philip , Konietzke Marilisa , Wielpütz Mark O. ,   the International Workshop for Pulmonary Functional Imaging (IWPFI)
Published: July 2023

“Lung perfusion” in the context of imaging conventionally refers to the delivery of blood to the pulmonary capillary bed through the pulmonary arteries originating from the right ventricle required for oxygenation. The most important physiological mechanism in the context of imaging is the so‐called hypoxic pulmonary vasoconstriction (HPV, also known as “Euler‐Liljestrand‐Reflex”), which couples lung perfusion to lung ventilation. In obstructive airway diseases such as asthma, chronic‐obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma, HPV downregulates pulmonary perfusion in order to redistribute blood flow to functional lung areas in order to conserve optimal oxygenation. Imaging of lung perfusion can be seen as a reflection of lung ventilation in obstructive airway diseases. Other conditions that primarily affect lung perfusion are pulmonary vascular diseases, pulmonary hypertension, or (chronic) pulmonary embolism, which also lead to inhomogeneity in pulmonary capillary blood distribution. Several magnetic resonance imaging (MRI) techniques either dependent on exogenous contrast materials, exploiting periodical lung signal variations with cardiac action, or relying on intrinsic lung voxel attributes have been demonstrated to visualize lung perfusion. Additional post‐processing may add temporal information and provide quantitative information related to blood flow. The most widely used and robust technique, dynamic‐contrast enhanced MRI, is available in clinical routine assessment of COPD, CF, and pulmonary vascular disease. Non‐contrast techniques are important research tools currently requiring clinical validation and cross‐correlation in the absence of a viable standard of reference. First data on many of these techniques in the context of observational studies assessing therapy effects have just become available.

Level of Evidence

5

Technical Efficacy

Stage 5
A pharmacokinetic study to correlate the hypoglycemic effect of phlorizin in rats: Identification of metabolites as inhibitors of sodium/glucose cotransporters
Authors: Borkar Roshan M. , Kanwal Abhinav , Raju Bandu , Pulimamidi Sai Sharanya , Das Agneesh Pratim , Agarwal Subhash Mohan , Banerjee Sanjay K. , Srinivas Ragampeta
Published: July 2023

Phlorizin (PRZ) is a natural product that belongs to a class of dihydrochalcones. The unique pharmacological property of PRZ is to block glucose absorption or reabsorption through specific and competitive inhibitors of the sodium/glucose cotransporters (SGLTs) in the intestine (SGLT1) and kidney (SGLT2). This results in glycosuria by inhibiting renal reabsorption of glucose and can be used as an adjuvant treatment for type 2 diabetes. The pharmacokinetic profile, metabolites of the PRZ, and efficacy of metabolites towards SGLTs are unknown. Therefore, the present study on the characterization of hitherto unknown in vivo metabolites of PRZ and pharmacokinetic profiling using liquid chromatography‐electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) and accurate mass measurements is undertaken. Plasma, urine, and feces samples were collected after oral administration of PRZ to Sprague–Dawley rats to identify in vivo metabolites. Furthermore, in silico efficacy of the identified metabolites was evaluated by docking study. PRZ at an intraperitoneal dose of 400 mg/kg showed maximum concentration in the blood to 439.32 ± 8.84 ng/mL at 1 h, while phloretin showed 14.38 ± 0.33 ng/mL at 6 h. The pharmacokinetic profile of PRZ showed that the maximum concentration lies between 1 and 2 h after dosing. Decreased blood glucose levels and maximum excretion of glucose in the urine were observed when the PRZ and metabolites were observed in plasma. The identification and characterization of PRZ metabolites by LC/ESI/MS/MS further revealed that the phase I metabolites of PRZ are hydroxy (mono‐, di‐, and tri‐) and reduction. Phase II metabolites are O‐methylated, O‐acetylated, O‐sulfated, and glucuronide metabolites of PRZ. Further docking study revealed that the metabolites diglucuronide metabolite of mono‐hydroxylated PRZ and mono‐glucuronidation of PRZ could be considered novel inhibitors of SGLT1 and SGLT2, respectively, which show better binding affinities than their parent compound PRZ and the known inhibitors.
Detection of parechovirus‐A in hospitalized children with acute lower respiratory infection in Myanmar, 2017–2018
Authors: Tachikawa Jun , Aizawa Yuta , Kobayashi Tetsuya , Ikuse Tatsuki , Kamata Kazuhiro , Win Su Mon Kyaw , Di Ja Lasham , Thein Khin Nyo , Win Nay Chi , Thida Aye , Tun Aye , Suzuki Yuko , Ito Ai , Osada Hidekazu , Chon Irina , Phyu Wint Wint , Ota Tomomi , Kyaw Yadanar , Tin Htay Htay , Watanabe Kanako , Shobugawa Yugo , Watanabe Hisami , Saito Reiko , Saitoh Akihiko
Published: July 2023

Parechovirus‐A (PeV‐A) causes emerging infection in children, and clinical presentation depends on genotype. The virus has been investigated mainly in developed countries; however, data from developing countries, especially in Asia, are sparse. This study investigated whether PeV‐A circulated in children in Myanmar. This retrospective study evaluated PeV‐A in nasopharyngeal samples from children aged 1 month to 12 years who were hospitalized with acute lower respiratory infection at Yankin Children Hospital, Yangon, Myanmar, during the period from May 2017 to April 2019. Real‐time polymerase chain reaction (PCR) was used to detect PeV‐A, and PCR‐positive samples were used for genotyping and phylogenetic analysis. In total, 11/570 (1.9%) of samples were positive for PeV‐A; 7 were successfully genotyped by sequencing the VP3/VP1 region, as follows: PeV‐A1 (n = 4), PeV‐A5 (n = 1), PeV‐A6 (n = 1), and PeV‐A14 (n = 1). Median age was 10.0 months (interquartile range 4.0–12.0 months), and other respiratory viruses were detected in all cases. Phylogenetic analysis showed that all detected PeV‐A1 strains were in clade 1 A, which was a minor clade worldwide. Four PeV‐A genotypes were detected in Myanmar. The clinical impact of PeV‐A in children should be evaluated in future studies.
KCa2.2 (KCNN2): A physiologically and therapeutically important potassium channel
Authors: Rahman Mohammad Asikur , Orfali Razan , Dave Nikita , Lam Elyn , Naguib Nadeen , Nam Young‐Woo , Zhang Miao
Published: July 2023

One group of the K+ ion channels, the small‐conductance Ca2+‐activated potassium channels (KCa2.x, also known as SK channels family), is widely expressed in neurons as well as the heart, endothelial cells, etc. They are named small‐conductance Ca2+‐activated potassium channels (SK channels) due to their comparatively low single‐channel conductance of about ~10 pS. These channels are insensitive to changes in membrane potential and are activated solely by rises in the intracellular Ca2+. According to the phylogenic research done on the KCa2.x channels family, there are three channels' subtypes: KCa2.1, KCa2.2, and KCa2.3, which are encoded by KCNN1, KCNN2, and KCNN3 genes, respectively. The KCa2.x channels regulate neuronal excitability and responsiveness to synaptic input patterns. KCa2.x channels inhibit excitatory postsynaptic potentials (EPSPs) in neuronal dendrites and contribute to the medium afterhyperpolarization (mAHP) that follows the action potential bursts. Multiple brain regions, including the hippocampus, express the KCa2.2 channel encoded by the KCNN2 gene on chromosome 5. Of particular interest, rat cerebellar Purkinje cells express KCa2.2 channels, which are crucial for various cellular processes during development and maturation. Patients with a loss‐of‐function of KCNN2 mutations typically exhibit extrapyramidal symptoms, cerebellar ataxia, motor and language developmental delays, and intellectual disabilities. Studies have revealed that autosomal dominant neurodevelopmental movement disorders resembling rodent symptoms are caused by heterozygous loss‐of‐function mutations, which are most likely to induce KCNN2 haploinsufficiency. The KCa2.2 channel is a promising drug target for spinocerebellar ataxias (SCAs). SCAs exhibit the dysregulation of firing in cerebellar Purkinje cells which is one of the first signs of pathology. Thus, selective KCa2.2 modulators are promising potential therapeutics for SCAs.
Critical appraisal tools used in systematic reviews of in vitro cell culture studies: A methodological study
Authors: Paiva Barbosa Victor , Bastos Silveira Bruna , Amorim dos Santos Juliana , Monteiro Mylene Martins , Coletta Ricardo D. , De Luca Canto Graziela , Stefani Cristine Miron , Guerra Eliete Neves Silva
Published: July 2023

Systematic reviews (SRs) of preclinical studies are marked with poor methodological quality. In vitro studies lack assessment tools to improve the quality of preclinical research. This methodological study aimed to identify, collect, and analyze SRs based on cell culture studies to highlight the current appraisal tools utilized to support the development of a validated critical appraisal tool for cell culture in vitro research. SRs, scoping reviews, and meta‐analyses that included cell culture studies and used any type of critical appraisal tool were included. Electronic search, study selection, data collection and methodological quality (MQ) assessment tool were realized. Further, statistical analyses regarding possible associations and correlations between MQ and collected data were performed. After the screening process, 82 studies remained for subsequent analysis. A total of 32 different appraisal tools were identified. Approximately 60% of studies adopted pre‐structured tools not designed for cell culture studies. The most frequent instruments were SYRCLE (n = 14), OHAT (n = 9), Cochrane Collaboration's tool (n = 7), GRADE (n = 6), CONSORT (n = 5), and ToxRTool (n = 5). The studies were divided into subgroups to perform statistical analyses. A significant association (OR = 5.00, 95% CI = 1.54–16.20, p = 0.008) was found between low MQ and chronic degenerative disorders as topic of SR. Several challenges in collecting information from the included studies led to some modifications related to the previously registered protocol. These results may serve as a basis for further development of a critical appraisal tool for cell culture studies capable of capturing all the essential factors related to preclinical research, therefore enhancing the practice of evidence‐based.
In vitro gastrointestinal digestion of highland barley protein: identification and characterization of novel bioactive peptides involved in gut cholecystokinin secretion
Authors: Huang Kai , Wang Qingyu , Song Hongdong , Cao Hongwei , Guan Xiao
Published: July 2023

BACKGROUND

The satiety hormone cholecystokinin (CCK) plays an important role in food intake inhibition. Its secretion is regulated by dietary components. The search for bioactive compounds that induce CCK secretion is currently an active area of research. The objective of this study was to evaluate the ability of highland barley protein digest (HBPD) to stimulate CCK secretion in vitro and in vivo and identify the responsible peptide sequences.

RESULTS

HBPD was prepared by in vitro gastrointestinal digestion model. Peptides of <1000 Da in HBPD accounted for 82%. HBPD was rich in essential amino acids Leu, Phe and Val, but lack in sulfur amino acids Met and Cys. HBPD treatment at a concentration of 5 mg mL−1 significantly stimulated CCK secretion from enteroendocrine STC‐1 cells (P < 0.05). Moreover, oral gavage with HBPD in mice significantly increased plasma CCK level. Chromatographic separation was performed to isolate peptide fractions involved in CCK secretion and peptide sequence was determined by ultra‐performance liquid chromatography–tandem mass spectrometry. Two novel CCK‐releasing peptides, PDLP and YRIVPL, were pointed out for their outstanding CCK secretagogue activity.

CONCLUSION

This study demonstrated for the first time that HBPD had an ability to stimulate CCK secretion in vitro and in vivo and determined the bioactive peptides exerting CCK secretagogue activity in HBPD. © 2023 Society of Chemical Industry.
Frozen Section Timeout: Pilot Study to Reconcile Margins Using 3D Resected Specimen and Defect Scans
Authors: Kapustin Danielle A. , Yun Jun , Su Vivian , Rubin Samuel J. , Modica Ippolito , Chung Daniel , Fan Jun , Khan Mohemmed N. , Chai Raymond L. , Karasick Michael , Doyle Scott , Brandwein‐Weber Margaret , Urken Mark L.
Published: July 2023

Objective

Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a “frozen section timeout” that centers around visualization of the paired resection specimen and surgical defect—facilitating effective, bidirectional exchange of information.

Methods

We designed an interactive form for use during the “frozen section timeout” including annotated 3D virtual models of the resected specimen and surgical defect, plus a “line‐item” table for primary and supplemental margin results. The “timeout” was conducted over a Zoom call between the operating room and frozen section laboratory. The form was simultaneously projected and discussed while all members of the surgical care team stopped activities. Nurses, co‐surgeons, and all other members of the surgical team were encouraged to take part in this process.

Results

Twenty‐six frozen section timeouts were conducted during head and neck surgeries in the Department of Otolaryngology at Mount Sinai West Hospital. These timeouts were facilitated by the lead surgeon, and all other activities were halted to ensure that critical information was shared, documented, and agreed upon. During the timeout, the annotated specimen and defect scans were displayed, clearly demonstrating the at‐risk margins and the corresponding location and breadth of supplemental margins harvested.

Conclusion

Incorporating a frozen section timeout can improve intraoperative communication, increase transparency, and potentially eliminate uncertainty regarding margin status and tumor clearance. Visualization of at‐risk margins and the corresponding location and breadth of supplemental margins promises an unprecedented level of documentation and understanding. This novel technique can establish a new and improved standard of care.

Level of Evidence

NA Laryngoscope, 134:725–731, 2024
A comparative study on different neural network architectures to model inelasticity
Authors: Rosenkranz Max , Kalina Karl A. , Brummund Jörg , Kästner Markus
Published: July 2023

The mathematical formulation of constitutive models to describe the path‐dependent, that is, inelastic, behavior of materials is a challenging task and has been a focus in mechanics research for several decades. There have been increased efforts to facilitate or automate this task through data‐driven techniques, impelled in particular by the recent revival of neural networks (NNs) in computational mechanics. However, it seems questionable to simply not consider fundamental findings of constitutive modeling originating from the last decades research within NN‐based approaches. Herein, we propose a comparative study on different feedforward and recurrent neural network architectures to model 1D small strain inelasticity. Within this study, we divide the models into three basic classes: black box NNs, NNs enforcing physics in a weak form, and NNs enforcing physics in a strong form. Thereby, the first class of networks can learn constitutive relations from data while the underlying physics are completely ignored, whereas the latter two are constructed such that they can account for fundamental physics, where special attention is paid to the second law of thermodynamics in this work. Conventional linear and nonlinear viscoelastic as well as elastoplastic models are used for training data generation and, later on, as reference. After training with random walk time sequences containing information on stress, strain, and—for some models—internal variables, the NN‐based models are compared to the reference solution, whereby interpolation and extrapolation are considered. Besides the quality of the stress prediction, the related free energy and dissipation rate are analyzed to evaluate the models. Overall, the presented study enables a clear recording of the advantages and disadvantages of different NN architectures to model inelasticity and gives guidance on how to train and apply these models.