bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis
Authors: Liang Hai‐Feng , Zou Yan‐Pei , Hu An‐Nan , Wang Ben , Li Juan , Huang Lei , Chen Wei‐Sin , Su Di‐Han , Xiao Lan , Xiao Yin , Ma Yi‐Qun , Li Xi‐Lei , Jiang Li‐Bo , Dong Jian
Published: September 2023

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone‐mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the β‐sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical‐size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin‐2‐mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+/calmodulin/calmodulin‐dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.
18.6% Efficiency All‐Polymer Solar Cells Enabled by a Wide Bandgap Polymer Donor Based on Benzo[1,2‐d:4,5‐d′]bisthiazole
Authors: Wu Peixi , Duan Yuwei , Li Yinfeng , Xu Xiaopeng , Li Ruipeng , Yu Liyang , Peng Qiang
Published: September 2023

The limited selection of wide bandgap polymer donors for all‐polymer solar cells (all‐PSCs) is a bottleneck problem restricting their further development and remains poorly studied. Herein, a new wide bandgap polymer, namely PBBTz‐Cl, is designed and synthesized by bridging the benzobisthiazole acceptor block and chlorinated benzodithiophene donor block with thiophene units for application as an electron donor in all‐PSCs. PBBTz‐Cl not only possesses wide bandgap and deep energy levels but also displays strong absorption, high‐planar structure, and good crystallinity, making it a promising candidate for application as a polymer donor in organic solar cells. When paired with the narrow bandgap polymer acceptor PY‐IT, a fibril‐like morphology forms, which facilitates exciton dissociation and charge transport, contributing to a power conversion efficiency (PCE) of 17.15% of the corresponding all‐PSCs. Moreover, when introducing another crystalline polymer acceptor BTP‐2T2F into the PBBTz‐Cl:PY‐IT host blend, the absorption ditch in the range of 600–750 nm is filled, and the blend morphology is further optimized with the trap density reducing. As a result, the ternary blend all‐PSCs achieve a significantly improved PCE of 18.60%, which is among the highest values for all‐PSCs to date.
Artificial intelligence for neurodegenerative experimental models
Authors: Marzi Sarah J. , Schilder Brian M. , Nott Alexi , Frigerio Carlo Sala , Willaime‐Morawek Sandrine , Bucholc Magda , Hanger Diane P. , James Charlotte , Lewis Patrick A. , Lourida Ilianna , Noble Wendy , Rodriguez‐Algarra Francisco , Sharif Jalil‐Ahmad , Tsalenchuk Maria , Winchester Laura M. , Yaman Ümran , Yao Zhi ,   The Deep Dementia Phenotyping (DEMON) Network, Ranson Janice M. , Llewellyn David J.
Published: September 2023

INTRODUCTION

Experimental models are essential tools in neurodegenerative disease research. However, the translation of insights and drugs discovered in model systems has proven immensely challenging, marred by high failure rates in human clinical trials.

METHODS

Here we review the application of artificial intelligence (AI) and machine learning (ML) in experimental medicine for dementia research.

RESULTS

Considering the specific challenges of reproducibility and translation between other species or model systems and human biology in preclinical dementia research, we highlight best practices and resources that can be leveraged to quantify and evaluate translatability. We then evaluate how AI and ML approaches could be applied to enhance both cross‐model reproducibility and translation to human biology, while sustaining biological interpretability.

DISCUSSION

AI and ML approaches in experimental medicine remain in their infancy. However, they have great potential to strengthen preclinical research and translation if based upon adequate, robust, and reproducible experimental data.

Highlights

There are increasing applications of AI in experimental medicine.

We identified issues in reproducibility, cross‐species translation, and data curation in the field.

Our review highlights data resources and AI approaches as solutions.

Multi‐omics analysis with AI offers exciting future possibilities in drug discovery.
A multidomain intervention against cognitive decline in an at‐risk‐population in Germany: Results from the cluster‐randomized AgeWell.de trial
Authors: Zülke Andrea E. , Pabst Alexander , Luppa Melanie , Roehr Susanne , Seidling Hanna , Oey Anke , Cardona Maria Isabel , Blotenberg Iris , Bauer Alexander , Weise Solveig , Zöllinger Isabel , Sanftenberg Linda , Brettschneider Christian , Döhring Juliane , Lunden Laura , Czock David , Haefeli Walter E. , Wiese Birgitt , Hoffmann Wolfgang , Frese Thomas , Gensichen Jochen , König Hans‐Helmut , Kaduszkiewicz Hanna , Thyrian Jochen René , Riedel‐Heller Steffi G.
Published: September 2023

INTRODUCTION

We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster‐randomized trial.

METHODS

Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain‐specific neuropsychological tests).

RESULTS

Of 1030 participants at baseline, n = 819 completed the 24‐month follow‐up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: –0.113, 0.133) were found between groups at follow‐up. Perceived restrictions in intervention conduct by the COVID‐19 pandemic did not impact intervention effectiveness.

DISCUSSION

The intervention did not improve global cognitive performance.

Highlights

Overall, no intervention effects on global cognitive performance were detected.

The multidomain intervention improved health‐related quality of life in the total sample.

In women, the multidomain intervention reduced depressive symptoms.

The intervention was completed during the COVID‐19 pandemic.
Numerical study of paraffin and glass fiber composites for thermal management of lithium‐ion battery packs
Authors: Huo Zhaorui , Hong Xiaobo , Li Yanyan , Chen Zihan , Ruan Dianbo
Published: September 2023

Phase change materials (PCMs) have garnered significant interest in the field of passive cooling for lithium‐ion batteries in recent years due to their simple structure, low cost, and stable performance. This paper introduces a passive thermal management strategy based on nonuniform paraffin (PA) and glass fiber for battery modules. It explores the impact of glass fiber on the thermal conductivity and structural strength of PA, as well as the thermal management performance of the composite phase change battery module that combines the two materials. The findings reveal that the composite phase change module with a glass fiber mass fraction of 60%, operating at a discharge rate of 3C, maintains a temperature 0.76°C lower than that of the air‐cooling module. This reduction results in a decreased maximum temperature difference between the modules from 7.3 to 5.0°C and a decrease in the maximum temperature ratio from 16.9% to 11.6%. Moreover, compared to the PA phase change module, heat transfer to adjacent cells decreases by approximately 10% during thermal runaway, effectively suppressing thermal propagation. Additionally, the incorporation of glass fiber in this scheme enhances the compressive strength of the module by a factor of 9.81. This study presents a novel method to address the thermal management needs of batteries for heat dissipation and thermal insulation.
Molecular docking, synthesis, anticancer activity, and metabolomics study of boronic acid ester‐containing fingolimod derivatives
Authors: Doyduk Doğukan , Derkus Burak , Sari Buse , Eylem Cemil Can , Nemutlu Emirhan , Yıldırır Yılmaz
Published: September 2023

In recent years, drugs that contain boronic acid groups, such as ixazomib (Ninlaro™) and bortezomib (Velcade™), have been used in the treatment of bone marrow cancer. The activity of compounds has been found to increase with the addition of boron atoms to the structure. In addition to these compounds, studies have found that fingolimod (FTY720) is more effective against breast cancer than cisplatin. Therefore, in this study, the first examples of boron‐containing derivatives of fingolimod were designed and synthesized; in addition, their structures were confirmed by spectroscopic techniques. The synthesized boron‐containing drug candidates were found to significantly inhibit cell proliferation and induce apoptosis‐mediated cell death in HT‐29 (colorectal cells), SaOs‐2 (osteosarcoma cells), and U87‐MG (glioblastoma cells). Moreover, we revealed that the anticancer effects of boron‐containing fingolimod compounds were found to be significantly enhanced over boron‐free control groups and, strikingly, over the widely used anticancer drug 5‐fluorouracil. The metabolomic analysis confirmed that administration of the boron‐containing drug candidates induces significant changes in the metabolite profiles in HT‐29, SaOs‐2, and U87‐MG cells. Altogether, our results showed that boron‐containing fingolimod compounds can be further examined to reveal their potential as anticancer drug candidates.
Über das Verhalten von Stickstoff gegenüber flüssigem Eisen und über die Entkohlungsreaktion
Authors: von Bogdandy L. , Schmolke R. , Stranski I. N.
Published: September 2023

Reaktionsgeschwindigkeiten der Gase N2, CO und CO2 mit flüssigem Eisen werden im Induktionsofen bei kontrollierter Gaszusammensetzung und verschiedenen Drucken untersucht. Es wird gezeigt, daß für den Übergang der Gase in das Metall und umgekehrt die Diffusion durch eine dünne Grenzschicht der flüssigen Phase geschwindigkeitsbestimmend ist.

Eine Untersuchung der Keimbildung von CO‐Gasblasen in der flüssigen Phase geht von theoretischen Betrachtungen aus. Gemäß der Theorie von Volmer und Stranski kann eine homogene Keimbildung wegen der sehr hohen Keimbildungsarbeiten nicht stattfinden. Die Entstehung von Gasblasen ist an Grenzflächen gebunden. Es werden deshalb die geometrischen Verhältnisse an Grenzflächen, wie der Einfluß von Rissen und Zerklüftungen, diskutiert. Hieraus folgt, daß vor allem der Benetzungswinkel zwischen flüssigem Eisen, Gasphase und Tiegelmaterial von Bedeutung ist.

Die Bedingungen für den störungsfreien Ablauf der CO‐Blasenkeimbildung und damit für die technisch betriebene Entkohlungsreaktion wurden klargestellt.
Untersuchung des Kristallfeldeinflusses auf die 35Cl‐Kernquadrupolresonanz in C‐Cl‐Bindungen
Authors: Biedenkapp Dieter , Weiss Alarich
Published: September 2023

An einer Reihe von Molekülverbindungen der Trichloressigsäure mit Aldehyden, Ketonen, Säuren, Estern, Alkoholen, Phenolen und Äthern sowie an Salzen der Trichloressigsäure wurden die 35Cl‐Kernquadrupolresonanzfrequenzen bei 77 °K untersucht. Aus den Messungen wird der Einfluß des Kristallfeldes auf die Kernquadrupolresonanz von 35Cl in C‐Cl‐Bindungen abgeschätzt. Es ergibt sich eine auf das Kristallfeld zurückzuführende mittlere Frequenzverschiebung in den Molekülverbindungen von ±0,6 MHz. Diese Verschiebung ist als Unsicherheitsfaktor bei der Diskussion der C‐Cl‐Bindung auf Grund KQR‐spektroskopischer Untersuchungen zu beachten. Einige Schlüsse über die Struktur der Trichloressigsäureadditionsverbindungen sowie der Salze der Trichloressigsäure werden mit Hilfe der Kernquadrupolresonanz an 35Cl gezogen.
Dampfdruck von Mehrkomponenten‐Elektrolytlösungen
Authors: Schönert Hansjürgen
Published: September 2023

Es wird eine Methode beschrieben, die es gestattet, aus Dampfdruckmessungen an Lösungen mit zwei nichtflüchtigen Elektrolyten die Aktivitätskoeffizienten der zwei gelösten Komponenten zu berechnen. Sie wird an den Systemen H2O‐CsCl‐KCl, H2O‐LiCl‐KCl und H2O‐LiCl‐CsCl vorgeführt.
Dampfdruckmessungen an dem System Wasser‐Chlorwasserstoff Wolframatokieselsäure bei 25°C
Authors: Pelzer Heinz , Schönert Hansjürgen
Published: September 2023

Es werden Dampfdruckmessungen an wäßrigen Lösungen von Salzsäure und Wolframatokieselsäure mitgeteilt, die in einer nach der Mitführungsmethode arbeitenden Apparatur durchgeführt worden sind. Aus den osmotischen Koeffizienten werden die Aktivitätskoeffizienten der zwei gelösten Komponenten berechnet und mit solchen in Systemen mit zwei niedrigmolekularen Elektrolyten verglichen.
Phosphine‐Catalyzed [4+3] Annulation Reaction of Indole Derivatives with MBH Carbonates: A Facile Access to Indole‐1,2‐fused 1,4‐Diazepinones and Azepines
Authors: Zhu Yannan , Jiang Haoran , Wang Yi‐Ning
Published: September 2023

Comprehensive Summary

A phosphine‐catalyzed [4+3] annulation between dinucleophilic indole derivatives and Morita−Baylis−Hillman (MBH) carbonates was discovered by using the N1 and N4′/C4′ nucleophilicities of the indole precursors, in which indoles act as four atom synthons. This protocol provides an efficient and facile access to indole‐1,2‐fused 1,4‐diazepinones and azepines in good to high yields in one step, which illustrates potential synthetic utilities in drug discovery.
On the questionable use ofCIEL* to infer geometric properties of achromatic perception
Authors: Berthier Michel , Provenzi Edoardo
Published: September 2023

In the paper “The non‐Riemannian nature of perceptual color space,” the authors analyze the data of visual experiments conducted using triad of CIE achromatic stimuli. The statistical analysis of their results leads them to claim that the axis cannot be endowed with a Riemannian metric coherent with observers' responses. In this communication we provide a mathematical analysis which, in our opinion, refutes the main claim of the quoted paper. Furthermore, we raise questions on the soundness of using an achromatic perceptual coordinate to describe non‐chromatic perception. We inform about an alternative in which achromaticity emerges from the very act of observing colors (Provenzi E. SIAM J Imag Sci, 15(4):1944–1976, 2022; Berthier M, Provenzi E. Proc R Soc A, 478(2258):20210508, 2022).
TIMP1 is an early biomarker for detection and prognosis of lung cancer
Authors: Dantas Ezequiel , Murthy Anirudh , Ahmed Tanvir , Ahmed Mujmmail , Ramsamooj Shakti , Hurd Maurice A. , Lam Tiffany , Malbari Murtaza , Agrusa Christopher , Elemento Olivier , Zhang Chen , Pappin Darryl J. , McGraw Timothy E. , Stiles Brendon M. , Altorki Nasser K. , Goncalves Marcus D.
Published: September 2023

Background

Lung cancer remains the major cause of cancer‐related deaths worldwide. Early stages of lung cancer are characterized by long asymptomatic periods that are ineffectively identified with the current screening programs. This deficiency represents a lost opportunity to improve the overall survival of patients. Serum biomarkers are among the most effective strategies for cancer screening and follow up.

Methods

Using bead‐based multiplexing assays we screened plasma and tumours of the KrasG12D/+; Lkb1f/f (KL) mouse model of lung cancer for cytokines that could be used as biomarkers. We identified tissue inhibitor of metalloproteinase 1 (TIMP1) as an early biomarker and validated this finding in the plasma of lung cancer patients. We used immunohistochemistry (IHC), previously published single‐cell RNA‐seq and bulk RNA‐seq data to assess the source and expression of TIMP1in the tumour. The prognostic value of TIMP1 was assessed using publicly available human proteomic and transcriptomic databases.

Results

We found that TIMP1 is a tumour‐secreted protein with high sensitivity and specificity for aggressive cancer, even at early stages in mice. We showed that TIMP1 levels in the tumour and serum correlate with tumour burden and worse survival in mice. We validated this finding using clinical samples from our institution and publicly available human proteomic and transcriptomic databases. These data support the finding that high tumour expression of TIMP1 correlates with an unfavorable prognosis in lung cancer patients.

Conclusion

TIMP1 is a suitable biomarker for lung cancer detection.
Beyond protected areas: The importance of mixed‐use landscapes for the conservation of Sumatran elephants (Elephas maximus sumatranus)
Authors: Imron Muhammad Ali , Glass Danielle M. , Tafrichan Muhammad , Crego Ramiro D. , Stabach Jared A. , Leimgruber Peter
Published: September 2023

Elephants were once widely distributed across the Indonesian island of Sumatra but now exist in small, isolated populations. Using the best data available on elephant occurrence, we aimed to (a) predict potential habitat suitability for elephants (Elephas maximus sumatranus) across the island of Sumatra and (b) model landscape connectivity among the extant elephant populations. We used direct sightings and indirect observations of elephant signs, as well as six remotely sensed proxies of surface ruggedness, vegetation productivity and structure, and human land use and disturbance, to model habitat suitability in a Google Earth Engine (GEE) environment. We validated the habitat suitability prediction using 10‐fold spatial block cross validation and by calculating the area under the precision‐recall curve (AUC‐PR), sensitivity, and specificity for each model iteration. We also used a geolocation dataset collected from global positioning system (GPS) collars fitted on elephants as an independent validation dataset. Models showed good predictive performance with a mean AUC‐PR of 0.73, sensitivity of 0.76, and specificity of 0.68. Greater than 83% of the independent GPS collar geolocations were located in predicted suitable habitat. We found human modification, surface ruggedness, and normalized difference vegetation index to be the most important variables for predicting suitable elephant habitat. Thirty‐two percent, or 135,646 km2, of Sumatra's land area was predicted to be suitable habitat, with 43 patches of suitable habitat located across Sumatra. Areas with high connectivity were concentrated in the Riau and North Sumatra provinces. Though our analysis highlights the need to improve the quality of data collected on Sumatran elephants, more suitable habitat remains on Sumatra than is used by known populations. Targeted habitat conservation, especially of the suitable habitat in and around the Lamno, Balai Raja, Tesso Tenggara, Tesso Utara, Bukit Tigapuluh, Seblat, Padang Sugihan, and Bukit Barisan Selatan ranges, may improve the long‐term viability of this critically endangered species.
Stochastic simulation of earthquake ground motions for the seismic assessment of monumental masonry structures: Source‐based vs site‐based approaches
Authors: Karimzadeh Shaghayegh , Funari Marco F. , Szabó Simon , Hussaini S. M. Sajad , Rezaeian Sanaz , Lourenço Paulo B.
Published: September 2023

Earthquakes are among the most destructive natural disasters and have resulted in a massive number of fatalities and economic losses all over the world. Simulated ground motion records are valuable, particularly for regions lacking seismic stations or with a limited history of large‐magnitude earthquakes. Notably, a significant percentage of monumental masonry buildings are located in regions with limited access to real records; hence, simulated records play a paramount role in their seismic protection. However, few studies have investigated the structural response of heritage buildings via response history analyses to assess the performance of simulated earthquakes against real ones. To accomplish this, this study simulates the recorded time‐series of the 9th of July 1998 Faial earthquake in the Azores (Mw = 6.2) at four available stations, using two different simulation approaches, that is, a source‐based stochastic finite‐fault method and a site‐based broadband stochastic method. First, two masonry facades with sidewalls characterized by different slenderness levels are adopted to conduct this research. Moreover, the proposed approach is also applied to an existing monumental structure, that is, São Francisco Church, located at Horta, which was affected by damage during the Faial earthquake. Results demonstrate that both simulation approaches provide similar results in terms of structural response prediction. The proposed framework also demonstrates that a small mismatch in terms of predicted damage patterns can result in a significant relative error in terms of displacement predictions.
Controversies in Antithrombotic Therapy for Patients with Mechanical Heart Valves
Authors: Bussey Henry I. , Lyons Roger M.
Published: September 2023

Current anticoagulation guidelines for patients with mechanical heart valves are based on studies that are seriously flawed in that they used prothrombin time ratios rather than the international normalized ratio (INR) and failed to consider the level of anticoagulation actually achieved. Available data suggest that the appropriate INR range varies according to risk factors and that “tight control” of the INR is of critical importance in reducing thromboembolic and hemorrhagic events. Whether antiplatelet therapy adds benefit to an appropriately controlled level of anticoagulation is not clear. During pregnancy, warfarin is contraindicated; adjusted‐dose heparin is recommended by published American and European guidelines. Even so, one small study suggests that this may be inadequate. Topical antifibrinolytic agents can negate the need to alter systemic anticoagulation during dental surgery.
Mibefradil, a Pharmacologically Distinct Calcium Antagonist
Authors: Ernst Michael E. , Kelly Michael W.
Published: September 2023

Mibefradil is the prototype of a new class of calcium antagonists that selectively block T‐type voltage‐gated plasma membrane calcium channels in vascular smooth muscle. The drug is structurally and pharmacologically different from traditional calcium antagonists. It does not have negative inotropism at therapeutic concentrations, and is not associated with reflex activation of neurohormonal and sympathetic systems. In clinical studies of hypertension, mibefradil 50 and 100 mg/day reduced trough sitting diastolic and systolic blood pressures in a dose‐related manner. Dosages exceeding 100 mg/day generally did not result in significantly greater efficacy, but were associated with a higher frequency of adverse events. No first‐dose hypotensive phenomenon was observed. Mibefradil has antiischemic properties resulting from dilation of coronary and peripheral vascular smooth muscle, and a slight reduction in heart rate. In clinical studies of chronic stable angina pectoris, dose‐related increases in exercise duration, time to onset of angina, and time to 1‐mm ST‐segment depression during exercise tolerance tests occurred. Mibefradil reduced the number and duration of ischemic events recorded by 48‐hour ambulatory electrocardiograph (ECG) monitoring, as well as number of anginal episodes and nitroglycerin consumption. Favorable hemodynamic and clinical profiles are reported, including high trough:peak ratios (> 80%), high oral bioavailability, and long elimination half‐life (17–25 hrs) permitting once/day dosing. Dizziness, headache, leg edema, and lightheadedness are frequently reported, but overall the agent is well tolerated. First‐degree atrioventricular block and sinus bradycardia are the most frequent ECG changes caused by the drug. In vitro studies indicate mibefradil inhibits cytochrome P450 1A2, 2D6, and 3A4, resulting in elevated plasma concentrations of drugs metabolized by those isoenzymes. Therefore, it is contraindicated in patients receiving terfenadine, astemizole, cisapride, lovastatin, or simvastatin.
A Review of Anticonvulsants in Treating Agitated Demented Elderly Patients
Authors: Grossman Fred
Published: September 2023

Agitation in the elderly, manifested by verbal and physical aggression, frequently results in increased morbidity and mortality for nursing home residents and reduced morale for the family and nursing home staff. It is also responsible for increased costs associated with caring for these residents. Pharmacologic interventions are often used but are frequently ineffective and associated with significant adverse effects. Few controlled studies of drug treatment are available, but divalproex sodium and carbamazepine are effective and well tolerated by this population. Divalproex sodium has advantages of fewer adverse side effects and drug‐drug interactions.
Rapid discrimination of urine specific gravity using spectroscopy and a modified combination method based on SPA and spectral index
Authors: Yang Cheng‐bo , Cai Zhi‐long , Li Qing‐zhi , Tang Feng , Wu Jing‐jun , Yang Jia , Zhang Yu‐rong , Li Bo , Yang Ping , Ye Xin , Yang Li‐ming
Published: September 2023

To achieve high‐accuracy urine specific gravity discrimination and guide the design of four‐waveband multispectral sensors. A modified combination strategy was attempted to be proposed based on the successive projections algorithm (SPA) and the spectral index (SI) in the present study. First, the SPA was used to select four spectral variables in the full spectra. Second, the four spectral variables were mathematically transformed by SI to obtain SI values. Then, SPA gradually fusions the SI values and establishes models to identify USG. The results showed that the SPA can screen out the four characteristic wavelengths related to the measured sample attributes. SIs can be used to improve the performance of constructed prediction models. The best model only involves four spectral variables and 1 SI value, with high accuracy (91.62%), sensitivity (0.9051), and specificity (0.9667). The results reveal that m‐SPA‐SI can effectively distinguish USG and provide design guidance for 4‐wavelength multispectral sensors.
Feasibility of Enteral Protein Supplementation in Critically Ill Children
Authors: Moreno Yara M. F. , Hauschild Daniela B. , Martins Mayara D. , Bechard Lori J. , Mehta Nilesh M.
Published: September 2023

Background

We describe the protein type and concentration in standard enteral nutrition (EN) formulas and the effect of protein supplementation on the osmolality of standard formulas. We also aimed to examine factors associated with optimal protein delivery in critically ill children.

Methods

Protein content and other characteristics of pediatric EN formulas used worldwide were recorded. Factors associated with achievement of recommended protein delivery and tolerance of protein‐supplemented formulas were recorded prospectively in a cohort of critically ill children. A range of protein supplement doses was added to 2 standard formulas and water, and the osmolality was recorded by cryoscopy in a bench experiment.

Results

We reviewed 125 formulas used in a multicenter study including sites from >13 countries. A majority of the EN formulas (73.6%) were polymeric, with a nonprotein calorie/nitrogen ratio of 182 ± 66 and protein content of 3.53 ± 2.00 g/100 mL. In the cohort of critically ill children, 28.5% achieved protein intake goal within 4 days, with no intolerance. In addition to optimal protein prescription (P < 0.001), protein supplementation (P = 0.018) and early EN initiation (P = 0.006) were associated with significantly higher odds of achieving goal protein intake. Formulas supplemented with up to 8 g/100 mL polymeric protein had osmolality <450 mOsm/kg.

Conclusions

The protein content of current pediatric formulas may be inadequate to meet the needs of critically ill children. Protein supplementation of formulas allows early achievement of goal and is likely to be safe.)
Modelling clinical narrative as computable knowledge: The NICE computable implementation guidance project
Authors: Scott Philip , Heigl Michaela , McCay Charles , Shepperdson Polly , Lima‐Walton Elia , Andrikopoulou Elisavet , Brunnhuber Klara , Cornelius Gary , Faulding Susan , McAlister Ben , Rowark Shaun , South Matthew , Thomas Mark R. , Whatling Justin , Williams John , Wyatt Jeremy C. , Greaves Felix
Published: September 2023

Introduction

Translating narrative clinical guidelines to computable knowledge is a long‐standing challenge that has seen a diverse range of approaches. The UK National Institute for Health and Care Excellence (NICE) Content Advisory Board (CAB) aims ultimately to (1) guide clinical decision support and other software developers to increase traceability, fidelity and consistency in supporting clinical use of NICE recommendations, (2) guide local practice audit and intervention to reduce unwarranted variation, (3) provide feedback to NICE on how future recommendations should be developed.

Objectives

The first phase of work was to explore a range of technical approaches to transition NICE toward the production of natively digital content.

Methods

Following an initial ‘collaborathon’ in November 2022, the NICE Computable Implementation Guidance project (NCIG) was established. We held a series of workstream calls approximately fortnightly, focusing on (1) user stories and trigger events, (2) information model and definitions, (3) horizon‐scanning and output format. A second collaborathon was held in March 2023 to consolidate progress across the workstreams and agree residual actions to complete.

Results

While we initially focussed on technical implementation standards, we decided that an intermediate logical model was a more achievable first step in the journey from narrative to fully computable representation. NCIG adopted the WHO Digital Adaptation Kit (DAK) as a technology‐agnostic method to model user scenarios, personae, processes and workflow, core data elements and decision‐support logic. Further work will address indicators, such as prescribing compliance, and implementation in document templates for primary care patient record systems.

Conclusions

The project has shown that the WHO DAK, with some modification, is a promising approach to build technology‐neutral logical specifications of NICE recommendations. Implementation of concurrent computable modelling by multidisciplinary teams during guideline development poses methodological and cultural questions that are complex but tractable given suitable will and leadership.
Biomimetic Therapeutics for Bone Regeneration: A Perspective on Antiaging Strategies
Authors: Miszuk Jacob , Sun Hongli
Published: September 2023

Advances in modern medicine and the significant reduction in infant mortality have steadily increased the population's lifespan. As more and more people in the world grow older, incidence of chronic, noncommunicable disease is anticipated to drastically increase. Recent studies have shown that improving the health of the aging population is anticipated to provide the most cost‐effective and impactful improvement in quality of life during aging‐driven disease. In bone, aging is tightly linked to increased risk of fracture, and markedly decreased regenerative potential, deeming it critical to develop therapeutics to improve aging‐driven bone regeneration. Biomimetics offer a cost‐effective method in regenerative therapeutics for bone, where there are numerous innovations improving outcomes in young models, but adapting biomimetics to aged models is still a challenge. Chronic inflammation, accumulation of reactive oxygen species, and cellular senescence are among three of the more unique challenges facing aging‐induced defect repair. This review dissects many of the innovative biomimetic approaches research groups have taken to tackle these challenges, and discusses the further uncertainties that need to be addressed to push the field further. Through these research innovations, it can be noted that biomimetic therapeutics hold great potential for the future of aging‐complicated defect repair.
Switchable frequency‐selective rasorber/absorber based on single‐sheet structure
Authors: Yu Weiliang , Cheng Mengmeng , Huang Zhixiang , Liu Leilei , Luo Guo Qing
Published: September 2023

A single‐sheet structure‐based switchable broadband FSR/absorber is proposed. The lossy layers I, II, and the FSS are printed along the direction of electromagnetic (EM) wave propagation (z‐direction) at the top, middle, and bottom positions of the substrate, respectively. A PIN diode is used in the lossy layer II and the FSS to switch their operating states. By activating or deactivating the PIN diodes, the design can operate as either an FSR or absorber. The FSR achieves a passband with an insertion loss of 0.64 dB at 3.9 GHz, and two absorption bands with fractional bandwidth of 87.6% and 20.8%, respectively. The absorber has a wide absorption band from 1.6 to 5.4 GHz (109%). It is transparent to EM waves of orthogonal polarization. The measured and simulated results are in close agreement, which exhibits stable performance under 30° of oblique incidence in both the xz‐ and yz‐planes.
1D elastic viscoplastic consolidation analysis of bi‐layered soft ground under time‐dependent drainage boundary and ramp load
Authors: Cui Penglu , Cao Wengui , Lin Congyu , Liu Yangyang , Chen Ming , Zhang Jiachao
Published: September 2023

The elastic viscoplastic properties are non‐negligible factors of clays that cause the deviation between the theoretical and the measured values, which were rarely incorporated in layered consolidation problems. Thus, this paper extended a generalized bi‐layered one‐dimensional (1D) consolidation model for soft ground under ramp load, simultaneously incorporating elastic viscoplastic deformation, non‐Darcy flow (NDF), and time‐dependent drainage boundary (TDB) condition. The finite volume technique was employed to numerically solve the control equation. Then, the proposed method solutions were verified by comparing with degenerated cases, including oedometer experimental results, analytical and semi‐analytical solutions with different boundary conditions. Furthermore, parametric studies were conducted on the bi‐layered clay creep consolidation characteristics by investigating the effect of the loading rate, interface and flow parameters, and the relative soil layer properties. The results demonstrate that the entire dissipation rate of the excess pore‐water pressure (EPWP) and settlement rate in the bi‐layered ground become faster as the soil thickness with high permeability or low compressibility increases. When considering the viscosity of soft clay, the EPWP exceeding the overlying construction load value can occur in poorly drained locations. Neglecting loading rate, time‐dependent drainage boundary (TDB), and NDF can result in a significant overestimation of consolidation and settlement proceedings.
Glucocorticosteroid interactions with natural toxins: A mini review
Authors: Harvey Philip W. , Healing Guy , Rees Stephen J. , Everett David J. , Cockburn Andrew
Published: September 2023

A growing area of research in pharmacology and toxicology is concerned with the role of adrenal glucocorticosteroids (predominantly corticosterone in rats and mice, and cortisol in humans) in modulating toxicological responses. These steroids are secreted from the adrenal cortex, and in laboratory rodents secretion occurs particularly in response to stressful environmental change or noxious challenge, which can include a toxic insult. Glucocorticoids have profound biochemical effects in diverse tissues (e.g., inhibition of DNA and RNA synthesis; effects on carbohydrate metabolism, protein catabolism, and immunosuppression, and anti‐inflammatory effects). Given this range of pharmacological actions of glucocorticoids, effects on the response and tolerance to a toxic insult can be hypothesised. Indeed, it is now becoming clear that the toxicological response to a toxin can be modulated by pretreatment with, or coadministration of, natural glucocorticosteroids or their synthetic analogues. As achieving the maximum tolerated dose (MTD) in an experimental animal, whether via a natural toxin or a synthetic chemical, can be stressful, the implications of these findings are far reaching. This review is intended to illustrate the principle that the toxicological responses to natural toxins (e.g., kainic acid, aflatoxin B1, trichothecenes) can be modulated by corticosterone and other natural and synthetic glucocorticosteroids. Particular emphasis is given to neurotoxicity and hepatotoxicity in laboratory rodent models, but nephrotoxicity and cardiotoxicity, of which there are fewer studies, are also covered. Glucocorticoids can both enhance toxicity or protect against toxicity, and the direction of the effect depends on the target organ, the particular steroid, the properties of the toxin, and the temporal relationship of the coadministration regime.
Poison ivy (Toxicodendron radicans) leaf shape variability: Why plant avoidance‐by‐identification recommendations likely do not substantially reduce poison ivy rash incidence
Authors: Jelesko John G. , Thompson Kyla , Magerkorth Noah , Verteramo Elizabeth , Becker Hannah , Flowers Joy G. , Sachs Jonathan , Datta Jyotishka , Metzgar Jordan
Published: September 2023

Societal Impact Statement

Avoidance of poison ivy plants is currently the primary approach to prevent the estimated 30–50 million annual poison ivy skin rash cases. The “leaves of three let it be” mnemonic device lacks specificity to differentiate poison ivy from other three‐leaflet native plants. This report demonstrated that poison ivy leaves show marked total leaf shape variability that likely confounds accurate poison ivy plant identification, and significantly undermines a poison ivy avoidance strategy for mitigating poison ivy rash cases. Therefore, there is an ongoing need to develop prophylactic medical procedures to prevent poison ivy rash that do not depend on human poison ivy plant identification.

Urushiol is the natural product produced by poison ivy (Toxicodendron radicans) that is responsible for millions of cases of delayed contact allergenic dermatitis in North America each year. Avoidance of poison ivy plant material is the clinically recommended strategy for preventing urushiol‐induced dermatitis symptoms. However, poison ivy leaf shape is anecdotally notoriously variable, thereby confounding accurate poison ivy identification. This study focused on quantitative analyses of poison ivy and a common poison ivy look‐alike (American hog peanut) leaf shape variability in North America to empirically validate the high degree of poison ivy leaf shape plasticity.

Poison ivy and American hog peanutiNaturalist.orgrecords were scored for seven attributes of compound leaf shape that were combined to produce a total leaf complexity score. Both the mean and the distribution of poison ivy total leaf complexity scores were significantly greater than that of American hog peanut. Non‐metric multidimensional scaling analyses corroborated a high degree of poison ivy leaf shape variability relative to American hog peanut. A poison ivy accession producing frequent palmate penta‐leaflet compound leaves was evaluated using linear regression modeling.

Poison ivy total leaf complexity was exceedingly variable across a given latitude or longitude. With that said, there was a small but significant trend of poison ivy total leaf complexity increasing from east to west. Palmate penta‐leaflet formation was significantly correlated with a stochastic leaflet deep‐lobing developmental process in one unusual poison ivy accession.

The empirically‐validated poison ivy leaf shape hypervariability described in this report likely confounds accurate poison ivy identification, thereby likely resulting in many accidental urushiol‐induced clinical allergenic dermatitis cases each year.
Effective delivery and selective insecticidal activity of double‐stranded RNA via complexation with diblock copolymer varies with polymer block composition
Authors: Pugsley Charlotte E. , Isaac R. Elwyn , Warren Nicholas J. , Stacey Martin , Ferguson Calum T. J. , Cappelle Kaat , Dominguez‐Espinosa Rosa , Cayre Olivier J.
Published: September 2023

BACKGROUND

Chemical insecticides are an important tool to control damaging pest infestations. However, lack of species specificity, the rise of resistance and the demand for biological alternatives with improved ecotoxicity profiles means that chemicals with new modes of action are required. RNA interference (RNAi)‐based strategies using double‐stranded RNA (dsRNA) as a species‐specific bio‐insecticide offer an exquisite solution that addresses these issues. Many species, such as the fruit pest Drosophila suzukii, do not exhibit RNAi when dsRNA is orally administered due to degradation by gut nucleases and slow cellular uptake pathways. Thus, delivery vehicles that protect and deliver dsRNA are highly desirable.

RESULTS

In this work, we demonstrate the complexation of D. suzukii‐specific dsRNA for degradation of vha26 mRNA with bespoke diblock copolymers. We study the ex vivo protection of dsRNA against enzymatic degradation by gut enzymes, which demonstrates the efficiency of this system. Flow cytometry then investigates the cellular uptake of Cy3‐labelled dsRNA, showing a 10‐fold increase in the mean fluorescence intensity of cells treated with polyplexes. The polymer/dsRNA polyplexes induced a significant 87% decrease in the odds of survival of D. suzukii larvae following oral feeding only when formed with a diblock copolymer containing a long neutral block length (1:2 cationic block/neutral block). However, there was no toxicity when fed to the closely related Drosophila melanogaster.

CONCLUSION

We provide evidence that dsRNA complexation with diblock copolymers is a promising strategy for RNAi‐based species‐specific pest control, but optimisation of polymer composition is essential for RNAi success. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Pleiotropic effects of N‐acylhomoserine lactone synthase ExpI on virulence, competition, and transmission in Pectobacterium carotovorum subsp. carotovorum Pcc21
Authors: Kang Jihee , Yoon Hye Min , Jung Jaejoon , Yu Seonmi , Choi Shin‐Yae , Bae Hee‐Won , Cho You‐Hee , Chung Eui‐Hwan , Lee Yunho
Published: September 2023

BACKGROUND

Pectobacterium species are necrotrophic phytopathogenic bacteria that cause soft rot disease in economically important crops. The successful infection of host plants relies on interactions among virulence factors, competition, and transmission within hosts. Pectobacteria primarily produce and secrete plant cell‐wall degrading enzymes (PCWDEs) for virulence. The regulation of PCWDEs is controlled by quorum sensing (QS). Thus, the QS system is crucial for disease development in pectobacteria through PCWDEs.

RESULTS

In this study, we identified a Tn‐insertion mutant, M2, in the expI gene from a transposon mutant library of P. carotovorum subsp. carotovorum Pcc21 (hereafter Pcc21). The mutant exhibited reduced production and secretion of PCWDEs, impaired flagellar motility, and increased sensitivity to hydrogen peroxide, resulting in attenuated soft rot symptoms in cabbage and potato tubers. Transcriptomic analysis revealed the down‐regulation of genes involved in the production and secretion in the mutant, consistent with the observed phenotype. Furthermore, the Pcc21 wild‐type transiently colonized in the gut of Drosophila melanogaster within 12 h after feeding, while the mutant compromised colonization phenotype. Interestingly, Pcc21 produces a bacteriocin, carocin D, to compete with other bacteria. The mutant exhibited up‐regulation of carocin D‐encoding genes (caroDK) and inhibited the growth of a closely related bacterium, P. wasabiae.

CONCLUSION

Our results demonstrated the significance of ExpI in the overall pathogenic lifestyle of Pcc21, including virulence, competition, and colonization in plant and insect hosts. These findings suggest that disease outcome is a result of complex interactions mediated by ExpI across multiple steps. © 2023 Society of Chemical Industry.
Enhancing resilience assessment and bus bridging service design for large‐scale rail transit systems under disruptions
Authors: Gong Xuanjing , Song Zihao , Xu Lei , Luo Chunling
Published: September 2023

This paper proposes a more computationally efficient approach for resilience assessment of rail transit system under disruptions. An improved linear programming model is developed to depict commuter flows and estimate system statuses. To address the computational challenge caused by the complexity of system, a four‐step approach is proposed based on the proposed commuter flow model. In the first step, Origin‐Destination (OD) pairs are divided into smaller groups and their flows under normal conditions are estimated by the proposed model separately, with the assumption that the railway capacity is sufficient relative to demand. Next, overall system statuses under normal conditions, including commuters on each train and spare capacities of each train are calculated by integrating results obtained in the first step. In the third step, system statuses under disruptions are estimated. In this step, we assume that unaffected commuters will not change their routes and flows of all affected commuters are estimated by a modified commuter model with given spare space of trains. Based on these outputs, several critical measures are introduced and calculated to quantify the resilience, resistance, and recovery ability of rail network systematically. We also demonstrate how our approach could be used to facilitate design and evaluation of bus bridging service. The proposed approach is demonstrated on the core part of Hangzhou rail transit network.
Modulation of various host cellular machinery during COVID‐19 infection
Authors: Malvankar Shivani , Singh Anjali , Ravi Kumar Y. S. , Sahu Swetangini , Shah Megha , Murghai Yamini , Seervi Mahendra , Srivastava Rupesh K. , Verma Bhupendra
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID‐19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID‐19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host's machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS‐CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular‐level interaction between the host and the pathogen. In this review, we describe how SARS‐CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post‐transcription, translation, post‐translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS‐CoV2 infection.