bluuebunny/crossref_metadata_2025 huggingface dataset:
A medical odyssey of a 72‐year‐old man with Charcot–Marie–Tooth disease type 2 newly diagnosed with biallelic variants in SORD gene causing sorbitol dehydrogenase deficiency
Authors: Furuta Yutaka , Nelson Erica T. , Neumann Serena M. , Phillips John A. , Hamid Rizwan , Tinker Rory J. , Cogan Joy D. , Rives Lynette , Newman John H. ,   the Undiagnosed Diseases Network
Published: August 2023

A 72‐year‐old man was referred to the Undiagnosed Diseases Network (UDN) because of gradual progressive weakness in both lower extremities for the past 45 years. He was initially diagnosed as having Charcot–Marie–Tooth disease type 2 (CMT2) without a defined molecular genetic cause. Exome sequencing (ES) failed to detect deleterious neuromuscular variants. Very recently, biallelic variants in sorbitol dehydrogenase (SORD) were discovered to be a novel cause of inherited neuropathies including CMT2 or distal hereditary motor neuropathy (dHMN) referred to as Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy (SORDD, OMIM 618912). The most common variant identified was c.757delG; p.A253Qfs*27. Through the Vanderbilt UDN clinical site, this patient was formally diagnosed with SORDD after the identification of homozygosity for the above SORD frameshift through UDN Genome Sequencing (GS). His medical odyssey was solved by GS and detection of extremely high levels of sorbitol. The diagnosis provided him the opportunity to receive potential treatment with an investigational drug in a clinical trial for SORDD. We suggest that similar studies be considered in other individuals thought to possibly have CMT2 or dHMN.
Multisystem inflammatory syndrome in adults with COVID‐19 requiring mechanical ventilation: A retrospective cohort study
Authors: Kato Fumito , Bunya Naofumi , Nakayama Ryuichi , Narimatsu Eichi , Ohshimo Shinichiro , Shime Nobuaki , Kushimoto Shigeki , Hashimoto Satoru , Takeda Shinhiro
Published: August 2023

Aim

Multisystem inflammatory syndrome in adults (MIS‐A) is a hyperinflammatory multisystem condition associated with coronavirus disease (COVID‐19). Critically ill COVID‐19 patients may develop multiorgan damage and elevated inflammatory responses, thus making it difficult to differentiate between progression to organ damage due to COVID‐19 itself or MIS‐A. This study aimed to explore the characteristics and complications of MIS‐A in critical COVID‐19 patients.

Methods

The Japan Extracorporeal Membrane Oxygenation (ECMO) Network and ICU Collaboration Network developed a web‐based database system called the CRoss Intensive Care Unit Searchable Information System (CRISIS) to monitor critical COVID‐19 patients throughout Japan. We retrospectively identified patients with MIS‐A among critical COVID‐19 patients enrolled from March 2020 to December 2021, using CRISIS. Our MIS‐A definition required patients to be at least 18 years of age, have laboratory evidence of inflammation, severe dysfunction of at least two extrapulmonary organ systems, and no plausible alternative diagnoses.

Results

Of the 1052 patients, 26 (2.5%) were diagnosed with MIS‐A. The MIS‐A patients had a higher likelihood of using ECMO (13% vs. 46%, p < 0.001) and lower overall survival (77% vs. 42%, p < 0.001) than non‐MIS‐A patients. More than 80% of the MIS‐A cases occurred 3 weeks after the COVID‐19 onset.

Conclusion

Multisystem inflammatory syndrome in adults can occur in 2.5% of critically ill COVID‐19 patients, and the mortality rate is high. Multisystem inflammatory syndrome in adults may be considered when there is a re‐elevation of the unexplained inflammatory response and severe dysfunction of at least two extrapulmonary organ systems several weeks after the onset of COVID‐19.
Copper (II) complexes of a hydrazone ligand bearing quinoline moiety: Preparation, spectral, antitumor, and molecular docking studies
Authors: El‐Inany Gaber A. , Seleem Hussein S. , El‐Shetary Basheir A. , El‐Shafiy Hoda F. , Nabeel Asmaa I. , Madyan Aml , Shebl Magdy
Published: August 2023

Reaction of 1‐(4‐methylquinoline‐2‐yl)hydrazine with Alloxan yielded a new hydrazone ligand (AlloxHQ). Binary copper (II) AlloxHQ complexes have been successfully prepared utilizing different copper (II) salts (chloride, bromide, sulfate, and acetate). Moreover, ternary complexes have been prepared by using secondary ligands; 1,10‐phenanthroline and oxine. The structures of AlloxHQ and Cu (II)‐AlloxHQ complexes have been investigated with the aid of elemental analysis, nuclear magnetic resonance, infrared, electronic, mass, and electron spin resonance spectra, thermal analysis in addition to measurements of molar conductivity and magnetic susceptibility. Mono‐, bi‐, and tri‐nuclear complexes were obtained, reflecting that the coordinating manner of AlloxHQ is extremely influenced by both the nature of the counter anion and the pH of the medium. AlloxHQ acts as a tri‐, bi‐, or penta‐dentate ligand with different modes of bonding. AlloxHQ and its copper (II) complexes exhibited antitumor activity towards Ehrlich Ascites Carcinoma and coordination with copper improved the antitumor activity. The biological activity was confirmed by molecular docking study to investigate how the title compounds bind to the CDK‐5 inhibitor‐crystal structure of inhibitor EFP with CDK‐2 (PDB ID: 3IG7).
Batch process quality monitoring based on temporal convolutional networks with depthwise separable coordinated attention module
Authors: Zhao Xiaoqiang , Tuo Benben , Mou Miao , Liu Kai
Published: August 2023

Quality monitoring is an important tool for ensuring the safe operation of batch processes and the high quality of the final products. However, the inherent non‐linear, dynamic, and batch characteristics make the quality monitoring of batch process still have some difficulties. To solve these problems, this paper proposes a batch quality monitoring model based on a temporal convolutional network with a depthwise separable coordinated attention module. Firstly, a method of data unfolding incorporating sliding windows is proposed to unfold and stack the data along the direction of the variables, and a variable selection method of maximum information coefficient fused with Monte Carlo sampling is proposed to select the process variables related to the quality variables. Secondly, we take the traditional temporal convolutional network as the base network and decouple the correlation between the batch data by using depthwise separable convolution. At the same time, we utilize coordinate attention to extract data features in different spatial directions to ensure the effectiveness of quality monitoring. Finally, the feasibility and robustness of the proposed model are verified by a nonlinear numerical example and an industrial‐scale penicillin fermentation process. The experimental results show the proposed model has lower false alarm rate and false negative rate and can be used to maintain the product quality of the actual batch process.
Degradation of polyethylene particles by Trichoderma harzianum and recombinant laccase cloned from the strain
Authors: Ruan Yongqiang , Hu Fanghui , Zhao Jindi , Li Yunhan , Ling Jiahuan , Cao Jianan , Zhang Lihui
Published: August 2023

Polyethylene (PE) is a convenient and inexpensive polymer that is widely used in daily life. However, PE products are recalcitrant to degradation in the environment, leading to increasing plastic pollution. This has inspired the search for effective microorganisms and enzymes that can biodegrade PE. In this study, a fungal strain that degrades PE was isolated from soil contaminated with plastic and identified as Trichoderma harzianum. The strain was cultured with PE as the sole carbon source for 30 days, and the weight loss of PE particles was 3.39 ± 0.3%. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectra showed holes and oxygenated functional groups on the surface of the degraded PE particles. Gas chromatography–mass spectrometry (GC–MS) detected products with different carbon atom numbers. In addition, a potential PE degrading enzyme was screened from T. harzianum and identified as laccase. After PE was incubated with the recombinant laccase for 96 h, SEM, FTIR, and GC–MS showed the degradation of PE particles. The results showed that T. harzianum had the ability to degrade PE, which probably was attributed to the laccase produced by this strain. This study contributes promising tools for the degradation of PE enzyme.
Development of an all‐electrospun high‐performance textile supercapacitor for wearable device applications
Authors: Martínez‐Pérez Rosa V. , Manríquez Juan , Aldeco‐Pérez Eugenia , Baldenegro‐Pérez Leonardo A. , España‐Sánchez Beatriz Liliana , Ávila‐Niño José A.
Published: August 2023

This paper reports the synthesis and electrochemical performance of electrospun polyaniline (PANI) nanofiber membranes that work as high‐performance electrodes in an all‐textile supercapacitor (SC). The electrospun separator membrane consists of a mix of polyacrylonitrile (PAN) and poly (ethylene sulfonate) (PES). The all‐textile SC consists of a PES‐PAN membrane, previously soaked in an electrolyte, stacked between two PANI fiber electrodes. Scanning electron microscopy and Fourier‐transform infrared spectroscopy are carried out to characterize the morphology and chemical structure of the PANI and PES‐PAN fiber membranes. Cyclic voltammetry, galvanostatic charge–discharge, and electrochemical impedance spectroscopy are carried out to characterize the electrochemical properties of the SCs. The all‐textile SC shows very competitive specific capacitances of 275 F/g at 0.25 A/g and a maximum specific power of 1350 Wkg−1. These all‐electrospun SCs show higher performance than the SCs using PANI films and commercial cellulose as separators. Finally, we report a flexible all‐electrospun and all‐solid‐state SC was fabricated using flexible substrates and a gel‐type electrolyte. Flexible SC has a specific capacitance of 270 F/g, confirming that the performance of all‐electrospun SCs is a promising approach for future textile energy storage devices for its potential use in wearable devices.
Student perceptions of hybrid delivery of interprofessional anatomy—The best of both worlds?
Authors: Oliveira Ana , Mezil Yasmeen , Akhtar‐Danesh Noori , Palombella Andrew , Rockarts Jasmine , Wojkowski Sarah , Wainman Bruce
Published: August 2023

Interprofessional anatomy dissection (IAD) courses increase students' readiness for interprofessional education (IPE) both in‐person and online. During the COVID‐19 pandemic, virtual environments for anatomy learning were perceived as less effective. Hybrid instruction approaches emerged but have been scarcely evaluated. This study assessed students' experiences with a hybrid IAD course's virtual and in‐person components. A hybrid IAD course consisting of virtual and in‐person anatomy laboratory‐based instruction was offered to 32 students from different health sciences programs. Before and after the full course, students completed the Readiness for Interprofessional Learning Scale (RIPLS) and the Interdisciplinary Education Perception Scale (IEPS). After the virtual and the in‐person course components, students completed a Q‐methodology survey to assess their perceptions of the course. Twenty‐eight students (20 females; 24.8 ± 6.3 years old) from different programs (4 Physician Assistant; 2 Midwifery; 3 Speech‐Language Pathology; 4 Physiotherapy; 3 Occupational therapy; 4 Nursing; 8 Medicine) participated. The total RIPLS score improved after the 8‐week course (Median 84 interquartile range [78–87] vs. 87 [85–90]; p = 0.0145). The Q‐methodology identified three factors: IPE & Virtual Enthusiasts, Introspective Learners, and IPE & Virtual Skeptics. Factors represented different levels of students' engagement with the IPE and virtual environment. The transition to in‐person resulted in all factors praising the experience. Health science students showed improvements in their readiness for IPE after an 8‐week hybrid IAD course. The main differences in the evaluations of the virtual and in‐person components were related to engagement and the ability to learn anatomy; no differences were noted between settings regarding engagement in IPE.
Location bias: A “Hidden Variable” in GPCR pharmacology
Authors: Eiger Dylan Scott , Hicks Chloe , Gardner Julia , Pham Uyen , Rajagopal Sudarshan
Published: August 2023

G protein‐coupled receptors (GPCRs) are the largest family of transmembrane receptors and primarily signal through two main effector proteins: G proteins and β‐arrestins. Many agonists of GPCRs promote “biased” responses, in which different cellular signaling pathways are activated with varying efficacies. The mechanisms underlying biased signaling have not been fully elucidated, with many potential “hidden variables” that regulate this behavior. One contributor is “location bias,” which refers to the generation of unique signaling cascades from a given GPCR depending upon the cellular location at which the receptor is signaling. Here, we review evidence that GPCRs are expressed at and traffic to various subcellular locations and discuss how location bias can impact the pharmacologic properties and characterization of GPCR agonists. We also evaluate how differences in subcellular environments can modulate GPCR signaling, highlight the physiological significance of subcellular GPCR signaling, and discuss the therapeutic potential of exploiting GPCR location bias.
A meta‐analysis of the accessory left atrial appendage and the left atrial diverticulum
Authors: Ratusznik Jakub , Ratusznik Filip , Pękala Jakub R. , Krager Eirik , Hołda Mateusz , Sarata Victoria , Łazarz Dominik , Raputa Wiktor , Tomaszewski Krzysztof A.
Published: August 2023

Left atrial (LA) structures, including the accessory left atrial appendage (aLAA) and left atrial diverticulum, have been studied based on their prevalence, shape, and association with arrhythmia and thrombi formation. A pooled prevalence with morphometric data has not been determined in previous research. Our goal is to provide structured, clinically relevant information on said structures for clinical practitioners to use in their daily work. We propose that morphometric data of additional LA structures is necessary when considering the possible complications during cardiac interventions. We conducted a meta‐analysis of all relevant studies which used electrocardiogram (ECG)‐gated computed tomography (CT) imaging to determine the prevalence of LA structures and record their morphometric characteristics as well as the presence of thrombi. Data were extracted from 19 studies (n = 6643 hearts). The pooled prevalence estimate of left atrial diverticulum and/or aLAAs were reported from 14 studies and was 28.8%. The most common location noted was anterosuperior in the LA with 70.2% of structures found there. Data regarding thrombi presence in left atrial diverticulums or aLAAs were extracted from 11 studies and a thrombus was present in 0.2%. The prevalence rates of aLAAs and left atrial diverticulums are essential in performing uncomplicated cardiac interventions and reducing risk of electrophysiological procedures. Our findings show a considerable prevalence of LA structures in varying populations, provides information regarding the general characteristics of said structures, and does not support the previously theorized associated risk of thrombus formation in relation to LA structure presence.
Efficiency Analysis of the Discrete Element Method Model in Gas‐Fluidized Beds
Authors: Aghel Babak , Alobaid Falah , Graf Christoph , Epple Bernd
Published: August 2023

The efficiency and accuracy of the Euler‐Lagrange/discrete element method model were investigated. Accordingly, the stiffness coefficient and fluid time step were changed for different particle numbers and diameters. To derive the optimum parameters for simulations, the obtained results were compared with the measurements. According to the results, the application of higher stiffness coefficients improves the simulation accuracy slightly, however, the average computing time increases exponentially. For time intervals larger than 5 ms, the results indicated that the average computation time is independent of the applied fluid time step, while the simulation accuracy decreases extremely by increasing the size of the fluid time step. Nevertheless, using time steps smaller than 5 ms leads to negligible improvements in the simulation accuracy, though to an exponential rise in the average computing time.
Fire design approach for modern vehicles with combustion or electrical engine
Authors: Zehfuß Jochen , Sander Lisa , Schaumann Peter , Meyer Patrick
Published: August 2023

Due to climate changes and environmental considerations, the current transportation changes to modern vehicles with different vehicles models and engine types. Especially vehicles with alternative types of drive, such as electrical vehicles, are increasing. This raises the question of whether modern vehicles, such as electric vehicles, lead to an increased fire risk as well as an increased heat release rate (HRR). In this article, a new fire design approach for modern vehicles is presented to evaluate the fire risk of electric vehicles compared to vehicles with combustion engines with respect to the fire resistance of the structural elements in open car parks. For this purpose, HRRs of different vehicles are analyzed and an approximated approach for modern vehicles is derived. The methodology can be used for performance‐based design, where the HRR plays a fundamental role. Furthermore, modeling approaches of the vehicle dimensions are presented, which are based on statistical data of the German Federal Motor Transport Authority. The vehicle dimensions are used to determine the fire spread time between vehicles using a parameter study. Based on the statistical data analyses and the parameter studies, this article provides a new fire design approach for modern vehicles in fire.
Cold Plasma for Green Advanced Reduction/Oxidation Processes (AROPs) of Organic Pollutants in Water**
Authors: Tomei Giulia , Saleem Mubbshir , Ceriani Elisa , Pinton Anna , Marotta Ester , Paradisi Cristina
Published: August 2023

Cold plasma is gaining increasing attention as a novel tool to activate energy demanding chemical processes, including advanced reduction/oxidation processes (AROPs) of organic pollutants in water. The very complex milieu generated by discharges at the water/plasma interface comprises photons, strong oxidants and strong reductants which can be exploited for achieving the degradation of most any kind of pollutants. Despite the complexity of these systems, the powerful arsenal of mechanistic tools and chemical probes of physical organic chemists can be usefully applied to understand and develop plasma chemistry. Specifically, the added value of air plasma generated by in situ discharge with respect to ozonation (ex situ discharge) is demonstrated using phenol and various phenol derivatives and mechanistic evidence for the prevailing role of hydroxyl radicals in the initial attack is presented. On the reduction front, the impressive performance of cold plasma in inducing the degradation of recalcitrant perfluoroalkyl substances, which do not react with OH radicals but are attacked by electrons, is reported and discussed. The widely different reactivities of perfluorooctanoic acid (PFOA) and of perfluorobutanoic acid (PFBA) underline the crucial role played in these processes by the interface between plasma and solution and the surfactant properties of the treated pollutants.
Covalent Organic Frameworks in Aqueous Zinc‐Ion Batteries
Authors: Li Lihua , Yang Haohao , Peng Hui , Lei Ziqiang , Xu Yuxi
Published: August 2023

The development and utilization of green renewable energy are imperative with the aggravation of environmental pollution and energy crisis. In recent years, the exploration of electrochemical energy storage systems has gradually become a research hotspot in energy. Among them, aqueous zinc‐ion batteries (ZIBs) have progressively developed into highly competitive and efficient energy storage devices owing to their inherent safety, natural abundance, and higher theoretical capacity. However, the practical application of ZIBs suffers from the limitation of challenges such as the absence of proper cathode materials and the unavoidable zinc dendrites and side reactions of Zn anode. Covalent organic frameworks (COFs) are an attractive class of electrode materials due to their inherent advantages, like structural designability, high stability, and ordered‐open channels, bestowing them with great potential to overcome the problems of ZIBs. In this review, we concentrate on the discussion of designed strategies of COFs applied to ZIBs. Furthermore, the methods of using COFs to solve the challenging problems of cathode development, anode modification, and electrolyte optimization for ZIBs are summarized. Finally, the existing difficulties, solution measures, and prospects of COFs for ZIBs applications are discussed. Our commentary hopes to serve as a valuable reference for developing COFs‐based ZIBs.
Feasibility and reaction process for recovery of Si and Pb from high‐calcium zinc extraction residue by alkali roasting
Authors: Zhang Shanshan , Shen Xiaoyi , Shao Hongmei , Han Mingyu , Chen Jianshe , Zhai Yuchun
Published: August 2023

To explore the feasibility of Si and Pb recovery from high‐calcium zinc extraction residues via alkali roasting, NaOH molten roasting is performed and the reaction process is discussed. Under the optimal reaction conditions—residue–alkali ratio of 1:5.0, reaction time of 1.75 h, and reaction temperature of 500°C—the Si and Pb extraction ratios remained stable at 74.00% and 40.00%, respectively. The X‐ray diffraction patterns of the specimens roasted at different temperatures indicated that the main factor affecting the extraction process was the presence of Na2CaSiO4, Ca2PbO4, and quartz. Further, the phase transformations and reaction processes of Si and Pb were determined. In the final phases, the specimen roasted at 550°C included quartz, Na4SiO4, Na2CaSiO4, Ca2PbO4, and Na2SO4. The kinetics data calculated using the unreacted shrinking core model showed that the roasting process followed a mixed control mechanism with an apparent activation energy of 16.99 kJ · mol−1.
Influence of different nanoparticles on the gas injection performance in EOR operation: Parametric and CFD simulation study
Authors: Gharibshahi Reza , Jafari Arezou , Asadzadeh Naser
Published: August 2023

This study aims to simulate the process of enhanced oil recovery (EOR) during gas injection along with nanoparticles and investigate the affecting parameters in a conventional carbonate oil reservoir. Ansys Fluent software with a suitable multiphase model was used to simulate natural gas injection with a nanoparticle into a core sample. The simulation model was validated with a laboratory test of natural gas injection. Then, to obtain the optimal values of each of the parameters affecting the process of EOR during the natural gas injection along with nanoparticles, the design of the experiment was carried out with the help of Qualitek‐4 software and the Taguchi method. Therefore, three factors, including nanoparticle type (clay, titanium oxide, and silica nanoparticles), nanoparticle diameter (2–50 nm), and the volume fraction of nanoparticles in the base fluid (0.5–5 vol.%), as influential factors on the EOR during natural gas injection along with nanoparticles were chosen. The results of the numerical study indicated that silica nanoparticles significantly affect EOR more than clay and titanium oxide nanoparticles. Moreover, the smaller the diameter of nanoparticles (close to 2 nm) and the more significant the volume fraction of nanoparticles in the base fluid (close to 5 vol.%), the higher the oil recovery factor will be. This phenomenon occurs due to changes in the density and viscosity of the base fluid and, consequently, improves the mobility ratio of the injected fluid. On the other hand, the tiny size of nanoparticles allows them to easily enter the pores of the reservoir rock without entrapping and producing oil from them. Eventually, the highest oil recovery factor (59%) was obtained using silica nanoparticles with a diameter of 2 nm and a volume fraction of 5 vol.% in natural gas injection.
The correlation of left atrial diameter with preserved ejection fraction, reduced ejection fraction, and mid‐range ejection fraction
Authors: Lin Jing , Wu Huajui , Zhang Tianwen
Published: August 2023

Background

In patients with heart failure, left atrial remodeling often occurs to varying degrees. Left atrial enlargement has been proved to be an important predictor of cardiovascular‐related adverse events. However, the relationship between left atrial diameter (LAD) with heart failure (HF) with preserved ejection fraction (HFpEF), reduced ejection fraction (HFrEF) and mid‐range ejection fraction (HFmrEF) remains unclear.

Hypothesis

We want to explore the correlation between left atrial diameter and HFpEF, HFmrEF, and HFrEF.

Methods

A total of 210 patients with heart failure who underwent hospitalization in Ningbo Medical Center Lihuili Hospital, Zhejiang, China, from January 1, 2020, to June 31, 2021, were reviewed. The basic demographic characteristics, blood test, and the related indexes of echocardiography of the subjects were collected and analyzed.

Results

There is a significant difference between HFpEF and HFrEF group in LAD (p = .007), and LAD is negatively correlated with left ventricular ejection fraction (LVEF) (p = .002, r = −.209).

Conclusion

LAD is negatively correlated with LVEF, which may predict the prevalence of HFrEF.
Photonanozyme with Light Mediated Activity
Authors: Gong Zeyu , Tong Linjing , Wang Junhui , Huang Siming , Chen Guosheng , Ouyang Gangfeng
Published: August 2023

Since the discovery that Fe3O4 nanoparticle has intrinsic natural peroxidase‐like activity by Yan et al in 2007, mimicking native enzymes via nano‐engineering (named as nanozyme) pays a new avenue to bypass the fragility and recyclability of natural enzymes and thus expedites the biocatalysis in multidisciplinary applications. In addition, the high programmability and structural stability attributes of nanozyme afford the ease of coupling with electromagnetic waves of different energies, providing great opportunities to construct photo‐responsive nanozyme under user‐defined electromagnetic waves, which is known as photo‐nanozyme. In this concept, we aim to providing a summary of how electromagnetic waves with varying wavelengths can serve as external stimuli to induce or enhance the biocatalytic performance of photo‐nanozymes, thereby offering fascinating functions that cannot be achieved by pristine nanozyme.
Effect of Conversion, Temperature and Feed Ratio on In2O3/In(OH)3 Phase Transitions in Methanol Synthesis Catalysts: A Combined Experimental and Computational Study
Authors: Kampe Philipp , Wesner Anne , Schühle Patrick , Hess Franziska , Albert Jakob
Published: August 2023

Catalytic hydrogenation of CO2 to methanol has attracted lots of attention as it makes CO2 useable as a sustainable carbon source. This study combines theoretical calculations based on the dummy catalytic cycle model with experimental studies on the performance and degradation of indium‐based model catalysts for methanol synthesis. In detail, the reversibility of phase transitions in the In2O3/In(OH)3 system under industrial methanol synthesis conditions are investigated depending on conversion, temperature and feed ratio. The dummy catalytic cycle model predicts a peculiar degradation behavior of In(OH)3 at 275 °C depending on the water formed either by methanol synthesis or the competing reverse water‐gas‐shift reaction. These results were validated by dedicated experimental studies confirming the predicted trends. Moreover, X‐ray diffraction and thermogravimetric analysis proved the ensuing phase transition between the indium species. Finally, the validated model is used to predict how hydrogen drop out will affect the stability of the catalyst and derive practical strategies to prevent irreversible catalyst degradation.
Incorporation and Performance Verification of Hepatic Portal Blood Flow Shunting in Minimal and Full PBPK Models of Liver Cirrhosis
Authors: Small Ben G. , Hatley Oliver , Jamei Masoud , Gardner Iain , Johnson Trevor N.
Published: August 2023

Patho‐physiological changes in liver cirrhosis create portacaval shunts that allow blood flow to bypass the hepatic portal vein into the systemic circulation affecting drug pharmacokinetics (PKs). The objectives of this work were to implement a physiologically‐based pharmacokinetic (PBPK) framework describing shunted blood flows in virtual patients with differing degrees of liver cirrhosis; and to assess the minimal and full PBPK model's performance using drugs with intermediate to high hepatic extraction. Single dose concentration‐time profiles and PK parameters for oral ibrutinib, midazolam, propranolol, and buspirone were simulated in healthy volunteers (HVs) and subjects with cirrhosis (Child‐Pugh severity score (CP‐A, CP‐B, or CP‐C)). Model performance was verified by comparing predicted to observed fold‐changes in PK parameters between HVs and cirrhotic subjects. The verified model was used to simulate the PK changes for simvastatin in patients with cirrhosis. The predicted area under the curve ratios (AUCCirr:AUCHV) for ibrutinib were 3.38, 6.87, and 11.46 using the minimal PBPK model with shunt and 1.61, 2.58, and 4.33 without the shunt, these compared with observed values of 4.33, 8.14, and 9.04, respectively. For ibrutinib, propranolol, and buspirone, including a shunt in the PBPK model improved the prediction of the AUCCirr:AUCHV and maximum plasma concentration ratios (CmaxCirr:CmaxHV). For midazolam, an intermediate extraction drug, the differences were less clear. Simulated simvastatin dose adjustments in cirrhosis suggested that 20 mg in CP‐A and 10 mg in CP‐B could be used clinically. A mechanistic model‐informed understanding of the anatomic and pathophysiology of cirrhosis will facilitate improved dose prediction and adjustment in this vulnerable population.
Patient satisfaction following resin‐bonded fixed dental prostheses cemented by using the Dahl concept
Authors: Lim Tong Wah , Idris Rostam Iffendi , Mahmud Melati
Published: August 2023

Objective

Resin‐bonded fixed dental prostheses (RBFDPs) cemented at an increased occlusal vertical dimension (OVD) (the Dahl concept) to create space for a metal retainer remains controversial because of the lack of reported clinical studies. This study analyzed the demographic (age and sex) and clinical factors (location and arch of prosthesis) affecting the patients' perception of RBFDPs cemented at an increased OVD.

Material and Methods

Twenty‐eight participants treated with cantilevered RBFDP at an increased OVD were prospectively recruited. They were asked to answer a validated patient satisfaction questionnaire based on six parameters during the 12‐week review visit.

Results

71.4% of the participants were completely satisfied with the color, shape, and function. Twenty‐one (75%) participants reported no complaints about the prostheses. 89.3% will recommend this treatment option to others. There was a significant difference between males and females in avoiding loading on the prostheses (p = 0.015). The level of satisfaction did not differ by age, ethnicity, location, and arch of the prostheses (p > 0.05).

Conclusions

Patient satisfaction toward RBFDP cemented by using the Dahl approach was generally high on all the parameters at the 12‐week review visit.
Mitigating the socioeconomic impacts of the mining industry through Social Technologies: Guidelines for technology transfer between universities and communities
Authors: Nogueira Marcela Aguiar , Costa Lais Cristina , Resende Douglas Mol , Carvalho Victor Rezende , Mendes Júlia Castro , Peixoto Ricardo André Fiorotti
Published: August 2023

The mineral sector causes socioeconomic and environmental impacts on the surrounding communities. Thus, Social Technologies (STs) developed by universities are an alternative for improving the quality of life of the people affected by mining activities. STs are a Latin American practice comprising solutions for social inclusion and economic development. Thus, this article critically investigates the impacts of mining and STs, reinforcing the potential applications of STs in this field. Additionally, the work discusses the possibilities of technology transfer from the university to society through a comprehensive literature review, and the authors developed guidelines to mitigate the impacts of mining activities using STs implementation with technology transfer as a tool. The literature review showed that, although multiple STs aim at social inclusion, the success of the ST depends on the socio‐technical suitability of each community, an efficient training process, and the capacity for self‐management by the social actors. The guideline created includes aspects of: approach and scenario reconstruction, mapping, identification of vocations, training, and technical support for affected communities. Additionally, the mining sector can use these guidelines as a Corporate Social Responsibility tool.
High Formate Selectivity and Deactivation Mechanism of CuS Nanoparticles in CO2 Electrocatalytic Reduction Reaction
Authors: Wang Min , Li Xiaoyao , Ma Xia , Wang Jie , Jin Xixiong , Zhang Lingxia , Shi Jianlin
Published: August 2023

CO2 electroreduction into liquid fuels is of broad interest and benefits reducing the energy crisis and environment burdens. CuS has been reported to be a desirable candidate for CO2 electroreduction into formate; however, its formate selectivity and stability are still far from the demands of practical application. Herein, we report CuS nanoparticles exhibiting good Faradaic efficiency of formate (about 98 %) in CO2 electroreduction and its deactivation mechanism during the reaction. The deactivation of CuS was found to be associated with the reconstruction and S loss of CuS, which deteriorates the Faradaic efficiency of formate. Combined with ionic and gas analyses, the S atom in CuS was lost in the form of H2S, SO2, and SO42−, followed by the reconstruction of CuS into copper oxides. Such a catalyst reconstruction facilitates electroreductions of CO2 and H2O, respectively, into CO and H2, etc., resulting in the degradation of catalytical performance of CO2 electroreduction into formate. This work reveals the important role of S loss and reconstruction of metal sulfide catalysts during the electroreduction reaction, which may benefit the further development of CuS‐based electro‐catalyst for CO2 electroreduction.
Different solubilizing ability of cyclodextrin derivatives for cholesterol in Niemann–Pick disease type C treatment
Authors: Yamada Yusei , Fukaura‐Nishizawa Madoka , Nishiyama Asami , Ishii Akira , Kawata Tatsuya , Shirakawa Aina , Tanaka Mayuko , Kondo Yuki , Takeo Toru , Nakagata Naomi , Miwa Toru , Takeda Hiroki , Orita Yorihisa , Motoyama Keiichi , Higashi Taishi , Arima Hidetoshi , Seki Takahiro , Kurauchi Yuki , Katsuki Hiroshi , Higaki Katsumi , Minami Kentaro , Yoshikawa Naoki , Ikeda Ryuji , Matsuo Muneaki , Irie Tetsumi , Ishitsuka Yoichi
Published: August 2023

Background

Niemann–Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear.

Methods

We estimated CD–UC complexation for nine CD derivatives derived from native α‐, β‐, and γ‐CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models.

Findings

We found that shuttle and sink activities of CDs are dependent on cavity size‐dependent stoichiometry and substituent‐associated stability of CD–UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability.

Conclusions

Our findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC.
Split‐Cas9‐based targeted gene editing and nanobody‐mediated proteolysis‐targeting chimeras optogenetically coordinated regulation of Survivin to control the fate of cancer cells
Authors: Deng Changping , Li Shihui , Liu Yuping , Bao Wen , Xu Chengnan , Zheng Wenyun , Wang Meiyan , Ma Xingyuan
Published: August 2023

Background

Precise regulation of partial critical proteins in cancer cells, such as anti‐apoptotic proteins, is one of the crucial strategies for treating cancer and discovering related molecular mechanisms. Still, it is also challenging in actual research and practice. The widely used CRISPR/Cas9‐based gene editing technology and proteolysis‐targeting chimeras (PROTACs) have played an essential role in regulating gene expression and protein function in cells. However, the accuracy and controllability of their targeting remain necessary.

Methods

Construction of UMUC‐3‐EGFP stable transgenic cell lines using the Sleeping Beauty system, Flow cytometry, quantitative real‐time PCR, western blot, fluorescence microplate reader and fluorescence inverted microscope analysis of EGFP intensity. Characterization of Survivin inhibition was done by using Annexin V‐FITC/PI apoptosis, calcein/PI/DAPI cell viability/cytotoxicity assay, cloning formation assay and scratch assay. The cell‐derived xenograft (CDX) model was constructed to assess the in vivo effects of reducing Survivin expression.

Results

Herein, we established a synergistic control platform that coordinated photoactivatable split‐Cas9 targeted gene editing and light‐induced protein degradation, on which theSurvivingene in the nucleus was controllably edited by blue light irradiation (named paCas9‐Survivin) and simultaneously the Survivin protein in the cytoplasm was degraded precisely by a nanobody‐mediated target (named paProtacL‐Survivin). Meanwhile, in vitro experiments demonstrated that reducing Survivin expression could effectively promote apoptosis and decrease the proliferation and migration of bladder cancerous cells. Furthermore, the CDX model was constructed using UMUC‐3 cell lines, results from animal studies indicated that both the paCas9‐Survivin system and paProtacL‐Survivin significantly inhibited tumour growth, with higher inhibition rates when combined.

Conclusions

In short, the coordinated regulatory strategies and combinable technology platforms offer clear advantages in controllability and targeting, as well as an excellent reference value and universal applicability in controlling the fate of cancer cells through multi‐level regulation of key intracellular factors.
Estimates of diagnosed dementia prevalence and incidence among diverse beneficiaries in traditional Medicare and Medicare Advantage
Authors: Haye Sidra , Thunell Johanna , Joyce Geoffrey , Ferido Patricia , Tysinger Bryan , Jacobson Mireille , Zissimopoulos Julie
Published: August 2023

Approximately half of Medicare beneficiaries are enrolled in Medicare Advantage (MA), a private plan alternative to traditional Medicare (TM). Yet little is known about diagnosed dementia rates among MA enrollees, limiting population estimates. All (100%) claims of Medicare beneficiaries using encounter data for MA and claims for TM for the years 2015 to 2018 were used to quantify diagnosed dementia prevalence and incidence rates in MA, compare rates to TM, and provide estimates for the entire Medicare population and for different racial/ethnic populations. In 2017, dementia incidence and prevalence among MA beneficiaries were 2.54% (95% confidence interval [CI]: 2.53 to 2.55) and 7.04% (95% CI: 7.03 to 7.06). Comparison to TM adjusted for sociodemographic and health differences among beneficiaries in MA and TM; the prevalence of diagnosed dementia among beneficiaries in MA was lower (7.1%; 95% CI: 7.12 to 7.13) than in TM (8.7%; 95% CI: 8.71 to 8.72). The diagnosed dementia incidence rate was also lower in MA (2.50%; 95% CI: 2.50 to 2.50) compared to TM (2.99%; 95% CI: 2.99 to 2.99). There were lower rates in MA compared to TM for men and women and White, Black, Hispanic, Asian, American Indian/Alaska Native persons. Diagnosed dementia prevalence and incidence for the entire Medicare population was 7.9% (95% CI: 7.91 to 7.93) and 2.8% (95% CI: 2.77 to 2.78). Lower diagnosed dementia rates in MA compared to TM may exacerbate racial/ethnic disparities in diagnosed dementia. Rates tracked over time will provide understanding of the impact on dementia diagnosis of 2020 MA risk adjustment for dementia.
Mandating disability education in medicine: A call to action
Authors: Jordan Julia , Petersen Kristina H.
Published: August 2023

Healthcare clinicians frequently treat persons with disabilities, yet disability is often overlooked in medical education. Fewer than half of U.S. medical schools include disability education in their undergraduate medical education curriculum.1 When included, it is often superficial and insufficient to apply to patient care. Although 98% of students at one institution reported receiving disability education, 80% reported that it was inadequate, and 64% of them felt unprepared to evaluate, diagnose, and treat people with disabilities.2 This trend continues in graduate medical education (GME), with only 43% of emergency medicine programs including disability content.3
Extensive introgression among strongylocentrotid sea urchins revealed by phylogenomics
Authors: Glasenapp Matthew R. , Pogson Grant H.
Published: August 2023

Gametic isolation is thought to play an important role in the evolution of reproductive isolation in broadcast‐spawning marine invertebrates. However, it is unclear whether gametic isolation commonly evolves early in the speciation process or only accumulates after other reproductive barriers are already in place. It is also unknown whether gametic isolation is an effective barrier to introgression following speciation. Here, we used whole‐genome sequencing data and multiple complementary phylogenomic approaches to test whether the well‐documented gametic incompatibilities among the strongylocentrotid sea urchins have limited introgression. We quantified phylogenetic discordance, inferred reticulate phylogenetic networks, and applied the Δ statistic using gene tree topologies reconstructed from multiple sequence alignments of protein‐coding single‐copy orthologs. In addition, we conducted ABBA–BABA tests on genome‐wide single nucleotide variants and reconstructed a phylogeny of mitochondrial genomes. Our results revealed strong mito‐nuclear discordance and considerable nonrandom gene tree discordance that cannot be explained by incomplete lineage sorting alone. Eight of the nine species examined demonstrated a history of introgression with at least one other species or ancestral lineage, indicating that introgression was common during the diversification of the strongylocentrotid urchins. There was strong support for introgression between four extant species pairs (Strongylocentrotus pallidus ⇔ S. droebachiensis, S. intermedius ⇔ S. pallidus, S. purpuratus ⇔ S. fragilis, and Mesocentrotus franciscanus ⇔ Pseudocentrotus depressus) and additional evidence for introgression on internal branches of the phylogeny. Our results suggest that the existing gametic incompatibilities among the strongylocentrotid urchin species have not been a complete barrier to hybridization and introgression following speciation. Their continued divergence in the face of widespread introgression indicates that other reproductive isolating barriers likely exist and may have been more critical in establishing reproductive isolation early in speciation.
The existence and strength of higher order interactions is sensitive to environmental context
Authors: Fox Jeremy W.
Published: August 2023

One strategy for understanding the dynamics of any complex system, such as a community of competing species, is to study the dynamics of parts of the system in isolation. Ecological communities can be decomposed into single species, and pairs of interacting species. This reductionist strategy assumes that whole‐community dynamics are predictable and explainable from knowledge of the dynamics of single species and pairs of species. This assumption will be violated if higher order interactions (HOIs) are strong. Theory predicts that HOIs should be common. But it is difficult to detect HOIs, and to infer their long‐term consequences for species coexistence, solely from short‐term data. I conducted a protist microcosm experiment to test for HOIs among competing bacterivorous ciliates, and test the sensitivity of HOIs to environmental context. I grew three competing ciliate species in all possible combinations at each of two resource enrichment levels, and used the population dynamic data from the one‐ and two‐species treatments to parameterize a competition model at each enrichment level. I then compared the predictions of the parameterized model to the dynamics of the whole community (three‐species treatment). I found that the existence, and thus strength, of HOIs was environment dependent. I found a strong HOI at low enrichment, which enabled the persistence of a species that would otherwise have been competitively excluded. At high enrichment, three‐species dynamics could be predicted from a parameterized model of one‐ and two‐species dynamics, provided that the model accounted for nonlinear intraspecific density dependence. The results provide one of the first rigorous demonstrations of the long‐term consequences of HOIs for species coexistence, and demonstrate the context dependence of HOIs. HOIs create difficult challenges for predicting and explaining species coexistence in nature.
Danish nearshore wind energy policy: Exploring actors, ideas, discursive processes and institutions via discursive institutionalism
Authors: Dyrhauge Helene , Fairbrass Jenny
Published: August 2023

This article explores Danish renewable energy policy and policymaking, focusing on the development of nearshore wind energy and the role played by various actors, their competing ideas, the discursive processes in which they participate, and the institutional settings where exchanges occur. The research employs a case study design, concentrating on the Vesterhav Syd nearshore windfarm project. Drawing on semi‐structured interviews, the paper exploits Discursive Institutionalism and one of its recent refinements, labelled Ideational Power that highlights power over, through and in ideas. The data gathered provides compelling evidence of the ways in which actors struggle for dominance, each seeking to persuade others of their preferred policy problem definition and solutions: a process that oscillates between highly technical coordinative discourses among government agencies and business organisations and more politicised communicative discourses among a wider set of actors that includes community groups. Significantly, this case reveals the power of various policy stakeholders in Danish energy policy, suggesting that once decisions are taken at the national level of governance to construct a windfarm, only limited influence can be exerted by local groups on the outcomes. Our findings raise wider questions about such processes beyond the Danish case.