bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Titanium Aluminides via Powder‐Cored Wire Arc Additive Manufacturing: Microstructural and Mechanical Characterization
Authors: Zhang Liang , Wang Ting , Yuan Bo , Yu Bin , Chen Zhichao
Published: April 2023

Herein, an innovative powder‐cored wire arc additive manufacturing (PC‐WAAM) process is proposed to fabricate γ‐TiAl thin‐walled intermetallic alloy. The metallography, phase composition, and mechanical properties at different thin‐wall locations are characterized. The results show that the alternatively distributed layer‐like microstructure composed of α2 (Ti3Al) and γ (TiAl) phases is obtained along the building direction. The content of α2 phase exhibits the tendency of decreasing from the bottom to top region. This unique microstructure characteristic is closely related to the typical thermal cycling history during deposition. Moreover, the tensile strength and microhardness of the top region are lower than the middle and bottom region. In general, the current PC‐WAAM technique shows promising capability of fabricating γ‐TiAl intermetallic alloy with low cost. This work becomes a valuable reference for understanding the evolution mechanism of microstructure and paves the way for the flexible and customized additive manufacturing of γ‐TiAl alloy.
Chemical Stability and Hydrogen Reaction Behavior of SmCo 2:17‐Type Permanent Magnets
Authors: Schönfeldt Mario , Opelt Konrad , Betz Stefan , Metzmacher Christof , Yoon Songhak , Gassmann Jürgen
Published: April 2023

Herein, the reaction behavior and chemical stability of two commercially available SmCo 2:17‐type sintered magnets with nominal composition of Sm23.75Co48.67FebalCu4.91Zr2.37and Sm24.95Co48.80FebalCu4.46Zr2.68(wt%) are investigated. The magnets are placed in a hydrogen atmosphere with systematically varied pressure, exposure time, and temperature ranging from 1–11 bar, 2–10 d, and 25–500 °C, respectively. Hydrogen content, magnetic properties, microstructure, and lattice constants are characterized in detail. It is found that for short exposure times like 2 d an activation temperature of 120 °C is necessary to initiate the reaction and to increase the amount of hydrogen in the Sm–Co material. Hydrogen absorption starts at lower temperatures with longer exposure times. An increase in exposure time, temperature, or pressure leads to a higher hydrogen content and a decrease in remanenceBr, energy product (BH)max, and coercivityHcB. Lattice expansion, estimated by X‐ray diffraction analysis, correlates with the increasing amount of hydrogen in the Sm–Co magnets. With respect to all varied parameters under investigation, the exposure temperature has the highest impact on the observed property changes followed by reaction time and H2pressure.
Aligned Ice Templated Biomaterial Strategies for the Musculoskeletal System
Authors: Diaz Florencia , Forsyth Nicholas , Boccaccini Aldo R.
Published: April 2023

Aligned pore structures present many advantages when conceiving biomaterial strategies for treatment of musculoskeletal disorders. Aligned ice templating (AIT) is one of the many different techniques capable of producing anisotropic porous scaffolds; its high versatility allows for the formation of structures with tunable pore sizes, as well as the use of many different materials. AIT has been found to yield improved compressive properties for bone tissue engineering (BTE), as well as higher tensile strength and optimized cellular alignment and proliferation in tendon and muscle repair applications. This review evaluates the work that has been done in the last decade toward the production of aligned pore structures by AIT with an outlook on the musculoskeletal system. This work describes the fundamentals of the AIT technique and focuses on the research carried out to optimize the biomechanical properties of scaffolds by modifying the pore structure, categorizing by material type and application. Related topics including growth factor incorporation into AIT scaffolds, drug delivery applications, and studies about immune system response will be discussed.
Antithermal Quenching and Multiparametric Temperature Sensing from Mn2+/Tb3+‐Codoped Ca2LaTaO6 Phosphor
Authors: Chen Yuqi , Li Guixian , Ding Yang , Mao Qinan , Liu Meijiao , Wang Chunhua , Zheng Runtian , Su Bao-Lian , Zhong Jiasong
Published: April 2023

Luminescence thermometry plays significant roles in various fields including industrial production, environmental detection, aerospace, and medicine. However, its accuracy improvement remains highly challenging due to the thermal quenching effect of phosphors. Herein, for the first time, a thermal‐activated electron compensation Mn2+‐ and Tb3+‐codoped Ca2LaTaO6 phosphor is developed for multiparametric temperature sensing with tunable emission of Mn2+ and antithermal quenching emission of Tb3+, leading to excellent accuracy at high temperatures. By virtue of the deep electron trap states induced by Mn2+ dopant, the electrons in the deep trap can be thermally activated at high temperatures, which can replenish the attenuated Tb3+ emission caused by thermal quenching, thus bringing out the antithermal quenching phenomenon. On account of the prominent emission properties, the luminescence intensity ratio (LIR) readout and lifetime‐based thermometry are designed, providing a maximum relative sensitivity SR of 3.603% and 1.941% K−1, respectively. Multiparametric temperature sensing and novel data analysis are also employed to further improve the accuracy of the luminescence thermometer. The outstanding relative thermal sensitivity ranging from 8.72% to 16.11% K−1 and temperature uncertainty order of 10−3 are achieved. These results demonstrate that the designed Ca2LaTaO6:Mn2+/Tb3+ phosphor material is a promising thermal‐sensing candidate.
An effect of canopy bridges on monkey‐vehicle collision hotspots: Spatial and spatiotemporal analyses
Authors: Cunneyworth Pamela M. K. , Andrášik Richard , Bíl Michal
Published: April 2023

Almost one‐quarter of primate species are reported to be involved in vehicle collisions. To mitigate these collisions, canopy bridges are used though their effectiveness is not broadly substantiated. We studied bridge impact on 23 years of vehicle collisions (2000–2022:N = 765) with colobus (Colobus angolensis palliatus), Sykes' (Cercopithecus mitis albogularis), and vervet (Chlorocebus pygerythrus hilgerti) monkeys in Diani, Kenya. Along a 9 km road, collisions did not decrease over the study duration, although bridges increased from 8 to 30. Using the kernel density estimation plus (KDE+) method, collisions appeared highly concentrated at some locations. These concentrations, called hotspots, represent hazardous road segments, though the hotspots for all three species overlapped for only 3% of the road length. We then inspected the collision hotspots over time, using the spatiotemporal extension of the KDE+ method. We compared hotspot presence in the 3 years before and after bridge installation to determine if bridges mitigated these hotspots. Hotspots disappeared for ~60% of bridges postinstallation, suggesting that bridges effectively reduce some collisions. However, of the bridges installed in locations that were not hotspots, 13% had hotspots emerge. Surprisingly, regardless of preinstallation hotspot occurrence, almost one‐fifth of bridges had postinstallation hotspots. To understand the extent to which bridges mitigate collisions, other factors need consideration, including species attributes and crossing behavior, and road features and vehicle volume. We used the novel analytical method because it best suited our data set, given the challenges of determining the bridge impact zone and the low collision frequency.
Current distribution of two species of Chinese macaques (Macaca arctoides and Macaca thibetana) and the possible influence of climate change on future distribution
Authors: Li Wen‐Bo , Yang Pei‐Pei , Xia Dong‐Po , Li Ming , Li Jin‐Hua
Published: April 2023

Predicting the spatial distribution of species and suitable areas under global climate change could provide a reference for species conservation and long‐term management strategies. Macaca thibetana and Macaca arctoides are two endangered species of Chinese macaques. However, limited information is available on their distribution, and their habitat needs lack proper assessment due to complicated taxonomy and less research attention. In recent years, scholars widely used the maximum entropy (MaxEnt) model to predict the impact of global climate and certain environmental factors on species distribution. Therefore, we used the MaxEnt model to predict the spatiotemporal distribution of both macaque species under six climate change scenarios using occurrence and high‐resolution ecological data. We identified climatic factors, elevation, and land cover that shape their distribution range and determined shifts in their habitat range. The results demonstrated that temperature range, annual precipitation, forest land cover, and temperature seasonality, including the precipitation of the driest month are the main factors affecting their distribution. Currently, M. thibetana is mainly concentrated in central, eastern, southern, and southwestern China, and M. arctoides is mainly concentrated in three provinces (Yunnan, Guangxi, and Guangdong) in southern China. The MaxEnt model predicted that the suitable habitat for both species will increase with increased greenhouse emission scenarios. We also found that with the further increase in greenhouse emissions M. thibetana is expected to migrate to western China, and M. arctoides is expected to migrate to western or eastern China. This reinterpretation of the distribution of M. thibetana and M. arctoides in China, and predicted potential suitable habitat and possible migration direction, may provide new insights into the future conservation and management of these two species.
Fine‐Tuning Redox Properties of Heteroleptic Molybdenum Complexes through Ligand‐Ligand‐Cooperativity
Authors: Elvers Benedict J. , Pätsch Sebastian , Bandaru Siva S. M. , Krewald Vera , Schulzke Carola , Fischer Christian
Published: April 2023

Heteroleptic molybdenum complexes bearing 1,5‐diaza‐3,7‐diphosphacyclooctane (P2N2) and non‐innocent dithiolene ligands were synthesized and electrochemically characterized. The reduction potentials of the complexes were found to be fine‐tuned by a synergistic effect identified by DFT calculations as ligand‐ligand cooperativity via non‐covalent interactions. This finding is supported by electrochemical studies combined with UV/Vis spectroscopy and temperature‐dependent NMR spectroscopy. The observed behavior is reminiscent of enzymatic redox modulation using second ligand sphere effects.
Laccase immobilization on bacterial cellulose produced in a mulberry pomace waste extract medium: Characterization and use for dye decolorization
Authors: Unlu Fevziye , Boran Filiz , Yesilada Ozfer , Koytepe Suleyman
Published: April 2023

The present study aimed to immobilize laccase on dry bacterial cellulose (BC) produced by Komagataeibacter xylinus B759 in mulberry pomace waste extract as a low‐cost and natural waste by‐product and to determine the effectiveness of the obtained laccase immobilized BC (Lac/BC) for textile dye decolorization. The highest BC yield obtained after optimization studies was as 1.70 g/L in pH 8.0 medium at 32°C after 15 days. BC and Lac/BC structures were characterized by different instrumental techniques. A transition to more amorphous character was observed with the binding of the enzyme structure. The morphological properties and fiber structure of the BC and enzyme‐linked cellulose structures were examined by SEM and AFM analyses. Obtained Lac/BC pieces were used for the decolorization of Reactive Blue 171 (RB 171) and Reactive Blue 198 (RB 198) diazo dyes during the repeated‐batch process. As a result of using 12 pieces of Lac/BC, 93% and 98% decolorization values were obtained for the RB 171 and RB 198 dyes in the first use, while the color removal was still 83% and 51% at the 8th use, respectively. The results showed that BC produced in a mulberry pomace waste extract can be used for laccase immobilization and Lac/BC is an effective and promising system for textile dye decolorization.
Amelioration of Fibrotic Remodeling of Human 3‐Dimensional Full‐Thickness Skin by Transglutamase 2 Inhibition
Authors: Zhou Xiang , Trinh‐Minh Thuong , Matei Alexandru‐Emil , Györfi Andrea‐Hermina , Hong Xuezhi , Bergmann Christina , Schett Georg , Atkinson John , Bowcutt Rowann , Patel Jessal , Johnson Timothy S. , Distler Jörg H. W.
Published: April 2023

Objective

Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts.

Methods

We assessed TG2 expression and activity using TG2 staining, Western blotting, and TG2 activity assays. We inhibited TG2 in fibroblasts cultured under standard 2‐dimensional conditions and in a 3‐dimensional full‐thickness equivalent skin model using monoclonal inhibitory anti‐TG2 antibodies.

Results

TG2 expression was increased in the skin of patients with SSc compared with healthy controls, with levels particularly high in patients with SSc‐associated interstitial lung disease. TG2 expression and TG2 activity were also increased in SSc dermal fibroblasts. Moreover, the levels of circulating TG2 in the plasma samples from SSc patients were increased versus samples from healthy controls. Anti‐TG2 antibodies did not show consistent antifibrotic effects across different fibroblast cell lines under 2‐dimensional culture conditions; however, anti‐TG2 antibodies effectively reduced transforming growth factor β–induced dermal thickening, myofibroblast differentiation, and collagen accumulation in the 3‐dimensional full‐thickness model of human skin.

Conclusion

We provide the first evidence, to our knowledge, that inhibition of TG2 might be a potential antifibrotic approach in SSc. Our findings have translational potential as anti‐TG2 antibodies are currently evaluated in a phase II clinical trial in chronic allograft injury and would thus be available for clinical studies in SSc (ClinicalTrials.gov identifier: NCT04335578).

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First UK patient cohort treated with stereotactic ablative radiotherapy for primary kidney cancer
Authors: Zarkar Anjali , Henderson Dan , Carver Antony , Heyes Geoff , Harrop Victoria , Tutill Sarah , Kilkenny Julie , Marshall Andrea , Elbeltagi Nada , Howard Helen
Published: April 2023

Aims

Stereotactic ablative radiotherapy (SABR) for primary renal cell carcinoma (RCC) is a promising non‐invasive ablative treatment option. A prospective interventional clinical trial published showed that treatment was feasible and well tolerated. We present the first single‐institution UK cohort of patients with primary RCC receiving protocol‐based SABR with prospective follow‐up. We also present a protocol that could be used to facilitate more widespread use of the treatment.

Materials and methods

Nineteen biopsy‐proven primary RCC patients were treated with either 42 Gy in three fractions on alternate days or 26 Gy in a single fraction based on predefined eligibility criteria using either Linear Accelerator or CyberKnife platform. Prospective toxicity data using CTCAE V4.0 and outcome data such as estimated glomerular filtration rate (eGFR) and tumour response using CT thorax, abdomen and pelvis (CT‐TAP) were collected at 6 weeks, 3, 6, 12, 18 and 24 months post treatment.

Results

The 19 patients had a median age of 76 years (interquartile range [IQR] 64–82 years) and 47.4% were males, and they had a median tumour size of 4.5 cm (IQR 3.8–5.2 cm). Single and fractionated treatment was well tolerated and there were no significant acute side effects. The mean drop from baseline in eGFR at 6 months was 5.4 ml/min and that at 12 months was 8.7 ml/min. The overall local control rate at both 6 and 12 months was 94.4%. Overall survival at 6 and 12 months was 94.7% and 78.3%, respectively. After a median follow‐up of 17 months, three patients experienced a Grade 3 toxicity, which was resolved with conservative management.

Conclusion

SABR for primary RCC is a safe and feasible treatment for medically unfit patients, which can be delivered in most UK cancer centres using standard Linear Accelerator as well as CyberKnife platforms.
A new application of isoindole fluorophore derivative in sitagliptin antidiabetic medication assay: Application to dosage forms and biological fluid evaluation
Authors: El Hamd Mohamed A. , Soltan Osama M. , Abdelrahman Kamal S. , Alsaggaf Wejdan T. , Abu‐hassan Ahmed A.
Published: April 2023

Dipeptidyl peptidase‐4 enzyme suppressant is a unique category of oral antidiabetic medication. Sitagliptin (STG) is a perfect member of this category and is pharmaceutically marketed alone or in combination with metformin. Here, the ideal application of an isoindole derivative for STG assay was developed using a feasible, easy‐to‐use, economic, and affordable method. STG as an amino group donor can form a luminescent derivative: isoindole on interaction with o‐phthalaldehyde and the existence of (2‐mercaptoethanol) 0.02% (v/v) as a thiol group donor. Excitation (339.7 nm) and emission (434.6 nm) wavelengths were used to monitor the isoindole fluorophore yield; moreover, each experimental variable was carefully investigated and adjusted. The calibration graph was constructed by plotting fluorescence intensities against STG concentrations, and controlled linearity was observed at concentrations ranging from 50 to 1000 ng/ml. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were analyzed in depth to prove the technique validation. The implementation of the present technique was extended successfully to the evaluation of various types of STG dose forms and spiking samples of human plasma and urine. The developed technique was shown to be an effective, simple, and quick replacement for quality control and clinical study evaluation of STG.
Knowledge, attitudes, views and experiences of fathers toward child sexual abuse: A mixed‐method study
Authors: Apaydin Cirik Vildan , Bulut Elif , Aksoy Bahar
Published: April 2023

This study aims to evaluate (i) the knowledge levels and attitudes of fathers toward child sexual abuse (CSA), (ii) factors influencing their knowledge and attitudes, and (iii) views on the CSA, using a sequential exploratory mixed method and a cross‐sectional and phenomenological approach. The quantitative stage was conducted with the fathers of 258 children in a public primary school in Turkey between June and August 2021. In the qualitative stage, data were collected through face‐to‐face interviews with 14 fathers between October 2021 and January 2022 using a sociodemographic form, the CSA Knowledge/Attitude Scale (CSAKAS) and a semi‐structured interview form. The mean total CSAKAS score was 129.51 ± 20.23. CSAKAS total scores were found to be higher in those with bachelor's or higher education degrees (F = 3.374, p = 0.019), background knowledge of CSA (t = 4.291, p < 0.001), receiving information about protecting their child from sexual abuse (t = 3.633, p < 0.001) and having a higher level of communication with their children (r = 0.422, p < 0.001). In the analysis of the qualitative data, three main themes emerged: the emotional conceptualization of CSA, potential drivers of CSA and protectors against CSA. According to the results, fathers do not take responsibility for CSA, so it is recommended to plan educational programs.
Tuning the Photophysical Properties and Photostability of Bis(naphthobipyrrolylmethene) Derived BODIPY via Functionalization
Authors: Sucharita Sahoo Sipra , Sarma Tridib , Shivaprakash Srivishnu Kalavala , Panda Pradeepta K.
Published: April 2023

A series of NIR absorbing and emitting, naphthobipyrrole derived BODIPY dyes are reported. These dyes possess different functional groups viz. −CHO, −CN, −NO2, ‐Br and Ph at its α,α′‐positions. All the derivatives were characterized thoroughly via various spectroscopic means as well as single‐crystal X‐ray structural analyses. Impacts of functionalization on its photophysical properties as well as photostability were evaluated. For instance, incorporation of the phenyl moieties at the α, α′‐positions by Suzuki coupling of the dibromo‐derivative 4 with phenyl boronic acid led to substantial bathochromic shift in absorption (762 vs 727 nm) and emission (778 vs 744 nm) relative to the unsubstituted parent dye VI. Theoretical calculations have been performed by ground state optimization to evaluate the electronic transitions which supports experimental observation.
NAGNet: A novel framework for real‐time students' sentiment analysis in the wisdom classroom
Authors: Zhu Huihui , Hu Pengyun , Tang Xianpiao , Xia Daoxun , Huang Haifeng
Published: April 2023

Facial expression is the basis of human emotion recognition, and we can infer the emotional state of human beings by analysing facial expressions. As the main method of human emotional expression, facial expression contains much information about inner emotional changes. In recent years, with the wide application of artificial intelligence in education, related research on student sentiment analysis has become a hot topic in the educational technology field. Analysing affective data is helpful for understanding students' learning status and provides an important basis for the effective implementation of learning interventions, which is of great significance for the evaluation of teaching effects and changes in teaching methods. However, traditional learner emotion recognition methods have some problems, such as low recognition rates, complex algorithms, poor robustness, and easy loss of the key information of facial expression features. Therefore, this article proposes a learner emotion recognition method based on NAGNet. The network model is composed of Res2Net, nonlocal attention and GeM pooling, which can fuse global expression feature information to realize fine‐grained sentiment analysis. Additionally, we conducted training and experiments on the large‐scale learner emotion dataset FERPlus. The NAGNet model trained by the public emotion dataset FERPlus has a recognition accuracy of 89.3% for eight kinds of student emotions. The experimental results show that the method can quickly and accurately identify learner emotional states. We conduct experiments in a real classroom scenario, and use the NAGNet model proposed in this article to analyse and detect students' real‐time sentiment. Then teachers improve teaching methods by understanding the feedback of students' classroom status. Therefore, this method has important reference significance in the construction of wisdom classrooms and wisdom learning environments.
Titanium Doping Induced the Suppression of Irreversible Phase Transformation at High Voltage for V‐based Phosphate Cathodes of Na‐Ion Batteries
Authors: Tong Shuai , Pan Hui , Liu Hang , Zhang Xiaoyu , Liu Xiangyu , Jia Min , Kang Yahao , Yuan Yong , Du Xinyi , Yan Xiaohong
Published: April 2023

Polyanionic material, specifically the NASICON‐type material, is considered a promising cathode material for Na‐ion batteries (SIBs) because of its stable structure and high operating voltage. Further, it improves the energy density correlated with the well utilization of all Na in the compound. For Na3V2(PO4)2F3 (NVPF), the extraction of the third Na, reported as the electrochemical inactivated, can be realized at a high voltage region while forming an irreversible tetragonal phase. In this study, we introduce Ti doping to the Na2VTi(PO4)2F3 (NVTPF) material; we reveal that the Ti‐doped NVTPF could effectively suppress the irreversible phase transformation, thus successfully harnessing Na in a wide voltage range. Experimental study discloses that the Ti‐substituted Na2VTi(PO4)2F3 could take up the Na+ from Amam phase to Cmc21 phase between 1.0 V and 4.8 V reversibly accounting for the 2 Na+ transportation that shows favorable Na+ kinetics and structural stability. Our research provides the strategy to stabilize the polyanion structure upon charging at a high voltage range and inspires the utilization of full sodium in the polyanionic materials, which could be considered as a material design for future conventional applications.
Simple and rapid detection of Alternaria alternata using an excreted redox‐active species
Authors: Kwon Jungwook , Jeon Jun Hui , Yang Sung Ik , Yang Haesik
Published: April 2023

Airborne fungi pose a serious threat to public health. Alternaria alternata (A. alternata) is a fungus that has been associated with the development of asthma. Detection using redox‐active species excreted from fungi is an effective method for a simple electrochemical fungal biosensor. The achievable electrochemical signal in most fungi, however, is exceptionally low because of the low amount of excreted redox‐active species and their slow excretion rates. Herein, we report that A. alternata excretes an exceptionally large amount of a redox‐active species that can be used for sensitive and selective detection of A. alternata. The excretion rate is enhanced in Tris buffer, and the electrochemical‐chemical redox cycling involving excreted redox‐active species significantly increases the electrochemical signals. Only A. alternata among five common airborne fungi provides large electrochemical signals, which allows selective detection of A. alternata. The calculated detection limit for A. alternata is ~20 spores/mL with an incubation period of 10 min, indicating that the detection method is highly sensitive and rapid. The detection method does not require complicated procedures or harsh pretreatment and is optimal for point‐of‐care testing of A. alternata.
An approach for application of ozone bleaching and nano‐filler loading on quality of papermaking from sorghum bagasse as a promise alternative non‐wood fiber
Authors: Said Abd El‐Aziz A. , Aly Aref A. M. , Mostafa Atef H. , Ahmed Hazem S. , Goda Mohamed N.
Published: April 2023

Over the past years, non‐stop research and development has continued to find the most suitable bleaching sequence for each source of fibrous raw materials, both wood and non‐wood, by improving mixing technology. In this work, the role of ozone bleaching and nano‐filler loading on the quality of papermaking from sorghum bagasse as an alternative available agriculture residue in Egypt was studied. We bleached the sorghum Kraft pulp using D0EOD1 and ZEOD sequences to achieve a final high brightness and suitable mechanical strength. The quality of the pulp obtained is proved to be excellent for paper industry. CaCO3 nano‐filler was applied on bleached pulp sheets in order to decrease the production costs through increasing filler loading. The FTIR spectrum of this filler loaded on the pulp indicates the existence of some kind of bonds between them. In addition, it was observed that the particle size was reduced after the milling process. The nano‐filler significantly enhanced the retention and consequently all the paper optical properties. Addition of nano‐filler loading leads to improving brightness, opacity, scattering coefficient, and acceptable mechanical strength of sheet formation needed for papermaking. It is of interest to note that adopting the ZEOD sequence gave a brightness increase from 86 ISO in case of DoEOD1 to 90 ISO. Furthermore, the paper sheets filled with the nano‐filler, according to this sequence, improved the brightness to be 94.6 ISO, a value higher than that produced by the standard commercial filler of 93.3 ISO.
Machine learning model of imipenem‐resistant Klebsiella pneumoniae based on MALDI‐TOF‐MS platform: An observational study
Authors: Zeng Yu , Wang Chao , Ye Qing , Liu Gang , Zhang Lixia , Wan Jingjing , Zhu Yu
Published: April 2023

Background and Aim

Machine learning is an important branch and supporting technology of artificial intelligence, we established four machine learning model for the drug sensitivity of Klebsiella pneumoniae to imipenem based on matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) and compared their diagnostic effect.

Methods

The data of MALDI‐TOF‐MS and imipenem sensitivity of 174 cases of K. pneumoniae isolated from clinical specimens in the laboratory of microbiology department of Tianjin Haihe Hospital from 2019 January to 2020 December were collected. The mass spectrometry and imipenem sensitivity of 70 cases of imipenem‐sensitive and 70 resistant cases were randomly selected to establish the training set model, 17 cases of sensitive and 17 cases of resistant cases were randomly selected to establish the test set model. Mass spectral peak data were subjected to orthogonal partial least squares discriminant analysis (OPLS‐DA), the training set data model was established by machine learning least absolute shrinkage and selection operator (LASSO) algorithm, logistic regression (LR) algorithm, support vector machines (SVM) algorithm, neural network (NN) algorithm, the area under the curve (AUC) and confusion matrix of training set and test set model were calculated and selected by Grid search and 3‐fold Cross‐validation respectively, the accuracy of the prediction model was verified by test set confusion matrix.

Results

The R²Y and Q² of OPLS‐DA were 0.546 and 0.0178. The AUC of the best training set and test set models were 0.9726 and 0.9100, 1.0000 and 0.8581, 0.8462 and 0.6263, 1.0000 and 0.7180 evaluated by LASSO, LR, SVM and NN model respectively. The accuracy of the LASSO, LR, SVM and NN model were 87%, 79%, 62%, and 68% in test set, respectively.

Conclusion

The LASSO prediction model of K. pneumoniae sensitivity to imipenem established in this study has a high accuracy rate and has potential clinical decision support ability.
Self‐assessed medication risk factors as part of comprehensive health screening in home‐dwelling older adults
Authors: Kanninen Jonna‐Carita , Puustinen Juha , Airaksinen Marja , Kautiainen Hannu , Koivisto Anna‐Liisa , Hietasalo Pauliina , Heikkilä Anna‐Maija , Kunvik Susanna , Toivo Terhi , Dimitrow Maarit , Bergman Jussi , Holm Anu
Published: April 2023

Background

Poor medication management may negatively impact the health and functional capacity of older adults. This cross‐sectional study aimed to identify medication‐related risk factors in home‐dwelling residents using a validated self‐assessment as part of comprehensive health screening.

Methods

The data were derived from comprehensive health screening (PORI75) for older adults of 75 years living in Western Finland in 2020 and 2021. One of 30 validated measures in health screening focused on identifying medication‐related risk factors (LOTTA Checklist). The Checklist items were divided into (1) systemic risk factors (10 items) and (2) potentially drug‐induced symptoms (10 items). Polypharmacy was categorized according to the number of used drugs: (1) no polypharmacy (<5 drugs), (2) polypharmacy (≥5 and <10), and (3) excessive polypharmacy (≥10). The linearity across these three polypharmacy groups was evaluated using the Cochran–Armitage test.

Results

Altogether, 1024 out of 1094 residents who participated in the health screening consented to this study (n = 569 in 2020 and n = 459 in 2021). The mean number of all drugs in use was 7.0 (range 0−26; SD 4.1), with 71% of the residents using >5 drugs, that is, having polypharmacy. Of the systemic risk factors most common was that the resident had more than one physician responsible for the treatment (48% of the residents), followed by missing drug list (43%), missing regular monitoring (35%), and unclear durations of the medication (35%). The most experienced potentially drug‐induced symptoms were self‐reported constipation (21%), urinating problems (20%), and unusual tiredness (17%). An increasing number of drugs in use, particularly excessive polypharmacy, was associated with various medication‐related risk factors.

Conclusion

As a part of comprehensive health screening the LOTTA Checklist provides useful information to prevent medication‐related risk factors in home‐dwelling older adults. The Checklist could be used to guide planning and implementing health services in the future.
DETECTION OF CLONALLY EXPANDED SALIVARY GLAND LYMPHOCYTES IN SJÖGREN'S SYNDROME
Authors: Freimark Bruce , Fantozzi Richard , Bone Robert , Bordin Gerald , Fox Robert
Published: April 2023

Recurrent swelling of the parotid and submandibular salivary glands occurs in some patients with Sjögren's syndrome (SS). Using Southern blot methods, we analyzed immunoglobulin and T cell antigen receptor (TCAR) gene rearrangements in DNA obtained from salivary gland lymphocytes of 9 SS patients. Based on histologic appearance of the biopsy specimens, these patients were diagnosed as having myoepithelial sialadenitis. We found oligoclonal rearrangements of the κ gene (4 patients) and λ gene (1 patient), and oligoclonal rearrangement of the TCAR β chain in 2 additional SS patients. Patients with Ig gene rearrangements did not show rearrangements of their TCAR gene, nor did patients with TCAR rearrangements exhibit Ig rearrangements. The observed oligoclonal rearrangements probably derive from 5‐10% of the salivary gland B cells or T cells. Three of these SS patients developed non‐Hodgkin's lymphoma 2‐8 years after the initial biopsy. Our results suggest that minor populations of B cells or T cells may clonally expand in the salivary gland tissues of SS patients with pseudolymphoma, and that such lymphocyte expansions may be controlled by the endogenous immune response and/or medications. However, continued lymphoproliferation in these salivary gland tissues may eventually lead to emergence of a neoplastic clone that escapes immunologic control and develops into a non‐Hodgkin's lymphoma as a result of a multistep process.
ANTIBODIES TO HISTONES H1 AND H5 IN SERA OF PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS
Authors: Pauls John D. , Silverman Earl , Laxer Ronald M. , Fritzler Marvin J.
Published: April 2023

The specificity of juvenile rheumatoid arthritis (JRA) sera for histone subclasses was examined by immunoblotting. Antibodies to H1 alone were found in 4 of 21 pauciarticular‐onset JRA sera, 4 of 19 polyarticular‐onset JRA sera, and 2 of 11 systemic‐onset JRA sera. Antibodies to H5 alone were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and 3 of 11 systemic JRA sera. Antibodies to both H1 and H5 were found in 4 of 21 pauciarticular JRA sera, 4 of 19 polyarticular JRA sera, and 1 of 11 systemic JRA sera. Antibodies to the core histones (H2A and H2B) were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and no systemic JRA sera. No reactivity to histones was observed in 30 sera from age‐matched children with nonrheumatic diseases. The presence of H1 and H5 antibodies did not correlate with antinuclear antibody titers or with a homogeneous pattern of immunofluorescence. The predominance of H1 and H5 antibodies and relative absence of antibodies binding to core histones in JRA contrast with findings in adult systemic lupus erythematosus. Further, the presence of antibodies to H5 alone in some of the JRA patients indicates that the immune response in these patients is directed to determinants that are not shared by sequences of mammalian proteins.
REACTIVITY OF ANTINUCLEAR ANTIBODIES WITH HISTONES AND OTHER ANTIGENS IN JUVENILE RHEUMATOID ARTHRITIS
Authors: Malleson Peter , Petty Ross E. , Fung Marinda , Candido E. Peter M.
Published: April 2023

Antinuclear antibodies are found in serum samples from most children with juvenile rheumatoid arthritis (JRA), but the antigenic specificities of these antibodies are not known. Using an immunoblot technique, we found that JRA patients' sera react with a variety of proteins in the nuclei of HEp‐2 cells. Antibody to histone H1 was found in 42% of the JRA serum samples. An IgG antibody to a 45‐kd protein was found in serum samples from some patients without uveitis, but it was not found in any sample from patients with uveitis. The immunoblot reactivity patterns do not appear to be useful in distinguishing between disease onset types or disease course types in patients with JRA.
Effects of exercise habits in adolescence and older age on sarcopenia risk in older adults: the Bunkyo Health Study
Authors: Tabata Hiroki , Otsuka Hikaru , Shi Huicong , Sugimoto Mari , Kaga Hideyoshi , Someya Yuki , Naito Hitoshi , Ito Naoaki , Abudurezake Abulaiti , Umemura Futaba , Kiya Mai , Tajima Tsubasa , Kakehi Saori , Yoshizawa Yasuyo , Kawamori Ryuzo , Watada Hirotaka , Tamura Yoshifumi
Published: April 2023

Background

Sarcopenia, defined as an age‐associated loss of skeletal muscle mass and function, is a major risk factor for requiring long‐term care. Because physical activity in adolescence and older age enhances peak muscle function in youth and prevents muscle function decline in older age, older adults with exercise habits during both periods may be at a lower risk for sarcopenia. We investigated the relationship between exercise habits in adolescence and older age and sarcopenia and its components in community‐dwelling older Japanese adults.

Methods

This study included 1607 community‐dwelling individuals (aged 65–84, medians 73 years, 679 men and 928 women) with complete health examinations, including measurements of skeletal muscle index, handgrip strength and gait speed, who were enrolled in the Bunkyo Health Study. We divided the participants into four groups according to exercise habits in adolescence and older age: no exercise in either period (none‐none; NN), exercise only in adolescence (active‐none; AN), exercise only in older age (none‐active; NA) and exercise in both periods (active‐active; AA). Multivariate‐adjusted logistic regression models were used to estimate the odds ratios (ORs) and associated 95% confidence intervals (CIs) in each group for the prevalence of sarcopenia, defined as low muscle mass and low muscle performance, as compared with the NN group. Low muscle performance was defined as low muscle strength and/or low gait speed.

Results

The total prevalence of sarcopenia was 6.6% (45/679) in men and 1.7% (16/928) in women, the total prevalence of low muscle mass was 14.3% (97/679) in men and 5.2% (48/928) in women, and the total prevalence of low muscle performance was 25.6% (174/679) in men and 19.6% (182/928) in women. In men, the ORs (95% CIs) for sarcopenia, low muscle mass and low muscle performance were significantly lower in the AA group (sarcopenia: 0.29 [0.09–0.95], P = 0.041; low muscle mass: 0.21 [0.09–0.52], P = 0.001; and low muscle performance: 0.52 [0.28–0.97], P = 0.038). In women, the OR (95% CI) for low muscle performance was significantly lower in the AA group than in the other groups (0.48 [0.27–0.84], P = 0.010), whereas none of the ORs for sarcopenia and low muscle mass were significant.

Conclusions

Older men with exercise habits in both adolescence and older age were at a lower risk of sarcopenia, low muscle mass and low muscle performance, whereas older women with exercise habits at both time periods were at a lower risk of low muscle performance.
Instability of fecal glucocorticoid metabolites at 4°C: Time to freeze matters
Authors: Carbillet Jeffrey , Palme Rupert , Maublanc Marie‐Line , Cebe Nicolas , Gilot‐Fromont Emmanuelle , Verheyden Hélène , Rey Benjamin
Published: April 2023

The use of fecal corticosteroid metabolites (FCMs) has proven to be well suited to evaluate adrenocortical activity, a major component of the stress response, particularly in wildlife. As with any tools, confounding factors and drawbacks must be carefully considered. Among them, sample preservation and storage are of particular importance, as they can affect stability of FCMs and lead to biased results and interpretations. Arguably, immediate freezing of fecal samples upon collection is the best practice to preserve FCM integrity, however, for logistical reasons, this condition is rarely feasible in the field. It is generally argued that temporary storage of samples at low above‐zero temperature is an acceptable way of preserving samples in the field before freezing them for long‐term storage. However, to our knowledge, there is no empirical study that demonstrates the stability of fecal metabolites in samples stored at +4°C. In this study, we collected a fresh fecal sample from 20 captive roe deer, each of which was homogenized and split into three subsamples (60 subsamples in total) to investigate the effects on FCMs levels of temporary storage at +4°C for 24 h and 48 h before freezing versus immediate freezing at −20°C after feces collection. Compared to immediate freezing, mean FCMs levels decreased by 25% every 24 h when feces were stored at +4°C before freezing. The variance of FCMs levels followed the same pattern, leading to a clear reduction in the ability to detect biological effects. Minimizing the storage time at +4°C before freezing should therefore be seriously considered when establishing sampling and storage protocols for feces in the field for adequate hormonal profiling.
TRIM21 promotes ubiquitination of SARS‐CoV‐2 nucleocapsid protein to regulate innate immunity
Authors: Mao Shenglan , Cai Xuefei , Niu Siqiang , Wei Jie , Jiang Ning , Deng Haijun , Wang Wen , Zhang Jing , Shen Shimei , Ma Yuanyan , Wu Xiaoli , Peng Qiling , Huang Ailong , Wang Deqiang
Published: April 2023

The innate immune response is the first line of host defense against viral infections, but its role in immunity against SARS‐CoV‐2 remains unclear. By using immunoprecipitation coupled with mass spectroscopy, we observed that the E3 ubiquitin ligase TRIM21 interacted with the SARS‐CoV‐2 nucleocapsid (N) protein and ubiquitinated it at Lys375. Upon determining the topology of the TRIM21‐mediated polyubiquitination chain on N protein, we then found that polyubiquitination led to tagging of the N protein for degradation by the host cell proteasome. Furthermore, TRIM21 also ubiquitinated the N proteins of SARS‐CoV‐2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron together with SARS‐CoV and MERS‐CoV variants. Herein, we propose that ubiquitylation and degradation of the SARS‐CoV‐2 N protein inhibited SARS‐CoV‐2 viral particle assembly, by which it probably involved in preventing cytokine storm. Eventually, our study has fully revealed the association between the host innate immune system and SARS‐CoV‐2 N protein, which may aid in developing novel SARS‐CoV‐2 treatment strategies.
Metformin promotes bacterial surface aggregation by inhibiting the swimming motility of flagellated Escherichia coli
Authors: Jiang Panmei , Ye Yingxiang , Liu Jian , Wang Fangbin
Published: April 2023

The antiglycemic drug metformin, which is widely prescribed as a first‐line drug for the treatment of type 2 diabetes, has become a concern for emerging pollutants in natural ecosystems. However, its effects on bacterial swimming motility remain unclear. In this study, we showed that metformin promotes bacterial surface aggregation by tracking swimming and by measuring the density distribution of Escherichia coli cultured with metformin near a surface in a homogeneous environment. Flagella are essential for the promotion of bacterial surface aggregation by metformin. Swimming motility, which is mediated by flagella, determines bacterial surface aggregation. The promotion of bacterial surface aggregation by metformin is caused by a reduction in swimming motility, which is governed by a decrease in the proton motive force. Our results reveal that metformin has a pronounced effect on flagellated bacterial motility associated with surface sensing and aggregation.
Questionnaire survey on the conceptual framework, optimal evaluation, and support measures for children's language disorders in Japan using the Delphi method
Authors: Iwamura Kenji , Isaki Motohiro , Uchiyama Chizuko , Nomura Keiko , Tanimoto Ayumi , Kuroiwa Hajime , Kozono Machiko , Iwashita Yoshihiro , Iwamura Junko , Hyodo Masamitsu
Published: April 2023

Objectives

To compile the opinions of native Japanese speakers on the conceptual framework, optimal evaluation, and support measures for children with language disorders to devise materials on which a consensus can be formed.

Design

A quantitative descriptive study using the Delphi method.

Setting

Using the Delphi method, 43 clinicians with at least 15 years of experience working professionally with children's language disorders in Japan were surveyed three times via a web‐based questionnaire. Thirty‐nine items that were carefully selected by the working group were surveyed, and the agreement level was set to ≥80%.

Main Outcome Measures

We investigated the following aspects related to developmental language disorder (DLD) among Japanese children: definition, core symptoms, evaluation of core symptoms, relationship with a second language, relationship with other related disorders, support systems, and information availability.

Results

Overall, 43 qualified panel members were included in this study. Among the 39 items in the questionnaire, a high level of consensus (≥80%) from the responses of the participants was achieved for five items in Round 1, whereas no consensus (<50%) was achieved for seven items. After revising and integrating the questionnaires into 22 items, we conducted Rounds 2 and 3 and obtained high and medium levels of agreement in 20 items on disease concept, core symptoms, coexisting disorders, and manner of support of DLD in children.

Conclusion

Our results clarify the previously ambiguous image of DLD in Japan. Information‐sharing strategies that connect professionals, patients, their families, and community members are required in the future.

Level of Evidence

5
The new guideline for evaluating effects of psychotropic drugs on the performance to drive a motor vehicle in Japan: Comparison with US FDA guideline
Authors: Iwamoto Kunihiro , Nakabayashi Tetsuo , Yamaguchi Akiko , Konishi Yuki , Saji Momoe , Yoshimura Reiji , Kanemoto Kousuke , Aoki Hirofumi , Ando Masahiko , Ozaki Norio
Published: April 2023

In December 2022, the new guideline for evaluating the effect of psychotropic drugs on the performance to drive a motor vehicle was issued by the Ministry of Health, Labour and Welfare (MHLW) and implemented in Japan. Of the safety information, information on the influence of medications on driving performance is particularly important because it can be relevant to the social functioning of patients. In principle, the package inserts of medications are designed based on evidence and provide precautions regarding the operation of heavy machinery such as automobiles in Japan, the United States, and Europe. The effects of medications on driving performance are generally evaluated in a tiered approach involving nonclinical and clinical studies. Because of the wide variety of functional domains involved in automobile driving, the selection of evaluation methods for a given medication depends on their characteristics, which is a complicated method. Therefore, to evaluate the effects of psychotropic drugs on driving performance efficiently and appropriately, we developed the MHLW guideline that specifically defines the evaluation methods used in pharmacological studies, the neuropsychological tests used in pharmacodynamic studies, and the situations in which driving studies are necessary. Regarding the planning of appropriate drug development strategies, we review the background of the MHLW guideline and its differences from the US Food and Drug Administration (FDA) guideline.