bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐resolution model reconstruction and bridge damage detection based on data fusion of unmanned aerial vehicles light detection and ranging data imagery
Authors: Li Hongze , Chen Yanli , Liu Jia , Che Changtong , Meng Ziyao , Zhu Hang
Published: December 2023

Damage detection is essential for the maintenance of transportation infrastructure that experiences high daily traffic levels in potentially extreme environments and changes in use patterns. However, traditional physical inspection is always labor‐intensive, subjective, and biased, lacking the objective perspective required for a comprehensive and reliable assessment. Recently, unmanned aerial vehicles (UAVs) combined with emerging high‐performance sensor(s) have been intensively researched. Here, we present an aerial bridge surface survey method that can be used to assess damage. Existing damage detection methods focus on single types of damage and are limited in locating global damage, whereas our method detects two types of damage on the surface and marks them in a panoramic image. The workflow involves three steps: data acquisition using a meticulous UAV flight strategy that covers the entire surface, data processing using image‐based and point‐cloud models after polynomial rectification, and data output (i.e., damage detected by the combined models). To verify the method, a field test detected damage to two real bridges. A UAV equipped with a camera and light detection and ranging (LiDAR) equipment was employed. Experiments demonstrate the effectiveness of the proposed method, which is capable of producing accurate outputs and detecting damage with an average position error of 13.37 mm and a relative size error of 25.25%. Owing to the data fusion model taking advantage of two‐dimensional (2D) images and 3D LiDAR data, it outputs a high‐resolution 3D model and avoids environmental disturbances. After decision‐making‐level damage fusion, all position and size properties of damage information are computed into a panoramic damage image. This panoramic image showing all detecting damage helps technicians perform maintenance; the image can be zoomed to focus on any issue individually.
Marginalization and women's healthcare in Ghana: Incorporating colonial origins, unveiling women's knowledge, and empowering voices
Authors: Bawafaa Eunice
Published: December 2023

The origins of marginalization in nursing and the health sector in Ghana can be traced to colonialism and how a colonial era laid a solid foundation for inequities and entrenched disparities, as well as the subsequent normalization of marginalizing acts, in the health sector, particularly for women. Drawing upon varied literature over a 60‐year period and perspectives from feminist theory, this paper considers the lasting impact of Ghanaian women's historical position during the colonial era and within the patriarchal system that ensued. Through this process, it becomes possible to shed light on the crucial role that colonialism has played in women's experiences, perspectives, and health‐seeking behaviors, and the manner in which it has created a healthcare sector that marginalizes women's health. Although women possess valuable knowledge which should be an asset to consider when providing healthcare services, marginalization of that knowledge has become normalized across society and the healthcare system. There is an urgent need to disrupt and challenge this normalization, and to advocate empowerment and recognition of women's valuable knowledge and experiences, providing women a voice in health decision‐making discourses and in the research processes by which we understand and develop healthcare. Through this, healthcare in Ghana could become more empowering, inclusive, and responsive to the unique experiences and needs of Ghanaian women. By understanding something of the historical origins of women's health marginalization within colonialism, nurses can begin to appreciate women's knowledge and integrate it into healthcare strategies that are more gender‐sensitive and equitable.
Comparison of Bone‐setting Robots and Conventional Reduction in the Treatment of Intertrochanteric Fracture: A Retrospective Study
Authors: Xu Zhanmin , Zhang Xinan , Wang Yongqing , Hao Xiaohui , Liu Meiyue , Sun Jingtao , Zhao ZhiHui
Published: December 2023

Objective

Intertrochanteric fracture of the femur is a common fracture in older people. Due to the poor systemic condition and prognosis of elderly patients, it is prone to more complications. We introduce the bone‐setting concept in the design of the robots, which are used for intertrochanteric fracture of the femur reduction. The purpose of this study is to compare the effect of bone‐setting robots and conventional reduction in the treatment of intertrochanteric fracture of the femur (IFF).

Methods

From June 2021 to January 2023, 60 patients with IFF who were treated surgically were assigned to bone‐setting robots group and conventional reduction methods group in this retrospective study. The reduction time, operation time, total time, intraoperative blood loss, incision length, fluoroscopy time, and the follow‐up time were reviewed. The visual analogue scale (VAS) and Harris scores were used for functional assessment. For continuous variables, independent t‐tests were applied; for categorical data, the chi‐square test was applied. The significance level as p < 0.05.

Results

Among the 60 patients with IFF, 31 were assigned to the bone‐setting robots group, and 29 were assigned to the conventional reduction methods group. Both groups with a similar baseline in the number, gender, age, and classification (p > 0.05). The reduction time, operation time, total time, intraoperative blood loss, and fluoroscopy time were less than those in the bone‐setting robots reduction group compared to the conventional reduction group. In the bone‐setting robots reduction group, the preoperative VAS score was 6.2 ± 1.3, the Harris score was 35.3 ± 3.1, 1 week after surgery VAS score was 3.3 ± 1.2, the Harris score was 57.3 ± 3.7, and at the last follow‐up VAS score was 2.4 ± 0.8, and the Harris score was 88.7 ± 3.4. While in the conventional reduction group, the preoperative VAS score was 6.3 ± 1.3, the Harris score was 35.9 ± 2.9, 1 week after surgery VAS score was 4.8 ± 1.4, the Harris score was 46.8 ± 2.8, and at the last follow‐up VAS score was 2.6 ± 0.8, and the Harris score was 87.3 ± 3.3. There were no significant differences between the two groups at the preoperative and 6‐month postoperative follow‐ups in VAS score and Harris score (p > 0.05, p > 0.05, respectively). But the difference was statistically significant at the one‐week postoperative follow‐up in VAS and Harris scores (p < 0.001).

Conclusion

The bone‐setting robots can better protect the “fracture environment” and have the advantages of being precise, minimally invasive, simple, short time, low radiation, and rapid fracture recovery. The clinical effect of closed repair of IFF is ideal.
Electrical storm following pregnancy in systemic scleroderma: A case report
Authors: Emkanjoo Zahra , Shirazi Samira , Kamali Farzad , Pouraliakbar Hamid , Nourani Mahsa , Balavandi Firouz
Published: December 2023

Introduction

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by immune dysfunction, vascular damage, and fibrosis affecting the skin and multiple internal organs, such as the cardiovascular and respiratory systems. In some women with preexisting SSc, pregnancy is associated with negative maternal outcomes. Tachyarrhythmia is a common clinical manifestation of cardiovascular damage in SSc patients. However, few studies have reported the use of catheter ablation and an implantable cardioverter defibrillator (ICD) in patients with SSc complicated by ventricular tachycardia (VT).

Case

A 19‐year‐old woman known case of SSc referred to our center with recurrent VT during pregnancy and after delivery. Two‐dimensional Echocardiogram showed severe systolic dysfunction with a left ventricular ejection fraction (LVEF) of 30%. Considering, recurrent VT despite medical treatment and the progressive nature of systemic sclerosis radiofrequency catheter (RF) ablation and ICD implantation were performed.

Conclusion

We report a case of systemic sclerosis complicated by VT and left ventricular (LV) dysfunction during pregnancy that was successfully treated with RF ablation.
Repetitive deep TMS in alcohol dependent patients halts progression of white matter changes in early abstinence
Authors: Selim Mohamed Kotb , Harel Maayan , De Santis Silvia , Perini Irene , Sommer Wolfgang H. , Heilig Markus , Zangen Abraham , Canals Santiago
Published: December 2023

Aim

Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter.

Methods

A total of 37 (14 females) AUD treatment‐seeking patients were randomized to sham or active Deep TMS. Twenty (six females) age‐matched healthy controls were included. White matter integrity was evaluated by fractional anisotropy (FA). Secondary measures included brain functional connectivity and self‐reports of craving and drinking units in the 3 months of follow‐up period.

Results

White matter integrity was compromised in patients with AUD relative to healthy controls, as reflected by the widespread reduction in FA. This alteration progressed during early abstinence (3 weeks) in the absence of Deep TMS. However, stimulation of midline frontocortical areas arrested the progression of FA changes in association with decreased craving and relapse scores. Reconstruction of axonal tracts from white‐matter regions showing preserved FA values identified cortical regions in the posterior cingulate and dorsomedial prefrontal cortices where functional connectivity was persistently modulated. These effects were absent in the sham‐stimulated group.

Conclusions

By integrating brain structure and function to characterize the alcohol‐dependent brain, this study provides mechanistic insights into the TMS effect, pointing to myelin plasticity as a possible mediator.
Enhanced Ca2+ binding to EF‐hands through phosphorylation of conserved serine residues activates MpRBOHB and chitin‐triggered ROS production
Authors: Hashimoto Takafumi , Hashimoto Kenji , Shindo Hiroki , Tsuboyama Shoko , Miyakawa Takuya , Tanokura Masaru , Kuchitsu Kazuyuki
Published: December 2023

NADPH oxidases/RBOHs catalyze apoplastic ROS production and act as key signaling nodes, integrating multiple signal transduction pathways regulating plant development and stress responses. Although RBOHs have been suggested to be activated by Ca2+ binding and phosphorylation by various protein kinases, a mechanism linking Ca2+ binding and phosphorylation in the activity regulation remained elusive. Chitin‐triggered ROS production required cytosolic Ca2+ elevation and Ca2+ binding to MpRBOHB in a liverwort Marchantia polymorpha. Heterologous expression analysis of truncated variants revealed that a segment of the N‐terminal cytosolic region highly conserved among land plant RBOHs encompassing the two EF‐hand motifs is essential for the activation of MpRBOHB. Within the conserved regulatory domain, we have identified two Ser residues whose phosphorylation is critical for the activation in planta. Isothermal titration calorimetry analyses revealed that phosphorylation of the two Ser residues increased the Ca2+ binding affinity of MpRBOHB, while Ca2+ binding is indispensable for the activation, even if the two Ser residues are phosphorylated. Our findings shed light on a mechanism through which phosphorylation potentiates the Ca2+‐dependent activation of MpRBOHB, emphasizing the pivotal role of Ca2+ binding in mediating the Ca2+ and phosphorylation‐driven activation of MpRBOHB, which is likely to represent a fundamental mechanism conserved among land plant RBOHs.
Soil health assessment of an acidic red soil agricultural area and its restoration with biochar soil conditioners
Authors: Li Qiang , Jiang Wanting , Lyu Junxiao
Published: December 2023

In light of growing concerns regarding food security and soil health, there is increasing emphasis on the assessment of soil health and efforts to improve or maintain the soil health of cultivated land. This case study Niutian Town in Jiangxi Province in southern China was selected as a typical red soil and a major grain‐producing area. This research involves an integrated evaluation model based on Entropy weight TOPSIS and emergy analysis to assess the soil health of cultivated land. An evaluation system was developed, comprising 31 indicators selected on the basis of resources and environments, with an emphasis on sensitive and promising microorganisms category indicators. Additionally, experiments were conducted to assess the ecological risk of soil pollution and develop novel soil conditioners. Our results indicate that Pb, Hg and Cd present a moderate ecological risk on 92.1% of the cultivated land. Furthermore, 56.8% of the cultivated land was ‘sub‐healthy’ or ‘unhealthy’. Biochar was found to be a soil conditioner with a good adsorption effect, with absorption rates reaching up to 99.9% and 88.3% for Pb and Cd, respectively. Additionally, g‐C3N4 was added to address pesticide contamination, which showed an adsorption rate of up to 75.2% for atrazine. This work develops a targeted remediation approach based on assessment results to address regional cropland soil health issues.
Risk factors for venous ulceration in patients with varicose veins of lower extremities
Authors: Yin Chaonan , Tang Fang , Lao Jiahui , Yang Yang , Li Mingzhuo , Cao Jia , Song Ru , Wu Peng , Wang Yibing
Published: December 2023

The aim of this case–control study was to explore the potential risk factors for venous ulceration in patients with varicose veins of lower extremities and to establish a simplified diagnostic score model. Seventy subjects with varicose veins of lower extremities and venous ulceration were compared with 1164 controls with varicose veins of lower extremities and no history of venous ulceration. Stepwise multivariate logistic regression analysis was used to identify the risk factors for venous ulceration. The steps in developing the diagnostic score model were based on the Framingham Heart study. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic ability of the diagnostic score model. Multivariate analysis showed that men, overweight, obesity, longer duration varicose veins, deep venous valve insufficiency, low lymphocyte counts, and high fibrinogen content were independently associated with an increased risk of venous ulceration. The AUC for the diagnostic score model was 0.75, which indicated good discriminatory ability. Special attention should be paid to the high‐risk group of patients with lower extremity varicose veins. The diagnostic score model might be a useful screening tool for clinicians, policy makers, and patients.
Motor Bearing Fault Diagnosis in an Industrial Robot Under Complex Variable Speed Conditions
Authors: Gong Tao , Wang Zhongqiu , Ma Qiang , Yang Jianhua
Published: December 2023

Motor bearing is the key vulnerable part of the servomotor in an industrial robot, which is always arranged at the joint that is the main load area. In the movement process of the robot, motor bearing bears a great impact due to the frequent movement of joints, which is easily damaged. The fault characteristic information of a bearing in these complex conditions shows strong nonstationary characteristics. Early nonstationary fault signals are often weak and submerged in background noise. The nonstationary signal processing method using computed order analysis and the weak signal enhancement method using adaptive stochastic resonance both show good performances for the above problems. Inspired by these, a hybrid diagnosis strategy for motor bearing under these speed conditions is proposed. Firstly, the nonstationary fault signals of the motor bearing are transformed into stationary angular signals via computed order analysis. Then, the fault modes are identified via resonance demodulation and variational mode decomposition in the order spectrum. Finally, adaptive stochastic resonance is used to extract the fault features reflecting the bearing operation state. Two types of typical speed conditions are considered, which are representative of the joint. Numerical simulation analysis and experiments verify the effectiveness of the diagnosis method.
Multiscale Feature Fusion Convolutional Neural Network for Surface Damage Detection in Retired Steel Shafts
Authors: Liu Weiwei , Qiu Jiahe , Wang Yujiang , Li Tao , Liu Shujie , Hu Guangda , Xue Lin
Published: December 2023

The detection of surface damage is an important part of the process before remanufacturing a retired steel shaft (RSS). Traditional damage detection is mainly done manually, which is time-consuming and error-prone. In recent years, computer vision methods have been introduced into the community of surface damage detection. However, some advanced typical object detection methods perform poorly in the detection of surface damage on RSS due to the complex surface background and rich diversity of damage patterns and scales. To address these issues, we propose a Faster R-CNN–based surface damage detection method for RSS. To improve the adaptability of the network, we endow it with a feature pyramid network (FPN) as well as adaptable multiscale information modifications to the region proposal network (RPN). In this paper, a detailed study of an FPN-based feature extraction network and the multiscale object detection network is conducted. Experimental results show that our method improves the mean average precision (mAP) score by 8.9% compared with the original Faster R-CNN for surface damage detection of RSS, and the average detection accuracy for small objects is improved by 18.2%. Compared with the current advanced object detection methods, our method is more advantageous for the detection of multiscale objects.
Using AI-Enabled Divergence and Convergence Patterns as a Quantitative Artifact in Design Education
Authors: Chiu Matt , Sim Wang Lin , Mun Nigel , Silva Arlindo
Published: December 2023

Design education has traditionally relied heavily on physical integration as it involves a lot of hands-on work, group critiques, and collaborative projects, but the COVID-19 pandemic has fundamentally shifted the way teaching is done, which resulted in many institutions adapting to remote teaching and learning environments. This has created challenges for design educators who have had to find ways to evaluate students’ progress in the absence of in-person interactions. In this paper, we are proposing a dashboard visualization approach that helps educators monitor the progression of the entire class of students using artificial intelligence (AI) by tracking a time-based evolution of a design statement. This approach uses various natural language processing (NLP) models to produce stock-like charts, which represent students’ and student groups’ progression through a series of divergence and convergence phases. These charts become a form of design artifact that allows educator(s) to gain a bird’s-eye view of the class and react to groups that may require assistance; at the same time, it becomes a qualitative means of evaluation and comparison across students and groups. Toward the end, this paper also showcases a web-based platform that is publicly available using such methodology, a case study that applied so methodology and recommendations of future works possible.
The neuronal implementation of representational geometry in primate prefrontal cortex
Authors: Lin Xiao-Xiong , Nieder Andreas , Jacob Simon N.
Published: December 2023

Modern neuroscience has seen the rise of a population-doctrine that represents cognitive variables using geometrical structures in activity space. Representational geometry does not, however, account for how individual neurons implement these representations. Leveraging the principle of sparse coding, we present a framework to dissect representational geometry into biologically interpretable components that retain links to single neurons. Applied to extracellular recordings from the primate prefrontal cortex in a working memory task with interference, the identified components revealed disentangled and sequential memory representations including the recovery of memory content after distraction, signals hidden to conventional analyses. Each component was contributed by small subpopulations of neurons with distinct spiking properties and response dynamics. Modeling showed that such sparse implementations are supported by recurrently connected circuits as in prefrontal cortex. The perspective of neuronal implementation links representational geometries to their cellular constituents, providing mechanistic insights into how neural systems encode and process information.
Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma
Authors: Oyoshi Hidekazu , Du Junyan , Sakai Shunsuke A. , Yamashita Riu , Okumura Masayuki , Motegi Atsushi , Hojo Hidehiro , Nakamura Masaki , Hirata Hidenari , Sunakawa Hironori , Kotani Daisuke , Yano Tomonori , Kojima Takashi , Nakamura Yuka , Kojima Motohiro , Suzuki Ayako , Zenkoh Junko , Tsuchihara Katsuya , Akimoto Tetsuo , Shibata Atsushi , Suzuki Yutaka , Kageyama Shun-Ichiro
Published: December 2023

Radiotherapy (RT) combined with immunotherapy is promising; however, the immune response signature in the clinical setting after RT remains unclear. Here, by integrative spatial and single-cell analyses using multiplex immunostaining (CODEX), spatial transcriptome (VISIUM), and single-cell RNA sequencing, we substantiated the infiltration of immune cells into tumors with dynamic changes in immunostimulatory and immunosuppressive gene expression after RT. In addition, our comprehensive analysis uncovered time- and cell type–dependent alterations in the gene expression profile after RT. Furthermore, myeloid cells showed prominent up-regulation of immune response–associated genes after RT. Notably, a subset of infiltrating tumor-associated myeloid cells showing PD-L1 positivity exhibited significant up-regulation of immunostimulatory (HMGB1 and ISG15), immunosuppressive (SIRPA and IDO1), and protumor genes (CXCL8, CCL3, IL-6, and IL-1AB), which can be targets of immunotherapy in combination with PD-L1. These datasets will provide information on the RT-induced gene signature to seek an appropriate target for personalized immunotherapy combined with RT and guide the timing of combination therapy.
In-memory analog solution of compressed sensing recovery in one step
Authors: Wang Shiqing , Luo Yubiao , Zuo Pushen , Pan Lunshuai , Li Yongxiang , Sun Zhong
Published: December 2023

Modern analog computing, by gaining momentum from nonvolatile resistive memory devices, deals with matrix computations. In-memory analog computing has been demonstrated for solving some basic but ordinary matrix problems in one step. Among the more complicated matrix problems, compressed sensing (CS) is a prominent example, whose recovery algorithms feature high-order matrix operations and hardware-unfriendly nonlinear functions. In light of the local competitive algorithm (LCA), here, we present a closed-loop, continuous-time resistive memory circuit for solving CS recovery in one step. Recovery of one-dimensional (1D) sparse signal and 2D compressive images has been experimentally demonstrated, showing elapsed times around few microseconds and normalized mean squared errors of 10
−2
. The LCA circuit is one or two orders of magnitude faster than conventional digital approaches. It also substantially outperforms other (electronic or exotically photonic) analog CS recovery methods in terms of speed, energy, and fidelity, thus representing a highly promising technology for real-time CS applications.
Phase engineering of anomalous Josephson effect derived from Andreev molecules
Authors: Matsuo Sadashige , Imoto Takaya , Yokoyama Tomohiro , Sato Yosuke , Lindemann Tyler , Gronin Sergei , Gardner Geoffrey C. , Manfra Michael J. , Tarucha Seigo
Published: December 2023

A Josephson junction (JJ) is a key device for developing superconducting circuits, wherein a supercurrent in the JJ is controlled by the phase difference between the two superconducting electrodes. When two JJs sharing one superconducting electrode are coherently coupled and form the Andreev molecules, a supercurrent of one JJ is expected to be nonlocally controlled by the phase difference of another JJ. Here, we evaluate the supercurrent in one of the coupled two JJs as a function of local and nonlocal phase differences. Consequently, the results exhibit that the nonlocal phase control generates a finite supercurrent even when the local phase difference is zero. In addition, an offset of the local phase difference giving the JJ ground state depends on the nonlocal phase difference. These features demonstrate the anomalous Josephson effect realized by the nonlocal phase control. Our results provide a useful concept for engineering superconducting devices such as phase batteries and dissipationless rectifiers.
High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1
Authors: Bolland William , Michel Vincent , Planas Delphine , Hubert Mathieu , Staropoli Isabelle , Guivel-Benhassine Florence , Porrot Françoise , N'Debi Mélissa , Rodriguez Christophe , Fourati Slim , Prot Matthieu , Planchais Cyril , Hocqueloux Laurent , Simon-Lorière Etienne , Mouquet Hugo , Prazuck Thierry , Pawlotsky Jean-Michel , Bruel Timothée , Schwartz Olivier , Buchrieser Julian
Published: December 2023

SARS-CoV-2 variants with undetermined properties have emerged intermittently throughout the COVID-19 pandemic. Some variants possess unique phenotypes and mutations which allow further characterization of viral evolution and Spike functions. Around 1,100 cases of the B.1.640.1 variant were reported in Africa and Europe between 2021 and 2022, before the expansion of Omicron. Here, we analyzed the biological properties of a B.1.640.1 isolate and its Spike. Compared to the ancestral Spike, B.1.640.1 carried 14 amino acid substitutions and deletions. B.1.640.1 escaped binding by some anti-N-terminal domain and anti-receptor-binding domain monoclonal antibodies, and neutralization by sera from convalescent and vaccinated individuals. In cell lines, infection generated large syncytia and a high cytopathic effect. In primary airway cells, B.1.640.1 replicated less than Omicron BA.1 and triggered more syncytia and cell death than other variants. The B.1.640.1 Spike was highly fusogenic when expressed alone. This was mediated by two poorly characterized and infrequent mutations located in the Spike S2 domain, T859N and D936H. Altogether, our results highlight the cytopathy of a hyper-fusogenic SARS-CoV-2 variant, supplanted upon the emergence of Omicron BA.1. (This study has been registered at ClinicalTrials.gov under registration no. NCT04750720.)

IMPORTANCE

Our results highlight the plasticity of SARS-CoV-2 Spike to generate highly fusogenic and cytopathic strains with the causative mutations being uncharacterized in previous variants. We describe mechanisms regulating the formation of syncytia and the subsequent consequences in a primary culture model, which are poorly understood.
Genome sequences of bacteriophage Shambre1 and Renna12, isolated from
Arthrobacter globiformis
Authors: Dojs Madeline , Fleischacker Christine , Ackerman Skylar , Boyle Blaise , Feiring Shambre , Fleischacker Thomas , Frank Jaycee , Jackson Sarah , Schaefbauer Ashlin , Vigness Corinna , Webb Rylie
Published: December 2023

Bacteriophages Shambre1 and Renna12 were isolated from soil in Bismarck, ND, using
Arthrobacter globiformis
. Genomic characterization and analyses allowed Renna12 to be assigned to phage cluster AS3, while Shambre1, which is not closely related to any phage, is a singleton.
IS
26
drives the dissemination of
bla
CTX-M
genes in an Ecuadorian community
Authors: Salinas Liseth , Cárdenas Paúl , Graham Jay P. , Trueba Gabriel
Published: December 2023

The rapid dissemination of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, mainly
Escherichia coli
carrying
bla
CTX-M
genes, is a major public health concern due to its successful spread in hospital settings as well as among humans and animals in the community. We characterized ESBL-producing
E. coli
isolates from children and domestic animals in semirural communities of Ecuador to assess the contribution of horizontal gene transfer of the
bla
CTX-M
genes among
E. coli
isolates. From 20 selected
E. coli
isolates (from children and domestic animals) harboring
bla
CTX-M
allelic variants, we identified 16 plasmids carrying
bla
CTX-M-55
(
n
= 9),
bla
CTX-M-65
(
n
= 5), and
bla
CTX-M-27
(
n
= 2), as well as four chromosomes carrying
bla
CTX-M-65
. The backbone structure of plasmids, including replication, maintenance, and plasmid transfer genes, and the synteny was conserved in all plasmids carrying the same
bla
CTX-M
allelic variant. In all plasmids and chromosomes, the
bla
CTX-M
genes were bracketed by two IS
26
transposable elements. This study highlights the critical role of the IS
26
transposable element for the current mobility of
bla
CTX-M
genes among plasmids or from plasmids to chromosomes, suggesting that IS
26-bla
CTX-M
brackets could be used to study
bla
CTX-M
transmission between humans, domestic animals, and the environment.

IMPORTANCE

The horizontal gene transfer events are the major contributors to the current spread of CTX-M-encoding genes, the most common extended-spectrum β-lactamase (ESBL), and many clinically crucial antimicrobial resistance (AMR) genes. This study presents evidence of the critical role of IS
26
transposable element for the mobility of
bla
CTX-M
gene among
Escherichia coli
isolates from children and domestic animals in the community. We suggest that the nucleotide sequences of IS
26
-
bla
CTX-M
could be used to study
bla
CTX-M
transmission between humans, domestic animals, and the environment, because understanding of the dissemination patterns of AMR genes is critical to implement effective measures to slow down the dissemination of these clinically important genes.
Effect of Raw Material on the Properties of LuAG:Cr4+ Ceramics
Authors: Lopukhin K. V. , Balashov V. V. , Kozlova S. M. , Kanaev A. Yu. , Efimov A. A. , Faikov P. P.
Published: December 2023

Samples of Cr4+:LuAG ceramics have been synthesized using commercial and reprecipitated Lu2O3 powders. The optimum conditions for the synthesis of the reprecipitated Lu2O3 powder have been established, a dilatometric analysis of the ceramics has been carried out, and the effect of the initial Lu2O3 powder on the optical properties of the ceramics has been studied.
Dissipative Transport and Field Emission of Electrons in 2D Carbon Heterostructures with a Quantum Barrier
Authors: Yafarov R. K. , Shabunin N. O.
Published: December 2023

The influence of the thickness of a tunnel-thin carbon layer depleted in charge carriers in an enriched noncrystalline carbon matrix on the non-dissipative transport and field emission of electrons is studied. It has been established that the “geometric” increase in the electron self-energy increases the transparency of potential barriers for non-dissipative transport in the heterostructure and at the solid–vacuum interface. It is shown that the introduction of a quantum barrier into the carbon matrix increases the transverse current and rectifying properties of heterostructures, increases the field current density and the steepness of the current–voltage characteristics.
Immunocompetent Mice As a Model for Preclinical Studies of mRNA Vaccine Immunogenicity
Authors: Shkurnikov M. Yu. , Tonevitskaya S. A. , Stepanova E. V. , Slobodov S. A.
Published: December 2023

Conducting preclinical studies of mRNA vaccines is complicated by the lack of relevant animal models of the human immune system. Immunocompetent mice are widely used in biomedical research. However, critical differences in the genetics and immune system of mice and humans prevent the study of unique human immune responses in mice. Within the framework of this work, the possibility of modeling the cytotoxic T-cell response to mRNA vaccines encoding the S-protein of the SARS-CoV-2 virus was investigated. High-affinity peptides from S-protein were analyzed for the most frequent allelic variants of human MHC-I, two immunocompetent mouse lines (C57BL/6, BALB/c) and an outbred mouse model of IRC. The results of computer modeling have shown that mouse models can be used in preclinical studies of mRNA vaccines against SARS-CoV-2. Mouse MHC-I is able to present virus peptides that are highly affine for human MHC-I. Moreover, the immunogenicity of some of them has already been confirmed by examining blood samples from patients who have had COVID-19.
Fetal single ventricle journey to first postnatal procedure: a multicentre UK cohort study
Authors: Lillitos Peter John , Nolan Oscar , Cave Daniel G W , Lomax Catherine , Barwick Shuba , Bentham James R , Seale Anna N
Published: December 2023

Objectives

UK single ventricle (SV) palliation outcomes after first postnatal procedure (FPP) are well documented. However, survival determinants from fetal diagnosis to FPP are lacking. To better inform parental-fetal counselling, we examined factors favouring survival at two large UK centres.

Design

Retrospective multicentre cohort study.

Setting

Two UK congenital cardiac centres: Leeds and Birmingham.

Patients

SV fetal diagnoses from 2015 to 2021.

Main outcome measures

Survival from fetal diagnosis with intention to treat (ITT) to birth and then FPP. Maternal, fetal and neonatal risk factors were assessed.

Results

There were 666 fetal SV diagnoses with 414 (62%) ITT. Of ITT, 381 (92%) were live births and 337 (81%) underwent FPP. Survival (ITT) to FPP was notably reduced for severe Ebstein’s 14/22 (63.6%), unbalanced atrioventricular septal defect 32/45 (71%), indeterminate SV 3/4 (75%), mitral atresia 8/10 (80%) and hypoplastic left heart syndrome 127/156 (81.4%). Biventricular pathway was undertaken in five (1%). After multivariable adjustment, prenatal risk factors for mortality were increasing maternal age (OR 1.05, 95% CI 1.0 to 1.1), non-white ethnicity (OR 2.6, 95% CI 1.4 to 4.8), extracardiac anomaly (OR 6.34, 95% CI 1.8 to 22.7) and hydrops (OR 7.39, 95% CI 1.2 to 45.1). Postnatally, prematurity was significantly associated with mortality (OR 6.3, 95% CI 2.3 to 16.8).

Conclusions

Around 20% of ITT fetuses diagnosed with SV will not reach FPP. Risk varies according to the cardiac lesion and is significantly influenced by the presence of an extracardiac anomaly, fetal hydrops, ethnicity, increasing maternal age and gestation at birth. These data highlight the need for fetal preprocedure data to be used in conjunction with procedural outcomes for fetal counselling.
Light exposure therapy for myopia control: a systematic review and Bayesian network meta-analysis
Authors: Zaabaar Ebenezer , Zhang Xiu Juan , Zhang Yuzhou , Bui Christine H. T. , Tang Fang Yao , Kam Ka Wai , Szeto Simon K. H. , Young Alvin L. , Wong Ian C. K. , Ip Patrick , Tham Clement C. , Pang Chi Pui , Chen Li Jia , Yam Jason C.
Published: December 2023

Aims

To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA).

Methods

The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA.

Results

When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), −0.38 mm (−0.59 mm to −0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (−0.28 mm (−0.40 mm to −0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively).

Conclusion

Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective.

PROSPERO registration number

Clinical studies: CRD42022368998; animal studies: CRD42022368671.
Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer
Authors: Ben-Ami Roni , Wang Qiao-Li , Zhang Jinming , Supplee Julianna G , Fahrmann Johannes F , Lehmann-Werman Roni , Brais Lauren K , Nowak Jonathan , Yuan Chen , Loftus Maureen , Babic Ana , Irajizad Ehsan , Davidi Tal , Zick Aviad , Hubert Ayala , Neiman Daniel , Piyanzin Sheina , Gal-Rosenberg Ofer , Horn Amit , Shemer Ruth , Glaser Benjamin , Boos Natalia , Jajoo Kunal , Lee Linda , Clancy Thomas E , Rubinson Douglas A , Ng Kimmie , Chabot John A , Kastrinos Fay , Kluger Michael , Aguirre Andrew J , Jänne Pasi A , Bardeesy Nabeel , Stanger Ben , O'Hara Mark H , Till Jacob , Maitra Anirban , Carpenter Erica L , Bullock Andrea J , Genkinger Jeanine , Hanash Samir M , Paweletz Cloud P , Dor Yuval , Wolpin Brian M
Published: December 2023

Objective

Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.

Design

To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.

Results

Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92).

Conclusion

A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.
Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8+T cell-mediated antitumour immunity and improves anti-PD-1 efficacy
Authors: Cai Ning , Cheng Kun , Ma Yue , Liu Sha , Tao Ran , Li Yani , Li Danfeng , Guo Bin , Jia Wenlong , Liang Huifang , Zhao Jianping , Xia Limin , Ding Ze-yang , Chen Jinhong , Zhang Wanguang
Published: December 2023

Objective

The gain of function (GOF) CTNNB1 mutations (CTNNB1GOF) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1GOFHCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC.

Design

RNA sequencing was performed to identify the key downstream genes of CTNNB1GOFassociated with immune escape. An in vitro coculture system, murine subcutaneous or orthotopic models, spontaneously tumourigenic models in conditional gene-knock-out mice and flow cytometry were used to explore the biological function of matrix metallopeptidase 9 (MMP9) in tumour progression and immune escape. Single-cell RNA sequencing and proteomics were used to gain insight into the underlying mechanisms of MMP9.

Results

MMP9 was significantly upregulated in CTNNB1GOFHCC. MMP9 suppressed infiltration and cytotoxicity of CD8+T cells, which was critical for CTNNB1GOFto drive the suppressive tumour immune microenvironment (TIME) and anti-PD-1 resistance. Mechanistically, CTNNB1GOFdownregulated sirtuin 2 (SIRT2), resulting in promotion of β-catenin/lysine demethylase 4D (KDM4D) complex formation that fostered the transcriptional activation of MMP9. The secretion of MMP9 from HCC mediated slingshot protein phosphatase 1 (SSH1) shedding from CD8+T cells, leading to the inhibition of C-X-C motif chemokine receptor 3 (CXCR3)-mediated intracellular of G protein-coupled receptors signalling. Additionally, MMP9 blockade remodelled the TIME and potentiated the sensitivity of anti-PD-1 therapy in HCC.

Conclusions

CTNNB1GOFinduces a suppressive TIME by activating secretion of MMP9. Targeting MMP9 reshapes TIME and potentiates anti-PD-1 efficacy in CTNNB1GOFHCC.
Adolescents at the skatepark: identifying design features and youth behaviours that pose risk for falls
Authors: Morrongiello Barbara A. , Amir Maria , Corbett Michael R , Zolis Caroline , Russell Kelly
Published: December 2023

Background

Skateboarding is an increasingly popular leisure activity for youth, yet injuries due to falls are common. This study aimed to identify the features at skateparks and tricks performed by youth that pose an increased risk of falls in skateboarders.

Method

Video recordings were unobtrusively taken at a large skatepark of youth designated as young (11–15 years) or old (16–20 years). Videos were coded to identify the popular skatepark features used and tricks performed, and to assign a fall severity outcome rating for each feature and each type of trick attempted.

Results

The results identify features and tricks that pose increased risk of falling for youth at skateparks.

Conclusions

Implications for injury prevention are discussed, including a consideration of environmental (skatepark design) and individual (youth behaviour) factors relevant to reducing skateboarding injuries due to falls among youth.
Estimated glucose disposal rate and risk of arterial stiffness and long-term all-cause mortality: a 10-year prospective study
Authors: Sun Jin , Wang Ning , Li Shengxiang , Li Man , Zhang Anhang , Qin Bangguo , Bao Qiligeer , Cheng Bokai , Cai Shuang , Wang Shuxia , Zhu Ping
Published: December 2023

Background

To assess the applicability of the association between estimated glucose disposal rate (eGDR) and all-cause mortality in the elderly population, and the mediating role of brachial-ankle pulse wave velocity (baPWV).

Methods

This was a follow-up cohort study based on the cross-sectional survey of community-dwelling elderly. All participants in the study were included between September 2009 and June 2010, and the follow-up time was December 2020. Participants included 1862 Chinese community-dwelling elderly aged 60 years and above. Insulin resistance assessed by eGDR and arterial stiffness assessed by baPWV were the primary exposures of interest. Mortality, which was followed up until December 2020, was the primary outcome. Cox proportional hazards regression models were used to estimate the association of eGDR with mortality. The mediating effect of baPWV in this association was assessed by mediation analysis.

Results

A total of 1826 participants with a mean age of 71.03 years old were included in the study. During the median follow-up of 10.75 years, 334 participants died. The adjusted HR comparing the highest versus the lowest eGDR quartile was 0.22 (95% CI 0.09 to 0.54; p<0.001) in the Cox proportional hazards model. The results of mediation analysis showed that baPWV had a significant mediation impact on the link between eGDR and all-cause mortality both as continuous or categorical variables.

Conclusion

eGDR is an independent predictor of all-cause mortality in the elderly population. baPWV partially mediated the association of eGDR and long-term all-cause mortality as a mediator factor.
XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, demonstrates tumor-growth inhibition and tumor-selective pharmacodynamics in mouse models of cancer
Authors: Jenkins Kurt A , Park Miso , Pederzoli-Ribeil Magali , Eskiocak Ugur , Johnson Parker , Guzman Wilson , McLaughlin Megan , Moore-Lai Deborah , O’Toole Caitlin , Liu Zhen , Nicholson Benjamin , Flesch Veronica , Qiu Huawei , Clackson Tim , O’Hagan Ronan C , Rodeck Ulrich , Karow Margaret , O’Neil Jennifer , Williams John C
Published: December 2023

Introduction

The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

Methods

XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region of XTX101 were included to enhance affinity for FcγRIII, which is expected to enhance potency through antibody-dependent cellular cytotoxicity.

Results

Biophysical, biochemical, and cell-based assays demonstrate that the function of XTX101 depends on proteolytic activation. In human CTLA-4 transgenic mice, XTX101 monotherapy demonstrated significant tumor growth inhibition (TGI) including complete responses, increased intratumoral CD8+T cells, and regulatory T cell depletion within the TME while maintaining minimal pharmacodynamic effects in the periphery. XTX101 in combination with anti-PD-1 mAb treatment resulted in significant TGI and was well tolerated in mice. XTX101 was activated in primary human tumors across a range of tumor types including melanoma, renal cell carcinoma, colon cancer and lung cancer in an ex vivo assay system.

Conclusions

These data demonstrate that XTX101 retains the full potency of an Fc-enhanced CTLA-4 antagonist within the TME while minimizing the activity in non-tumor tissue, supporting the further evaluation of XTX101 in clinical studies.