bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of an artificial intelligence algorithm for assisting the Paris System in reporting urinary cytology: A pilot study
Authors: Ou Yen‐Chuan , Tsao Tang‐Yi , Chang Ming‐Chen , Lin Yi‐Sheng , Yang Wei‐Lei , Hang Jen‐Fan , Li Chi‐Bin , Lee Ching‐Ming , Yeh Cheng‐Hung , Liu Tien‐Jen
Published: June 2022

Background

The Paris System for Reporting Urinary Cytology (TPS) has been shown to improve bladder cancer diagnosis. Advances in artificial intelligence (AI) may assist and improve the clinical workflow by applying TPS in routine diagnostic services.

Methods

A deep‐learning–based algorithm was developed to identify urothelial cancer candidate cells using whole‐slide images (WSIs). In the testing cohort, 131 urine cytology slides were retrospectively retrieved and analyzed using this AI algorithm. The authors compared the performance of one cytopathologist and two cytotechnologists using AI‐assisted digital urine cytology. Then, the AI‐assisted WSIs were evaluated in the clinical workflow. The cytopathologist first made a diagnosis by reviewing the AI‐inferred WSIs and quantitative data (nuclear‐to‐cytoplasmic ratio and nuclear size) for each sample. After a washout period, the same cytopathologist made a diagnosis for the same samples using direct microscopy. All diagnosis results were compared with the expert panel consensus.

Results

The AI‐assisted diagnosis by the two cytotechnologists and the one cytopathologist demonstrated performance results that were comparable to the expert panel consensus (sensitivity, 79.5% and 82.1% vs. 92.3%, respectively; specificity, 100% and 98.9% vs. 100%, respectively). Furthermore, the performance of the AI‐assisted WSIs compared with the microscopic diagnosis by the cytopathologist demonstrated superior sensitivity (92.3% vs. 87.2%) and negative predictive value (96.8% vs. 94.8%). In addition, the AI‐assisted reporting demonstrated near perfect agreement with the expert panel consensus (κ = 0.944) and the microscopic diagnosis (κ = 0.862).

Conclusions

The AI algorithm developed by the authors effectively assisted TPS‐based reporting by providing AI‐inferred WSIs and quantitative data.
Mindfulness as taught in Dialectical Behaviour Therapy: A scoping review
Authors: Eeles Jennifer , Walker Dawn‐Marie
Published: June 2022

This scoping review considers 11 studies that have focussed on the effect of teaching the mindfulness element of Dialectical Behaviour Therapy (DBT) on clinical outcomes. These articles utilized either mindfulness skills as embedded into the full DBT‐Skills programme or a stand‐alone mindfulness skills module (DBT‐M), as treatment for clinical populations. The review of the research found that clinical application of mindfulness as taught in DBT leads to increases in self‐reported mindfulness—especially non‐judgemental awareness along with psychological measures that suggests an increase in mindfulness, for example, improved attention. The studies demonstrated that an increase in mindfulness had a positive effect on some clinical symptoms such as symptoms of Borderline Personality Disorder. Not all of the studies controlled for the effect of group, amount of practice or other elements of DBT therapy. The findings suggest that more needs to be done to establish the underlying mechanisms of change when being taught mindfulness in DBT.
Constructing Bimetallic ZIF‐Derived Zn,Co‐Containing N‐Doped Porous Carbon Nanocube as the Lithiophilic Host to Stabilize Li Metal Anodes in Li−O2 Batteries
Authors: Zhao Huimin , Yin Huixiang , Fu Ziqi , Chi Zhenzhen , Li Lin , Zhang Qingwei , Guo Ziyang , Wang Lei
Published: June 2022

Li metal, because of its ultrahigh theoretical capacity, has attracted extensive attention. However, uncontrollable dendritic Li formation and infinite electrode dimensional variation hinder application of Li anodes. Herein, Zn,Co bimetallic zeolitic imidazolate frameworks (ZIFs) were synthesized and further pyrolyzed to obtain Zn,Co‐containing N‐doped porous carbon nanocube (Zn/Co−N@PCN), which was further applied as lithiophilic host to construct the lithiated Zn/Co−N@PCN (Li−Zn/Co−N@PCN). Zn vapor produced many pores on the carbon framework during calcination process that could store enough Li and thus inhibit the huge electrode volume change. Additionally, there were abundant lithiophilic groups in Zn/Co−N@PCN, such as N‐ or Co/Zn‐based species, which were beneficial to uniform Li deposition. Moreover, the stable and conductive carbon‐based matrix could ensure superior and reproducible Li plating/stripping behavior in Zn/Co−N@PCN over cycling. As a result, the Li−Zn/Co−N@PCN anode showed a steady and high columbic efficiency of around 99.0 % for 600 cycles at 0.5 mA cm−2. The Li−Zn/Co−N@PCN‐based Li−O2 battery could continuously work beyond 200 cycles, superior to a cell with a Li−Cu anode. These results in this work provide a novel way for construction of the advanced Li‐based anodes and the corresponding high‐performance Li−O2 batteries.
Advances in understanding epigenetic impacts on dendritic cell regulation and function
Authors: Verlander Zachary , Cummings Alisa , Brown Heather M. , Sen Rwik
Published: June 2022

Dendritic cells (DCs) are the only cells empowered with inducing primary immune response among resting naïve T lymphocytes, hence it is crucial to understand the regulation and function of DCs. During an adaptive immune response, DCs acquire antigens from invasive entities and present the antigens on their own cell surface, hence they are also known as professional antigen‐presenting cells. Epigenetic modifications to the genome play an important role in both the development and the function of DCs. In this direction, significant advancements have been made using high‐throughput methods like ATAC‐seq, ChIP‐seq, RNA‐seq, bisulfite‐seq and so forth to uncover chromatin accessibility landscape, genome‐wide transcription factor (TF) binding, complete transcriptomic profiles, and DNA methylation, respectively. DCs lineage specification and function are determined by TF binding, which is dependent on epigenetic modifications. However, major gaps in knowledge still exist regarding how and why aberrant epigenetic modifications result in defective development and function of DCs leading to an impaired immune system. Hence, this review compiles up‐to‐date literature regarding the exquisite regulation of DCs via epigenetic regulation, to emphasize the potential of further epigenetics research on DCs for addressing current gaps of knowledge in the field. The review also briefly highlights recent findings on DC defects in coronavirus disease 2019 revealed by single‐cell RNA‐seq, and the importance of DCs in clinical trials. Overall, the review highlights how epigenetics‐based state‐of‐the‐art high‐throughput technology can help discoveries on DCs which are crucial to the immune system and pathogenesis, and how DCs are currently targeted for therapeutic developments and clinical trials.
Diffuse intestinal ulcerations: Diagnostic challenge in a patient with complicated celiac disease
Authors: Kalauz Mirjana , Cukovic Cavka Silvija , Domislovic Viktor , Pourmodjib Kiarash , Kalauz Matija , Dotlic Snjezana , Grubelic Ravic Katja , Krznaric Zeljko
Published: June 2022

A 48‐year‐old female patient presented with longstanding unrecognized celiac disease (CD), a family history of CD, and a short duration of alarming symptoms. The diagnostic evaluation revealed the concomitant presence of small and large bowel ulcers raised a dilemma about differential diagnosis in her case. Pathologic examination of tissue specimens from the jejunal ulcer led to the diagnosis of enteropathy‐associated T‐cell lymphoma. In recent years, the availability of modern cross‐sectional imaging and endoscopy modalities has dramatically improved the detection and characterization of small bowel lesions. Characterization of small bowel ulcers by endoscopy and radiology imaging in a patient with suspected complicated CD (CCD) needs to be made in conjunction with all clinical factors, as there is a wide overlap of the possible etiologic factors. Enteropathy‐associated T‐cell lymphoma is a highly aggressive T‐cell lymphoma with a poor prognosis, since early diagnosis and appropriate treatment may be delayed due to nonspecific clinical and endoscopic presentation. Therefore, it is crucial to timely recognize patients with suspected CCD and properly navigate diagnostic imaging tools, acquire adequate biopsy, and perform immunophenotyping to set early diagnosis in patients with diffuse intestinal ulcers and CD.
Structure and evolution of neuronal wiring receptors and ligands
Authors: Cortés Elena , Pak Joseph S. , Özkan Engin
Published: June 2022

One of the fundamental properties of a neuronal circuit is the map of its connections. The cellular and developmental processes that allow for the growth of axons and dendrites, selection of synaptic targets, and formation of functional synapses use neuronal surface receptors and their interactions with other surface receptors, secreted ligands, and matrix molecules. Spatiotemporal regulation of the expression of these receptors and cues allows for specificity in the developmental pathways that wire stereotyped circuits. The families of molecules controlling axon guidance and synapse formation are generally conserved across animals, with some important exceptions, which have consequences for neuronal connectivity. Here, we summarize the distribution of such molecules across multiple taxa, with a focus on model organisms, evolutionary processes that led to the multitude of such molecules, and functional consequences for the diversification or loss of these receptors.
An occurrence data set for invasive and naturalized alien plants in India
Authors: Prajapati Jyoti , Singh Abhijit , Patil Kshitij , Bhowmick Amiya Ranjan , Mukherjee Abhishek , Huang Yelin , Banerjee Achyut Kumar
Published: June 2022

India has numerous invasive alien plant species (IAPSs), which seriously impact biodiversity, ecosystem services, and economic development. The availability of reliable occurrence records of IAPSs is of great importance for their successful management, prediction of distribution across time and space, and other research and development efforts. Global databases of occurrence data, like the Global Biodiversity Information Facility (GBIF), are often not exhaustive, especially for India, and poorly represent the actual distribution of IAPSs in the country. Our objective in creating this data set was threefold: (1) to compile occurrence data for the invasive and naturalized alien plant species of India, (2) to collect spatial and temporal information associated with occurrence records, and (3) to share the data in an accessible format so every record is traceable to its sources and allow users to submit data to increase the resolution of the data set. To achieve these objectives, we extracted data from 3137 literature records and 357 herbarium sheets. For each occurrence record, we curated information for 20 variables, which were arranged in a table with the Darwin Core (DwC) terms as column names. All data were subjected to technical validation before being included in the database. A total of 12,347 occurrence records were obtained for 362 species (195 invasive aliens and 167 naturalized aliens). The number of collected occurrence records was much higher for the invasive aliens (73.7%) than for the naturalized alien species (26.3%). Our data set will supplement the GBIF data by 60.39%, and occurrence records will be added for 64 invasive and naturalized alien plant species. The data set, as a part of the larger database of the Indian Alien Flora Information (ILORA) database, is made available without any restrictions on use as long as this data paper is properly cited. We have also made provisions for users to submit occurrence‐related data following a data standard. The users are encouraged to cite the original reference when using a specific data record. The data set is expected to assist a wide range of stakeholders involved in India's scientific research, policy formulation, and decision‐making related to IAPSs.
Nonadditive effects of two contrasting introduced herbivores on the reproduction of a pollination‐specialized palm
Authors: Muñoz‐Gallego Raquel , Fedriani Jose M. , Serra Pau E. , Traveset Anna
Published: June 2022

Plant–animal interactions fall within a mutualism–antagonism continuum, exerting a wide range of effects on plant reproductive success. These effects become even more complex and diverse when several disparate animal species interact with the same plant species. Despite the increasing number of studies about the influence of herbivory on plant performance, the outcomes mediated by pollination and the combined impact of multiple herbivores on pollination‐specialized plants are underexplored. In this study, we chose the Mediterranean dwarf palmChamaerops humilis(Arecaceae) to illustrate the isolated and joint effect of two contrasting introduced herbivores, the palm borerPaysandisia archon(Lepidoptera, Castniidae) and feral goats, on pollinator abundance and plant reproductive success. To this aim, we monitored moth herbivory and goat herbivory in four palm populations in Mallorca (Balearic Islands) during 2019 and 2020. The effect of herbivory varied widely depending on both the herbivore and the pollinator species. Moth herbivory had a positive effect on pollinator abundance and fruit initiation, whereas goat herbivory had a negative effect on inflorescence production, pollinator abundance and fruit initiation. In addition, both herbivores exerted unexpected nonadditive effects on palm reproduction. Palms attacked by both herbivore species produced many more inflorescences (up to 18‐fold) but had a lower fruit initiation success (close to zero) than unattacked palms or those attacked by a single herbivore species. Interestingly, only one of the two main pollinator species (the nitidulid beetleMeligethinus pallidulus) was impacted by herbivory. Our study highlights the need to investigate the possible nonadditive effects of all coexisting herbivores on plant performance, especially when establishing conservation plans and pest control strategies.
Uncovering the genetic links of SARS‐CoV‐2 infections on heart failure co‐morbidity by a systems biology approach
Authors: Zhang Ge , Cui Xiaolin , Zhang Li , Liu Gangqiong , Zhu Xiaodan , Shangguan Jiahong , Zhang Wenjing , Zheng Yingying , Zhang Hui , Tang Junnan , Zhang Jinying
Published: June 2022

Aims

The co‐morbidities contribute to the inferior prognosis of COVID‐19 patients. Recent reports suggested that the higher co‐morbidity rate between COVID‐19 and heart failure (HF) leads to increased mortality. However, the common pathogenic mechanism between them remained elusive. Here, we aimed to reveal underlying molecule mechanisms and genetic correlation between COVID‐19 and HF, providing a new perspective on current clinical management for patients with co‐morbidity.

Methods

The gene expression profiles of HF (GSE26887) and COVID‐19 (GSE147507) were retrieved from the GEO database. After identifying the common differentially expressed genes (|log2FC| > 1 and adjusted P < 0.05), integrated analyses were performed, namely, enrichment analyses, protein–protein interaction network, module construction, critical gene identification, and functional co‐expression analysis. The performance of critical genes was validation combining hierarchical clustering, correlation, and principal component analysis in external datasets (GSE164805 and GSE9128). Potential transcription factors and miRNAs were obtained from the JASPER and RegNetwork repository used to construct co‐regulatory networks. The candidate drug compounds in potential genetic link targets were further identified using the DSigDB database.

Results

The alteration of 12 genes was identified as a shared transcriptional signature, with the role of immune inflammatory pathway, especially Toll‐like receptor, NF‐kappa B, chemokine, and interleukin‐related pathways that primarily emphasized in response to SARS‐CoV‐2 complicated with HF. Top 10 critical genes (TLR4, TLR2, CXCL8, IL10, STAT3, IL1B, TLR1, TP53, CCL20, and CXCL10) were identified from protein–protein interaction with topological algorithms. The unhealthy microbiota status and gut–heart axis in co‐morbidity were identified as potential disease roads in bridging pathogenic mechanism, and lipopolysaccharide acts as a potential marker for monitoring HF during COVID‐19. For transcriptional and post‐transcriptional levels, regulation networks tightly coupling with both disorders were constructed, and significant regulator signatures with high interaction degree, especially FOXC1, STAT3, NF‐κB1, miR‐181, and miR‐520, were detected to regulate common differentially expressed genes. According to genetic links targets, glutathione‐based antioxidant strategy combined with muramyl dipeptide‐based microbe‐derived immunostimulatory therapies was identified as promising anti‐COVID‐19 and anti‐HF therapeutics.

Conclusions

This study identified shared transcriptomic and corresponding regulatory signatures as emerging therapeutic targets and detected a set of pharmacologic agents targeting genetic links. Our findings provided new insights for underlying pathogenic mechanisms between COVID‐19 and HF.
MACP: Multifactor Authentication using Physical Unclonable Function and Fuzzy Extractor based Chebyshev Polynomial for Industrial Internet of Things devices
Authors: Das Ayan Kumar , Afroz Sabana , Chandra Shivangi , Sinha Ditipriya
Published: June 2022

The Internet of Things adapted by the industries, known as Industrial Internet of Things (IIoT), increases the production rate by reducing the risk factor. The wireless devices deployed in the open places are always susceptible to various attacks including cloning and physical attacks. Thus security of IIoT devices becomes the primary concern of these days. The resource constraint IIoT devices demand light weight security schemes to authenticate communicating devices and protect the privacy of industrial data. In this article, an authentication scheme with low computation and communication cost has been proposed using multiple factors, namely smart card, password, physical unclonable function (PUF), and fuzzy extractor. PUF helps in preventing the cloning of smart card and generates unique challenge‐response pairs to authenticate the smart devices. The environmental noise, produced by the operation of PUF, is extracted by the use of fuzzy extractor. Real‐or‐Random (ROR) model and Burrows‐Abadi‐Needham (BAN) logic has been used for formal security analysis of the proposed scheme, which is resilience against replay attack, man‐in‐the‐middle attack, masquerading, forgery and impersonation attacks, camouflage attack and offline password guessing attack. The performance evaluation has been done using Raspberry Pi, lunchbox, and a laptop. The simulation results show that the proposed scheme outperforms the existing methodologies in terms of end‐to‐end delay, throughput, packet loss, computation cost, and communication cost.
Adaptive FRESH filter with vicarious reference for interference rejection: An application to signal detection in NOMA system
Authors: Garakyaragh Nooshin , Shahtalebi Kamal
Published: June 2022

Adaptive frequency shift (FRESH) filter is one of the most suggested methods for interference rejection. This filter extracts the desired cyclostationary signal by exploiting its spectral correlation through the adaptive periodically time‐varying filters. The reference signal in this filter has an essential role in the quality of the desired signal estimation. In this article, a vicarious signal is generated as a reference of an adaptive FRESH structure. Using the cyclostationary characteristics of the desired signal (eg, modulation, cyclic frequencies, etc.), the generated signal exhibits all feasible cyclostationary behaviors of the desired signal. The overall system significantly improves the performance of the FRESH filter. The advantage of using the vicarious signal is demonstrated with theoretical analysis. Furthermore, a multistage form of the proposed method is designed for severe noise and interference conditions. The method is used for signal detection in non‐orthogonal multiple access (NOMA) system. Simulation results validate its efficiency in this case and in different interference scenarios which include pulse chirp radar signal, orthogonal frequency division multiplexing (OFDM), and quadrature amplitude modulation (QAM).
The future of sustainable food consumption in China
Authors: Chu May , Anders Sven , Deng Qing , Contador Carolina A. , Cisternas Francisco , Caine Catherine , Zhu Ying , Yang Shuyuan , Hu Bo , Liu Zhiguang , Tse Lap Ah , Lam Hon‐Ming
Published: June 2022

Food production is one of the main contributors to greenhouse gas emissions and climate change. China, as a rapidly developing economy, contributes to an unsustainable food system as its consumption of animal products and meat has continued to grow in recent decades. Using the extended theory of planned behavior as the conceptual framework, this paper examines factors influencing consumers' intention to purchase sustainable food in China. To this end, a population‐based face‐to‐face survey was conducted with 2422 respondents in five provinces spanning the north and south of China. The results showed that the traditional constructs of behavioral attitude, subjective norms, perceived behavioral control, and the additional construct of perceived quality are significant in inducing such intentions. This paper suggests that to enhance consumers' willingness to shift to sustainable food consumption, appropriate regulation and monitoring framework is needed to increase consumers' trust toward sustainable food. The government can also cooperate with the media, experts, and social media opinion leaders to ensure that messages on sustainable development are promoted in effective ways.
EBV protection‐ and susceptibility‐related HLA alleles and EBV status in the Chinese population: A single‐center study
Authors: Suolitiken Dina , Wang Yini , Jin Zhili , Wang Zhao
Published: June 2022

Background

Although most adults are infected by Epstein‐Barr virus (EBV), some patients develop highly lethal diseases associated with EBV infection, including EBV‐hemophagocytic lymphohistiocytosis (EBV‐HLH), chronic active EBV infections (CAEBV), and lymphoma, the pathogeneses of which remain to be investigated. The human leukocyte antigen (HLA) complex may be associated with the viral infection pathway, and, therefore, HLA alleles may be associated with EBV‐related diseases and subpopulations of infected cells, studies related to EBV‐associated diseases, and subpopulations of infected cells that were conducted in China are scarce.

Methods

In this study, we analyzed the high‐resolution HLA genotypes of 269 patients with EBV‐associated diseases and 213 EBV‐seronegative hematopoietic stem cell donors using PCR‐SBT assay and elucidated the associations of HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 alleles with EBV‐associated diseases in the Chinese population, Benjamini–Hochberg correction to adjust for multiple testing. HLA genotypes were also analyzed in patients with EBV‐associated diseases showing EBV‐infected lymphocyte subpopulations.

Results

We found that individuals carrying the following alleles showed the following levels of risks: HLA‐DRB1*11 allele, reduced risk of EBV‐related disease (OR [odds ratio]: 0.56; 95% confidence interval [95% CI]: 0.32–0.99; p < .05; Adjust p = .71); HLA‐DQB1*06:02 allele, reduced risk (OR: 0.5699; 95% CI: 0.3486–0.9317; p < .05; Adjust p = .57); and HLA‐B*15:01 allele, increased risk (OR: 1.763; 95% CI: 0.3486–0.9317; p < .05; Adjust p = .57). Patients with EBV‐associated diseases showing the B*15:01 genotype had a higher risk of T‐cell, NK‐cell, and multicell infections than those with other genotype subgroups.

Conclusions

These findings highlight the importance of HLA genotype for assessing EBV infectivity.
A composite device for viscosupplementation treatment resistant to degradation by reactive oxygen species and hyaluronidase
Authors: Toropitsyn Evgeniy , Pravda Martin , Rebenda David , Ščigalková Ivana , Vrbka Martin , Velebný Vladimír
Published: June 2022

Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half‐life. In this article we describe a novel device for viscosupplementation (NV) based on the cross‐linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500–2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500–2000 kDa and cross‐linked material without CS.
Out of water in the dark: Plasticity in visual structures and function in an amphibious fish
Authors: Rossi Giulia S. , Labbé Daniel , Wright Patricia A.
Published: June 2022

Many fishes encounter periods of prolonged darkness within their lifetime, yet the consequences for the visual system are poorly understood. We used an amphibious fish (Kryptolebias marmoratus) that occupies dark terrestrial environments during seasonal droughts to test whether exposure to prolonged darkness diminishes visual performance owing to reduced optic tectum (OT) size and/or neurogenesis. We performed a 3‐week acclimation with a 2  2 factorial design, in which fish were either acclimated to a 12 h:12 h or 0 h:24 h light:dark photoperiod in water or in air. We found that water‐exposed fish had poorer visual acuity when acclimated to the dark, while air‐acclimated fish had poorer visual acuity regardless of photoperiod. The ability of K. marmoratus to capture aerial prey from water followed a similar trend, suggesting that good vision is important for hunting effectively. Changes in visual acuity did not result from changes in OT size, but air‐acclimated fish had 37% fewer proliferating cells in the OT than water‐acclimated fish. As K. marmoratus are unable to eat on land, reducing cell proliferation in the OT may serve as a mechanism to reduce maintenance costs associated with the visual system. Overall, we suggest that prolonged darkness and air exposure can impair vision in K. marmoratus, and that changes in visual performance may be mediated, in part, by OT neurogenesis. More broadly, we show that plastic changes to the visual system of fishes can have potential consequences for organismal performance and fitness.
CAR‐T cells derived from multiple myeloma patients at diagnosis have improved cytotoxic functions compared to those produced at relapse or following daratumumab treatment
Authors: Abecassis Audrey , Roders Nathalie , Fayon Maxime , Choisy Caroline , Nelson Elisabeth , Harel Stephanie , Royer Bruno , Villesuzanne Camille , Talbot Alexis , Garrick David , Goodhardt Michele , Fermand Jean‐Paul , Burbridge Mike , Arnulf Bertrand , Bories Jean‐Christophe
Published: June 2022

Chimeric antigen receptor T cells (CAR‐T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR‐T directed against CS1 or B Cell Maturation antigen. We found a decrease in naive T cells and elevated frequencies of exhaustion markers in T cells from treated MM patients. Interestingly, individuals treated with daratumumab display elevated ratios of central memory T cells. CAR‐T derived from patients at relapse show reduced in vitro expansion and cytotoxic capacities in response to MM cells compared to those produced at diagnosis. Of note, CAR‐T from daratumumab treated patients display intermediate defects. Reduced anti‐myeloma activity of CAR T cells from treated patients was also observed in a mouse model. Our findings suggest that T cell defects in MM patients, specifically during relapse, have a major impact on their capacity to generate efficient therapeutic CAR‐T. Selecting naive or central memory T cell subsets to generate therapeutic T cells could improve the CAR‐T therapy for MM.
Klf10 favorsMycobacterium tuberculosissurvival by impairing IFN-γ production and preventing macrophages reprograming to macropinocytosis
Authors: Madrid-Paulino Edgardo , Mata-Espinosa Dulce , León-Contreras Juan Carlos , Serrano-Fujarte Isela , Díaz de León-Guerrero Sol , Villaseñor Tomás , Ramon-Luing Lucero , Puente José L , Chavez-Galan Leslie , Hernández-Pando Rogelio , Pérez-Martínez Leonor , Pedraza-Alva Gustavo
Published: June 2022

Mycobacterium tuberculosis has developed diverse mechanisms to survive inside phagocytic cells, such as macrophages. Phagocytosis is a key process in eliminating invading pathogens; thus, M. tuberculosis efficiently disrupts phagosome maturation to ensure infection. However, inflammatory cytokines produced by macrophages in response to early M. tuberculosis infection are key to promoting bacterial clarification. IFN-γ enhances M. tuberculosis engulfment and destruction by reprogramming macrophages from phagocytosis to macropinocytosis. Here, we show that the transcription factor Krüppel-like factor 10 (Klf10) plays a positive role in M. tuberculosis survival and infection by negatively modulating IFN-γ levels. Naïve Klf10-deficient macrophages produce more IFN-γ upon stimulation than wild-type macrophages, thus enhancing bacterial uptake and bactericidal activity achieved by macropinocytosis. Moreover, Klf10⁻/⁻ macrophages showed cytoplasmic distribution of coronin 1 correlated with increased pseudopod count and length. In agreement with these observations, Klf10⁻/⁻ mice showed improved bacterial clearance from the lungs and increased viability. Altogether, our data indicate that Klf10 plays a critical role in M. tuberculosis survival by preventing macrophage reprogramming from phagocytosis to macropinocytosis by negatively regulating IFN-γ production upon macrophage infection.
Perfusion Maps Acquired From Dynamic Angiography MRI Using Deep Learning Approaches
Authors: Asaduddin Muhammad , Roh Hong Gee , Kim Hyun Jeong , Kim Eung Yeop , Park Sung‐Hong
Published: June 2022

Background

A typical stroke MRI protocol includes perfusion‐weighted imaging (PWI) and MR angiography (MRA), requiring a second dose of contrast agent. A deep learning method to acquire both PWI and MRA with single dose can resolve this issue.

Purpose

To acquire both PWI and MRA simultaneously using deep learning approaches.

Study type

Retrospective.

Subjects

A total of 60 patients (30–73 years old, 31 females) with ischemic symptoms due to occlusion or ≥50% stenosis (measured relative to proximal artery diameter) of the internal carotid artery, middle cerebral artery, or anterior cerebral artery. The 51/1/8 patient data were used as training/validation/test.

Field Strength/Sequence

A 3 T, time‐resolved angiography with stochastic trajectory (contrast‐enhanced MRA) and echo planar imaging (dynamic susceptibility contrast MRI, DSC‐MRI).

Assessment

We investigated eight different U‐Net architectures with different encoder/decoder sizes and with/without an adversarial network to generate perfusion maps from contrast‐enhanced MRA. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), mean transit time (MTT), and time‐to‐max (Tmax) were mapped from DSC‐MRI and used as ground truth to train the networks and to generate the perfusion maps from the contrast‐enhanced MRA input.

Statistical Tests

Normalized root mean square error, structural similarity (SSIM), peak signal‐to‐noise ratio (pSNR), DICE, and FID scores were calculated between the perfusion maps from DSC‐MRI and contrast‐enhanced MRA. One‐tailed t‐test was performed to check the significance of the improvements between networks. P values < 0.05 were considered significant.

Results

The four perfusion maps were successfully extracted using the deep learning networks. U‐net with multiple decoders and enhanced encoders showed the best performance (pSNR 24.7 ± 3.2 and SSIM 0.89 ± 0.08 for rCBV). DICE score in hypo‐perfused area showed strong agreement between the generated perfusion maps and the ground truth (highest DICE: 0.95 ± 0.04).

Data Conclusion

With the proposed approach, dynamic angiography MRI may provide vessel architecture and perfusion‐relevant parameters simultaneously from a single scan.

Evidence Level

3

Technical Efficacy

Stage 5
Recovery of denitrification and dissimilatory nitrate reduction to ammonium following reoxygenation of sediments from a periodically hypoxic temperate lagoon
Authors: Roberts Keryn L. , Wong Wei Wen , Shimeta Jeff , Kessler Adam J. , Cook Perran L. M.
Published: June 2022

Eutrophication and stratification events have increased the incidences of hypoxia and anoxia in coastal environments. The depletion of oxygen in these environments can lead to a shift in biogeochemical processes such as denitrification and dissimilatory nitrate reduction to ammonium (DNRA). The balance between denitrification and DNRA is critical because denitrification leads to a loss of bioavailable nitrogen and DNRA maintains it within the system. This study examined the effects of reoxygenation on denitrification and DNRA in sediments collected from a periodically hypoxic system (Gippsland Lakes, Australia) and subjected to experimental hypoxia using a modified 15N‐isotope pairing technique. For freshly collected sediments, the ratio of denitrification : DNRA was generally < 1 indicating a dominance of DNRA. After 3–4 weeks of oxygenation, denitrification increased relative to DNRA resulting in a denitrification : DNRA ratio > 1. Profiles of 15N‐N2 and accumulation in these experiments showed denitrification and DNRA generally only took place in the surface ~ 2 cm of sediment. Prolonged experiments with reoxygenated sediments showed a decrease in the denitrification : DNRA to < 1 after 56 d coincident with deep accumulation of within the sediment (2–5 cm) suggesting faunal irrigation enhanced DNRA deep in the sediment. An experiment with bromide tracer confirmed the occurrence of DNRA deep within the sediment at 2–6 cm was coincident with tracer penetration, and there was a significant positive relationship between bioirrigation and DNRA. We suggest DNRA deep within the sediment was enhanced by increased availability of organic carbon, reduced solutes, and possibly exposure of reworked sediment to .
Ultra‐Sensitive and Low‐Power‐Consumption Organic Phototransistor Enables Nighttime Illumination Perception for Bionic Mesopic Vision
Authors: Deng Wei , Lv You , Ruan Xiaobin , Zhang Xiujuan , Jia Ruofei , Yu Yongqiang , Liu Zeke , Wu Di , Zhang Xiaohong , Jie Jiansheng
Published: June 2022

Emulating human vision using solid‐state devices is critical in the fields of robotics, artificial intelligence, and visual prostheses, driving intense research interest. However, bionic vision devices made from routine structures suffer from low light‐perception sensitivity to nighttime low illuminations and high power consumption, impeding their applications in many advanced scenarios from nighttime autopilot to night vision neuroprosthesis. Here, an ultrasensitive and low‐power‐consumption organic phototransistor that consists of a unique Schottky‐barrier structure and separated light absorption and carrier transport layers is reported. This device design shuns the introduction of trap states into the carrier transport route, which guarantees an ultra‐steep subthreshold swing and thus significantly amplifies the photocurrent while lowering operation voltage. In consequence, the weak‐light detection capacity for this device is enhanced dramatically, which can perceive nighttime low light illuminations with ultrahigh light‐perception sensitivity of 102–104 and low power consumption of <10 nW. Leveraging these findings, it is demonstrated that the phototransistor has neuromorphic vision perception behaviors and energy efficiency like human brain under faint light, opening a new opportunity for artificial vision.
Decreased synapse‐associated proteins are associated with the onset of epileptic memory impairment in endothelial CDK5‐deficient mice
Authors: Li Zheng‐Mao , Liu Xiu‐Xiu , Li Chen , Wei Zhao‐Cong , Shi Yi , Song Heng‐Yi , Chen Xiang , Zhang Yu , Li Jia‐Wei , Zhu Rui‐Fang , Hu Ben‐Hui , Ye Wei‐Feng , Huo Da , Jiang Guo‐Jun , Sasaki Takuya , Zhang Li , Han Feng , Lu Ying‐Mei
Published: June 2022

Accumulating evidence indicates that epilepsy has a higher risk of inducing memory impairment and dementia. However, the underlying onset mechanism remains unclear. Here, we found that mice with spontaneous epilepsy induced by endothelial CDK5 deficiency exhibited hippocampal‐dependent memory impairment at 6 months of age, but not at 2 months of age. Moreover, the persistent epileptic seizures induce aberrant changes in phosphorylation of CaMKII protein in the hippocampus of spontaneous epileptic mice. Using genome‐wide RNA sequencing and intergenic interaction analysis of STRING, we found that in addition to epilepsy‐related genes, there are changes in synaptic organization pathway node genes, such as Bdnf and Grin1. The synapse‐related proteins by Western blot analysis, such as NMDA receptors (NR1 and NR2B), PSD95, and the phosphorylation of synapsin1, are progressively decreased during epileptic seizures in Cdh5‐CreERT2;CDK5f/f mice. Notably, we found that valproate (VPA) and phenytoin (PHT) augment mRNA expression and protein levels of synapse‐related genes and ameliorate memory impairment in Cdh5‐CreERT2;CDK5f/f mice. Our study elucidates a potential mechanism of memory deficits in epilepsy, and pharmacological reversal of synaptic pathology targeting might provide a new therapeutic intervention for epileptic memory deficits.
Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson's Disease Dementia: A 36 Months Follow Up Study
Authors: Cappon Davide , Gratwicke James , Zrinzo Ludvic , Akram Harith , Hyam Jonathan , Hariz Marwan , Limousin Patricia , Foltynie Thomas , Jahanshahi Marjan
Published: June 2022

Background

Degeneration of the nucleus basalis of Meynert (NBM) and cortical cholinergic dysfunction are hallmarks of Parkinson's disease dementia (PDD). There is no effective therapy for PDD. Deep brain stimulation of the NBM (NBM‐DBS) has been trialed as a potential treatment.

Objective

Our primary aim was to evaluate the sustained tolerability of NBM‐DBS in PDD, and its impact on global cognition, behavioral symptoms, quality of life and caregiver burden and distress. Second, we aimed to determine whether baseline measures of arousal, alertness, and attention were predictive of the three year response to NBM‐DBS in PDD patients.

Methods

Five of the six PDD patients who completed the baseline assessment participated in a 3 year follow up assessment. We assessed the participants after three years of NBM‐DBS on the Mini Mental State Examination, Dementia Rating Scale‐2, Blessed Dementia Rating Scale, Neuropsychiatric Inventory, and the SF36.

Results

The five patients showed varying trajectories of cognitive decline, with two showing a slower progression over the three‐year follow‐up period. A slower progression of decline on global cognition was associated with higher baseline accuracy on the Posner covert orienting of attention test, and less daytime sleepiness.

Conclusions

Whether slower progression of cognitive decline in two patients was in any way related to individual variability in responsiveness to NBM‐DBS requires confirmation in a larger series including an unoperated PDD control group. Higher accuracy in covertly orienting attention and better sleep quality at baseline were associated with better cognitive outcomes at 36 months assessment. These results require validation in future studies with larger samples.
Hyaline fibromatosis syndrome with a novel 4.41‐kb deletion in ANTXR2 gene: A case report and literature review
Authors: Zhu Yunqian , Du Xiaonan , Sun Li , Wang Huijun , Wang Dahui , Wu Bingbing
Published: June 2022

Background

Hyaline fibromatosis syndrome is a rare autosomal recessive disorder with ANTXR2 mutations characterised by the accumulation of hyaline substances in tissues. We present a case with the severe form—infantile systemic hyalinosis (ISH)—with long survival and review the literature.

Methods and results

Trio‐exome sequencing revealed compound heterozygous mutations, including a novel 4.41 kb deletion on 4q21.21 and the previously reported c.1294C > T mutation, in the ANTXR2 gene. He was diagnosed with ISH and treated symptomatically. After follow‐ups until 4 years of age, his recurrent respiratory infections and diarrhoea improved after one severe diarrhoea attack treated with intravenous gamma globulin. He is now awaiting surgical excision of gingival hypertrophy and joint contractures.

Conclusion

The novel gross deletion in ANTXR2 enriches the genetic mutation spectrum of hyaline fibromatosis syndrome. The manifestation of decreased foetal movement, acute‐infection attack or intravenous gamma globulin treatment may be associated with hyaline fibromatosis syndrome. A review of 116 reported cases reveals that missense mutations in the vWA domain are associated with joint symptoms, respiratory tract infection and diarrhoea, while frameshift mutations are associated with facial deformities and speech delays.

We have enriched the current knowledge of the clinical manifestations and genetic mutation spectrum of HFS.
Asymptomatic ASS1 carriers with high blood citrulline levels
Authors: Chen Hui‐An , Hsu Rai‐Hseng , Chang Kai‐Ling , Huang Yi‐Chen , Chiang Yun‐Chen , Lee Ni‐Chung , Hwu Wuh‐Liang , Chiu Pao‐Chin , Chien Yin‐Hsiu
Published: June 2022

Introduction

Citrullinemia Type 1 (CTLN1) is an autosomal recessive disorder caused by variants in the ASS1 gene. This study intends to clarify the etiology of false positives in newborn screening for citrullinemia.

Method

Newborns who had elevated dried‐blood spot citrulline levels were enrolled, and medical records were reviewed retrospectively. Common ASS1 variants were screened using high‐resolution melting analysis.

Result

Between 2011 and 2021, 130 newborns received confirmatory testing for citrullinemia, 4 were found to be patients for CTLN1; 11 were patients with citrin deficiency; and 49 newborns were confirmed to be carrying one pathogenic ASS1 variant. The incidence of CTLN1 was 1 in 188,380 (95% confidence interval: 1 in 73,258 to 1 in 484,416). All ASS1 variants studied in this cohort were located in exons 11 to 15, which encode the tetrameric interface regions of the ASS1 protein. Among 10 ASS1 carriers with elevated citrulline levels and complete sequence data, four (40%) revealed additional non‐benign ASS1 variants; in contrast, only 2 of the 26 controls (7.7%), with normal citrulline levels, had additional ASS1 variants.

Conclusion

Heterozygote ASS1 variants may lead to a mild elevation of blood citrulline levels: about 2–6 times the population mean. Molecular testing and family studies remain critical for precise diagnosis, genetic counseling, and management.
(S)‐3‐aminopiperidine‐2,6‐dione is a biosynthetic intermediate of microbial blue pigment indigoidine
Authors: Zhang Zhilong , Li Pengwei , Wang Min , Zhang Yan , Wu Bian , Tao Yong , Pan Guohui , Chen Yihua
Published: June 2022

The biosynthetic investigations of microbial natural products continuously provide powerful biocatalysts for the preparation of valuable chemicals. Practical methods for preparing (S)‐3‐aminopiperidine‐2,6‐dione (2), the pharmacophore of thalidomide (1) and its analog drugs, are highly desired. To develop a biocatalyst for producing (S)‐2, we dissected the domain functions of IdgS, which is responsible for the biosynthesis of indigoidine (3), a microbial blue pigment that consists of two 2‐like moieties. Our data supported that the L‐glutamine tethered to the indigoidine assembly line is first offloaded and cyclized by the thioesterase domain to form (S)‐2, which is then dehydrogenated by the oxidation (Ox) domain and finally dimerized to yield 3. Based on this, we developed an IdgS‐derived enzyme biocatalyst, IdgS‐Ox* R539A, for preparing enantiomerically pure (S)‐2. As a proof of concept, one‐pot chemoenzymatic synthesis of 1 was achieved by combining the biocatalytic and chemical approaches.
Borcs6 is required for endo‐lysosomal degradation during early development
Authors: Bell Charlotte J. , Gupta Neha , Tremblay Kimberly D. , Mager Jesse
Published: June 2022

Early development and differentiation require precise control of cellular functions. Lysosomal degradation is a critical component of normal cellular homeostasis, allowing for degradation of signaling molecules, proteins, and other macromolecules for cellular remodeling and signaling. Little is known about the role of lysosomal function in mammalian embryos before gastrulation. Borcs6 is a protein involved in lysosomal trafficking as well as endo‐lysosomal and autophagosome fusion. Here, we show that Borcs6 is necessary for efficient endo‐lysosomal degradation in the early embryo. Although embryos lacking Borcs6 are developmentally comparable to control littermates at E5.5, they are characterized by large cells containing increased levels of late endosomes and abnormal nuclei. Furthermore, these embryos display a skewed ratio of extraembryonic and embryonic cell lineages, are delayed by E6.5, and do not undergo normal gastrulation. These results demonstrate the essential functions of lysosomal positioning and fusion with endosomes during early embryonic development and indicate that the early lethality of BORCS6 mutant embryos is primarily due to defects in the HOPS‐related function of BORC rather than lysosomal positioning.
Using machine learning algorithms to enhance the diagnostic performance of electrical impedance myography
Authors: Pandeya Sarbesh R. , Nagy Janice A. , Riveros Daniela , Semple Carson , Taylor Rebecca S. , Hu Alice , Sanchez Benjamin , Rutkove Seward B.
Published: June 2022

Introduction/Aims

We assessed the classification performance of machine learning (ML) using multifrequency electrical impedance myography (EIM) values to improve upon diagnostic outcomes as compared to those based on a single EIM value.

Methods

EIM data was obtained from unilateral excised gastrocnemius in eighty diseased mice (26 D2‐mdx, Duchenne muscular dystrophy model, 39 SOD1G93A ALS model, and 15 db/db, a model of obesity‐induced muscle atrophy) and 33 wild‐type (WT) animals. We assessed the classification performance of a ML random forest algorithm incorporating all the data (multifrequency resistance, reactance and phase values) comparing it to the 50 kHz phase value alone.

Results

ML outperformed the 50 kHz analysis as based on receiver‐operating characteristic curves and measurement of the area under the curve (AUC). For example, comparing all diseases together versus WT from the test set outputs, the AUC was 0.52 for 50 kHz phase, but was 0.94 for the ML model. Similarly, when comparing ALS versus WT, the AUCs were 0.79 for 50 kHz phase and 0.99 for ML.

Discussion

Multifrequency EIM using ML improves upon classification compared to that achieved with a single‐frequency value. ML approaches should be considered in all future basic and clinical diagnostic applications of EIM.