bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafast ultrasound coded vector Doppler imaging of blood flow velocity and resistivity
Authors: YAN Shaoyuan , DING Yiming , MA Guoao , FU Yapeng , XU Kailiang , TA Dean ,   Department of Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China,   State Key Laboratory of Integrated Chips and Systems, Fudan University, Shanghai 201203, China,   Poda Medical Technology Co., Ltd., Shanghai 200438, China
Published: November 2024

Dynamic and precise measurement of cerebral blood flow velocity plays a critical role in neuroscience and the diagnosis of cerebrovascular diseases. Traditional color Doppler ultrasound can only measure the velocity component along the ultrasound beam, thus limiting its ability to accurately capture the full blood flow vector in complex environments. To break through these limitations, we propose an ultrafast pulse-coded vector Doppler (PC-UVD) imaging method, by using Hadamard matrix pulse encoding to enhance velocity estimation accuracy in low signal-to-noise ratio (SNR) conditions. Our study includes spiral flow simulations and in vivo rat brain experiments, which demonstrate significantly improved measurement precision compared with traditional ultrafast vector Doppler (UVD). This novel approach can measure dynamic cerebral blood flow velocity within a single cardiac cycle, presenting insights into cerebrovascular resistivity characteristics.

The proposed PC-UVD method encodes plane waves with Hadamard matrices and can increase SNR without sacrificing temporal or spatial resolution. Velocity vectors are then estimated using a weighted least squares (WLS) approach, where iterative residual-based weight optimization enhances robustness to noise and reduces contributions of outliers. The effectiveness of this technique is validated through simulations using a spiral blood flow phantom, indicating a substantial improvement in velocity estimation accuracy, especially in deep imaging regions with significant signal attenuation. In vivo experiments on rat brains further corroborate that the proposed method has higher accuracy than existing UVD approaches, especially for small vessels. Notably, our method can accurately distinguish between arterial flow and venous flow by analyzing pulsatility and resistivity within the cerebral vascular network.

This work demonstrates the potential of PC-UVD in complex vascular imaging, providing high SNR, high temporal and spatial resolution, and accurate vectorized flow measurements. Our results highlight its ability to non-invasively evaluate hemodynamic parameters and its potential application in the diagnosis of cerebrovascular diseases, particularly in small vessels.
Modeling corticotroph deficiency with pituitary organoids supports the functional role of NFKB2 in human pituitary differentiation
Authors: Mac Thi Thom , Fauquier Teddy , Jullien Nicolas , Romanet Pauline , Etchevers Heather , Barlier Anne , Castinetti Frederic , Brue Thierry
Published: November 2024

Deficient Anterior pituitary with common Variable Immune Deficiency (DAVID) syndrome results from NFKB2 heterozygous mutations, causing adrenocorticotropic hormone deficiency (ACTHD) and primary hypogammaglobulinemia. While NFKB signaling plays a crucial role in the immune system, its connection to endocrine symptoms is unclear. We established a human disease model to investigate the role of NFKB2 in pituitary development by creating pituitary organoids from CRISPR/Cas9-edited human induced pluripotent stem cells (hiPSCs). Introducing homozygous TBX19K146R/K146R missense pathogenic variant in hiPSC, an allele found in congenital isolated ACTHD, led to a strong reduction of corticotrophs number in pituitary organoids. Then, we characterized the development of organoids harboring NFKB2D865G/D865G mutations found in DAVID patients. NFKB2D865G/D865G mutation acted at different levels of development with mutant organoids displaying changes in the expression of genes involved on pituitary progenitor generation (HESX1, PITX1, LHX3), hypothalamic secreted factors (BMP4, FGF8, FGF10), epithelial-to-mesenchymal transition, lineage precursors development (TBX19, POU1F1) and corticotrophs terminal differentiation (PCSK1, POMC), and showed drastic reduction in the number of corticotrophs. Our results provide strong evidence for the direct role of NFKB2 mutations in the endocrine phenotype observed in patients leading to a new classification of a NFKB2 variant of previously unknown clinical significance as pathogenic in pituitary development.
A deep learning approach for automated scoring of the Rey–Osterrieth complex figure
Authors: Langer Nicolas , Weber Maurice , Hebling Vieira Bruno , Strzelczyk Dawid , Wolf Lukas , Pedroni Andreas , Heitz Jonathan , Müller Stephan , Schultheiss Christoph , Troendle Marius , Lasprilla Juan Carlos Arango , Rivera Diego , Scarpina Federica , Zhao Qianhua , Leuthold Rico , Wehrle Flavia , Jenni Oskar , Brugger Peter , Zaehle Tino , Lorenz Romy , Zhang Ce
Published: November 2024

Memory deficits are a hallmark of many different neurological and psychiatric conditions. The Rey–Osterrieth complex figure (ROCF) is the state-of-the-art assessment tool for neuropsychologists across the globe to assess the degree of non-verbal visual memory deterioration. To obtain a score, a trained clinician inspects a patient’s ROCF drawing and quantifies deviations from the original figure. This manual procedure is time-consuming, slow and scores vary depending on the clinician’s experience, motivation, and tiredness. Here, we leverage novel deep learning architectures to automatize the rating of memory deficits. For this, we collected more than 20k hand-drawn ROCF drawings from patients with various neurological and psychiatric disorders as well as healthy participants. Unbiased ground truth ROCF scores were obtained from crowdsourced human intelligence. This dataset was used to train and evaluate a multihead convolutional neural network. The model performs highly unbiased as it yielded predictions very close to the ground truth and the error was similarly distributed around zero. The neural network outperforms both online raters and clinicians. The scoring system can reliably identify and accurately score individual figure elements in previously unseen ROCF drawings, which facilitates explainability of the AI-scoring system. To ensure generalizability and clinical utility, the model performance was successfully replicated in a large independent prospective validation study that was pre-registered prior to data collection. Our AI-powered scoring system provides healthcare institutions worldwide with a digital tool to assess objectively, reliably, and time-efficiently the performance in the ROCF test from hand-drawn images.
CPT1A mediates radiation sensitivity in colorectal cancer
Authors: Chen Zhenhui , Yu Lu , Zheng Zhihao , Wang Xusheng , Guo Qiqing , Chen Yuchuan , Zhang Yaowei , Zhang Yuqin , Xiao Jianbiao , Chen Keli , Fan Hongying , Ding Yi
Published: November 2024

The prevalence and mortality rates of colorectal cancer (CRC) are increasing worldwide. Radiation resistance hinders radiotherapy, a standard treatment for advanced CRC, leading to local recurrence and metastasis. Elucidating the molecular mechanisms underlying radioresistance in CRC is critical to enhance therapeutic efficacy and patient outcomes. Bioinformatic analysis and tumour tissue examination were conducted to investigate the CPT1A mRNA and protein levels in CRC and their correlation with radiotherapy efficacy. Furthermore, lentiviral overexpression and CRISPR/Cas9 lentiviral vectors, along with in vitro and in vivo radiation experiments, were used to explore the effect of CPT1A on radiosensitivity. Additionally, transcriptomic sequencing, molecular biology experiments, and bioinformatic analyses were employed to elucidate the molecular mechanisms by which CPT1A regulates radiosensitivity. CPT1A was significantly downregulated in CRC and negatively correlated with responsiveness to neoadjuvant radiotherapy. Functional studies suggested that CPT1A mediates radiosensitivity, influencing reactive oxygen species (ROS) scavenging and DNA damage response. Transcriptomic and molecular analyses highlighted the involvement of the peroxisomal pathway. Mechanistic exploration revealed that CPT1A downregulates the FOXM1-SOD1/SOD2/CAT axis, moderating cellular ROS levels after irradiation and enhancing radiosensitivity. CPT1A downregulation contributes to radioresistance in CRC by augmenting the FOXM1-mediated antioxidant response. Thus, CPT1A is a potential biomarker of radiosensitivity and a novel target for overcoming radioresistance, offering a future direction to enhance CRC radiotherapy.
JAK inhibition decreases the autoimmune burden in Down syndrome
Authors: Rachubinski Angela L , Wallace Elizabeth , Gurnee Emily , Enriquez Estrada Belinda A , Worek Kayleigh R , Smith Keith P , Araya Paula , Waugh Katherine A , Granrath Ross E , Britton Eleanor , Lyford Hannah R , Donovan Micah G , Eduthan Neetha Paul , Hill Amanda A , Martin Barry , Sullivan Kelly D , Patel Lina , Fidler Deborah J , Galbraith Matthew D , Dunnick Cory A , Norris David A , Espinosa Joaquin M
Published: November 2024

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.
ConBGAT: a novel model combining convolutional neural networks, transformer and graph attention network for information extraction from scanned image
Authors: Ho Vo Hoang Duy , Vo Quoc Huy , Hung Bui Thanh
Published: November 2024

Extracting information from scanned images is a critical task with far-reaching practical implications. Traditional methods often fall short by inadequately leveraging both image and text features, leading to less accurate and efficient outcomes. In this study, we introduce ConBGAT, a cutting-edge model that seamlessly integrates convolutional neural networks (CNNs), Transformers, and graph attention networks to address these shortcomings. Our approach constructs detailed graphs from text regions within images, utilizing advanced Optical Character Recognition to accurately detect and interpret characters. By combining superior extracted features of CNNs for image and Distilled Bidirectional Encoder Representations from Transformers (DistilBERT) for text, our model achieves a comprehensive and efficient data representation. Rigorous testing on real-world datasets shows that ConBGAT significantly outperforms existing methods, demonstrating its superior capability across multiple evaluation metrics. This advancement not only enhances accuracy but also sets a new benchmark for information extraction in scanned image.
Effects of temperature and size class on the gut digesta microbiota of the sea urchin Tripneustes ventricosus
Authors: Rodríguez-Barreras Ruber , Tosado-Rodríguez Eduardo L. , Dominicci-Maura Anelisse , Godoy-Vitorino Filipa
Published: November 2024

Background

Understanding the dynamics of the gut microbiota in sea urchins is crucial for comprehending the ecological balance in marine ecosystems. The gut microbiota plays a vital role in nutrient metabolism, immune system modulation, and pathogen protection. The microbial composition and dynamics of naturally occurring sea urchin Tripneustes ventricosus have yet to be thoroughly investigated. We hypothesized the gut microbiota of T. ventricosus in the Caribbean, varies across life stages and seasons.

Methods

Thirty-six naturally occurring large individuals and six small individuals (42 animals) were collected from shallow waters on the northeastern coast of Puerto Rico in February and August of 2019. The fecal pellet’s microbiota was characterized by sequencing V4 region of the 16S rRNA gene.

Results

We found significant differences in the composition of fecal pellet microbiota between seasons and life stages. Phylum Bacteroidota had greater relative abundance in August, while Firmicutes was more dominant in February. Propionigenium and Roseimarinus had greater relative abundance in August, while Candidatus Hepatoplasma, and Kistimonas had greater relative abundance in February. Differences in the gut digest microbiota were not found between small and large urchins, but small urchins displayed a slightly higher diversity and dominance of Bacteroidota and Proteobacteria, while large urchins exhibited a greater relative abundance of Fusobacteria and Desulfobacterota. However, the genera Ferrominas and Propionigenium counts were significantly lower in small individuals.

Discussion

This is the first report for this species in the Caribbean region and adds to our comprehension of the microbiota of the white sea urchin across collection periods and size classes, highlighting the dynamic nature of the gut microbiota.
Exploration of severe early childhood caries microbiota through a novel developed nutrient enriched microbiological medium, high through-put 16S rRNA sequencing and culturomics
Authors: Zhang Yixin , Chen Yang , Diao Chang , Lin Haojie , Zhu Jingqi , Sun Ruiqing , Wang Meng , Chen Yuke , Zhou Hanzhang , Dong Zixi , Xia Bin , Wang Yixiang
Published: November 2024

Introduction

Severe early childhood caries (S-ECC) is a widespread disease that harms children physically and mentally. Microorganisms are regarded as the dominant etiology of caries, however, S-ECC microbiome remains largely unknown, nearly 1/4 of them remained uncultivated. To explore S-ECC microbiota, a new bacterial medium, nutrient-enriched microbiological medium (NEMM) was designed in this study.

Methods

Eleven fresh S-ECC dental plaque samples were collected and cultivated in both NEMM and SHI medium (reference medium) for 0, 1, 3, 6, 9, 15, 21 and 28 days under aerobic and anaerobic conditions. Thereafter, the cultures were harvested, together with their corresponding clinical S-ECC dental plaque samples, for high through-put 16S rRNA sequencing and culturomics. The single colonies were cultured for further confirmation by sequencing the full length of the 16S rRNA gene after bacterial genomic DNA extraction and PCR amplification.

Results

Either NEMM or SHI medium showed a significant decrease in bacterial alpha diversity compared to clinical dental plaque samples by high throughput 16S rRNA sequencing analysis, indicating a larger room for the improvement of both media. NEMM displayed more living bacteria, abundant bacteria species, uncultured bacteria and capacities in carbohydrate transport and metabolism than SHI medium. The dynamic changes in bacterial community composition over time indicated that some bacteria tended to be enriched at specific time points. Culturomics and identification of bacterial species results were further confirmed by the high throughput 16S rRNA sequencing results.

Conclusion

We developed a new medium NEMM that could support S-ECC microbiota growth with a higher yield of living bacteria, higher abundance and capacity, and be suitable for cultivating oral uncultured bacteria via culturomics technology.
Understanding the progress of COVID-19 transmission in a rural district: a social network approach
Authors: Mansor Juliana , Safian Nazarudin , Abdul Razak Fatimah , Ismail Halim , Ghazali Muhammad Haikal , Ismail Noriah
Published: November 2024

Background

Social interactions within and between communities influenced the spread of COVID-19. By using social network analysis (SNA), we aimed to understand the effect of social interaction on the spread of disease in a rural district.

Method

A retrospective record review study using positive COVID-19 cases and contact-tracing data from an area in Malaysia was performed and analysed using the SNA method through R software and visualised by Gephi software. The justification for utilizing SNA is its capability to pinpoint the individuals with the highest impact and accountability for the transmission of COVID-19 within the area, as determined through SNA.

Result

Analysis revealed 76 (4.5%) people tested positive for COVID-19 from 1,683 people, with 51 (67.1%) of the positive ones being male. Outdegrees for 38 positive people were between 1 and 12, while 41 people had 1–13 indegree. Older males have a higher outdegree, while younger females have a higher outdegree than other age groups among same-sex groups. Betweenness was between 0.09 and 34.5 for 15 people. We identified 15 people as super-spreaders from the 42 communities detected.

Conclusion

Women play a major role in bridging COVID-19 transmission, while older men may transmit COVID-19 through direct connections. Thus, health education on face mask usage and hand hygiene is important for both groups. Working women should be given priority for the work-from-home policy compared to others. A large gathering should not be allowed to operate, or if needed, with strict adherence to specific standard operating procedures, as it contributes to the spread of COVID-19 in the district. The SNA allows the identification of key personnel within the network. Therefore, SNA can help healthcare authorities recognise evolving clusters and identify potential super-spreaders; hence, precise and timely action can be taken to prevent further spread of the disease.
Análise probabilística da viabilidade de investimento calculando o VPL e utilizando a Simulação de Monte Carlo
Authors: Moreira Karina de Lourdes Binotti , Santos Andréa Alexandra , Melo Leandro de Araujo , Sanches Alexandre Leme , Medeiros Daniel Amaro Cirino de , Aguiar Helder de Souza
Published: November 2024

Este trabalho é uma análise probabilística de viabilidade de investimento, calculando o VPL e utilizando a simulação de Monte Carlo, para um investimento no segmento de marmitex delivery. O objetivo é realizar uma análise detalhada utilizando o cálculo de VPL e a simulação de Monte Carlo para calcular a rentabilidade e os riscos desse negócio. A ideia central da Simulação de Monte Carlo é modelar a probabilidade de diferentes resultados em um sistema ou processo, cujos resultados não podem ser facilmente previstos, devido à intervenção de uma série de variáveis. Após fazer a simulação de Monte Carlo, obtemos a distribuição de valor do VPL do investimento e dos riscos associados. Essa análise nos permitiu compreender melhor a volatilidade dos resultados e avaliar a probabilidade de atingir diferentes níveis de retorno do investimento.
Oxidation of Styrene to Benzaldehyde Using Environmentally Friendly Calcium Sulfate Hemihydrate-Supported Titania Catalysts
Authors: Koesnarpadi Soerja , Wirawan Teguh , Nurhadi Mukhamad , Wirhanuddin Wirhanuddin , Prananto Yuniar Ponco , Nazarudin Nazarudin , Degirmenci Volkan , Lai Sin Yuan , Nur Hadi
Published: November 2024

This paper presents the synthesis and characterization of calcium sulfate hemihydrate (CSH)-supported titania (TiO2) catalysts and their application in the environmentally friendly oxidation of styrene to benzaldehyde using hydrogen peroxide (H2O2) as the oxidant. The study explores the catalyst's structure-activity relationship, emphasizing the importance of mesoporous materials for enhanced catalytic performance. The CSH-Titania catalysts were synthesized using fish bone-derived CSH as a support, which aligns with green chemistry principles. Characterization techniques such as Fourier Transform Infra Red (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), and Brunauer-Emmett-Teller (BET) surface area analysis confirmed the successful impregnation of titania and its catalytic efficiency. The catalysts exhibited high selectivity for benzaldehyde, achieving up to 49.45% conversion of styrene, with benzaldehyde as being the main product. The research highlights that the catalyst’s performance decreased after calcination due to a reduced surface area and pore volume, yet it maintained recyclability across three cycles with minimal  lose  in selectivity loss. Overall, this study introduces a cost-effective and sustainable approach to styrene oxidation, demonstrating the potential for industrial application in producing high-value chemicals with minimal environmental impact. Copyright © 2024 by Authors, Published by BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Relationships between body mass index, lifestyle habits, and locomotive syndrome in young- and middle-aged adults: A cross-sectional survey of workers in Japan
Authors: Ohtsuki Makoto , Nishimura Akinobu , Kato Toshihiro , Sokejima Sigeru , Shibata Tomiko , Okada Hiromi , Nagao-Nishiwaki Rie , Sudo Akihiro
Published: April 2019

Objectives

Although many studies have examined locomotive syndrome (LS) among elderly people, few studies have examined LS in young- and middle-aged adults. This study aimed to provide basic data on the epidemiological characteristics of LS, including in young- and middle-aged adults.

Method

We conducted a cross-sectional survey of a nonrandom sample of 852 adults aged 18–64 (678 males, 174 females) working in five companies in Japan, between December 2015 and February 2018. LS stage was determined using the criteria proposed by the Japanese Orthopaedic Association (JOA). LS stage 0 was defined as No-LS, and stages 1 and 2 were defined as LS. Multiple logistic regression analysis was used to investigate the independent relationship between LS and sociodemographic, smoking, alcohol drinking (AD), frequency of breakfast consumption (FBC), dietary variety score (DVS), and the University of California Los Angeles (UCLA) activity score after adjusting for age and sex.

Results

We found that 23.1% of participants were evaluated as LS, including 21.5% of males and 29.3% of females (P < 0.05). Participants aged ≥45 years exhibited higher rates of LS (males: 23.1%, females: 43.6%) compared with those aged <45 years (P < 0.05). Logistic regression analysis revealed that age, body mass index (BMI), AD, UCLA activity score, and FBC were also related to LS.

Conclusion

Education initiatives about LS should be targeted not only to elderly populations but also to young- and middle-aged adults in the workplace.
The correlation between possible RBD and cognitive function in Parkinson's disease patients in China
Authors: Yan Ya‐yun , Lei Ke , Li Yuan‐yuan , Liu Xiu‐feng , Chang Ying
Published: April 2019

Objective

Cognitive impairment is an important symptom of Parkinson's disease (PD) and seriously affects patients’ quality of life and prognosis. However, its cause is still uncertain. In about one‐third of patients, PD is associated with rapid eye movement sleep behavior disorder (RBD), which is an independent risk factor for PD‐associated dementia; but whether or not it relates to the cognitive function of patients with nondemented PD is still controversial.

Methods

The data from 89 enrolled PD patients were retrospectively analyzed. The RBD Questionnaire Hong‐Kong (RBD‐HK) was used to diagnose possible RBD (pRBD). There are 46 patients with possible RBD (the PD‐pRBD) and 43 without (the PD‐npRBD). PD disease severity, neuropsychological function, overall cognitive function, and various cognitive functions were assessed.

Results

There were significant between‐group differences in scores on the Montreal Cognitive Assessment (MoCA), Mini‐Mental State Examination (MMSE), Digit Symbol Test (DST), Trail Making Test‐A (TMT‐A)‐Time, TMT‐Trail Making Test‐B (TMT‐B)‐Time, Stroop Color‐word Test, Clock Drawing Test (CDT), Boston Naming Test (BNT), Verbal Fluency Test (fruit), etc. (P < 0.05).

Interpretation

Patients in the PD‐pRBD group had more cognitive impairment.
Microstructured Actuation of Liquid Crystal Polymer Networks
Authors: Ge Feijie , Zhao Yue
Published: April 2019

Smart microstructured materials enable functions such as actuation, detection, transportation, and sensing with potential applications ranging from robotics and photonics to biomedical devices. Of the many materials systems, liquid crystal polymer networks (LCN) are fascinating owing to their ability to exhibit reversible macroscopic deformation driven by a molecular order–disorder phase transition. LCN have been increasingly explored for their utility in the design and fabrication of smart actuating devices capable of complex shape changes or motions upon external stimulation of humidity, heat, light, and other stimuli, and recent studies in this field show that their actuation complexity can be enriched and actuation performance enhanced by having some sort of microstructures. Herein, the recent progress in microstructured actuation of LCN materials with substructures in scale ranging from micrometer to millimeter is reported, placing the emphasis on the main approaches to generating a microstructure in LCN, which include patterned LC director fields, patterned chain crosslinking in LCN with uniaxial orientation of mesogens, 3D/4D printing, and replica molding. The potential applications in microstructured 3D actuators and devices as well as functional LCN surfaces are also highlighted, with an outlook on important issues and future trends in smart microstructured LCN materials and actuators.
A High‐Performance Self‐Regenerating Solar Evaporator for Continuous Water Desalination
Authors: Kuang Yudi , Chen Chaoji , He Shuaiming , Hitz Emily M. , Wang Yilin , Gan Wentao , Mi Ruiyu , Hu Liangbing
Published: April 2019

Emerging solar desalination by interfacial evaporation shows great potential in response to global water scarcity because of its high solar‐to‐vapor efficiency, low environmental impact, and off‐grid capability. However, solute accumulation at the heating interface has severely impacted the performance and long‐term stability of current solar evaporation systems. Here, a self‐regenerating solar evaporator featuring excellent antifouling properties using a rationally designed artificial channel‐array in a natural wood substrate is reported. Upon solar evaporation, salt concentration gradients are formed between the millimeter‐sized drilled channels (with a low salt concentration) and the microsized natural wood channels (with a high salt concentration) due to their different hydraulic conductivities. The concentration gradients allow spontaneous interchannel salt exchange through the 1–2 µm pits, leading to the dilution of salt in the microsized wood channels. The drilled channels with high hydraulic conductivities thus function as salt‐rejection pathways, which can rapidly exchange the salt with the bulk solution, enabling the real‐time self‐regeneration of the evaporator. Compared to other salt‐rejection designs, the solar evaporator exhibits the highest efficiency (≈75%) in a highly concentrated salt solution (20 wt% NaCl) under 1 sun irradiation, as well as long‐term stability (over 100 h of continuous operation).
Artificial Neuron and Synapse Realized in an Antiferromagnet/Ferromagnet Heterostructure Using Dynamics of Spin–Orbit Torque Switching
Authors: Kurenkov Aleksandr , DuttaGupta Samik , Zhang Chaoliang , Fukami Shunsuke , Horio Yoshihiko , Ohno Hideo
Published: April 2019

Efficient information processing in the human brain is achieved by dynamics of neurons and synapses, motivating effective implementation of artificial spiking neural networks. Here, the dynamics of spin–orbit torque switching in antiferromagnet/ferromagnet heterostructures is studied to show the capability of the material system to form artificial neurons and synapses for asynchronous spiking neural networks. The magnetization switching, driven by a single current pulse or trains of pulses, is examined as a function of the pulse width (1 s to 1 ns), amplitude, number, and pulse‐to‐pulse interval. Based on this dynamics and the unique ability of the system to exhibit binary or analog behavior depending on the device size, key functionalities of a synapse (spike‐timing‐dependent plasticity) and a neuron (leaky integrate‐and‐fire) are reproduced in the same material and on the basis of the same working principle. These results open a way toward spintronics‐based neuromorphic hardware that executes cognitive tasks with the efficiency of the human brain.
Sex and Laterality Differences in Medullary Humerus Morphology
Authors: Drew Alex J. , Tashjian Robert Z. , Henninger Heath B. , Bachus Kent N.
Published: April 2019

Percutaneous osseointegrated (OI) prosthetic limb attachment holds promise for transhumeral amputees. Understanding humeral medullary morphology is necessary for informed design of upper extremity OI systems, and is beneficial to the field of megaprosthetic reconstruction of the distal humerus where diaphyseal fixation is desired. The purpose of this study was to quantify the sex and laterality differences in humerus morphology, specifically over the diaphysis. Three‐dimensional surface reconstructions of 58 pairs of cadaveric humeri (43 male, 15 female) were generated from CT data. Measures describing periosteal and medullary morphology were collected relative to an anatomic coordinate system. Sex and laterality differences in biomechanical length (BML) were observed (P ≤ 0.001 and 0.022, respectively). Head radius was larger in males than females (P ≤ 0.001). Retroversion was increased in right humeri relative to left (P ≤ 0.001). Canal orientation exhibited a conformational shift from anteversion to retroversion distally at approximately 65% BML. Right humeri exhibited larger medullary diameters than left in the 1st and 2nd principal directions (P ≤ 0.024). Males displayed larger diameter medullary canals proximally (P ≤ 0.029) and an increased rate of divergence of the endosteal cortex in the proximal diaphysis (P ≤ 0.009). Females exhibited higher canal aspect ratios at mid‐shaft (P ≤ 0.014) and lower mean cortical thickness (P ≤ 0.001). Human humeral diaphysis morphology exhibits sex and laterality differences, which are dependent on position along the diaphysis. Understanding humeral morphology is necessary to achieve adequate primary stability and bone apposition in design of endoprosthetic stems for percutaneous OI implants, and distal humerus replacement. Anat Rec, 302:1709–1717, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association for Anatomy
A contextual approach to information privacy research
Authors: Wu Philip Fei , Vitak Jessica , Zimmer Michael T.
Published: April 2019

In this position article, we synthesize various knowledge gaps in information privacy scholarship and propose a research agenda that promotes greater cross‐disciplinary collaboration within the iSchool community and beyond. We start by critically examining Westin's conceptualization of information privacy and argue for a contextual approach that holds promise for overcoming some of Westin's weaknesses. We then highlight three contextual considerations for studying privacy—digital networks, marginalized populations, and the global context—and close by discussing how these considerations advance privacy theorization and technology design.
The relation between parent verbal responsiveness and child communication in young children with or at risk for autism spectrum disorder: A systematic review and meta‐analysis
Authors: Edmunds Sarah R. , Kover Sara T. , Stone Wendy L.
Published: April 2019

Among preschool‐age children with autism spectrum disorder (ASD) and typically developing children, parents' verbal responsiveness (PVR) has long been shown to predict children's later language ability. However, before the age of three, when language develops most rapidly, the early social communication deficits associated with ASD may impact parents' opportunities to facilitate early language development. The aim of this review was to characterize the relation between PVR and the vocal communication ability of children with or at high risk for ASD early in development. Specifically, we examined whether the relation between PVR and child communication varied by type of PVR and by child diagnostic status, as well as whether interventions increased PVR. A systematic multi‐database search yielded 25 empirical studies (804 parent–toddler dyads; 30 effect sizes) that met inclusion criteria and related a variable of PVR to a variable of child vocalization or language. Meta‐regression analyses revealed that the relation between PVR and child communication was significant regardless of PVR type or child diagnostic status. To date, interventions targeting both PVR and child communication were found to significantly increase PVR, but not child communication, for these populations. Future research should examine parent–child communication in a transactional, longitudinal manner. In addition, these findings have implications for interventions designed to target parents' responsiveness and child communication. Autism Research 2019, 12: 715–731. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

For families with children under 3 years old who are at risk for or diagnosed with ASD, this study revealed empirical evidence of a robust relation between parents'’ verbal responsiveness to their children's play and communication and children's communication ability. This relation is similar to that reported in research on typically developing children. Interventions designed to improve parent–child interaction in children with or at risk for ASD may be effective in increasing parents' responsiveness.
Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes
Authors: Wang Jiayu , Li Weiwei , Shi Yujian , Huang Yan , Sun Tao , Tang Lili , Lu Qing , Lei Qiumo , Liao Ning , Jin Feng , Li Hui , Huang Tao , Qian Jun , Pang Danmei , Wang Shusen , Fan Peizhi , Wu Xinhong , Lin Ying , Qin Haiyan , Xu Binghe
Published: April 2019

Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P < 0.01). Some pathogenic mutations were detected in the patients’ familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non‐BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high‐risk BC patients. Detailed family history can help to categorize new mutations.
Deciphering the ‘Elixir of Life’: Dynamic Perspectives into the Allosteric Modulation of Mitochondrial ATP Synthase by J147, a Novel Drug in the Treatment of Alzheimer's Disease
Authors: Emmanuel Iwuchukwu A. , Olotu Fisayo A. , Agoni Clement , Soliman Mahmoud E. S.
Published: April 2019

The discovery of J147 represented a significant milestone in the treatment of age‐related disorders, which was further augmented by the recent identification of mitochondrial ATP synthase as the therapeutic target. However, the underlying molecular events associated with the modulatory activity of J147 have remained unresolved till date. Herein, we present, for the first time, a dynamical approach to investigate the allosteric regulation of mATP synthase by J147, using a reliable human αγβ protein model. The highlight of our findings is the existence of the J147‐bound protein in distinct structural associations at different MD simulation periods coupled with concurrent open↔close transitions of the β catalytic and α allosteric (ATP5A) sites as defined by Cα distances (d), TriCα (Θ) and dihedral (φ) angular parameters. Firstly, there was an initial pairing of the αγ subunits away from the β subunit followed by the formation of the ‘non‐catalytic’ αβ pair at a distance from the γ subunit. Interestingly, J147‐induced structural arrangements were accompanied by the systematic transition of the β catalytic site from a closed to an open state, while there was a concurrent transition of the allosteric site from an open αE conformation to a closed state. Consequentially, J147 reduced the structural activity of the whole αγβ complex, while the unbound system exhibited high atomistic deviations and structural flexibility. Furthermore, J147 exhibited favorable binding at the allosteric site of mATP synthase with considerable electrostatic energy contributions from Gln215, Gly217, Thr219, Asp312, Asp313, Glu371 and Arg406. These findings provide details on the possible effects of J147 on mitochondrial bioenergetics, which could facilitate the structure‐based design of novel small‐molecule modulators of mATP synthase in the management of Alzheimer's disease and other neurodegenerative disorders.
Transition Metal‐dinitrogen Complex Embedded Graphene for Nitrogen Reduction Reaction
Authors: Yang Yulu , Liu Jiandong , Wei Zengxi , Wang Shuangyin , Ma Jianmin
Published: April 2019

Conversion of nitrogen to ammonia (NH3) is one of the most important issue in the modern chemical industry. Transition metals (TM) have the special unoccupied and occupied d orbitals to accept the electrons from and backdonate to N2, which is crucial in effective nitrogen reduction reaction (NRR). Herein, we propose TMN4 (TM=Fe, Co, Mo, W, Ru, Rh) embedded graphene as the catalysts for NRR by using the density functional theory calculations. Our results revealed that MoN4 embedded graphene exhibited outstanding catalytic activity for ammonia synthesis at ambient conditions along with small reaction energy barrier of 0.67 eV, as well as against hydrogen evolution reaction. These findings provide a potential paradigm for NRR.
Synthesis of N‐Heterocycles‐Fused Azasilines by Palladium‐Catalyzed Si‐Si Bond Activation
Authors: Noël‐Duchesneau Ludovik , Maddaluno Jacques , Durandetti Muriel
Published: April 2019

Azasilines fused nitrogen heterocycles are prepared in excellent yields (from 74 to 98 % according to the structures) for the first time in one operation with high regio‐ and stereoselectivities. The key step consists of an intramolecular palladium‐catalyzed cyclisation reaction of heteroaryl disilane cores, bearing double or triple bond. We first studied the reactivity of pyridyl heterocycles, using xylenes as solvent and Pd(dba)2‐P(OEt)3 as catalyst at 130 °C. The Z configuration of the adducts suggested that the reaction proceeds following a syn addition on the alkyne. This strategy has then been illustrated by the synthesis of complex polyheterocyclic scaffolds (phenothiazine, indole, carbazole, quinoline and tetrahydroquinoline) starting from other nitrogen heteroaryl compounds, to demonstrate the potential of the process, in order to obtain promising biological scaffolds.
Successful defibrillation verification in subcutaneous implantable cardioverter‐defibrillator recipients by low‐energy shocks
Authors: Biffi Mauro , Ziacchi Matteo , Angeletti Andrea , Castelli Andrea , Massaro Giulia , Martignani Cristian , Lovecchio Mariolina , Valsecchi Sergio , Diemberger Igor
Published: April 2019

Background

The subcutaneous implantable cardioverter‐defibrillator (S‐ICD) is an effective alternative to the transvenous one. Defibrillation efficacy depends on maximum device output and on the optimal device location at device implantation.

Hypothesis

We sought to investigate the defibrillation safety margin in real life clinical practice.

Methods

We sought to understand what is the efficacy of induced ventricular fibrillation (VF) termination at S‐ICD implantation using lower energies than the recommended 65 J.

Results

Sixty‐four consecutive S‐ICD recipients underwent VF termination attempts at implantation with energies ranging from 20 to 50 J. Overall, VF termination occurred in 84% of patients with ≤40 J, in 88% with 45 J, and in 100% with 60 J. Intermuscular S‐ICD placement was associated with 94% VF termination at ≤40 J. An ejection fraction <35% was associated to higher energy requirement for defibrillation; however, an intermuscular S‐ICD placement conferred 90% defibrillation efficacy at 31 ± 5 J in this patients subset.

Conclusions

This is a hypothesis‐generating observation that prompts a methodologically correct investigation to prove that a 60 J output S‐ICD can provide an adequate safety margin to terminate VF in clinical practice. This would enable superior device longevity and/or device downsizing for pediatric/small size patients.
Calculation of Larmor precession frequency in magnetically heterogeneous media
Authors: Ruh Alexander , Kiselev Valerij G.
Published: April 2019

Calculation of the Larmor frequency of NMR‐reporting spins is reviewed in detail, including the Fourier transformation of the dipole field and the Lorentz sphere construction. Special attention is paid to the physical picture, which helps to keep calculations simple and to resolve apparently mathematical problems. The paper is thought as a comprehensive recipe for practical applications and includes a review on the recent progress in understanding the phase contrast in the human brain.
Sensitivity analysis for the mechanics of tendons and ligaments: Investigation on the effects of collagen structural properties via a multiscale modeling approach
Authors: Hamdia Khader M. , Marino Michele , Zhuang Xiaoying , Wriggers Peter , Rabczuk Timon
Published: April 2019

The effects of the stochasticity of collagen‐related structural properties on the biomechanical properties of tendons and ligaments are investigated in this study. The tissue mechanics is modeled by means of a macroscale constitutive model based on a multiscale structural approach. This rationale allows to introduce model parameters directly associated with tissue structural and biochemical features, opening to physically motivated parametric studies. Variance and density‐based global sensitivity analyses are employed, together with the quantification of output uncertainty due to stochastic variations of parameters. Novel insights on tissue structure‐mechanics relationship are provided, quantifying the dependence between mechanical output quantities on specific collagen‐related structural features. Moreover, the uncertainty quantification shows that model predictions provided by the multiscale structural approach are reliable with respect to inevitable uncertainties in tissue structure. Addressing rat tail tendons, the use of average values in tissue properties returns a constitutive response that fits well‐available experimental data, and it is robust with respect to parameter stochasticity.
Generation of Macrophages from Cynomolgus‐Monkey Bone Marrow as a Model to Evaluate Effects of Drugs on Innate Immunity
Authors: Li Nianyu , Ludmann Susan A. , Anest Lisa , He Ching , Narayanan Padma Kumar
Published: April 2019

Macrophages are innate immune cells that play important roles in various physiological and pathological processes. Evaluation of pro‐inflammatory effects of drugs on macrophages has become commonplace in preclinical drug development prior to human clinical trials. Despite their body‐wide distribution, tissue macrophages are often difficult to collect from large animals and humans in a noninvasive manner. Therefore, in vitro–differentiated macrophages are important tools to facilitate cross‐species analysis of macrophage function. Although cynomolgus monkeys are an essential non‐rodent species for preclinical research, in vitro differentiation of cynomolgus‐monkey macrophages has been poorly characterized. In the present unit, we describe a protocol to differentiate cynomolgus‐monkey macrophages from isolated bone marrow mononuclear cells (BMMCs). In contrast to monocytes, cynomolgus‐monkey BMMCs show robust expansion in the presence of macrophage colony–stimulating factor in vitro, which allows expansion of many cells from a single animal donor. Macrophages differentiated from BMMCs retain many of the macrophage phenotypes and functions, including phagocytosis and cytokine release, and therefore can be used as a surrogate to assess effects of drugs on cynomolgus‐monkey macrophages. © 2019 by John Wiley & Sons, Inc.
Analysis of Human Mitochondrial DNA Content by Southern Blotting and Nonradioactive Probe Hybridization
Authors: Wheeler Joel H. , Young Carolyn K. J. , Young Matthew J.
Published: April 2019

A single cell can contain several thousand copies of the mitochondrial DNA genome or mtDNA. Tools for assessing mtDNA content are necessary for clinical and toxicological research, as mtDNA depletion is linked to genetic disease and drug toxicity. For instance, mtDNA depletion syndromes are typically fatal childhood disorders that are characterized by severe declines in mtDNA content in affected tissues. Mitochondrial toxicity and mtDNA depletion have also been reported in human immunodeficiency virus–infected patients treated with certain nucleoside reverse transcriptase inhibitors. Further, cell culture studies have demonstrated that exposure to oxidative stress stimulates mtDNA degradation. Here we outline a Southern blot and nonradioactive digoxigenin‐labeled probe hybridization method to estimate mtDNA content in human genomic DNA samples. © 2019 by John Wiley & Sons, Inc.