bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis
Authors: Gen Soei , Tanaka Ichidai , Morise Masahiro , Koyama Junji , Kodama Yuta , Matsui Akira , Miyazawa Ayako , Hase Tetsunari , Hibino Yoshitaka , Yokoyama Toshihiko , Kimura Tomoki , Yoshida Norio , Sato Mitsuo , Hashimoto Naozumi
Published: March 2022

Background: Osimertinib—the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)—has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs.Methods: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n=183), afatinib (n=55), or osimertinib (n=150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR).Results: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs.Conclusion: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.
The tool-use cortical network contributes to semantic neural representations
Authors: Thibault Simon , Koun Eric , Salemme Romeo , Boulenger Véronique , Roy Alice Catherine , Brozzoli Claudio
Published: March 2022

Tool use and language are two highly refined human abilities which may have co-evolved, thus resulting in neural commonalities. We recently provided evidence for shared neural resources between tool use and syntax. However, the debate is still open on whether semantics and phonology also recruit neurofunctional supplies common to tool use. Here we tested the hypothesis that activity within the tool-use network contributes to semantic and phonological neural representations. To this aim, we identified the tool-use network with fMRI while participants used pliers. The same participants underwent, a semantic and a phonological task to evidence the underlying networks. Through a series of representational similarity analyses we tested whether activity in tool-use clusters contributed to neural representations of semantic and phonological stimuli. The results revealed that semantic activity patterns within the left inferior frontal gyrus and left occipitotemporal cortex, activated by tool use, displayed significant similarity between nouns belonging to the same semantic category. Activity in tool-use related areas therefore contributes to semantics. By contrast, no significant relationship was observed for the activity patterns elicited by phonological stimuli. These findings suggest that semantics is grounded within the tool-use network, reinforcing the hypothesis of a functional link between semantics and tool use.
Assessing energy transition vulnerability over nations and time
Authors: Shen Yifan , Shi Xunpeng , Zhao Zhibo
Published: March 2022

While achieving the Paris climate goals and sustainable development goals (SDGs) are two major global challenges of our time, energy transition that plays an essential role in achieving climate targets may create socio-economic hardship. A quantitative assessment of the vulnerability of energy transitions is a prerequisite for national and international policymakers to advance a just energy transition that looks after coordination between energy transitions and socio-economic development. This study proposes to measure energy transition vulnerability from the dimensions of exposure, sensitivity, and adaptive capacity. The results of energy transition vulnerability index (ETVI) scores for 135 nations reveal a huge inequality across nations; moreover, the COVID-19 pandemic has interrupted the decade-long continuous improvement of energy transition vulnerability. Developed countries usually have low energy transition vulnerability than developing countries and the gaps even have been widened. The existing global transition vulnerability could be mitigated by 12.3 p.p and 5.2 p.p if each nation could follow the path of global or climate party group frontiers in achieving the SDGs, despite the scale and drivers of mitigation vary across countries. The study also suggests that heterogeneous transition policies that consider both emissions and vulnerability are required. Our framework and findings could advise policymakers to formulate policies and cooperation strategies to reduce vulnerability, protect vulnerable countries, and make fair energy transition policies nationally and internationally.
Reassessing the performance of the “step-by-step” approach to febrile infants aged 90 days and younger in the context of the COVID-19 pandemic: a multicentric retrospective study
Authors: Rybak Alexis , Aupiais Camille , Cotillon Marie , Basmaci Romain , de Pontual Loïc , Bonacorsi Stéphane , Mariani Patricia , Landraud Luce , Brichler Ségolène , Poilane Isabelle , Ouldali Naïm , Titomanlio Luigi
Published: March 2022

BackgroundInfants with COVID-19 can often present with fever without source which is a challenging situation in infants < 90 days old. The “step-by-step” algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm.MethodsWe performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the “step-by-step” algorithm to four clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk.ResultsAmong the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but one infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill appearance (72%), an age ≤ 21 days (27%) and/or leukocyturia (19%). All these infants had procalcitonin values < 0.5 ng/mL and only one had C-reactive protein level > 20 mg/L.ConclusionsThe “step-by-step” algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants < 90 days old.
Turing patterns with high-resolution formed without chemical reaction in thin-film solution of organic semiconductors
Authors: Li Shunpu , Xiang Zezhong , Li Jin , You Peng , han Linbo , Qiu Mingxia , Chen Gengliang , He Yu , Xiang Boyuan , Su Yaorong , An Hongyu
Published: March 2022

Regular patterns can form spontaneously in chemical reaction-diffusion systems under non-equilibrium conditions as proposed by Alan Turing. Here, we found that regular patterns can be generated in uphill-diffusion solution systems without a chemical reaction process through both in-situ and ex-situ observations. Organic semiconductor solution is confined between two parallel plates with controlled micron/submicron-meter distance, to minimize convection of the liquid and avoid spinodal precipitation at equilibrium. The solvent evaporation concentrates the solution gradually into an oversaturated non-equilibrium condition, under which a phase-transition occurs and ordered concentration-waves are generated. By proper tuning of the experimental parameter, multiple regular patterns with micro/nano-meter scaled features (line, square-grid, zig-zag, and fence-like patterns etc.) were observed. We explain the observed phenomenon as Turing-pattern generation resulted from uphill-diffusion and solution oversaturation. The generated patterns in the solutions can be condensed onto substrates to form structured micro/nanomaterials. We have fabricated organic semiconductor devices with such patterned materials to demonstrate the potential applications. Our observation may serve as a milestone in the progress towards a fundamental understanding of pattern formation in nature, like in biosystem, and pave a new avenue in developing self-assembling techniques of micro/nano structured materials.
The resilience of nursing staffs in nursing homes: Concept development of a hybrid model
Authors: CHANG Sung Ok , KIM Eun Young
Published: March 2022

Aim
To identify the definition and conceptual characteristics of the concept of resilience of nursing home (NH) nursing staffs.
Method
In this study, the concept was developed using a hybrid model that included theoretical, fieldwork, and final analysis stages. In the theoretical stage, a literature review on the definition and measurement of concepts was performed. For the fieldwork stage, in-depth interviews with seven NH nursing staff members were performed. During the final analysis stage, the results of the theoretical and field work stages were integrated.
Results
Three dimensions, eight attributes, and three types were identified. The three dimensions are internal resources, external support, and positive coping with situations as they arise; the eight attributes are optimism, patience, mindfulness, supportive relationships, available resources, work-life boundary setting, self-development, and growth; and the three types are those who want to adapt themselves to the situation, those who actively seek to cope with stressful situations, and those who hold positive expectations for the future.
Conclusion
Coping with difficult situations using internal resources and external support was a unique trait revealed in the resilience of NH nursing staff members. This study provided future research directions to improve the resilience of NH nursing staffs by revealing the characteristics of their resilience.
Application of PID control based on bacterial foraging-particle swarm hybrid algorithm optimization in variable fertilization system
Authors: Changxin Fu , Lixin Zhang , Xiao Ma , Huaisheng Li
Published: March 2022

In the irrigation process and fertilization process of agricultural production, the accuracy of fertilizer application and water use is kept at a relatively low level, which leads to soil slumping and waste of resources. In order to solve the above problems, this study investigates the demand for fertilizer application accuracy in the field and builds a mathematical model of variable fertilizer application system. Considering a large number of defects of the system, such as poor fertilization accuracy, long response time, and unstable regulation process, combined with MATLAB/Simulink platform, this study designs a PID algorithm based on bacterial foraging-particle swarm hybrid algorithm to control the fertilization and irrigation process of the variable fertilizer applicator. The precise fertilization control of the variable fertilizer system is mainly studied and the fuzzy proportional integral differential gain parameters of the variable fertilizer system by the hybrid algorithm are optimized. By comparing with the control algorithms (proportional-integral differential control, fuzzy proportional-integral differential control, and proportional-integral differential control with particle swarm optimization) commonly applied in the current fertilizer application system, the comparison results demonstrate that the control algorithm in this paper has better regulation, smaller overshoot, excellent stability and more rising steady-state time deficit, which can realize the precise control of the fertilizer system. Finally, this study designed fertilizer application accuracy tests under different pressure values. The results show that the algorithm proposed in this study has high fertilizer application accuracy under different pressures, which greatly reduces the waste of resources in the process of fertilizer application for crop irrigation.
Comparing the Efficacy and Safety of Cisplatin and other Platinum-based Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis
Authors: Kang Min , Li Zhiru , Li Chao , Yang Dong , Song Junmei , Liu Ting , Zhou Ziyan
Published: March 2022

Objectives: Cisplatin-based concurrent chemoradiotherapy has been identified as the primary and standard treatment for locally advanced nasopharyngeal carcinoma (NPC). The side effects of cisplatin affect the compliance to therapy. Thus, the search for a platinum-based substitute for NPC has always been a research focus. However, there is a variability in the efficacy of different platinum-based chemotherapy in the treatment of NPC. We performed a meta-analysis to compare between the efficacy and safety of the cisplatin-based regimens and the other platinum-based derivatives (carboplatin, nedaplatin, and lobaplatin) for locally advanced NPC. Methods: PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for all potentially eligible clinical trials as of February 15, 2022. The pooled hazard ratios, risk ratio, and 95% confidence interval were calculated using the Review Manager Software version 5.4. Results: A total of 1,907 patients with locally advanced NPC were eligible from the 1,265 retrieved records. This systematic review included eight articles, six of which were randomized controlled clinical trials. There was no significant difference in the 3- and 5-years overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival between cisplatin-based chemotherapy and other platinum-based chemotherapy. Severe acute hematological side effects (≥ grade 3) during treatment, such as neutropenia, leukopenia, and thrombocytopenia, are equivalent in both groups. However, the incidence of anemia is higher in patients receiving other platinum-based chemotherapy. Moreover, the risks of nausea, vomiting and weight loss were higher in the cisplatin group but there was no significant difference in the other non-hematological and late side effects between the two groups. Conclusion: Other types of platinum-based chemotherapy are as effective as cisplatin-based chemotherapy in the treatment of locally advanced NPC, thus acting as potential alternatives to cisplatin. Further studies providing high-level evidence are needed.
Utilization of long –acting contraceptive methods and associated factors among female health-care providers in South Wollo Zone hospitals, North East, Ethiopia. A cross sectional multicenter study
Authors: seid Mehdi , Yimer Aragaw , seid Ahmed , Fantaye Fasil , Damtie Yitayshi
Published: March 2022

Back ground: - Long-acting contraception method utilization was found low (22.7%) among female health care providers. However, to the best of our knowledge no study has been conducted on utilization long-acting contraception methods among female healthcare providers in the study area. These studies addressed important variable such as socio-demography and individual factors that might affect the use of long-acting contraceptive methods among female healthcare providers, but, limited studies have been in Ethiopia. Objective: - To assess the utilization of long-acting contraceptive methods and associated factors among healthcare providers in South Wollo Zone public hospitals, Amhara Region, Ethiopia 2021.Methods: An institutional-based cross-sectional study was conducted among 354 female healthcare workers in hospitals in the South Wollo Zone from March to April 22, 2021. The participants were selected using systematic random sampling technique. The data were collected using self-administered questionnaires. The data were entered Epi-data version 4.1 and export to SPSS versions 25 for analysis. Bivariable and multivariable logistic regression analyses were also performed. The Adjusted odds Ratio (AOR) along with a 95% confidence interval (CI) were estimated to measure the association and level of significance was declared at a P- value of less than 0.05.Result: -The current utilization of long-acting contraceptive methods among female health care providers was found to be 33.6% [95%, CI 29-39)], discuss with partner [AOR= 2.277,95% CI, (1.026-5.055)], method shift/switched [AOR=4.302,95% CI, (2.285-8.102)], knowledge of respondent [AOR= 1.887,95% CI, (1.020-3.491)], ever birth [AOR=15.670,95% CI, (5.065-48.49)] were significant factors towards the utilization of long-acting contraceptive methods. Conclusion and recommendation: -The current utilization of long-acting contraceptive methods was found low. Discus with partner, methods shift/switching, ever birth and knowledge of respondents were identified as significant factor. Therefore, encouraging partner discussion targeted Information Education Communication Intervention should be intensified to improve long-acting contraceptive methods utilization.
The Simplified Tailor-made Workflows for a 3D Slicer-based Craniofacial Implant Design
Authors: Tantisatirapong Suchada , Khunakornpattanakarn Sarunyapong , Suesatsakul Thanyakarn , Boonpratatong Amaraporn , Benjamin Itsara , Tongmeesee Somprasong , Kangkorn Tanasit , Chanwimalueang Theerasak
Published: March 2022

A specific design of craniofacial implant model is vital and urgent for traumatic head injury. A mirror technique is conventionally employed for modelling. However, such method requires healthy skull region identically opposite to a defect. We therefore propose the three processing workflows for modelling implants: mirror, baffle planner and baffle-based mirror guideline. The workflows are based on implementing extension modules on the 3D Slicer platform. We investigated the craniofacial CT datasets collected from the four accidental cases. The designed implant models were created from conducting the three workflows and compared to the reference models created by the experienced neurosurgeon. The spatial properties-based performance metrics were evaluated. The results show that the mirror method suits craniofacial cases whereby healthy skull region can be completely reflected to the defect region. The baffle planner module offers a flexible prototype model fit independently to any defect location. However, the baffle planner method requires customized refinement of contour and thickness to fill the missing region seamlessly. The process also relies on a user’s experience and expertise. The proposed baffle-based mirror guideline method strengthens the baffle planner method by tracing the mirrored surface. Such three proposed workflows simplify craniofacial implant modelling and can practically be employed for a variety of craniofacial scenarios.
Magma ascent and degassing processes of the 2011 and 2017-18 eruptions of Shinmoedake in Kirishima volcano group, Japan, based on petrological characteristics and volatile content of magmas
Authors: Saito Genji , Oikawa Teruki , Ishizuka Osamu
Published: March 2022

The eruption activity of Shinmoedake in the Kirishima volcanic group of Japan resumed in 2017–18 after a quiet period that lasted between 2011 and 2017. Subplinian eruptions preceded lava effusion in 2011; however, no subplinian eruption occurred in 2017–18. Petrological studies and melt inclusion analyses were conducted to investigate the ascent and degassing of the magma to understand the cause of the different eruption styles. Chemical analysis of the melt inclusions from the 2011 eruption indicates that mafic magma with high volatile content (6.2 wt% H2O, 1.4–0.25 wt% CO2) ascended into the shallow felsic magma (3.7–1.9 wt% H2O, 0.048–0.025 wt% CO2) at depths of 4–5 km. Calculations indicate that the mafic magmas were of lower density (1717–1835 kg m-3) than the felsic magma (2264–2496 kg m-3) at 125 MPa and that the two magmas were mixed. The 2011 mixed magma with high volatile content (4.0 wt% H2O, 0.14–0.70 wt% CO2) had a bubble volume of approximately 50 vol% at 50 MPa, which is likely to have caused the subplinian eruption. The whole-rock and chemical compositions of the plagioclase-, clinopyroxene-, and orthopyroxene phenocryst cores were similar in 2018 and 2011, suggesting that the 2018 magma was a remnant of the 2011 magma. Chemical analyses of the groundmass from 2018 and the MELTS calculation indicate that the magma approached chemical equilibrium over the period 2011 to 2018. Melt inclusion analyses and volcanic gas observation gave a lower bulk volatile content for the 2018 magma (3.0–2.1 wt% H2O, 0.10–0.087 wt% CO2) compared to the 2011 magma. Comparison of the degassed-magma volumes estimated from the S and Cl contents of the melt inclusions, SO2 flux and volcanic gas composition, and erupted-magma volume indicates that excess degassing has been occurring in the magma due to convection since March 2011, which may have decreased the volatile content of the magma. The relatively low volatile content meant that the 2018 magma could not erupt explosively and lava was instead erupted via effusion.
AIGDR: An Artificial Intelligence Framework for Disability Research – A Multiple Sclerosis Case
Authors: Aleid Maha , Alfantoukh Lina , Alarfaj Ohud , Alzeer Abdulla , Abomelha Eng. Faris
Published: March 2022

Background: Artificial intelligence (AI) is becoming an essential tool in the disability world. AI can be applied in a variety of contexts and domains, ranging from assistive devices for disabled individuals to decision-making systems that aid healthcare providers in the diagnosis and treatment of disabilities. Examples of these contexts include discrimination of behaviors, identifying and assessing disability-related problems, detecting abnormalities, classifying disabling diseases, predicting the progression of disabilities, and assisting and triaging patients.Methods: We investigated which AI predictive analytics models and features have been used in disability research locally and globally, focusing on multiple sclerosis. This allowed us to test multiple algorithms to determine which was best suited for each kind of data available locally. Results: We developed a framework called Artificial Intelligence Group for Disability Research (AIGDR) for disability-related research at King Salman Centre for Disability Research. The framework was influenced by existing AI use in disability research. Conclusions: The AIGDR framework uses existing predictive analytics models to generate dashboards and reports for decision-makers and produce a database that can help researchers conduct research. In the future, we plan to develop the proposed platform and apply it in various disability contexts in Saudi Arabia.
Exploring the protective mechanism of baicalin in treatment of atherosclerosis using endothelial cells degranulation model and network pharmacology
Authors: Ren Conglin , Li Mingshuang
Published: March 2022

Background: Baicalin is widely used in clinical practice. The present study aimed to assess the underlying mechanism of baicalin in treatment of atherosclerosis (AS) with the help of network pharmacology, molecular docking and experimental validation. Materials and methods: The target genes of baicalin and AS were identified from public databases, and the overlapping results were considered to be baicalin-AS targets. Core target genes of baicalin were obtained through the PPI network and clinical data sets GSE132651. Human aortic endothelial cells (HAECs) were treated with baicalin, followed by Lipopolysaccharide (LPS) to construct a model of endothelial injury. The expression of core targets was examined by real-time qPCR. Flow cytometry was used to detect reactive oxygen species (ROS) level. Results: NOX4 is likely to be the core target of baicalin for AS, and its expression was inhibited in AS patients compared to controls. Functional enrichment analysis demonstrated that most targets were involved in oxidative stress. Intervention with baicalin increased the expression levels of NOX4 and NOS3 (eNOS). Moreover, baicalin also blocked the LPS-induced ROS generation in HAECs. Conclusions: Baicalin might ameliorate oxidative stress on endothelial cells via targeting NOX4.
Quercetin treatment protects the Achilles tendons of rats from oxidative stress induced by hyperglycemia
Authors: Mifune Yutaka , Yoshikawa Tomoya , Inui Atsuyuki , Nishimoto Hanako , Yamaura Kohei , Mukohara Shintaro , Shinohara Issei , Kuroda Ryosuke
Published: March 2022

BackgroundQuercetin, a flavonoid abundantly in vegetables and fruits, exerts antioxidant and anti-inflammatory effects. We investigated the protective effects of quercetin against oxidative stress in the Achilles tendons of diabetic rats.MethodsCells were collected from the Achilles tendons of Sprague–Dawley rats and cultured under four conditions: regular glucose (RG) without quercetin (Quer-), RG with quercetin (Quer+), high-glucose (HG) Quer-, and HG Quer+. The expression of genes related to NADPH oxidase (NOX) and inflammation, reactive oxygen species accumulation, and apoptosis rates was analyzed. Additionally, diabetic rats were divided into two groups and subjected to quercetin (group Q) or no quercetin (group C) treatment. Histological evaluation and expression analysis of relevant genes in the Achilles tendon were performed.ResultsIn rat tendon-derived cells, the expression of Nox1, Nox4, and Il6; reactive oxygen species accumulation; and apoptosis rates were significantly decreased by quercetin treatment in the HG group. The collagen fiber arrangement was significantly disorganized in the diabetic rat Achilles tendons in group C compared with that in group Q. The mRNA and protein expression levels of NOX1 and NOX4 were significantly decreased upon quercetin treatment. Furthermore, the expression of Il6, type III collagen, Mmp2, and Timp2 was significantly decreased, whereas that of type I collagen was significantly increased in group Q compared with that in group C.ConclusionsQuercetin treatment decreases NOX expression and thus exerts antioxidant and anti-inflammatory effects in the Achilles tendons of diabetic rats. Quercetin treatment may be effective against diabetic tendinopathy.
GPOFWA: A hybrid greedy political optimizer with fireworks algorithm for numerical and engineering optimization problems
Authors: Dong Jian , Zou Heng , Li Wenyu , Wang Meng
Published: March 2022

This paper proposes a novel hybrid optimization algorithm named GPOFWA, which integrates political optimizer (PO) with fireworks algorithm (FWA) to solve numerical and engineering optimization problems. The original PO uses subgroup optimal solutions such as party leaders and constituency winners to guide the movement of the search agent. However, the number of such subgroup optimal solutions is limited, which leads to insufficient global exploration capabilities of PO. In addition, the recent past-based position updating strategy (RPPUS) of PO lacks effective verification of the updated candidate solutions, which reduces the convergence speed of the algorithm. The proposed hybrid algorithm uses the spark explosion mechanism in FWA to perform explosion spark and Gauss explosion spark operations on the subgroup optimal solutions (party leader and constituency winner) respectively based on the greedy strategy, which optimizes the subgroup optimal solution and enhances the exploitative ability of the algorithm. Moreover, Gaussian explosion sparks are also used to correct the candidate solutions after RPPUS, which makes up for the shortcomings of the original PO. In addition, a new subgroup optimal solution called the Converged Mobile Center (CMC) based on two-way consideration is designed to guide the movement of search agents. We test the presented hybrid algorithm on 30 well-known benchmark test functions and three engineering optimization problems. The experimental results show that GPOFWA is superior to nine state-of-the-art methods in terms of the quality of the resulting solution.
Towards a comprehensive approach for characterizing cell activity in low contrast microscopic images
Authors: Baar Stefan , Kuragano Masahiro , Tokuraku Kiyotaka , Watanabe Shinya
Published: March 2022

When studying physical cellular response observed by light microscopy, variations in cell behavior are difficult to quantitatively measure and are often only discussed on a subjective level. Hence, cell properties are described qualitatively based on a researcher’s impressions. In this study, we aim to define a comprehensive approach to estimate the physical cell activity based on migration and morphology based on statistical analysis of a cell population within a predefined field of view and timespan. We present quantitative measurements of the influence of drugs such as cytochalasin D and taxol on human neuroblastoma, SH-SY5Y cell populations. Both chemicals are well known to interact with the cytoskeleton and affect the cell morphology and motility. Being able to compute the physical properties of each cell for a given observation time, requires precise localization of each cell even when in an adhesive state. Also, the risk of confusion through contaminants is desired to be minimized. In relation to the cell detection process, we have developed a customized encoder-decoder based deep learning cell detection and tracking procedure. Further, we discuss the accuracy of our approach to quantify cell activity and its viability in regard to the cell detection accuracy.
Coherent consolidation of trillions of nucleations into a coplanar layer for a mono-atom step-level flat surface
Authors: Ha Taewoo , Seo Yu-Seong , Kim Teun-Teun , Lamichhane Bipin , Kim Young-Hoon , Kim Su Jae , Lee Yousil , Cheon Miyeon , Kim Jong , Park Sang Eon , Sim Kyung Ik , Kim Jae , Kim Yong In , Kim Seon Je , Jeong Hu Young , Lee Young Hee , Kim Seong-Gon , Kim Young-Min , Hwang Jungseek , Jeong Se-Young
Published: March 2022

Constructing a mono-atom step-level flat material surface is challenging, especially for thin films, because it is prohibitively difficult for trillions (1012) of clusters nucleated on a 2-inch wafer to coherently merge into a single-orientation thin film. The rough metal surface limits surface–plasmon propagation and acts as a valley for atoms deposited during the growth of the two-dimensional material. Recently, various flat-surface-assisted phenomena have been discovered, including large oxidation resistance of an atomically flat copper (Cu) surface. In this study, we describe in detail the initial growth of Cu(111) thin films with mono-atom step-level flat surfaces. We demonstrated experimentally that the individual deposition of single atoms using atomic sputtering epitaxy induces trillions of islands to coherently merge into a coplanar layer, eventually forming a mono-atom step-level flat surface. Theoretical calculations supported the fact that, when the sputtered particles are single atoms, rapid surface diffusion ensures the formation of highly aligned single-crystal nanodroplets that can be merged into a large domain with a coherent coplanar layer. These findings will open a new avenue in thin-film growth research and represent a watershed in terms of improved efficiency and lifespan of devices in most fields using metal electrodes, as well as metal nanoscience research.
Training for mental health professionals in responding to experienced and anticipated mental health related discrimination (READ-MH): protocol for an international multisite feasibility study
Authors: Henderson Claire , Ouali Uta , Bakolis Ioannis , Berbeche Nada , Bhattarai Kalpana , Brohan Elaine , Cherian Anish , Girma Eshetu , Gronholm Petra C , Gurung Dristy , Hanlon Charlotte , Kallakuri Sudha , Kaur Amanpreet , Ketema Bezawit , Lempp Heidi , Li Jie , Loganathan Santosh , Maulik Pallab , Mendon Gurucharan , Mulatu Tesfahun , Ma Ning , Romeo Renee , Venkatesh Rahul , Zgueb Yosra , Zhang Wu-Fang , Thornicroft Graham
Published: March 2022

Background: Mental health and other health professionals working in mental health care may contribute to the experiences of stigma and discrimination among mental health service users, but can also help reduce the impact of stigma on service users. However the few studies of interventions to equip such professionals to be anti-stigma agents those took place in High-Income Countries. This study assesses the feasibility, potential effectiveness and costs of Responding to Experienced and Anticipated Discrimination training for health professionals working in mental health care (READ-MH) across Low- and Middle-Income Countries (LMICs). Methods: This is an uncontrolled pre-post mixed methods feasibility study of READ-MH training at seven sites across five LMICs (China, Ethiopia, India, Nepal, and Tunisia). Outcome measures: knowledge based on course content; attitudes to working to address the impact of stigma on service users; and skills in responding constructively to service users’ reports of discrimination. The training draws upon the evidence bases for stigma reduction, health advocacy and medical education and is tailored to sites through situational analyses. Its content, delivery methods and intensity were agreed through a consensus exercise with site research teams. READ-MH will be delivered to health professionals working in mental health care immediately after baseline data collection; outcome measures will be collected post-training and three months post-baseline, followed by qualitative data collection. Fidelity will be rated during delivery of READ-MH, and data on training costs will be collected. Quantitative data will be assessed using generalised linear mixed models. Qualitative data will be evaluated by thematic analysis to identify feedback about the training methods and content, including the implementability of the knowledge and skills learned. Pooled and site-specific training costs per trainee and per session will be reported.﻿Conclusions: The training development used a participatory and contextualized approach. Evaluation design strengths include the diversity of settings; the use of mixed methods; the use of a skills-based measure; and knowledge and attitude measures aligned to the target population and training. Limitations are the uncertain generalisability of skills performance to routine care, and the impact of COVID-19 restrictions at several sites limiting qualitative data collection for situational analyses.
Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts
Authors: Jensen Emil , Deichmann Marcus , Ma Xin , Vilandt Rikke , Schiesaro Giovanni , Rojek Marie , Lengger Bettina , Eliasson Line , Vento Justin , Durmusoglu Deniz , Hovmand Sandie , Al'Abri Ibrahim , Zhang Jie , Crook Nathan , Jensen Michael
Published: March 2022

G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. GPCRs comprise the largest class of cell surface receptors in eukaryotes, and for more than three decades the pheromone-induced mating pathway in baker’s yeast Saccharomyces cerevisiae has served as a model for studying heterologous GPCRs (hGPCRs). Here we report transcriptome profiles following mating pathway activation in native and signalling yeast and use a model-guided approach to correlate gene expression to morphological changes. From this we demonstrate mating between haploid cells armed with hGPCRs and endogenous biosynthesis of their cognate ligands. Furthermore, we devise a ligand-free screening strategy for hGPCR compatibility with the yeast mating pathway and enable signalling in the probiotic yeast Saccharomyces boulardii. Combined, our findings enable new means to study mating, signalling, and cell-cell communication in a model eukaryote and yeast probiotics.
A personal acquisition time regimen of 68Ga-DOTATATE total-body PET/CT in patients with neuroendocrine tumor (NET): A feasibility study.
Authors: Xiao Jie , Yu Haojun , Sui Xiuli , Liu Guobing , Cao Yanyan , Yanzhao Zhao , Zhang Yiqiu , Hu Pengcheng , Cheng Dengfeng , Shi Hongcheng
Published: March 2022

Purpose: To propose a personal acquisition time regimen of 68Ga-DOTATATE total-body positron emission tomography-computed tomography (PET/CT) for acceptable and constant image quality of patients with neuroendocrine tumors (NETs).Methods: A development cohort consisting of 19 consecutive patients with full activity (88.7-204.9 MBq/kg) was used to establish the acquisition time regimen. The liver SNR (signal-to-noise ratio, SNRL) was normalized (SNRnorm) by the product of injected activity and acquisition time. Fitting of SNRnorm against body mass (BM) in linear correlation was performed. Subjective assessment of image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL, and an optimized acquisition regimen based on BM was proposed and validated using a cohort of 57 NET patients with half activity (66.9±11.3 MBq, 1.0±0.1 MBq/kg) in a fixed acquisition time regimen.Results: The linear correlation (R2=0.63) between SNRnorm and BM was SNRnorm=-0.01*BM+1.50. The threshold SNRL of acceptable image quality was 11.2. The patient-specific variable acquisition time regimen was then determined as t (min) = 125.4/(injective activity)*(-0.01*BM+1.50)2. Based on the regimen, the average acquisition time for acceptable image quality in the validation cohort was 2.99±0.91 min, ranging from 2.18 to 6.35 min, which was reduced by 36.50%~78.20% compared with the fixed acquisition time of 10 min. Subjective evaluation showed that acceptable image quality could be obtained at 3.00 min in the low-activity group, with an average score of 3.44±0.53 (kappa = 0.97, 95% CI: 0.96~0.98). Bland–Altman analysis revealed good agreement between the proposed regimen and the fixed acquisition time cohort.Conclusion: A personal acquisition time regimen was proposed and validated for NET patients for 68Ga-DOTATATE total-body PET/CT imaging. Based on the regimen, the image quality is feasible for a constant level, independent of body mass, with reasonable acquisition time.
Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2
Authors: Ji Young Rae , Tona Yosuke , Wafa Talah , Christman Matthew , Tourney Edward , Jiang Tao , Ohta Sho , Fitzgerald Tracy , Fritzsch Bernd , Jones Sherri M. , Cullen Kathleen , Wu Doris
Published: March 2022

A conserved line of polarity reversal (LPR) demarcates hair cells into two regions of opposite orientation in the otolith organs of the inner ear. The functional significance of this arrangement is not known. Using gene knockout and conditional knockouts (cKO) mice, we show that the Emx2 encoded transcription factor establishes the LPR and bidirectional sensitivity of the otolith organ by mediating hair bundle orientation in HCs and neuronal selectivity in HCs and supporting cells. In addition to Emx2 cKO, we generated another mouse strain without bidirectional sensitivity in otolith organs, Tmie cKO, in which HCs within the Emx2 expression domain lack mechanotransduction and thus are rendered non-functional. Behavioral analyses of both Emx2 cKO and Tmie cKO mice indicate that the LPR is specifically required for mice to swim comfortably and to traverse a balance beam efficiently, but LPR is not required for mice to stay on a rotating rod.
Homeostasis tissue-like P systems with cell separation
Authors: Luo Yueguo , Guo Ping
Published: March 2022

P systems are distributed, parallel biological computing models. Tissue P systems are an important variant of membrane computing model, where the environment can provide powerful energy support for cells. Hence, the environment plays a critical role. Nevertheless, in actual biological tissues, there exists a peculiar biological phenomenon called "homeostasis"; that is, the internal organisms maintain stable, thereby reducing their dependence on external conditions (i.e., the environment). In this work, considering cell separation, we construct a novel variant to simulate the mechanism of biological homeostasis, called homeostasis tissue-like P systems with cell separation. In this variant, objects in the environment are finite, and certain energy changes occur inside the cells; moreover, an exponential workspace can be obtained with cell separation in feasible time. The computational power of this model is studied by simulating register machines, and the results show that the variant is Turing universal as number computing devices. Furthermore, to explore the computational efficiency of the model, we use the variant to solve a classic NP-complete problem, the SAT problem, obtaining a uniform solution with a rule length of at most 3.
Upregulation of the oxytocin receptor in dorsal root ganglion mediated peripheral analgesia of oxytocin in chemotherapy-induced peripheral neuropathic pain
Authors: Li Lixuan , Li Pupu , Guo Jing , Wu Yifei , Zeng Qian , Li Nan , Huang Xiaoting , He Yongshen , Ai Wen , Sun Wuping , Liu Tao , Xiong Donglin , Xiao Lizu , Zhou Qiming , Wang Zilong , Jiang Changyu
Published: March 2022

Background: Currently, chemotherapy-induced peripheral neuropathic pain (CIPNP) has no effective treatment. Oxytocin (OXT) and the oxytocin receptor (OXTR) play roles in central analgesia. However, the expression and role of OXTR in the peripheral nervous system in CIPNP remain unclear. Here, we studied the peripheral analgesic profiles of OXTR and related mechanisms in CIPNP pain models.Methods: The chemotherapeutic agent paclitaxel (PTX) was used to establish CIPNP. qRT-PCR, fluorescent in situ hybridization, western blotting, and immunocytochemistry were used to observe the properties of OXTR expression in dorsal root ganglion (DRG). The analgesic effects were assessed by the hot plate and the Von Frey tests. The whole-cell patch-clamp was performed to record the effects of the OXTR activation on the excitability of DRG neurons and the excitatory transmissions from the primary afferents to the spinal cord.Results: The expression of OXTR in DRG neurons was boosted significantly after PTX treatment, which is rarely expressed in the vehicle group without sex difference. The activation of OXTR exhibited analgesic effects and decreased the excitability of DRG neurons. Additionally, the OXTR activation impaired the voltage-gated sodium current through the PLC/PKC pathway. Oxytocin also suppressed the excitatory transmission in the spinal dorsal horn and the excitatory inputs from the primary afferents in PTX-treated mice.Conclusions: Paclitaxel upregulates the expression of OXTR in DRG neurons. This upregulation leads to effective analgesic effects of peripheral oxytocin which is mediated by the reduction of the excitability of DRG neurons and the excitatory transmission in the spinal dorsal horn. Our results suggested that OXTR on peripheral sensory neurons can be utilized to relieve CIPNP.
Evaluation of fixation characteristics in amblyopia using microperimetry
Authors: Altinbay Deniz , Sahli Esra , Kiziltunc Pinar Bingol , Atilla Huban
Published: March 2022

Purpose: To evaluate fixation characteristics in amblyopia using macular analyzer integrity assessment (MAIA) microperimetry and to investigate the factors affecting fixation stability.Methods: This prospective, cross-sectional study enrolled a total of 58 amblyopic patients (8-55 years old). Average threshold macular sensitivity (AT) and fixation characteristics were assessed using the MAIA microperimetry (CenterVue, Padova, Italy). Two Bivariate contour ellipse areas (BCEA) fixation indices (63% and 95% proportional values) and the percentage of fixation points within 1° and 2° from the fovea (P1 and P2) were used to assess fixation stability. Results: AT and fixation stability parameters (P1, P2, BCEA 63%, BCEA 95%) were worse in the amblyopic eyes (p<0.05, for all). There was a positive correlation between BCVA, and AT, and P2, and negative correlations between BCVA, and BCEA 63%, and BCEA 95%. The eccentric fixation was 48% in the amblyopic eyes (25% in anisometropic group, 52% in strabismic group, 69% in combined group) and 32% in the non-amblyopic eye. The preferred fixation eccentricity in amblyopic eyes was significantly greater than the non-amblyopic eyes (p=0.004), and there was a negative correlation between preferred fixation eccentricity and BCVA (p=0.012, r=-.327).Conclusions: Our data showed a decrease in fixation stability, a positive correlation between fixation stability and BCVA, and a negative correlation between preferred fixation eccentricity and BCVA in amblyopic eyes. This result made us think that microperimetric acoustic biofeedback fixation training, which is used to increase fixation stability in low vision rehabilitation, may also be a useful approach in amblyopia.
Acute Myocardial Infarction caused by Kawasaki disease Requires more Intensive Therapy: Insights from the Japanese Registry of All Cardiac and Vascular Diseases— Diagnosis Procedure Combination
Authors: Anzai Fumiya , Yoshihisa Akiomi , Takeishi Ryohei , Hotsuki Yu , Sato Yu , Sumita Yoko , Nakai Michikazu , Misaka Tomofumi , Takeishi Yasuchika
Published: March 2022

Background
Kawasaki disease (KD) induces coronary arteritis which causes subsequent coronary aneurysms, and contributes to acute myocardial infarction (AMI). However, the difference of real-world treatment selection and mortality between AMI-complicated KD and AMI due to typical atherosclerosis (AMI-non KD) is unknown.
Method
The aim of the present study was to reveal the current treatment strategy and prognosis of AMI-complicated KD compared with AMI due to typical atherosclerosis using data from 2012 to 2019 of a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination.
Results
Compared with AMI-non KD (n = 70,227), AMI-complicated KD (n = 73) 1) underwent less percutaneous coronary intervention (PCI) and more coronary artery bypass grafting, intracoronary thrombolysis or intravenous coronary thrombolysis, 2) underwent stentless PCI using old balloon angioplasty or rotablator, when they underwent PCI, 3) needed in-hospital cardiopulmonary resuscitation and intensive mechanical therapy such as intra-aortic balloon pump, percutaneous cardiopulmonary support or respirator, whereas presented similar in-hospital mortality.
Conclusions
Compared with AMI-non KD, AMI-complicated KD underwent non-PCI strategy such as bypass surgery or thrombolysis, required intensive therapy with mechanical supports, and presented similar in-hospital mortality. When AMI-complicated KD underwent PCI, stentless PCI using balloon angioplasty or rotablator was more performed compared with AMI-non KD.