bluuebunny/crossref_metadata_2025 huggingface dataset:
Product allocation and network configuration in global production networks
Authors: Klenk Felix , Kerndl Felix , Heidinger Felix , Benfer Martin , Peukert Sina , Lanza Gisela
Published: July 2022

Driven by an increasing demand for individualized products and shorter product life-cycles, companies continuously extend their product portfolio. Simultaneously, companies expand into new markets to reach customers and to exploit varying location factors to reduce costs. Global production networks (GPNs) have to be adapted constantly to react to new circumstances and changes in the demand of products. To remain competitive, product allocation and production network configuration are essential. At the same time, companies face an increasing complexity while handling these tasks. This poses a challenge particularly for small and medium sized companies, which have limited planning capacities and management resources. Current literature describes optimization-based approaches for the integrated product allocation and network configuration of production networks. Yet, multi-objective models lack transparency of results and user friendliness. Therefore, this paper presents a multi-objective optimization model that incorporates flexibility and reconfiguration aspects to determine an optimal product allocation and network configuration of a GPN over a given planning horizon. The preemptive goal programming approach is used to identify Pareto-optimal solutions and to increase user friendliness. The subsequent verification, validation and post-optimality analysis combined in a structured process enables a wide range of companies to apply the approach. The model is successfully applied in the GPN of a special machine manufacturer, which produces high precision metrology machines. Due to its transparent approach for complex planning problems, the developed method provides a solid base for well-founded, objective decisions. Hence, the risk of costly errors in the planning phase is reduced.
Assessing medical students’ perception and educational experience during COVID-19 pandemic
Authors: Low Ernest Z. , O’Sullivan Niall J. , Sharma Vidushi , Sebastian Isabella , Meagher Roisin , Alomairi Dalal , Alhouti Ebraheem H. , Donohoe Claire L. , Kelly Michael E.
Published: July 2022

Introduction

The COVID-19 pandemic has significantly impacted the traditional delivery of medical education. Medical education programmes have had to cope with limitations on face-to-face learning, and accelerate the adoption of digital learning. In addition, the pandemic has potential serious implications on the psychological well-being of medical students. We aim to assess the changes in perceptions and experiences of medical students as a consequence of this pandemic.

Methods

Cross-sectional survey of medical students at Trinity College Dublin (TCD) between March and April 2022 was performed. The survey explored student satisfaction with the current education program, teaching delivery and the impact of COVID-19 on education and student well-being.

Results

175 medical students participated in the survey. Overall, the majority of students were happy/neutral with their medical education. 93 (53.1%) felt tutorials and problem-based learning (PBL) to be the most effective method of teaching, followed by laboratory and clinical placements in 78 participants (44.6%) and hybrid-learning in 85 participants (48.6%). There was a mixed reaction to the changes in the delivery of education brought about by the pandemic. 67 participants (40.6%) felt happy with the changes, another 64 participants (38.8%) felt neutral, whilst only 34 participants (20.6%) were unhappy. However, most participants felt the pandemic negatively impacted their mental health, with 96 participants (55.8%) reporting negative responses. 58% of participants (n= 102/175) reported utilising the student support services at university campus and 49% (n= 50) were satisfied with their services.

Conclusion

Digital content and delivery confer the benefit of greater flexibility in learning, the ability to learn at one’s own pace and in a preferred environment, however lacks the advantage of bedside teaching and hands-on training. Our findings reinforce the potential advantages of online learning.
Estimation of Calcium Titanate or Erbium Oxide Nanoparticles Induced Cytotoxicity and Genotoxicity in Normal HSF Cells
Authors: Mohamed Hanan R. H. , Ibrahim Maria M. H. , Soliman Esraa S. M. , Safwat Gehan , Diab Ayman
Published: July 2022

Extensive uses of calcium titanate nanoparticles (CaTiO3-NPs) and erbium oxide nanoparticles (Er2O3-NPs) increase their release into the environment and human exposure, particularly through skin contact. However, there are almost no studies available on the effect of these nanoparticles on skin integrity. Therefore, this study was undertaken to estimate CaTiO3-NP- or Er2O3-NP-induced cytotoxicity and genotoxicity in normal human skin fibroblast (HSF) cells. Cell viability was measured using sulforhodamine B (SRB) assay, while the level of DNA damage was detected using the alkaline comet assay. The intracellular levels of reactive oxygen species (ROS) as well as the expression level of p53, Bax, and Bcl2 genes were detected. Although the viability of HSF cells was non-markedly changed after 24 h, prolonged treatment with CaTiO3-NPs or Er2O3-NPs for 72 h induced concentration-dependent death of HSF cells. Treatment of normal HSF cells with IC50/72 h of CaTiO3-NPs or Er2O3-NPs did not cause marked changes in the intracellular level of ROS, DNA damage parameters, and expression levels of apoptosis genes compared to their values in the untreated HSF cells. We thus concluded that CaTiO3-NPs or Er2O3-NPs cause time- and concentration-dependent cytotoxicity toward normal HSF cells. However, safe and non-genotoxic effects were demonstrated by the apparent non-significant changes in intracellular ROS level, DNA integrity, and apoptotic genes’ expression after exposure of normal HSF cells to nanoparticles. Thus, it is recommended that further studies be conducted to further understand the toxic and biological effects of CaTiO3-NPs and Er2O3-NPs.
Exploring the use of self-sovereign identity for event ticketing systems
Authors: Feulner Simon , Sedlmeir Johannes , Schlatt Vincent , Urbach Nils
Published: July 2022

Ticket fraud and ticket scalping activities often cause high costs as well as trust concerns for fans buying event tickets, especially in the secondary ticketing market. To address these issues, several publications and projects have proposed using blockchain technology to enable digital trust and ticket verifiability and thus to improve event ticketing systems. However, these approaches exhibit considerable privacy challenges and fall short concerning reliable, efficient visitor identification, which is necessary for controlling secondary market transactions. We demonstrate how a novel paradigm for end-user digital identity management, called self-sovereign identity (SSI), can be utilized to gain secondary market control. To do so, we follow a rigorous design science research approach to build and evaluate an SSI-based event ticketing framework. Our findings demonstrate that SSI-based event ticketing can enable efficient secondary market control by facilitating a practical implementation of the centralized exchange model. To generalize our results, we derive design principles for the efficient, reliable, and privacy-oriented ticket and identity verification and the use of revocation registries.
A mathematical treatment of the bump structure of particle-laden flows with particle features
Authors: Matsue Kaname , Tomoeda Kyoko
Published: July 2022

In this study, we consider particle-laden flows on an inclined plane under the effect of gravity. Previous experimental works have noted that a particle-rich ridge is generated near the contact line. We investigate the bump structure observed in particle-rich ridges in terms of Lax’s shock waves in the mathematical theory of conservation laws, explicitly considering the effect of particles with nontrivial radii on morphology of particle-laden flows. We also extract the dependence of radius and concentration of particles on the bump structure.
Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: identification of a HAM-like phenotype in a proportion of asymptomatic carriers
Authors: Harding Daniel , Rosadas Carolina , Tsoti Sandra Maria , Heslegrave Amanda , Stewart Molly , Kelleher Peter , Zetterberg Henrik , Taylor Graham P. , Dhasmana Divya
Published: July 2022

Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (> 1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), β2-microglobulin (β2M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), β2M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and β2M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this ‘HAM-like’ profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.
Predicting the fate and the biological treatment parameters of phenol in a wastewater from its initial concentration
Authors: Lotfy Hesham R. , Rashed Ibrahim G.
Published: July 2022

Microbial degradation is an important process for removing many organic chemicals from natural waters. The estimation of biodegradability of chemicals which reach the aquatic environment is necessary in assessing the hazard associated with their use. Phenol has many industrial applications and it finds its way into wastewater streams. It is toxic to several biochemical reactions. However, biological transformation of phenol to non-toxic entities is possible. In this article, the data of biodegradation of phenol at different concentrations were studied. For phenol concentrations equal to or less than 147 mg/L, the plateau (the stage associated with the termination of carbon) BOD (biochemical oxygen demand) was calculated to be 169.47% of the corresponding initial phenol concentration, the BOD of the biomass produced up to the plateau was calculated to be 70% of the corresponding initial phenol concentration. This study shows that the biomass produced up to the plateau, the plateau BOD, and the ultimate BOD can all be estimated for phenol concentrations less than 147 mg/L just if the initial phenol concentration is known and without having to repeat the time-consuming BOD experiments.
Application of polyurethane foam/zinc oxide nanocomposite for antibacterial activity, detection, and removal of basic dyes from wastewater
Authors: Moawed E. A. , Eissa M. S. , Al-Tantawy S. A.
Published: July 2022

In this paper, a new multifunctional nanocomposite was synthesized to combine both the advantages of sorption properties and antibacterial efficiency. The thiourea polyurethane/zinc oxide nanocomposite was prepared by coupling thiourea polyurethane foam and zinc oxide nanoparticles. The thiourea polyurethane/zinc oxide was characterized using several tools. The change in the surface chemistry of the thiourea polyurethane/zinc oxide nanocomposite (surface area was increased from 2.8 to 10.6 m2/g), due to the attached functional groups, increased its sorption properties. Also, the thiourea polyurethane/zinc oxide showed a crystalline phase, embedded inside the amorphous structure, with good thermal stability to 230 °C. The pore volume and radius of thiourea polyurethane/zinc oxide were 0.017 cm3/g and 3.4 nm with mesopores/micropores ratio of 11:1. It combines collecting pollutants on its surface, the ability to degrade these pollutants, and a good antibacterial effect. Thiourea polyurethane/zinc oxide was applied for the removing toluidine blue and brilliant green basic dyes from the wastewater. Several parameters such as pH, dye concentration, temperature, and time were studied. The removal percentages of brilliant green and toluidine blue dyes from the wastewater were 92.4–98.2% at pH 3–12. Also, the removing rate of the dyes was very fast (3–5 min) at 25 °C. The estimated capacities of new nanocomposite for toluidine blue and brilliant green were 92 and 227 mg/g. The removal process was spontaneous (ΔG was − 7.3 and − 8.6). As a result, the applicability of thiourea polyurethane/zinc oxide as an effective renewable antibacterial sorbent for removing cationic dyes was maintained.
The association between childhood trauma and overweight and obesity in young adults: the mediating role of food addiction
Authors: Offer Samuel , Alexander Elise , Barbara Kelsie , Hemmingsson Erik , Flint Stuart W. , Lawrence Blake J.
Published: July 2022

Purpose

Childhood trauma is associated with increased risk of obesity during adulthood, which may be associated with the development of food addiction. This study examined whether food addiction mediated the relationship between childhood trauma and obesity in young adults.

Methods

A sample of 512 young adults, aged 18 to 30 years, living with overweight and obesity (Body Mass Index ≥ 25 kg/m2), from the United Kingdom participated in the study. Participants completed the Childhood Trauma Questionnaire (CTQ), the Yale Food Addiction Scale, and provided their current height and weight to compute their Body Mass Index (BMI).

Results

Using the PROCESS macro, a mediation analysis found that food addiction accounted for 45% of variance in the relationship between childhood trauma and BMI. Post hoc analyses were conducted to examine the mediating effect of food addiction across each of the five subscales of the CTQ (emotional/physical/sexual abuse and emotional/physical neglect). Food addiction accounted for 32% to 51% of the variance in the relationship between each CTQ subscale and BMI.

Conclusions

These findings suggest that experiences of childhood trauma are associated with the development of overweight and obesity during early adulthood and up to half of this relationship can be attributed to food addiction, which is likely used as a maladaptive coping mechanism in response to trauma. Young adults living with overweight and obesity who report experiences of childhood trauma may benefit from the support of clinical and counselling psychologists to improve their understanding of the underlying psychosocial factors that influence their eating behaviours.

Level of evidence

Level V, cross-sectional analytic study.
New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study
Authors: Gambineri A. , Scarano E. , Rucci P. , Perri A. , Tamburrino F. , Altieri P. , Corzani F. , Cecchetti C. , Dionese P. , Belardinelli E. , Ibarra-Gasparini D. , Menabò S. , Vicennati V. , Repaci A. , di Dalmazi G. , Pelusi C. , Zavatta G. , Virdi A. , Neri I. , Fanelli F. , Mazzanti L. , Pagotto U.
Published: July 2022

Purpose

Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course.

Methods

A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol.

Results

The study cohort was followed up for a median of 27 years (IQR 12–42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded.

Conclusions

This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.
Integrating Station-Area Development with Rail Transit Networks: Lessons from Japan Railway in Tokyo
Authors: Cao Zhejing
Published: July 2022

Rail transit is a primary transport mode in Tokyo and has become the backbone of its urban development. Tokyo rail transit networks consist of the subway in the central area, private railways in the suburban area, and Japan Railway (JR) in both central and suburban areas. Prior research revealed that JR has better coordination of transit node functions and station-area development than subway and private railway stations, but how Tokyo's JR station-area development integrates with its network growth is less explored. This work investigates how JR station-area development grows in tandem with network expansion, by revisiting different historical phases. The results show that, in the beginning of the twentieth century, JR connected major urban nodes in both central and suburban Tokyo, and therefore became the skeleton of Tokyo's transit systems. During the post-earthquake and post-war period, central subway and suburban private railways gradually met JR on the Yamanote line, enabling the major interchange stations to develop into urban centers. In the 1960s, JR increased its services to alleviate passenger congestion and undertook grade separation projects to reduce conflicts with road networks. The 1987 JR privatization marked a turning point of massive station-area redevelopment. JR station areas have been transformed from underutilized industrial land into high-density commercial use, and major JR stations were comprehensively replanned for identity and place-making. After a centennial development, JR stations have become important interchange and express-service nodes on Tokyo transit networks with intensive land use and different urban functions. The Tokyo JR case can provide insights for metropolitan cities on how to integrate rail transit infrastructure with station-area development, including matching critical nodes in transit networks with urban functions and high-density land use and connecting these urban functions through express line services.
Analysis of the chemical behavior at the molecular level of lined pipes with fluoropolymers in a sodium hypochlorite production line/bibliographic review
Authors: Beleño Rosero Andrea Angelica , Pareja Rodríguez Leonel , Andrade Fonseca Luis Fernando
Published: July 2022

This case study is about finding the best fluoropolymer coating for pipes that resists the sodium hypochlorite continue production, which is one of the most aggressive chemical processes that can lead to molecular attack in reactors made by lined pipes. There are several types of coatings pipe such as fiberglass, polymers and elastomers, but the fluoropolymers which have unique properties that make them resistant to chemical attack. In this production process, the premature deterioration of coating pipes is common, due to the expansion of chlorine at the inlet of the reactor, caused by the reaction of chlorine–sodium hydroxide, this is the critical point of the process. Some problems that we find is the chemical attack in that some fluoropolymers coating suffer premature degradation caused by the chemical compatibility, in this case, we explain in detail the chemical and molecular composition of each of the fluoropolymers and how this change occurs at the molecular level. While the lined pipes are the best economical option for chemicals applications, however, it is important to know the correct coating to ensure a long lifetime and avoid piping changes due to premature degradation. Based on the findings of the chemical resistance of each fluoropolymer under study, it is determined which is the best fluoropolymer that resists continuous production of sodium hypochlorite. Results were obtained by a systematic review of the literature.
The ixabepilone and vandetanib combination shows synergistic activity in docetaxel-resistant MDA-MB-231 breast cancer cells
Authors: Tam Stanton , Al-Zubaidi Yassir , Rahman Md Khalilur , Bourget Kirsi , Zhou Fanfan , Murray Michael
Published: July 2022

Background

The lack of drug targets is an obstacle to the treatment of patients with triple-negative breast cancer (TNBC). At present, non-specific cytotoxic drugs are first-line agents, but the development of resistance is a major problem with these agents. The epidermal growth factor receptor (EGFR) is a potential target in some TNBCs, because its tyrosine kinase activity drives tumorigenesis. Thus, small molecule inhibitors of the EGFR in combination with cytotoxic agents could be important for the treatment of TNBCs.

Methods

The present study evaluated the efficacies of clinically approved EGFR inhibitors in combination with the cytotoxic agent ixabepilone in parental and docetaxel-resistant MDA-MB-231 cells (231C and TXT cells, respectively). Cell viability was assessed using MTT reduction assays, cell death pathways were evaluated using annexin V/7-aminoactinomycin D staining and flow cytometry and Western immunoblotting was used to assess the expression of pro- and anti-apoptotic proteins in cells.

Results

Ixabepilone and the EGFR inhibitors gefitinib and vandetanib inhibited 231C and TXT cell proliferation, but the alternate EGFR inhibitors erlotinib and lapatinib were poorly active. Using combination analysis, ixabepilone/vandetanib was synergistic in both cell types, whereas the ixabepilone/gefitinib combination exhibited antagonism. By flow cytometry, ixabepilone/vandetanib enhanced 231C and TXT cell death over that produced by the single agents and also enhanced caspase-3 cleavage and the pro/anti-apoptotic Bcl-2 protein ratios over ixabepilone alone.

Conclusions

These findings suggest that the ixabepilone/vandetanib combination may have promise for the treatment of patients with drug-resistant TNBC.

Graphical abstract
Assigning Obligations in AI Regulation: A Discussion of Two Frameworks Proposed By the European Commission
Authors: Jacobs Mattis , Simon Judith
Published: July 2022

The emergence and increasing prevalence of Artificial Intelligence (AI) systems in a growing number of application areas brings about opportunities but also risks for individuals and society as a whole. To minimize the risks associated with AI systems and to mitigate potential harm caused by them, recent policy papers and regulatory proposals discuss obliging developers, deployers, and operators of these systems to avoid certain types of use and features in their design. However, most AI systems are complex socio-technical systems in which control over the system is extensively distributed. In many cases, a multitude of different actors is involved in the purpose setting, data management and data preparation, model development, as well as deployment, use, and refinement of such systems. Therefore, determining sensible addressees for the respective obligations is all but trivial. This article discusses two frameworks for assigning obligations that have been proposed in the European Commission’s whitepaper On Artificial Intelligence—A European approach to excellence and trust and the proposal for the Artificial Intelligence Act respectively. The focus is on whether the frameworks adequately account for the complex constellations of actors that are present in many AI systems and how the various tasks in the process of developing, deploying, and using AI systems, in which threats can arise, are distributed among these actors.
Gut Microbiome in Colorectal Cancer: Clinical Diagnosis and Treatment
Authors: Liu Yali , Lau Harry Cheuk-Hay , Cheng Wing Yin , Yu Jun
Published: July 2022

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and the leading cause of cancer-associated deaths. Epidemiological studies have shown that both genetic and environmental risk factors contribute to the development of CRC. Several metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal malignancy. Although enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC, the precise mechanisms involved remain elusive. Recent data have shown a direct causative role of the gut microbiome in DNA damage, inflammation, and drug resistance in CRC, suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and therapy. Here, we provide an overview of the relationship between gut microbiome and CRC, and explore relevant mechanisms of colorectal tumorigenesis. We next highlight the potential of bacterial species as clinical biomarkers, as well as their roles in therapeutic response. Factors limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.
Tree Mortality Risk Surges in Australian Rain Forests
Authors: Pardikar Rishika
Published: July 2022

Researchers link vulnerability to “atmospheric drought” associated with climate change.
Should Inhaled Anesthetics Be Swapped for IVs?
Authors: Donovan Robin
Published: July 2022

Using intravenous anesthetics instead of volatile ones could help curb greenhouse gas emissions, but there are challenges to making the switch.
Using Sap Flow to Infer Plant Hydraulic Properties
Authors: Rehnberg Morgan
Published: July 2022

The internal hydraulic properties of plants are difficult to measure but may be inferred from observable sap flow.
Disease progression, treatments, hospitalization, and clinical outcomes in acute GVHD: a multicenter chart review
Authors: Holtan Shernan G. , Yu Jingbo , Choe Hannah K. , Paranagama Dilan , Tang Jackson , Naim Ahmad , Galvin John , Joachim Deeg H.
Published: July 2022

Acute graft-versus-host disease (GVHD) remains a barrier to successful allogeneic hematopoietic cell transplantation (HCT) outcomes. This multicenter, retrospective chart review describes disease progression, treatment patterns, hospitalizations, and clinical outcomes among 475 patients (≥12 years old) who developed grades II–IV acute GVHD after their first HCT (January 2014–June 2016). Median (interquartile range) age at HCT was 55 (44–63) years. From the date of acute GVHD diagnosis, 190 patients (40.0%) experienced progression to more severe disease and/or developed new organ involvement. Among 431 patients with grades II–IV acute GVHD at diagnosis, 73.1% received first-line systemic corticosteroids. During follow-up (median 524 days since acute GVHD diagnosis), 23.4% of patients had an increase in steroid dose and 44.4% were unable to taper below 10 mg/day. Over half of patients (54.9%) required ≥1 hospital readmission within 100 days post-HCT (≥2 readmissions in 22.3%); mean inpatient length of stay upon readmission was 27.5 days. Approximately half of patients (52.8%) died during follow-up; 1-year overall mortality from date of acute GVHD diagnosis and nonrelapse mortality rates were 35.2% and 25.5%, respectively. Overall, patients who developed acute GVHD following HCT had poor clinical outcomes, highlighting the unmet need for early and effective treatment strategies.
Direct force measurement of microscopic droplets pulled along soft surfaces
Authors: Khattak Hamza K. , Karpitschka Stefan , Snoeijer Jacco H. , Dalnoki-Veress Kari
Published: July 2022

When a droplet is placed on a soft surface, surface tension deforms the substrate, creating a capillary ridge. We study how the motion of the ridge dissipates energy in microscopic droplets. Using a micropipette based method, we are able to simultaneously image and measure forces on a microscopic droplet moving at a constant speed along a soft film supported on a rigid substrate. Changing the thickness of the thin film tunes the effective stiffness of the substrate. Thus we can control the ridge size without altering the surface chemistry. We find that the dissipation depends strongly on the film thickness, decreasing monotonically as effective stiffness increases. This monotonic trend is beyond the realm of small deformation theory, but can be explained with a simple scaling analysis.
Structure-guided and phage-assisted evolution of a therapeutic anti-EGFR antibody to reverse acquired resistance
Authors: Zhuang Xinlei , Wang Zhe , Fan Jiansheng , Bai Xuefei , Xu Yingchun , Chou James J. , Hou Tingjun , Chen Shuqing , Pan Liqiang
Published: July 2022

Acquired resistance to cetuximab in colorectal cancers is partially mediated by the acquisition of mutations located in the cetuximab epitope in the epidermal growth factor receptor (EGFR) ectodomain and hinders the clinical application of cetuximab. We develop a structure-guided and phage-assisted evolution approach for cetuximab evolution to reverse EGFRS492R- or EGFRG465R-driven resistance without altering the binding epitope or undermining antibody efficacy. Two evolved cetuximab variants, Ctx-VY and Ctx-Y104D, exhibit a restored binding ability with EGFRS492R, which harbors the most common resistance substitution, S492R. Ctx-W52D exhibits restored binding with EGFR harboring another common cetuximab resistance substitution, G465R (EGFRG465R). All the evolved cetuximab variants effectively inhibit EGFR activation and downstream signaling and induce the internalization and degradation of EGFRS492R and EGFRG465R as well as EGFRWT. The evolved cetuximab variants (Ctx-VY, Ctx-Y104D and Ctx-W52D) with one or two amino acid substitutions in the complementarity-determining region inherit the optimized physical and chemical properties of cetuximab to a great extent, thus ensuring their druggability. Our data collectively show that structure-guided and phage-assisted evolution is an efficient and general approach for reversing receptor mutation-mediated resistance to therapeutic antibody drugs.
Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy
Authors: Prahl Mary , Golan Yarden , Cassidy Arianna G. , Matsui Yusuke , Li Lin , Alvarenga Bonny , Chen Hao , Jigmeddagva Unurzul , Lin Christine Y. , Gonzalez Veronica J. , Chidboy Megan A. , Warrier Lakshmi , Buarpung Sirirak , Murtha Amy P. , Flaherman Valerie J. , Greene Warner C. , Wu Alan H. B. , Lynch Kara L. , Rajan Jayant , Gaw Stephanie L.
Published: July 2022

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.
Optimization of the 4-anilinoquin(az)oline scaffold as epidermal growth factor receptor (EGFR) inhibitors for chordoma utilizing a toxicology profiling assay platform
Authors: Bieberich Andrew A. , Laitinen Tuomo , Maffuid Kaitlyn , Fatig Raymond O. , Torrice Chad D. , Morris David C. , Crona Daniel J. , Asquith Christopher R. M.
Published: July 2022

The 4-anilinoquin(az)oline is a well-known kinase inhibitor scaffold incorporated in clinical inhibitors including gefitinib, erlotinib, afatinib, and lapatinib, all of which have previously demonstrated activity against chordoma cell lines in vitro. We screened a focused array of compounds based on the 4-anilinoquin(az)oline scaffold against both U-CH1 and the epidermal growth factor receptor (EGFR) inhibitor resistant U-CH2. To prioritize the hit compounds for further development, we screened the compound set in a multiparameter cell health toxicity assay. The de-risked compounds were then screened against a wider panel of patient derived cell lines and demonstrated low micromolar efficacy in cells. We also investigated the properties that gave rise to the toxophore markers, including the structural and electronic features, while optimizing for EGFR in-cell target engagement. These de-risked leads present a potential new therapeutic avenue for treatment of chordomas and new chemical tools and probe compound 45 (UNC-CA359) to interrogate EGFR mediated disease phenotypes.
Deep-sea infauna with calcified exoskeletons imaged in situ using a new 3D acoustic coring system (A-core-2000)
Authors: Mizuno Katsunori , Nomaki Hidetaka , Chen Chong , Seike Koji
Published: July 2022

The deep ocean is Earth’s largest habitable space inhabited by diverse benthic organisms. Infauna play crucial roles in shaping sedimentary structures, relocating organic matter, porewater chemistry, and hence biogeochemical cycles. However, the visualization and quantification of infauna in situ inside deep-sea sediment has been challenging, due to their sparse distribution and that deep-sea cameras do not visualize animals living below the sediment surface. Here, we newly developed a 3D acoustic “coring” system and applied it to visualize and detect burrowing bivalves in deep-sea sediments. The in situ acoustic observation was conducted at a dense colony of vesicomyid clams in a hydrocarbon seep in Sagami Bay, Japan, focusing on a patch of juvenile clams with a completely infaunal life style. We clearly observed strong backscatters from the top and lower edges of animals in our 3D acoustic data. At least 17 reflectors were identified in the survey area (625 cm2), interpreted to correspond to living clams. The estimated depths of the lower edge of clams ranged between 41 and 98 mm. The acoustic system presented here is effective for detecting and monitoring infauna with calcified exoskeletons. This novel tool will help us better assess and understand the distribution of deep-sea infauna, particularly those groups with hard exoskeletons, as well as biogeochemical cycles.
Stochastic consolidation of lifelong memory
Authors: Shaham Nimrod , Chandra Jay , Kreiman Gabriel , Sompolinsky Haim
Published: July 2022

Humans have the remarkable ability to continually store new memories, while maintaining old memories for a lifetime. How the brain avoids catastrophic forgetting of memories due to interference between encoded memories is an open problem in computational neuroscience. Here we present a model for continual learning in a recurrent neural network combining Hebbian learning, synaptic decay and a novel memory consolidation mechanism: memories undergo stochastic rehearsals with rates proportional to the memory’s basin of attraction, causing self-amplified consolidation. This mechanism gives rise to memory lifetimes that extend much longer than the synaptic decay time, and retrieval probability of memories that gracefully decays with their age. The number of retrievable memories is proportional to a power of the number of neurons. Perturbations to the circuit model cause temporally-graded retrograde and anterograde deficits, mimicking observed memory impairments following neurological trauma.
Feeder delivery vehicle scheduling optimization of high-speed railway express based on trunk and branch intermodal transportation
Authors: Cui Yao , Zhou Xiaoye
Published: July 2022

In view of the traditional branch line end express delivery centralized mode cannot adapt to the growing demand of high-speed rail (HSR) express, resulting in poor connection between trunk and branch line, high cost and poor timeliness. In this paper, the problem of scheduling optimization of branch-line flexible distribution vehicles relying on intermodal transportation of trunk and branch lines is proposed. Considering the number of vehicles, vehicle capacity, customer service time window and other constraints, an integer linear programming mathematical model with the minimum total cost of vehicle transportation cost, usage cost and time window penalty cost as the optimization objective is established. A two-level nested heuristic algorithm with two-level coding structure is proposed to solve the problem. Finally, a simulation example is given to verify the effectiveness of the model and the algorithm. The results show that the vehicle scheduling optimization problem studied in this paper can effectively improve the timeliness and accuracy of HSR express delivery, and can significantly reduce the total vehicle delivery cost.
Maximize the use of municipal waste generated by the hydrogen peroxide industry in the production of high-quality refractory CAC
Authors: Amer Ahmed I. H. , El-Maddah A. A. , Abuelela Ahmed M. , Ahmed Y. M. Z. , Hassan Ali M. , El-Amir Ahmed A. M.
Published: July 2022

High-grade calcium aluminate cement (CAC) has been successfully synthesized from municipal alumina waste and limestone under mild reaction conditions. Mineralogical composition and microstructure of the sintered mixes were investigated using X-ray diffraction and FESEM; valuable cementing phases such as CA, CA2, and C12A7 were observed in addition to the C3A phase that was detected in the mixes with high CaCO3 content. Mix CA60 containing 60 wt% alumina waste has achieved the best sinterability (less than 1 vol% porosity) and the highest densification (~ 2.65 g/cm3 bulk density) at 1450 °C. Densification, cold-crushing strength (CCS), and microstructure of the hydrated cement samples (From Mix CA60) were investigated. The cast cement specimens revealed better density and CCS characteristics (63.1 and 74 MPa at 7 and 28 days, respectively) in comparison with the commercial cement. Conventional castables (5 × 5 × 5 cm3) were prepared from mixtures composed of 15 wt% cement and 85 wt% aggregates (40% Al2O3), where CA60 and commercial cement were used to compare the effect of the manufactured CA60 cement with the commercial one. The castables prepared with CA60 cement have shown a higher strength at 110 °C with 4.5 MPa when compared to the commercial CAC at the same temperature (1.8 MPa). Accordingly, this study contributes not only to preserving the environment from the accumulation of industrial wastes but also to valorizing and adding value to these wastes.
Stable isotopes unveil one millennium of domestic cat paleoecology in Europe
Authors: Krajcarz Magdalena , Van Neer Wim , Krajcarz Maciej T. , Popović Danijela , Baca Mateusz , De Cupere Bea , Goffette Quentin , Küchelmann Hans Christian , Gręzak Anna , Iwaszczuk Urszula , Ottoni Claudio , Van de Vijver Katrien , Wilczyński Jarosław , Mulczyk Anna , Wiejacki Jan , Makowiecki Daniel , Bocherens Hervé
Published: July 2022

The domestic cat is the world's most popular pet and one of the most detrimental predators in terrestrial ecosystems. Effective protection of wildlife biodiversity demands detailed tracking of cat trophic ecology, and stable isotopes serve as a powerful proxy in dietary studies. However, a variable diet can make an isotopic pattern unreadable in opportunistic predators. To evaluate the usefulness of the isotopic method in cat ecology, we measured C and N isotope ratios in hundreds of archaeological cat bones. We determined trends in cat trophic paleoecology in northern Europe by exploiting population-scale patterns in animals from diverse locations. Our dataset shows a high variability of isotopic signals related to the socio-economic and/or geomorphological context. This points toward regularities in isotopic patterns across past cat populations. We provide a generalized guide to interpret the isotopic ecology of cats, emphasizing that regional isotopic baselines have a major impact on the isotopic signal.
A multicenter study to compare the effectiveness of the inpatient post acute care program versus traditional rehabilitation for stroke survivors
Authors: Chang Ke-Vin , Chen Kai-Hua , Chen Ying-Hsun , Lien Wei-Chih , Chang Wei-Han , Lai Chung-Liang , Wu Cheng-Che , Chen Chia-Hsin , Chen Yu-Hsin , Wu Wei-Ting , Wang Tyng-Guey , Han Der-Sheng
Published: July 2022

There is insufficient evidence to prove the effect of the Post-acute Care (PAC) program on post-stroke recovery. This study aimed to determine the effectiveness of the PAC versus traditional inpatient rehabilitation (non-PAC) for middle- and old-aged stroke survivors. This multicenter cohort study enrolled 334 stroke patients admitted for post-stroke rehabilitation. The outcome variables included the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment-Short Form (MNA-SF), EuroQoL-5D (EQ-5D), Lawton–Brody Instrumental Activities of Daily Living (ADL) Scale, and Mini-Mental State Examination (MMSE). The inverse-probability-of-treatment-weighting method was used to analyze the differences in outcomes between the PAC and non-PAC groups. The PAC group showed better improvements in BI, MNA-SF, EQ-5D, Instrumental ADL, and MMSE compared to the non-PAC group, with differences in effect sizes of 0.54 (95% confidence interval [CI] 0.38–0.71), 0.26 (95% CI 0.10–0.42), 0.50 (95% CI 0.33–0.66), 0.44 (95% CI 0.28–0.60) and 0.34 (95% CI 0.17–0.50), respectively. The PAC project showed more improvement in basic and instrumental ADL and status of swallowing, nutrition, and cognition than those of non-PAC, which had less length of stay restricted by the National Health Insurance. More studies are warranted to investigate the influence of hospital stay and duration from stroke onset on the PAC’s effectiveness.
A comparison of IOLMaster 500 and IOLMaster 700 in the measurement of ocular biometric parameters in cataract patients
Authors: Jiang Jianhong , Pan Xiaojing , Zhou Mingming , Wang Xiaoyun , Zhu Hai , Li Dongfang
Published: July 2022

To compare the agreement of ocular biometric parameters measured by IOLMaster 500 and IOLMaster 700. This is a prospective study. IOLMaster 500 and IOLMaster 700 were used to measure the axial eye length (AL), corneal flat keratometry (Kf), corneal steep keratometry (Ks), mean keratometry (Km), corneal astigmatism(CA), J0, J45, anterior chamber depth (ACD) and corneal horizontal diameter (white-to-white distance, WTW) of 518 eyes (392 patients) with cataracts. Patients were enrolled unilaterally. Subgroup analyses were done according to the AL and Km. The intraclass correlation coefficient (ICC) and Bland–Altman analysis were used to evaluate the agreement. A total of 275 eyes were analyzed. The 95% confidence interval of ICC of the mean AL, Ks, Kf, Km, J0, and ACD values measured by the two instruments are indicative of excellent reliability (P < 0.001). The measurement results of WTW show good reliability (P < 0.001). The ICC of CA is of good reliability in CA < 0.5 D group (P = 0.000) and moderate reliability in the other two groups (P = 0.000). The WTW is the widest range among 95% consistency of the limit range measured by the two instruments. The results of IOLMaster 500 and IOLMaster 700 in measuring AL, keratometry, and ACD in cataract patients are of high agreement.
Comparison of sensory outcomes in patients with successful motor outcome versus recurrent exotropia after surgery for intermittent exotropia
Authors: Joo Hye Jun , Choi Jin Ju , Ro Jin Woo , Choi Dong Gyu
Published: August 2022

Here, we compared sensory outcomes between patients with successful motor outcomes and recurrent exotropia after intermittent exotropia surgery. We retrospectively analyzed 303 patients who underwent surgery for intermittent exotropia, divided into two groups: successful motor outcome defined as an alignment between 10 prism diopters (PD) exodeviation and 5PD esodeviation at the final follow-up (Group A, n = 177) and residual or recurrent exotropia defined as exodeviation > 10 PD (Group B, n = 126). Preoperative and postoperative (at final visit) sensory outcomes were compared using the Titmus stereotest and distance Worth 4-dot test. Stereoacuity significantly improved postoperatively in both successful motor outcome group (Group A) and residual or recurrent exotropia group (Group B). However, stereoacuity did not differ between groups preoperatively and postoperatively. On the other hand, fusion rates for the Worth 4-dot test were significantly higher in group A than in group B, preoperatively and postoperatively, and significantly increased postoperatively only in group A. Therefore, the distance Worth 4-dot test may be useful for evaluating postoperative prognosis and preoperative sensory status.
Production of pine sawdust biochar supporting phosphate-solubilizing bacteria as an alternative bioinoculant in Allium cepa L., culture
Authors: Blanco-Vargas Andrea , Chacón-Buitrago María A. , Quintero-Duque María C. , Poutou-Piñales Raúl A. , Díaz-Ariza Lucía A. , Devia-Castillo Carlos A. , Castillo-Carvajal Laura C. , Toledo-Aranda Daniel , da Conceição de Matos Christiano , Olaya-González Wilmar , Ramos-Monroy Oswaldo , Pedroza-Rodríguez Aura M.
Published: July 2022

We produced and characterised biochar made from Caribbean pine sawdust as raw material. The biochar (BC500) was used as biocompatible support to co-inoculate phosphate solubilizing bacteria (PSB) (BC500/PSB) on Allium cepa L., plants at a greenhouse scale for four months. The three biomaterials study included proximate analysis, elemental analysis, aromaticity analysis, scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), adsorption studies at different pH and PSB stability as a function of time. The results indicated that BC500 is suitable as organic support or solid matrix to maintain the viability of PSB able to solubilise P from phosphate rock (PR). The biofertilizer (BC500/PSB) allows increasing germination, seedling growth, nutrient assimilation, and growth of Allium cepa L., because PSB immobilised on BC500 promoted nutrient mobilisation, particularly P, during cultivation of Allium cepa L., at pots scale. The two treatments to evaluate the biofertilizer (BC500/PSB) showed the highest concentrations of total P with 1.25 ± 0.13 and 1.38 ± 0.14 mg bulb−1 in A. cepa L. This work presents the benefits of a new product based on bacteria naturally associated with onion and an organic material (BC500) serving as a bacterial carrier that increases the adsorption area of highly reactive nutrients, reducing their leaching or precipitation with other nutrients and fixation to the solid matrix of the soil.