bluuebunny/crossref_metadata_2025 huggingface dataset:
A Capstone Laboratory theme investigating properties of non‐steroidal anti‐inflammatory drugs and their solubilization by cationic surfactant micelles
Authors: Roach Jimmy D. , Nauman Areej , Mahmud Shamin , Chaari Ali , Bondaruk Mandy
Published: January 2022

Research experience is becoming an increasingly crucial element of today's undergraduate science curriculum. In recent years, the establishment of the Course‐Based Undergraduate Research Experience Network (CUREnet) has provided a framework for the development of courses aiming to cultivate students' proficiency in undergraduate research techniques while fostering scientific curiosity in a laboratory setting. Capstone Laboratory is one such course that was designed to provide second‐year pre‐medical students at Weill Cornell Medicine‐Qatar with exposure to laboratory techniques to develop their repertoire of research skills. For the past 3 years, Capstone Laboratory has incorporated a project‐based learning component involving non‐steroidal anti‐inflammatory drugs (NSAIDs). The research element of the NSAID‐surfactant theme investigated the partitioning of various drugs into cationic surfactant micelles. Structural elements and enzyme inhibition characteristics of NSAIDs were also investigated, while integrating principles of biochemistry, general chemistry, and experimental organic chemistry. By studying drug properties in these contexts, students integrate their learning and develop skills needed for the study and practice of medicine.
Characterization of m6A regulator‐mediated methylation modification patterns and tumor microenvironment infiltration in acute myeloid leukemia
Authors: Han Shiyu , Qi Jiaqian , Fang Kun , Wang Hong , Tang Yaqiong , Wu Depei , Han Yue
Published: January 2022

Background

Previous studies have confirmed the existence of epigenetic regulation of immune responses in acute myeloid leukemia. However, the potential role of RNA N6‐methyladenosine (m6A) remodeling in tumor microenvironment (TME) infiltration remains unclear.

Methods and Materials

m6A patterns of 469 AML patients (420 of which provided survival data) based on 18 m6A regulators were systematically evaluated. Based on the expression of 18 m6A regulators, unsupervised agglomerative cluster analysis was applied to recognize the various m6A modification types and to classify patients. We linked these patterns to TME infiltration characteristics and identified three distinct populations of m6A modifications.

Results

These three TME cell infiltration patterns are characterized by a high degree of concordance with the three tumor immunophenotypes, which include immunoinflammatory, immunorejection, and immune inert patterns. We showed that assessment of m6A modification patterns within individually neoplasms can forecast the stage of neoplasmic inflammation, TME basal activity, subtype, hereditary mutation, and clinical patient prognosis. Limited low m6Ascore, featuring increased mutational load and immune activation, indicates an inflammatory phenotype of TME with a 5‐year survival rate at 14.4% compared to the high‐m6Ascore group (40.9%).

Conclusions

Data from two different cohorts demonstrated that a higher m6Ascore showed a marked therapeutic superiority as well as clinical advantage. Assessing m6A modification patterns in AML patients could improve our knowledge of the TME infiltrative profile as well as directing effective immunotherapeutic approaches.
Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma
Authors: Su Cheng , Huang Rongzhi , Yu Zhenyuan , Zheng Jie , Liu Fengling , Liang Haiqi , Mo Zengnan
Published: January 2022

Nephroblastoma, also known as Wilms' tumor (WT), is the most common renal tumor that occurs in children. Although the efficacy of treatment has been significantly improved by a series of comprehensive treatments, some patients still have poor prognosis. Myelin and lymphocyte (MAL) protein, a highly hydrophobic integrated membrane‐bound protein, has been implicated in many tumors and is also closely linked to kidney development. However, the relationship between MAL and WT has not yet been elucidated. Therefore, we attempted to evaluate the feasibility of MAL as a promising prognosis factor for WT. The differential expression of MAL was investigated using TARGET database and was verified using the Gene Expression Omnibus database and real‐time quantitative PCR. The prognostic ability of MAL was determined using Kaplan–Meier and Cox regression analyses. Pearson correlation analysis was applied to explore the relationship between MAL expression and methylation sites. The ESTIMATE and CIBERSORT algorithms showed that MAL expression was associated with the WT tumor microenvironment. Gene Set Enrichment Analysis (GSEA) indicated that multiple signaling pathways closely associated with tumorigenesis were differentially enriched between the high‐ and low‐MAL groups. In conclusion, our study comprehensively explored the potential of MAL as a prognosis factor for WT. Meanwhile, we also demonstrated that MAL, as a prognostic factor for WT, may be closely related to the tumor microenvironment.
Protective Effects of Chrysin against Cyclophosphamide‐Induced Cardiotoxicity in Rats: A Biochemical and Histopathological Approach
Authors: Ye Bin , Ling Wenchao , Wang Yinhua , Jaisi Amit , Olatunji Opeyemi Joshua
Published: January 2022

Mounting evidences have indicated that cyclophosphamide (CyC)a potent anticancer and cytotoxic agent is associated with various organ and systemic toxicities and the cytotoxic effects observed after administration of CyC still challenges its clinical use. Chrysin (Chy) is a dietary flavonoid with prevailing antioxidant and anti‐inflammatory properties. This study evaluated the protective properties of Chy against CyC‐induced cardiotoxicity in rats. The animals were orally treated with Chy (25 and 50 mg/kg/day) for 35 days and exposed to CyC (i. p., 100 mg/kg) once a week for four weeks. The results indicated that CyC caused significant cardiotoxicity as manifested by notable increases in heart weight, cardiac function biomarkers such as lactate dehydrogenase (LDH), creatine kinase‐MB (CK‐MB), troponin T and aspartate transaminase (AST). In addition, cardiac malondialdehyde (MDA), tumor necrosis factor alpha (TNF‐α), interleukin 1β (IL1 β) and interleukin 6 (IL‐6) levels were considerably increased. Meanwhile, cardiac antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase (CAT), as well as glutathione (GSH) level were suppressed, while H&E stained histopathological assessment showed marked alterations in cardiac tissues. CyC also significantly lowered red blood cells (RBC) and white blood cells (WBC) parameters, whereas treatment with Chy significantly restored the altered biochemical and histopathological features. Conclusively, aforementioned results inferred that Chy offered cardioprotective potentials against CyC‐induced cardiotoxicity which may be due to its antioxidant, and anti‐inflammatory properties.
Androgen downregulates desmocollin‐2 in association with induction of mesenchymal transition of breast MDA‐MB‐453 cancer cells
Authors: Ahram Mamoun , Abdullah Mohammad S. , Mustafa Shahed A. , Alsafadi Dana B. , Battah Abdelkader H.
Published: January 2022

Desmosomes are cellular structures that are critical in cell–cell adhesion and in maintaining tissue architecture. Changes in the expression of desmocollin‐2 (DSC2) have been noted during tumor progression into an invasive phenotype and as cells undergo epithelial‐mesenchymal transition. We have previously reported that breast MDA‐MB‐453 cancer cells, a luminal androgen receptor (AR) model of triple‐negative breast cancer, acquire mesenchymal features when treated with the AR agonist, dihydrotestosterone (DHT). We have therefore investigated androgen regulation of the expression and cellular localization of DSC2 in MDA‐MB‐453 cells. Treatment of the cells with DHT resulted in a dose‐dependent reduction in DSC2 protein levels and dispersion of its membrane localization concomitant with AR‐ and β‐catenin‐mediated mesenchymal transition of cells. A significant correlation was revealed between decreased expression of AR and increased expression of DSC2 in patient samples. In addition, whereas lower expression of AR was associated with a reduced overall and recurrence‐free survival of breast cancer patients, higher expression of DSC2 was found in invasive breast tumors than in normal breast cells and was correlated with lower patient survival. Upon knocking down DSC2, the cells became elongated, mesenchymal‐like, and slightly, but insignificantly, more migratory. The addition of DHT further stimulated cell elongation and migration. DSC2 siRNA‐transfected cells reverted to a normal epithelial morphology upon inhibition of β‐catenin. These results highlight the role of DSC2 in maintaining the epithelial morphology of MDA‐MB‐453 cells and the negative regulation of the desmosomal protein by DHT during stimulation of the androgen‐induced, β‐catenin‐mediated mesenchymal transition of the cells.
Analyzing Catalytic Co‐operativity and Membrane Parameters in a Substrate‐driven Vesicular Assembly Modified by Nucleotides
Authors: Priyanka  , Kaur Brar Surinder , Maiti Subhabrata
Published: January 2022

Rationalizing changes in functional properties by an exogenous module in a synthetic nanoscale self‐organized system has broader significance in designing responsive biomimic materials having application in catalysis to therapeutics. Herein, we have developed a substrate‐driven nanoscale vesicular assembly of a metallosurfactant (with dipicolylamine co‐ordinated with zinc ion as headgroup) which simultaneously acts as a cooperative catalyst for the hydrolysis of the RNA‐model substrate, 2‐hydroxypropyl‐4‐nitrophenylphosphate (HPNPP). We have found out that both purine and pyrimidine‐based nucleoside monophosphates interact differently with the assembly, modulating the rate of catalytic cleavage. The different means of recognition of the nucleobases leads to alteration in membrane fluidity as well as surface charge of the vesicular aggregates whether the assembly is in catalytically active or inactive state. Then a systematic pattern for different nucleotides mediated vesicular nanoscale assembly composed of a catalytically‐active surfactant by statistically corelating alteration in dynamic membrane parameters (fluidity, surface charge) with its co‐operative phosphodiester hydrolyzing ability has been generated using principal component analysis as statistical tool. Overall, it showed a unique response pathway of a co‐operative functional assembly to different exogenous modules, and this perception of the deconvolution of collective property opens up an avenue for future development of advanced adaptive systems.
Electrically Induced Underwater Superaerophilicity/Superaerophobicity Switching on Polypyrrole‐Coated Mesh Films for Selective Bubble Permeation
Authors: Wang Ruijie , Liu Pengchang , Yu Xiaoyan , Sun Xinchao , Lai Hua , Cheng Zhongjun
Published: January 2022

Recently, materials with controllable superwettability have attracted much attention. However, almost all studies focused on controlling wetting of water and oil; research on underwater gas bubble wetting control is still rare. Herein, we report a mesh film prepared by coating polypyrrole (PPy) film on Ti mesh. Briefly, the film mesh is underwater superaerophilic when PPy is doped with perfluorooctanesulfonate ions (PFOS−), and becomes underwater superaerophobic as the PFOS− are removed. The transition of the wettability can be triggered by electrical stimuli, which is attributed to the cooperative effect between the rough structure and chemical components variation. The controllable wettability allows adjustable bubble permeation. It can be envisioned that the film will provide potential applications in the future, such as underwater bubble capture/release and microfluidic devices.
Stage‐Specific Generation of Human Pluripotent Stem Cell Derived Lung Models to Measure CFTR Function
Authors: Ngan Shuk Yee , Quach Henry T. , Laselva Onofrio , Huang Elena N. , Mangos Maria , Xia Sunny , Bear Christine E. , Wong Amy P.
Published: January 2022

Human embryonic stem cells (ES) and induced pluripotent stem cells (iPSC) are powerful tools that have the potential to generate in vitro human lung epithelial cells. However, challenges in efficiency and reproducibility remain in utilizing the cells for therapy discovery platforms. Here, we optimize our previously published protocols to efficiently generate three developmental stages of the lung model (fetal lung epithelial progenitors, fLEP; immature airway epithelial spheroid, AES; air‐liquid interface culture, ALI), and demonstrate its potential for cystic fibrosis (CF) drug discovery platforms. The stepwise approach directs differentiation from hPSC to definitive endoderm, anterior ventral foregut endoderm, and fetal lung progenitor cells. The article also describes the generation of immature airway epithelial spheroids in Matrigel with epithelial cells sorted by a magnetic‐activated cell sorting system, and the generation of adult‐like airway epithelia through air‐liquid interface conditions. We demonstrate that this optimized procedure generates remarkably higher cystic fibrosis transmembrane conductance regulator (CFTR) expression and function than our previous method, and thus is uniquely suitable for CF research applications. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: hESC/hiPSC differentiation to fetal lung progenitors

Basic Protocol 2: Formation of airway epithelial spheroids

Alternate Protocol 1: Cryopreservation of airway epithelial spheroids

Basic Protocol 3: Differentiation and maturation in air‐liquid interface culture

Alternate Protocol 2: Differentiation and maturation of epithelial progenitors from airway epithelial spheroids in ALI culture
Employee‐oriented corporate social responsibility, innovation, and firm value
Authors: Suto Megumi , Takehara Hitoshi
Published: January 2022

This study investigates whether and how non‐pecuniary employee rewards based on corporate social responsibility (CSR) in association with human resource management (HRM) affect firm value. In the context of Japanese manufacturing firms for the 2006–2019 period, the regression results provide several important findings. Non‐pecuniary rewards work individually and synergistically with pecuniary rewards to enhance employee motivations for innovation, through which the CSR‐HRM nexus increases firm value. However, non‐employee perception of employee‐oriented CSR negatively moderates the relationship between innovation and firm market value. In the Japanese market, investors are fully aware about the CSR‐HRM effect on employee motivations and highly concerned with risk due to conflicts of interest between employees and non‐employee stakeholders. This suggests the importance of stakeholder engagement to link organizational innovation capability with firm value. These findings provide useful implications for the alignment of CSR strategies with HRM policies for optimizing innovation performance for corporate sustainable development.
Eating disorder related research using Amazon Mechanical Turk (MTurk): Friend or foe?: Commentary on Burnette et al. (2021)
Authors: Vogel Matthias , Krüger Julia , Junne Florian
Published: January 2022

Burnette et al. reported a study that they sought to undertake to validate common eating disorder questionnaires in sexual and gender minorities. The researchers took advantage of the online recruitment platform Amazon Mechanical Turk (MTurk). Contrary to their expectations, the study proved not feasible due to invalid answering. Thus, Burnette et al. raise concerns against the trustworthiness of crowd‐sourced data that may be undermined by financial interests and other kinds of motivations. Our commentary highlights the potential of the COVID‐19 pandemic to inflate especially those intentions, which are monetary. Against the background of the COVID‐19 pandemic, a further problem seems to be that the anonymity of online crowd sourcing platforms might tempt participants to provide inconsistent answers, possibly reflecting tendencies of reactance. The reported pattern of paradoxical responses in Burnette et al.'s work does not reflect malingering; rather we believe that the study might have served some participants as an outlet for negative emotions. We discuss mechanisms of quality control and highlight the lack of interpersonal interaction associated with online data collections.
Iridium‐based electrocatalysts toward sustainable energy conversion
Authors: Huang Bo , Zhao Yulong
Published: January 2022

Electrocatalysis is an important branch in electrochemistry and also has a significant position in energy storage/conversion. Iridium (Ir)‐based electrocatalysts show promise because of the inherent redox property. Considering the abundance and expensive cost of such noble metal, significant efforts have been made to rationally improve the electrochemical performance of Ir‐based electrocatalysts during these years from the viewpoints of structural design and kinetic analysis. Most of the reports may aim to achieve high Ir atomic utilization with more exposed active sites, and both high electrochemical activity and durable stability are expected. In this case, Ir‐based single atoms, nanostructures, and composites are reported with various electrocatalytic applications of water splitting (involving hydrogen evolution and oxygen evolution reaction) and other electrocatalytic oxidation reactions (involving hydrogen oxidation reaction, methanol oxidation reaction, ammonia oxidation reaction, and formic acid oxidation reaction) as well as other electrocatalytic reduction reactions (involving oxygen reduction reaction, carbon dioxide reduction reaction, and nitrogen reduction reaction). These works deserve to be discussed and this review article comprehensively summarized the most significant reports. We analyzed Ir‐based electrocatalysts from the viewpoints of synthesis, structure, electrochemical property, and reaction mechanism. The challenges and outlooks in the future were also provided from the aspects of fundamental studies and industrial applications, which may attract more attention and provide new insight into the design of advanced Ir‐based electrocatalysts with high performance.

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Experimental investigation of stable the proton exchange membrane fuel cell control using magnetic sensor probes
Authors: Akimoto Yutaro , Izawa Yuta , Suzuki Shin‐nosuke , Okajima Keiichi
Published: January 2022

In proton exchange membrane fuel cells (PEMFCs), the avoidance and detection of failures such as flooding and dry‐out are crucial. Non‐destructive measurement approaches using magnetic sensors have been developed for this purpose. To reduce the number of sensors required to be installed in a PEMFC system for evaluation, we propose a control method for PEMFCs using the magnetic flux density as an index. The proposed method determines the failure conditions by calculating a simple current mapping with a reduced number of sensors. The results of four‐point magnetic flux densities under failure conditions and stable control using two‐point measurement indices are presented.
MAC2 is a long‐lasting marker of peripheral cell infiltrates into the mouse CNS after bone marrow transplantation and coronavirus infection
Authors: Hohsfield Lindsay A. , Tsourmas Kate I. , Ghorbanian Yasamine , Syage Amber R. , Jin Kim Sung , Cheng Yuting , Furman Susana , Inlay Matthew A. , Lane Thomas E. , Green Kim N.
Published: January 2022

Microglia are the primary resident myeloid cells of the brain responsible for maintaining homeostasis and protecting the central nervous system (CNS) from damage and infection. Monocytes and monocyte‐derived macrophages arising from the periphery have also been implicated in CNS pathologies, however, distinguishing between different myeloid cell populations in the CNS has been difficult. Here, we set out to develop a reliable histological marker that can assess distinct myeloid cell heterogeneity and functional contributions, particularly in the context of disease and/or neuroinflammation. scRNAseq from brains of mice infected with the neurotropic JHM strain of the mouse hepatitis virus (JHMV), a mouse coronavirus, revealed that Lgals3 is highly upregulated in monocyte and macrophage populations, but not in microglia. Subsequent immunostaining for galectin‐3 (encoded by Lgals3), also referred to as MAC2, highlighted the high expression levels of MAC2 protein in infiltrating myeloid cells in JHMV‐infected and bone marrow (BM) chimeric mice, in stark contrast to microglia, which expressed little to no staining in these models. Expression of MAC2 was found even 6–10 months following BM‐derived cell infiltration into the CNS. We also demonstrate that MAC2 is not a specific label for plaque‐associated microglia in the 5xFAD mouse model, but only appears in a distinct subset of these cells in the presence of JHMV infection or during aging. Our data suggest that MAC2 can serve as a reliable and long‐lasting histological marker for monocyte/macrophages in the brain, identifying an accessible approach to distinguishing resident microglia from infiltrating cells in the CNS under certain conditions.
Locational boundness of resource, compatibility of production, and downside risks of multinationality
Authors: Song Sangcheol
Published: January 2022

Research Summary

We extend the multinational operational flexibility literature by examining how the characteristics of resources and capabilities within a portfolio of international investments affect its downside risks. We postulate that non‐location bound resources and capabilities within an international investment portfolio are crucial to reducing switching costs and enhancing cross‐country switchability, thus curbing downside risks. Our large sample of Korean multinational corporations reveals that globally sourced production inputs or more technological capabilities help curb downside risks, while locally sourced inputs or more marketing capabilities do not. We additionally find that the positive effect of less locational boundness is more salient when the portfolio has a high product relatedness or standardization.

Managerial Summary

This study provides some managerial implications for international business managers. The findings suggest that the downside risk reduction effect of multinationality varies by heterogeneous resource and production conditions. They indicate that the locational boundness embedded in marketing capability, technological capability, and product type affects cross‐border switchability. IB managers make strategic decisions on resource and product types for their overseas manufacturing subsidiaries in the configuration and coordination processes of their internationalization to maximize multinational operational flexibility. A more effective alignment of resources and capabilities with the strategic intent of boosting geographic fungibility facilitates effective production shifts within the same production network.
Automatic brain segmentation in preterm infants with post‐hemorrhagic hydrocephalus using 3D Bayesian U‐Net
Authors: Largent Axel , De Asis‐Cruz Josepheen , Kapse Kushal , Barnett Scott D. , Murnick Jonathan , Basu Sudeepta , Andersen Nicole , Norman Stephanie , Andescavage Nickie , Limperopoulos Catherine
Published: January 2022

Post‐hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH) in very preterm infants. PHH monitoring and treatment decisions rely heavily on manual and subjective two‐dimensional measurements of the ventricles. Automatic and reliable three‐dimensional (3D) measurements of the ventricles may provide a more accurate assessment of PHH, and lead to improved monitoring and treatment decisions. To accurately and efficiently obtain these 3D measurements, automatic segmentation of the ventricles can be explored. However, this segmentation is challenging due to the large ventricular anatomical shape variability in preterm infants diagnosed with PHH. This study aims to (a) propose a Bayesian U‐Net method using 3D spatial concrete dropout for automatic brain segmentation (with uncertainty assessment) of preterm infants with PHH; and (b) compare the Bayesian method to three reference methods: DenseNet, U‐Net, and ensemble learning using DenseNets and U‐Nets. A total of 41 T2‐weighted MRIs from 27 preterm infants were manually segmented into lateral ventricles, external CSF, white and cortical gray matter, brainstem, and cerebellum. These segmentations were used as ground truth for model evaluation. All methods were trained and evaluated using 4‐fold cross‐validation and segmentation endpoints, with additional uncertainty endpoints for the Bayesian method. In the lateral ventricles, segmentation endpoint values for the DenseNet, U‐Net, ensemble learning, and Bayesian U‐Net methods were mean Dice score = 0.814 ± 0.213, 0.944 ± 0.041, 0.942 ± 0.042, and 0.948 ± 0.034 respectively. Uncertainty endpoint values for the Bayesian U‐Net were mean recall = 0.953 ± 0.037, mean  negative predictive value = 0.998 ± 0.005, mean accuracy = 0.906 ± 0.032, and mean AUC = 0.949 ± 0.031. To conclude, the Bayesian U‐Net showed the best segmentation results across all methods and provided accurate uncertainty maps. This method may be used in clinical practice for automatic brain segmentation of preterm infants with PHH, and lead to better PHH monitoring and more informed treatment decisions.
“An antibiotic turned contraceptive”: The tale of ampicillin‐cloxacillin
Authors: Iheanacho Chinonyerem O.
Published: January 2022

Antibiotic misuse is a major public health threat globally, requiring active efforts toward halting its progression. The African sub‐region is worst hit by communicable diseases, and also possesses weak health systems to effectively combat the menace of antimicrobial resistance. Meanwhile, antibiotics are among the most regularly misused medicines in Nigeria, particularly for inappropriate indication and duration. This is seen in its use as a contraceptive by young women in the country. This paper evaluates the reliance and use of an antibiotic for contraception, a practice that has continuously being a large source of antibiotic misuse in Nigeria. Its causes and effects are also evaluated in this commentary. To effectively combat the increasing antimicrobial misuse, correct use of antibiotics for their appropriate indications is highly essential. Adequate knowledge of contraception should be ensured among young women in developing countries, particularly in Nigeria.
Isolating forest process effects on modelled snowpack density and snow water equivalent
Authors: Bonner Hannah M. , Raleigh Mark S. , Small Eric E.
Published: January 2022

Understanding how the presence of a forest canopy influences the underlying snowpack is critical to making accurate model predictions of bulk snow density and snow water equivalent (SWE). To investigate the relative importance of forest processes on snow density and SWE, we applied the SUMMA model at three sites representing diverse snow climates in Colorado (USA), Oregon (USA), and Alberta (Canada) for 5 years. First, control simulations were run for open and forest sites. Comparisons to observations showed the uncalibrated model with NLDAS‐2 forcing performed reasonably. Then, experiments were completed to isolate how forest processes affected modelled snowpack density and SWE, including: (1) mass reduction due to interception loss, (2) changes in the phase and amount of water delivered from the canopy to the underlying snow, (3) varying new snow density from reduced wind speed, and (4) modification of incoming longwave and shortwave radiation. Delivery effects (2) increased forest snowpack density relative to open areas, often more than 30%. Mass effects (1) and wind effects (3) decreased forest snowpack density, but generally by less than 6%. The radiation experiment (4) yielded negligible to positive effects (i.e., 0%–10%) on snowpack density. Delivery effects on density were greatest at the warmest times in the season and at the warmest site (Oregon): higher temperatures increased interception and melted intercepted snow, which then dripped to the underlying snowpack. In contrast, mass effects and radiation effects were shown to have the greatest impact on forest‐to‐open SWE differences, yielding differences greater than 30%. The study highlights the importance of delivery effects in models and the need for new types of observations to characterize how canopies influence the flux of water to the snow surface.
Coaxial 3D bioprinting of tri‐polymer scaffolds to improve the osteogenic and vasculogenic potential of cells in co‐culture models
Authors: Shahabipour Fahimeh , Tavafoghi Maryam , Aninwene George E. , Bonakdar Shahin , Oskuee Reza Kazemi , Shokrgozar Mohammad Ali , Potyondy Tyler , Alambeigi Farshid , Ahadian Samad
Published: January 2022

The crosstalk between osteoblasts and endothelial cells is critical for bone vascularization and regeneration. Here, we used a coaxial 3D bioprinting method to directly print an osteon‐like structure by depositing angiogenic and osteogenic bioinks from the core and shell regions of the coaxial nozzle, respectively. The bioinks were made up of gelatin, gelatin methacryloyl (GelMA), alginate, and hydroxyapatite (HAp) nanoparticles and were loaded with human umbilical vascular endothelial cells (HUVECs) and osteoblasts (MC3T3) in the core and shell regions, respectively. Conventional monoaxial 3D bioprinting was used as a control method, where the hydrogels, HAp nanoparticles, MC3T3 cells, and HUVECs were all mixed in one bioink and printed from the core nozzle. As a result, the bioprinted scaffolds were composed of cell‐laden fibers with either a core‐shell or homogenous structure, providing a non‐contact (indirect) or contact (direct) co‐culture of MC3T3 cells and HUVECs, respectively. Both structures supported the 3D culture of HUVECs and osteoblasts over a long period. The scaffolds also supported the expression of osteogenic and angiogenic factors. However, the gene expression was significantly higher for the core‐shell structure than the homogeneous structure due to the well‐defined distribution of osteoblasts and endothelial cells and the formation of vessel‐like structures in the co‐culture system. Our results indicated that the coaxial bioprinting technique, with the ability to create a non‐contact co‐culture of cells, can provide a more efficient bioprinting strategy for printing highly vascularized and bioactive bone structures.
Environmental cue difference and training duration modulate spatial learning and cue preference in detour task
Authors: Sun Hua‐Ying , Wang Jian‐Hong , Li Lan‐Jiang , Liu Xiao‐Fen , Che Yi , Ma Yuan‐Ye
Published: January 2022

In this study, we investigated how different environmental cue and the proficiency of body motion influenced detour learning behaviour and cue preference in cue conflict situations. Domestic chicks were trained to detour around an obstacle and follow a fixed route to rejoin with their partners. When the environmental cue was red versus blue vertical stripes, the chicks learned the detour task quicker, and as the number of training trials after route acquisition increased, they switched their preference from the environmental cue to a body‐motion cue in the cue conflict test. On the other hand, when the environmental cue was vertical versus horizontal blue stripes, the chicks learned the detour task slower and showed a dependence on the body‐motion cue regardless of the number of training trials performed after route acquisition. When the environmental cue was removed, most chicks could still successfully detour according to the specific route on which they had been trained. Furthermore, a significant difference in detour latency was found between chicks using the environmental cue and chicks using the body‐motion cue, suggesting separate neuronal circuits responsible for processing the two types of information. Our results demonstrated that young domestic chicks could use both environmental cue and body‐motion cues to memorize the route during the detour learning task; however, the detour route preference could be dynamically modulated by difference of the environmental cue and the number of training trials they received.
Mitochondrial RNA processing defect caused by a SUPV3L1 mutation in two siblings with a novel neurodegenerative syndrome
Authors: van Esveld Selma L. , Rodenburg Richard J. , Al‐Murshedi Fathiya , Al‐Ajmi Eiman , Al‐Zuhaibi Sana , Huynen Martijn A. , Spelbrink Johannes N.
Published: January 2022

SUPV3L1 encodes a helicase that is mainly localized in the mitochondria. It has been shown in vitro to possess both double‐stranded RNA and DNA unwinding activity that is ATP‐dependent. Here we report the first two patients for this gene who presented with a homozygous preliminary stop codon resulting in a C‐terminal truncation of the SUPV3L1 protein. They presented with a characteristic phenotype of neurodegenerative nature with progressive spastic paraparesis, growth restriction, hypopigmentation, and predisposition to autoimmune disease. Ophthalmological examination showed severe photophobia with corneal erosions, optic atrophy, and pigmentary retinopathy, while neuroimaging showed atrophy of the optic chiasm and the pons with calcification of putamina, with intermittent and mild elevation of lactate. We show that the amino acids that are eliminated by the preliminary stop codon are highly conserved and are predicted to form an amphipathic helix. To investigate if the mutation causes mitochondrial dysfunction, we examined fibroblasts of the proband. We observed very low expression of the truncated protein, a reduction in the mature ND6 mRNA species as well as the accumulation of double‐stranded RNA. Lentiviral complementation with the full‐length SUPV3L1 cDNA partly restored the observed RNA phenotypes, supporting that the SUPV3L1 mutation in these patients is pathogenic and the cause of the disease.
Morphea After Liposuction Ultrasonography
Authors: Araneda‐Ortega Paulina , Poblete‐Villacorta María José , Muñoz‐López Camila , Vera‐Kellet Cristian , Wortsman Ximena
Published: January 2022

Liposuction is a common aesthetic procedure; however, to date, liposuction has not been linked to morphea. The aim was to review cases with a history of liposuction that presented active morphea lesions in the same surgery regions and were confirmed by ultrasound and histology. A retrospective descriptive analysis of the clinical, ultrasonographic, and pathology database took place (2014–2020). Eleven patients met the criteria. Ultrasound supported the diagnosis, and the ultrasonographic signs of activity in these cases matched the features described in the literature in 100% of cases. In summary, morphea may appear after liposuction and ultrasound can support its early detection.
Environmental lead reduces the resilience of bald eagle populations
Authors: Hanley Brenda J. , Dhondt André A. , Forzán María J. , Bunting Elizabeth M. , Pokras Mark A. , Hynes Kevin P. , Dominguez‐Villegas Ernesto , Schuler Krysten L.
Published: January 2022

Bald eagles (Haliaeetus leucocephalus) are considered a recovery success in the United States after rebounding from near extirpation due to widespread use of the insecticide dichlorodiphenyltrichloroethane (DDT) in the twentieth century. Although abundances of bald eagles have increased since DDT was banned, other contaminants have remained in the environment with unknown influence on eagle population trends. Ingestion of spent lead (Pb) ammunition, the source of Pb most available to eagles and other scavengers in the United States, is known to kill individual eagles, but the influence of the contaminant on overall population dynamics remains unclear, resulting in longstanding controversy over the continued legality of the use of Pb in terrestrial hunting ammunition. We hypothesized that mortalities from the ingestion of Pb reduced the long‐term growth rate and resiliency of bald eagles in the northeast United States over the last 3 decades. We used Holling's definition of resilience (the ability of a system to absorb changes of state variables, driving variables, and parameters and still persist) to quantify how reduction in survival from Pb‐associated mortalities reduced the likelihood of population persistence. We used a population matrix model and necropsy records gathered between 1990 and 2018 from a 7‐state area to compare population dynamics under current versus hypothetical Pb‐reduced and Pb‐free scenarios. Despite a robust increase in eagle abundances in the northeast United States over that period, we estimated that deaths arising from ingestion of Pb was associated with a 4.2% (females) and 6.3% (males) reduction in the asymptotic long‐term growth rate (lambda). Comparison between real (current) and counterfactual (Pb‐reduced and Pb‐free) population dynamics indicated that the deaths from acute Pb poisoning were additive because the mortality events were associated with marked reduction in annual survival performance of hatchlings and reproductive females. These shifts in survival performance were further associated with a reduction in resilience for hatchling (95.4%) and breeding (81.6%) female eagles. Counterintuitively, the current conditions produced an increase in resilience (68.9%) for immature and non‐breeding female eagles over hypothetical Pb‐free conditions, suggesting that the population of eagles in the northeast United States reorganized (in a population dynamics sense) to ensure population expansion despite additive mortalities associated with Pb. This study can be used by state and federal wildlife managers or non‐governmental organizations to inform policy surrounding the use of lead ammunition or to educate hunters on the population‐scale effects of their ammunition choices.
Voice emotion recognition by Mandarin‐speaking pediatric cochlear implant users in Taiwan
Authors: Lin Yung‐Song , Wu Che‐Ming , Limb Charles J. , Lu Hui‐Ping , Feng I. Jung , Peng Shu‐Chen , Deroche Mickael L. D. , Chatterjee Monita
Published: January 2022

Objectives

To explore the effects of obligatory lexical tone learning on speech emotion recognition and the cross‐culture differences between United States and Taiwan for speech emotion understanding in children with cochlear implant.

Methods

This cohort study enrolled 60 cochlear‐implanted (cCI) Mandarin‐speaking, school‐aged children who underwent cochlear implantation before 5 years of age and 53 normal‐hearing children (cNH) in Taiwan. The emotion recognition and the sensitivity of fundamental frequency (F0) changes for those school‐aged cNH and cCI (6–17 years old) were examined in a tertiary referred center.

Results

The mean emotion recognition score of the cNH group was significantly better than the cCI. Female speakers' vocal emotions are more easily to be recognized than male speakers' emotion. There was a significant effect of age at test on voice recognition performance. The average score of cCI with full‐spectrum speech was close to the average score of cNH with eight‐channel narrowband vocoder speech. The average performance of voice emotion recognition across speakers for cCI could be predicted by their sensitivity to changes in F0.

Conclusions

Better pitch discrimination ability comes with better voice emotion recognition for Mandarin‐speaking cCI. Besides the F0 cues, cCI are likely to adapt their voice emotion recognition by relying more on secondary cues such as intensity and duration. Although cross‐culture differences exist for the acoustic features of voice emotion, Mandarin‐speaking cCI and their English‐speaking cCI peer expressed a positive effect for age at test on emotion recognition, suggesting the learning effect and brain plasticity. Therefore, further device/processor development to improve presentation of pitch information and more rehabilitative efforts are needed to improve the transmission and perception of voice emotion in Mandarin.

Level of evidence

3.
Patient‐Specific Bioimplants and Reconstruction Plates for Mandibular Defects: Production Workflow and In Vivo Large Animal Model Study
Authors: Dienel Kasper , Abu‐Shahba Ahmed , Kornilov Roman , Björkstrand Roy , van Bochove Bas , Snäll Johanna , Wilkman Tommy , Mesimäki Karri , Meller Anna , Lindén Jere , Lappalainen Anu , Partanen Jouni , Seppänen‐Kaijansinkko Riitta , Seppälä Jukka , Mannerström Bettina
Published: January 2022

A major challenge with extensive craniomaxillofacial bone reconstruction is the limited donor‐site availability to reconstruct defects predictably and accurately according to the anatomical shape of the patient. Here, patient‐specific composite bioimplants, consisting of cross‐linked poly(trimethylene carbonate) (PTMC) networks and β‐tricalcium phosphate (β‐TCP), are tested in vivo in twelve Göttingen minipigs in a large mandibular continuity defect model. The 25 mm defects are supported by patient‐specific titanium reconstruction plates and receive either osteoconductive composite bioimplants (PTMC+TCP), neat polymer network bioimplants (PTMC), autologous bone segments (positive control), or are left empty (negative control). Postoperatively, defects treated with bioimplants show evident ossification at 24 weeks. Histopathologic evaluation reveals that neat PTMC bioimplant surfaces are largely covered with fibrous tissue, while in the PTMC+TCP bioimplants, bone attached directly to the implant surface shows good osteoconduction and histological signs of osteoinductivity. However, PTMC+TCP bioimplants are associated with high incidence of necrosis and infection, possibly due to rapid resorption and/or particle size of the used β‐TCP. The study highlights the importance of testing bone regeneration implants in a clinically relevant large animal model and at the in situ reconstruction site, since results on small animal models and studies in nonloadbearing areas do not translate directly.
Facile Preparation of Fluorine‐Free, Heat‐Resisting, Breathable, and Waterproof Nanofibrous Membranes from Polymers of Intrinsic Microporosity
Authors: Ren Hao , Lu Mingchen , Tang Qingquan , Yin Xianze , Wang Luoxin , Wang Hua
Published: January 2022

Waterproof and breathable membranes (WBMs) are widely applied in garment, electronics, and aerospace, however, it is challenging to fabricate WBMs by a facile and successive strategy with excellent comprehensive properties, including environmental friendliness, heat‐resistance, waterproofness, breathability, and mechanical properties. Herein, a straightforward method is developed to fabricate large‐sized WBMs with outstanding integrated performance by direct electrospinning of original polymerization solution from polymers of intrinsic microporosity (PIMs). As‐prepared nanofibrous WBMs perform comprehensive properties with the absence of fluorine, average nanofiber diameters of 278 nm, waterproofness of 88.7 kPa, breathability of 11.2 kg m−2 d−1, tensile strength of 4.2 MPa, and heat‐resistance of 200 °C, which are superior to most of that reported fluorine‐free WBMs. Most significantly, the avoidance of tedious and intermittent fabrication procedures to prepare high‐performant WBMs allows the achievement of the successive production, and the high heat‐resistance meets the requirement of harsh service conditions. This work not only confirms that PIMs can be a good candidate for preparing high‐performant WBMs, but also paves a new version for fabricating environmental benign WBMs in a facile and successive approach.
Surfaces close to the Severi lines
Authors: Conti Federico
Published: January 2022

Let X be a surface of general type with maximal Albanese dimension: if , one has . We give a complete classification of surfaces for which equality holds for : these are surfaces whose canonical model is a double cover of a product elliptic surface branched over an ample divisor with at most negligible singularities which intersects the elliptic fibre twice.

We also prove, in the same hypothesis, that a surface X with satisfies and we give a characterization of surfaces for which the equality holds. These are surfaces whose canonical model is a double cover of an isotrivial smooth elliptic surface branched over an ample divisor with at most negligible singularities whose intersection with the elliptic fibre is 4.
Are parturition scars truly signs of birth? The estimation of parity in a well‐documented modern sample
Authors: Waltenberger Lukas , Rebay‐Salisbury Katharina , Mitteroecker Philipp
Published: January 2022

Parturition scars have been frequently studied in the last decades, but their association with pregnancy and birth is still controversial. Other biomechanical, biometric, and lifestyle factors are also likely to influence the development of pelvic features. Most previous studies of pelvic features were based on skeletal collections with no reliable information on parity or even sex and thus were unable to disentangle these factors. Here, we study the association of pelvic features with birth and other body variables (age, stature, weight, osteoarthritis, and centrum–collum–diaphyseal angle) using multiple regression and path modeling in a modern sample of female individuals from New Mexico (USA) with detailed background information (n = 150). We also explored the utility of pelvic features to predict the number of births. To this end, we scored the expression of the preauricular sulcus, sacral preauricular extension, extended pubic tubercle, exostosis at the pectineal line, dorsal, and ventral pubic pitting using CT scans from the New Mexico Decedent Image Database. Quantitative measurements of pelvic features were then used as predictors of parity. Overall, the regression models accounted only for relatively small fractions of variance in pelvic feature expression. The only feature significantly associated with the number of births was dorsal pubic pitting (R2 = 0.2372), whereas the expression of most pelvic features increased with age, independent of parity. Presumably, the development of dorsal pubic pitting is affected both by biomechanical stress and the increased hormonal secretion during pregnancy and birth. The individual prediction of parity based on pelvic features is too imprecise for forensic or archeological applications. However, using a size score of dorsal pubic pitting allowed us to estimate the mean parity in groups of individuals relatively well. Hence, pelvic features may still be used to compare average parity across recent or historic populations.
The role of neurological soft signs in different mathematical skills in second and third grade children
Authors: Cai Dan , Wang Xingsong , Kong Li
Published: January 2022

Neurological soft signs (NSSs) are subtle motor and sensory deficits, and are associated with poor cognitive abilities. Although cognitive ability has been found to be a significant predictor for academic performance in children, it remains unclear whether NSSs could contribute to academic abilities such as mathematical skills, and its contribution varies according to grade level. Therefore, in this cross‐sectional study, we examined the relationships between NSSs and different mathematical skills (calculation fluency, numerical operations, and mathematical problem‐solving) in 105 Chinese children (Mean age = 7.76 years, SD age = 0.67 years; 52 from second grade, 53 from third grade; 56 boys and 49 girls) recruited from a primary public school located in Shanghai. The results of regression analyses revealed that NSSs significantly predicted calculation fluency (β = −.32, p < .050), numerical operations (β = −.38, p < .050), and mathematical problem‐solving (β = −0.40, p < .010) in second but not third grade, even controlling for cognitive processes. Our results implicate that NSSs could be a potential predictor for mathematical skills in the early years of primary school.