bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling TGFβR and Hh pathway regulation of prognostic matrisome molecules in ovarian cancer
Authors: Delaine-Smith Robin M. , Maniati Eleni , Malacrida Beatrice , Nichols Sam , Roozitalab Reza , Jones Roanne R. , Lecker Laura , Pearce Oliver M.T. , Knight Martin M. , Balkwill Frances R. 
Published: February 2021

AbstractIn a multi-level ‘deconstruction’ of omental metastases, we previously identified a prognostic matrisome gene expression signature in high-grade serous ovarian cancer (HGSOC) and twelve other malignancies. Here, our aim was to understand how six of these extracellular matrix, ECM, molecules, COL11A1, COMP, FN1, VCAN, CTSB and COL1A1, are up-regulated in cancer. Using biopsies, we identified significant associations between TGFβR activity, Hedgehog signalling and these ECM molecules and then studied the associations in mono-, co- and tri-culture. Activated omental fibroblasts produced more matrix than malignant cells, directed by TGFβR and Hedgehog signalling crosstalk. We ‘reconstructed’ omental metastases in tri-culture of HGSOC cells, omental fibroblasts and adipocytes. This combination was sufficient to generate all six ECM proteins and the matrisome expression signature. TGFβR and Hedgehog inhibitor combinations attenuated fibroblast activation, gel remodelling and ECM remodelling in these models. The tri-culture model reproduces key features of omental metastases and allows study of diseased-associated ECM.
Terpenoid components, antioxidant and antibacterial activities of essential oils from fresh immature and mature leaves ofBlumea balsamifera,extracted with different hydrodistillation periods
Authors: Jirakitticharoen Sirinapha , Wisuitiprot Wudtichai , Jitareerat Pongphen , Wongs-Aree Chalermchai 
Published: February 2021

AbstractVolatiles and antioxidant capacities in essential oils (EOs) from fresh immature and mature leaves ofBlumea balsamifera,extracted with different extraction periods of hydrodistillation, were investigated. There were seven major terpenoid compounds in the leaf extracts, including 2 monoterpenes of camphor and L-borneol, and 5 sesquiterpenes of silphiperfol-5-ene, 7-epi-silphiperfol-5-ene, ß-caryophyllene, ɤ-eudesmol, and α-eudesmol. Different hydrodistillation periods resulted in different quantitates and compositions of the terpenoids in EOs. The yield of EOs from the immature leaves was 1.4 times higher than the mature ones, whereas 73% of the yield was collected from the first 6 h of hydrodistillation. Camphor and L-borneol were almost collected in the first 6 h, while ß-caryophyllene, silphiperfolene, and 7-epi-silphiperfolene were above 80%, but ɤ-eudesmol and α-eudesmol were only 32 and 54% released. ß-Caryophyllene, ɤ-eudesmol, and α-eudesmol were found higher in the mature leaf EOs. Antioxidant capacities in EOs were positively related to terpenoid contents. Antibacterial activity of EOs from the immature leaves was subsequently tested. Although EOs from the hydrodistillation period of 12-18 h contained fewer terpenoid compositions, it showed the same minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) onEscherichia coliandPseudomonas aeruginosa,compared to 0-6 h EOs.
Synthetic Antigen-Presenting Cells for Adoptive T Cell Therapy
Authors: Dahotre Shreyas N. , Romanov Anna M. , Su Fang-Yi , Kwong Gabriel A. 
Published: February 2021

AbstractAdoptive T cell therapies are transforming the treatment of solid and liquid tumors, yet their widespread adoption is limited in part by the challenge of generating functional cells. T cell activation and expansion using conventional antigen-presenting cells (APCs) is unreliable due to the variable quality of donor-derived APCs. As a result, engineered approaches using nanomaterials presenting T cell activation signals are a promising alternative due to their ability to be robustly manufactured with precise control over stimulation cues. In this work, we design synthetic APCs that consist of liposomes surface-functionalized with peptide-major histocompatibility complexes (pMHC). Synthetic APCs selectively target and activate antigen-specific T cell populations to levels similar to conventional protocols using non-specific αCD3 and αCD28 antibodies without the need for costimulation signals. T cells treated with synthetic APCs produce effector cytokines and demonstrate cytotoxic activity when co-cultured with tumor cells presenting target antigenin vitro. Following adoptive transfer into tumor-bearing mice, activated cells control tumor growth and improve overall survival compared to untreated mice. Synthetic APCs could potentially be used in the future to improve the accessibility of adoptive T cell therapies by removing the need for conventional APCs during manufacturing.
Motor cortex activity across movement speeds is predicted by network-level strategies for generating muscle activity
Authors: Saxena Shreya , Russo Abigail A. , Cunningham John P. , Churchland Mark M. 
Published: February 2021

AbstractLearned movements can be skillfully performed at different paces. What neural strategies produce this flexibility? Can they be predicted and understood by network modeling? We trained monkeys to perform a cycling task at different speeds, and trained artificial recurrent networks to generate the empirical muscle-activity patterns. Network solutions reflected the principle that smooth well-behaved dynamics require low trajectory tangling. Network solutions had a consistent form, which yielded quantitative and qualitative predictions. To evaluate predictions, we analyzed motor cortex activity recorded during the same task. Responses supported the hypothesis that the dominant neural signals reflect not muscle activity, but network-level strategies for generating muscle activity. Single-neuron responses were better accounted for by network activity than by muscle activity. Similarly, neural population trajectories shared their organization not with muscle trajectories, but with network solutions. Thus, cortical activity could be understood based on the need to generate muscle activity via dynamics that allow smooth, robust control over movement speed.
Stochastic dynamics of consumer-resource interactions
Authors: Singh Abhyudai 
Published: February 2021

AbstractThe interaction between a consumer (such as, a predator or a parasitoid) and a resource (such as, a prey or a host) forms an integral motif in ecological food webs, and has been modeled since the early 20thcentury starting from the seminal work of Lotka and Volterra. While the Lotka-Volterra predator-prey model predicts a neutrally stable equilibrium with oscillating population densities, a density-dependent predator attack rate is known to stabilize the equilibrium. Here, we consider a stochastic formulation of the Lotka-Volterra model where the prey’s reproduction rate is a random process, and the predator’s attack rate depends on both the prey and predator population densities. Analysis shows that increasing the sensitivity of the attack rate to the prey density attenuates the magnitude of stochastic fluctuations in the population densities. In contrast, these fluctuations vary non-monotonically with the sensitivity of the attack rate to the predator density with an optimal level of sensitivity minimizing the magnitude of fluctuations. Interestingly, our systematic study of the predator-prey correlations reveals distinct signatures depending on the form of the density-dependent attack rate. In summary, stochastic dynamics of nonlinear Lotka-Volterra models can be harnessed to infer density-dependent mechanisms regulating consumer-resource interactions. Moreover, these mechanisms can have contrasting consequences on population fluctuations, with predator-dependent attack rates amplifying stochasticity, while prey-dependent attack rates countering to buffer fluctuations.
Targeted therapy forLIMD1-deficient non-small cell lung cancer subtypes
Authors: Davidson Kathryn , Grevitt Paul , Contreras G. Maria F. , Bridge Katherine S. , Hermida Miguel , Shah Kunal M. , Mardakheh Faraz K , Stubbs Mark , Clarke Paul A. , Burke Rosemary , Casado-Izquierdo Pedro , Cutillas Pedro R. , Martin Sarah A. , Sharp Tyson V. 
Published: February 2021

AbstractAn early event in lung oncogenesis is loss of the tumour suppressor geneLIMD1 (LIM domains containing 1);this encodes a scaffold protein, which suppresses tumourigenesis via a number of different mechanisms. Approximately 45% of non-small cell lung cancers (NSCLC) are deficient in LIMD11, yet this subtype of NSCLC has been overlooked in preclinical and clinical investigations. Defining therapeutic targets in these LIMD1 loss-of-function patients is difficult due to a lack of ‘druggable’ targets, thus alternative approaches are required. To this end, we performed the first drug repurposing screen to identify compounds that confer synthetic lethality with LIMD1 loss in NSCLC cells. PF-477736 was shown to selectively target LIMD1 deficient cellsin vitrothrough inhibition of multiple kinases, inducing cell death via apoptosis. Furthermore, PF-477736 was effective in treating LIMD1−/−tumors in subcutaneous xenograft models, with no significant effect in LIMD1+/+cells. We have identified a novel drug tool with significant preclinical characterization that serves as an excellent candidate to explore and define LIMD1-deficient cancers as a new therapeutic subgroup of critical unmet need.Significance StatementHere we provide the first proof-of-concept data validating the scope for development of a targeted therapy against the non-small cell lung cancers (NSCLC) subtypes deficient in expression of the LIMD1 tumor suppressor gene. Approximately 45% of NSCLC are deficient in LIMD11representing at least 1.2 million lung cancer patients worldwide; yet this subtype has been ignored in preclinical and clinical investigations with no targeted therapies available. This seminal study applied synthetic lethality drug screening to target the loss/reduction of LIMD1 in lung cancer and normal cell lines, identifying and validating the multi-kinase inhibitor PF-477736 as a selectively cytotoxic compound towards LIMD1 deficient cells. This study provides rationale for further investigation into targeting LIMD1 loss in lung cancer, thereby addressing a critical unmet need for therapeutic approached to targeting LIMD1-deficent cancer subtypes.
ESD1 Affects Seed Setting Rate in Rice by Controlling Embryo Sac Development
Authors: Wang Tiankang , Li Yixing , Song Shufeng , Qiu Mudan , Zhang Licheng , Li Chengxia , Dong Hao , Li Lei , Wang Jianlong , Li Li 
Published: February 2021

AbstractSeed setting rate is one of the critical factors that determine rice yield. Grain formation is a complex biological process, whose molecular mechanism is yet to be improved. Here we investigated the function of an OVATE family protein, Embryo Sac Development 1 (ESD1), in the regulation of seed setting rate in rice (Oryza sativa) by examining its loss-of-function mutants generated via CRISPR/Cas9 technology.ESD1was predominantly expressed at stage 6 of panicle development, especially in the ovules.esd1mutants displayed reduced seed setting rates with normal stamen development and pollen tube growth but abnormal pistil group. Investigation of embryo sacs revealed that during the mitosis of functional megaspores, some egg cells degraded during differentiation inesd1mutants, thereby hindering subsequent fertilization process and reducing seed setting rate. In addition, the transcriptional level ofOsAPC6,a reported embryo sac developing gene, was found to be significantly reduced inesd1mutants. These results support that ESD1 is an important modulator of embryo sac development and seed setting rate in rice. Together, this finding demonstrates that ESD1 positively regulates the seed setting rate by controlling embryo sac development in rice, and has implications for the improvement of rice yield.
Social media use by first-generation college students and two forms of social capital: a revealed causal mapping approach
Authors: Deng Xuefei (Nancy) , Fernández Yesenia , Zhao Meng 
Published: February 2021

PurposeThe purpose of this study is to examine social media use and its impacts on first generation students by answering the two questions: how do FGS use social media on college campuses, compared to their peers? How does the use of social media affect their academic experiences?Design/methodology/approachThis qualitative study adopted social capital theory as a sensitizing framework for understanding the social media (SM) use and the resources valued by first-generation students (FGS) and used a revealed causal mapping method to analyze the narratives of 96 informants to identify key constructs and linkages on SM use and perceived outcomes.FindingsThe revealed causal mapping (RCM) analysis revealed nine key constructs that shaped the SM use and academic experience of FGS and their peers. The linkages among the nine constructs: three types of social capital (bridging, family bonding and friend bonding), three types of SM use (social, cognitive and hedonic) and three outcomes (academic support, emotional support and distraction to work) were different between FGS and their peers. Among FGS, SM use and perceptions differed by gender.Originality/valueLeveraging social media is critical for universities to enhance FGS persistence, yet knowledge remains limited. This study showed FGS differed from their counterparts in the SM use and perceptions. Among FGS, the SM use and perceptions differed by gender. The research contributions are: (1) SM technology can empower FGS by building social capital, impacting their academic experiences and psychological well-being and (2) the intersection of gender and student generation status is worth investigation. This paper enriches FGS research by proposing a model of SM use and social capital.
Comparison of post‐operative pain in short versus long stitch technique for abdominal wall closure after elective laparotomy: a double‐blind randomized controlled trial
Authors: Lai Larry Weng‐Hong , Roslani April Camilla , Yan Yang‐Wai , Bhojwani Kavita M. , Jamaluddin Mohamad Fadhil Hadi 
Published: February 2021

AbstractBackgroundConventional mass closure uses suture‐to‐wound length ratio of 4:1 (‘long stitch’, LS). ‘Short stitch’ (SS) has a suture‐to‐wound length ratio of more than 4 and incorporates only the linea alba, which may reduce tension and pain. We compared the post‐operative pain after laparotomy closure using LS and SS.MethodsPatients undergoing elective midline laparotomy through standardized incisions in two tertiary hospitals from February 2017 to September 2018 were randomized to either LS or SS. The primary outcome was post‐operative patient‐controlled analgesia morphine usage at 24 h. Secondary outcomes were presence of surgical site infection and length of hospital stay (LOHS). Categorical variables were analysed using chi‐squared analysis. Outcomes of study were tested for normal distribution. Skewed data were analysed using Mann–Whitney U‐test.ResultsEighty‐six patients were recruited (42 SS and 44 LS). The median age was 66 (interquartile range (IQR) 15). Majority were males (62.8%) and Chinese (50%). The median incision length was 17 cm in both groups. The median patient‐controlled analgesia morphine usage 24 h post‐operatively did not differ significantly (SS 21 mg, IQR 28.3; LS 18.5 mg, IQR 33.8, P = 0.829). The median pain score at rest (SS 1, IQR 1; LS 1, IQR 2, P = 0.426) and movement (SS 3, IQR 1; LS 3, IQR 2, P = 0.307) did not differ significantly. LOHS was shorter in the SS group (SS 6, IQR 4; LS 8, IQR 5, P = 0.034). The rate of surgical site infection trended lower in the SS group with no statistical difference.ConclusionThere were no differences in post‐operative pain between SS and LS but we found that there were shorter LOHS in SS arm as secondary outcome.
Challenges in diagnosis and management of a spiradenocarcinoma: a comprehensive literature review
Authors: Wagner Katy , Jassal Karishma , Lee James C. , Ban Ee‐Jun , Cameron Rhoda , Serpell Jonathan 
Published: February 2021

AbstractBackgroundSpiradenocarcinoma is a rare skin adnexal neoplasm that may behave aggressively. It is often associated with a benign slow‐growing spiradenoma that has undergone malignant transformation. Given the paucity of cases in the literature, there is a lack of consensus on treatment.MethodsThe terms ‘malignant spiradenoma’ or ‘spiradenocarcinoma’ were systematically used to search the PubMed, MEDLINE and Google Scholar databases. A total of 182 cases of spiradenocarcinoma were identified as eligible for this comprehensive literature review.ResultsSpiradenocarcinoma was commoner in older age and Caucasian race. In most cases, surgical excision for local disease is the mainstay of treatment. Lymph node dissection is usually reserved for those with suspected or confirmed lymph node metastases. High rates of local recurrence (20.8%), metastasis (37.4%) and mortality (19.1%) were identified, prompting some authors to suggest regular follow up including chest X‐rays and liver function tests.ConclusionsPatients with spiradenocarcinoma may benefit from a magnetic resonance imaging and fluorodeoxyglucose‐positron emission tomography/computed tomography to establish the extent of disease. We recommend wide local excision as the treatment of choice to achieve surgical margins of ≥1 cm, with node resection to be determined on a case‐to‐case basis. Regular follow up is important given the high rate of local recurrence, metastasis and mortality. This should include an examination of the regional lymph nodes. Further research is required to refine an evidence‐based approach to spiradenocarcinoma.
Incidence of catheter‐associated right atrial thrombus detected by transthoracic echocardiogram
Authors: Clark Jeffrey R. , Hoffman Steven C. , Shlobin Nathan A. , Bavishi Aakash , Narang Akhil 
Published: February 2021

AbstractIntroductionThe development of right atrial (RA) thrombus (RAT) is a known complication of central venous catheter insertion (CVC). Deeper insertion of CVC within the RA may increase the risk for RAT development versus those placed at the superior vena cava (SVC)‐RA junction. We sought to evaluate the incidence of catheter‐associated RAT as detected by transthoracic echocardiograms (TTEs), characterize thrombi though multimodal imaging, and evaluate thrombi management with follow‐up imaging.MethodsA retrospective analysis was conducted of consecutive TTEs from our institution between October 1, 2018, and January 1, 2020, in which a venous catheter was visualized in the RA. Studies were reviewed in detail to determine the presence of suspected RAT. Demographic data, comorbidities, laboratory values, characteristics of the catheter and the thrombus, subsequent imaging and management, and outcomes were collected.ResultsA total of 364 TTEs were performed in 290 patients with a venous catheter visualized in the RA. Of these 290 patients, 15 had an imaging suspicion for RAT yielding an incidence of 5.2%. Management strategies included anticoagulation in 13 (86.7%) patients and catheter removal in 11 (73.3%) patients. At eight months of follow‐up, 11 (73.3%) patients had resolution of RAT based on subsequent imaging.ConclusionIn patients with deeply placed CVC catheters, the incidental detection of RAT by TTE was not trivial. Anticoagulation and catheter removal and replacement, if deemed safe, were effective methods of thrombus management. RAT as a complication of CVCs must be accounted for when addressing factors that influence depth of CVC insertion.
Financial flexibility demand and corporate financial decisions
Authors: Byoun Soku 
Published: February 2021

AbstractI develop a hypothesis that predicts nonlinear patterns of leverage and cash holdings over firms' financial flexibility (FF) demand stages. The hypothesis also predicts distinctive financing patterns over the FF demand stages. The empirical results support the hypothesis: Flexibility‐building firms maintain low leverage by issuing equity in order to raise cash; flexibility‐utilizing firms increase debt and use reserved cash to exercise investment options; and flexibility‐recharging firms repay debt and increase cash using internal funds. The pronounced nonlinear patterns in financial decisions over the FF demand stages have important implications for previously documented empirical regularities and for future theoretical considerations.
Critical amino acids in the TM2 of EAAT2 are essential for membrane‐bound localization, substrate binding, transporter function and anion currents
Authors: Mai Dongmei , Chen Rongqing , Wang Ji , Zheng Jiawei , Zhang Xiuping , Qu Shaogang 
Published: February 2021

AbstractExcitatory amino acid transporter 2 (EAAT2), the gene of which is known as solute carrier family 1 member 2 (SLC1A2), is an important membrane‐bound transporter that mediates approximately 90% of the transport and clearance of l‐glutamate at synapses in the central nervous system (CNS). Transmembrane domain 2 (TM2) of EAAT2 is close to hairpin loop 2 (HP2) and far away from HP1 in the inward‐facing conformation. In the present study, 14 crucial amino acid residues of TM2 were identified via alanine‐scanning mutations. Further analysis in EAAT2‐transfected HeLa cells in vitro showed that alanine substitutions of these residues resulted in a decrease in the efficiency of trafficking/targeting to the plasma membrane and/or reduced functionality of membrane‐bound, which resulted in impaired transporter activity. After additional mutations, the transporter activities of some alanine‐substitution mutants recovered. Specifically, the P95A mutant decreased EAAT2‐associated anion currents. The Michaelis constant (Km) values of the mutant proteins L85A, L92A and L101A were increased significantly, whereas R87 and P95A were decreased significantly, indicating that the mutations L85A, L92A and L101A reduced the affinity of the transporter and the substrate, whereas R87A and P95A enhanced this affinity. The maximum velocity (Vmax) values of all 14 alanine mutant proteins were decreased significantly, indicating that all these mutations reduced the substrate transport rate. These results suggest that critical residues in TM2 affect not only the protein expression and membrane‐bound localization of EAAT2, but also its interactions with substrates. Additionally, our findings elucidate that the P95A mutant decreased EAAT2‐related anion currents. Our results indicate that the TM2 of EAAT2 plays a vital role in the transport process. The key residues in TM2 affect protein expression in the membrane, substrate transport and the anion currents of EAAT2.
Anwulignan is a novel JAK1 inhibitor that suppresses non‐small cell lung cancer growth
Authors: Xie Xiaomeng , Wang Xiangyu , Shi Xiaodan , Zhang Yuanyuan , Laster Kyle Vaughn , Liu Kangdong , Dong Zigang , Kim Dong Joon 
Published: February 2021

AbstractAnwulignan is a monomer compound derived from Schisandra sphenanthera lignans. It has been reported to possess a spectrum of pharmacological activities, including anti‐bacterial, anti‐inflammatory, anticancer and hepatoprotective properties. However, its anticancer capacity and molecular mechanism(s) against non‐small cell lung cancer (NSCLC) have not been fully elucidated. Anwulignan significantly inhibited cell growth and increased G1‐phase cell cycle arrest in NSCLC cells. Anwulignan strongly attenuates the JAK1/STAT3 signalling pathway by directly targeting JAK1 protein kinase activity in vitro. The anticancer activity by Anwulignan is dependent upon the JAK1 protein expression. Remarkably, Anwulignan strongly inhibited tumour growth in vivo. In conclusion, Anwulignan is a novel JAK1 inhibitor that may have therapeutic implications for NSCLC management.