bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative STAU2 measurement in lymphocytes for breast cancer risk assessment
Authors: Puttipanyalears Charoenchai , Denariyakoon Sikrit , Angsuwatcharakon Phonthep , Aksornkitti Vitavat , Vongsaisuwan Mawin , Asayut Sutasinee , Thanasitthichai Somchai , Kongruttanachok Narisorn , Aporntewan Chatchawit , Mutirangura Apiwat 
Published: January 2021

AbstractAlthough mammograms play a key role in early breast cancer detection, the test is not applicable to all women, for example, women under the age of 40. The development of a noninvasive blood test with high sensitivity and accessibility will improve the effectiveness of breast cancer screening programmes. Secretory factors released from cancer cells can induce the expression of certain genes in a large number of white blood cells (WBCs). Therefore, cancer-dependent proteins in WBCs can be used as tumour markers with high sensitivity. Five proteins (LMAN1, AZI2, STAU2, MMP9 and PLOD1) from a systemic analysis of a variety of array data of breast cancer patients were subjected to immunofluorescence staining to evaluate the presence of fixed WBCs on 96-well plates from 363 healthy females and 358 female breast cancer patients. The results revealed that the average fluorescence intensity of anti-STAU2 and the percentage of STAU2-positive T and B lymphocytes in breast cancer patients (110.50 ± 23.38 and 61.87 ± 12.44, respectively) were significantly increased compared with those in healthy females (56.47 ± 32.03 and 33.02 ± 18.10, respectively) (p = 3.56 × 10–71, odds ratio = 24.59, 95% CI = 16.64–36.34). The effect of secreted molecules from breast cancer cells was proven by the increase in STAU2 intensity in PBMCs cocultured with MCF-7 and T47D cells at 48 h (p = 0.0289). The test demonstrated 98.32%, 82.96%, and 48.32% sensitivity and 56.47%, 83.47%, and 98.62% specificity in correlation with the percentage of STAU2-positive cells at 40, 53.34 and 63.38, respectively. We also demonstrated how to use the STAU2 test for the assessment of risk in women under the age of 40. STAU2 is a novel breast cancer marker that can be assessed by quantitative immunofluorescence staining of fixed WBCs that are transportable at room temperature via mail, representing a useful risk assessment tool for women without access to mammograms.
A non-inferiority randomised controlled trial comparing self-instruction with instructor-led method in training of layperson cardiopulmonary resuscitation
Authors: Ko Ying-Chih , Yang Chih-Wei , Lin Hao-Yang , Chiang Wen-Chu , Hsieh Ming-Ju , Ma Matthew Huei-Ming 
Published: January 2021

AbstractOur study aimed to compare the effect of self-instruction with manikin feedback to that of instructor-led method on cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) skill performance. In our randomized non-inferiority trial, 64 non-healthcare providers were randomly allocated into self-instruction and instructor-led groups. Both groups watched a 27-min standardized teaching video. Participants in the self-instruction group then performed hands-on practice on the Resusci Anne QCPR with a device-driven feedback, while those in the instructor-led group practiced manikins; feedback was provided and student’s questions were answered by instructors. Outcomes were measured by blinded evaluators and SkillReporter software. The primary outcome was the pass rate. Secondary outcomes were scores of the knowledge test and items of individual skill performance. The baseline characteristics of the two groups were similar. The pass rates were 93.8% in both group (absolute difference 0%, p = 0.049 for noninferiority). The knowledge test scores were not significantly different. However, the self-instruction group performed better in some chest compression and ventilation skills, but performed worse in confirming environmental safety and checking normal breathing. There was no difference in AED skills between the two groups. Our results showed the self-instruction method is not inferior to the instructor-led method.
TEM, SEM, and STEM-based immuno-CLEM workflows offer complementary advantages
Authors: Oorschot Viola , Lindsey Benjamin W. , Kaslin Jan , Ramm Georg 
Published: January 2021

AbstractIdentifying endogenous tissue stem cells remains a key challenge in developmental and regenerative biology. To distinguish and molecularly characterise stem cell populations in large heterogeneous tissues, the combination of cytochemical cell markers with ultrastructural morphology is highly beneficial. Here, we realise this through workflows of multi-resolutionimmuno-correlative light and electron microscopy (iCLEM) methodologies. Taking advantage of the antigenicity preservation of the Tokuyasu technique, we have established robust protocols and workflows and provide a side-by-side comparison ofiCLEM used in combination with scanning EM (SEM), scanning TEM (STEM), or transmission EM (TEM). Evaluation of the applications and advantages of each method highlights their practicality for the identification, quantification, and characterization of heterogeneous cell populations in small organisms, organs, or tissues in healthy and diseased states. TheiCLEM techniques are broadly applicable and can use either genetically encoded or cytochemical markers on plant, animal and human tissues. We demonstrate how these protocols are particularly suited for investigating neural stem and progenitor cell populations of the vertebrate nervous system.
Culture surface protein coatings affect the barrier properties and calcium signalling of hESC-RPE
Authors: Viheriälä Taina , Sorvari Juhana , Ihalainen Teemu O. , Mörö Anni , Grönroos Pyry , Schlie-Wolter Sabrina , Chichkov Boris , Skottman Heli , Nymark Soile , Ilmarinen Tanja 
Published: January 2021

AbstractHuman pluripotent stem cell-derived retinal pigment epithelium (RPE) transplantation is currently under evaluation as treatment for macular degeneration. For therapeutic applications, cryostorage during cell production is typically needed with potential consequences to cell functionality. We have previously shown that the culture substrate affects human embryonic stem cell-derived RPE (hESC-RPE) properties in fresh cultures. Here, we aimed to further identify the role of RPE basement membrane proteins type IV collagen (Col-IV), laminin (LN), and nidogen-1 in the maturation and functionality of hESC-RPE after cryopreservation. In addition to cell attachment and morphology, transepithelial electrical resistance, expression of key RPE proteins, phagocytosis capacity and Ca2+ signalling were analysed. After cryostorage, attachment of hESC-RPE on culture surfaces coated with Col-IV alone was poor. Combining Col-IV and LN with or without nidogen-1 significantly improved cell attachment and barrier properties of the epithelium. Furthermore, functional homogeneity of the hESC-RPE monolayer was enhanced in the presence of nidogen-1. Our results suggest that the choice of coating proteins for the cell culture may have implications to the functional properties of these cells after cryostorage cell banking.
Generation of westerly wind bursts by forcing outside the tropics
Authors: Sullivan Arnold , Zhong Wenxiu , Borzelli Gian Luca Eusebi , Geng Tao , Mackallah Chloe , Ng Benjamin , Hong Chi-Cherng , Cai Wenju , Huang An-Yi , Bodman Roger 
Published: January 2021

AbstractThe westerly wind burst (WWB) is an important triggering mechanism of El Niño and typically occurs in the western Pacific Ocean. The Fourier spectrum of the wind field over the western tropical Pacific is characterised by a large variety of peaks distributed from intra-seasonal to decadal time scales, suggesting that WWBs could be a result of nonlinear interactions on these time scales. Using a combination of observations and simulations with 15 coupled models from the Coupled Model Intercomparison Project Phase 6 (CMIP6), we demonstrate that the main drivers initiating WWBs are quantifiable physical processes rather than atmospheric stochastic signals. In this study, ensemble empirical mode decomposition (EEMD) from the Holo-Hilbert spectral analysis (HHSA) is used to decompose daily zonal winds over the western equatorial Pacific into seasonal, interannual and decadal components. The seasonal element, with prominent spectral peaks of less than 12 months, is not ENSO related, and we find it to be strongly associated with the East Asian monsoon (EAM) and cross-equatorial flow (CEF) over the Australian monsoon region. The CEF is directly related to the intensity of the Australian subtropical ridge (STR-I). Both the EAM and CEF are essential sources of these high-frequency winds over the western Pacific. In contrast, the interannual wind component is closely related to El Niño occurrences and usually peaks approximately two months prior to a typical El Niño event. Finally, the decadal element merely represents a long-term trend and thus has little to no relation to El Niño. We identified EAM- and CEF-induced westerly wind anomalies in December–January–February (DJF) and September–October–November (SON). However, these anomalies fade in March–April–May (MAM), potentially undermining the usual absence of WWBs in the boreal spring. Similar results are found in CMIP6 historical scenario data.
Epidural analgesia does not impact recurrence or mortality in patients after rectal cancer resection
Authors: Wu Hsiang-Ling , Tai Ying-Hsuan , Lin Shih-Pin , Yang Shung-Haur , Tsou Mei-Yung , Chang Kuang-Yi 
Published: January 2021

AbstractThe relationship between epidural analgesia and rectal cancer outcome is not fully clarified. We aimed to investigate the putative effect of epidural analgesia on the risks of recurrence and mortality after rectal tumour resection. In this monocentric cohort study, we consecutively enrolled patients with stage I–III rectal cancer who underwent tumour resection from 2005 to 2014. Patients received epidural analgesia or intravenous opioid-based analgesia for postoperative pain control. Primary endpoint was first cancer recurrence. Secondary endpoints were all-cause mortality and cancer-specific mortality. We collected 1282 patients in the inverse probability of treatment weighting analyses, and 237 (18.5%) used epidurals. Follow-up interval was median 46.1 months. Weighted Cox regression analysis showed the association between epidural analgesia and recurrence-free survival was non-significant (adjusted hazard ratio [HR] 0.941, 95% CI 0.791–1.119, p = 0.491). Similarly, the association between epidural analgesia and overall survival (HR 0.997, 95% CI 0.775–1.283, p = 0.984) or cancer-specific survival (HR 1.113, 95% CI 0.826–1.501, p = 0.482) was non-significant either. For sensitivity tests, quintile stratification and stepwise forward model selection analyses showed similar results. We did not find a significant association between epidural analgesia and risk of recurrence, all-cause mortality, or cancer-specific mortality in patients with rectal cancer undergoing tumour resection.
Peptidoglycan mediates Leptospira outer membrane protein Loa22 to toll-like receptor 2 for inflammatory interaction: a novel innate immune recognition
Authors: Hsu Shen-Hsing , Chang Ming-Yang , Lin Shih-Ming , Ko Yi-Ching , Chou Li-Feng , Tian Ya-Chung , Hung Cheng-Chieh , Yang Chih-Wei 
Published: January 2021

AbstractLeptospirosis is an overlooked zoonotic disease caused by pathogenic Leptospira depended on virulence of Leptospira and the host–pathogen interaction. Kidney is the major organ infected by Leptospira which causes tubulointerstitial nephritis. Leptospira outer membrane contains several virulence factors and an outer membrane protein A (OmpA) like protein (Loa22) is essential for virulence. Pull-down assays suggested that Loa22 was a potential Toll-Like Receptor 2 (TLR2) binding candidates from pathogenic Leptospira. Confocal microscopy was employed to observe the co-localization of TLR2 and Loa22-LPGN (Leptospira peptidoglycan) complexes. Atomic force microscopy (AFM), side-directed mutagenesis, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the affinity between rLoa22, LPGN, and TLR2. Real time PCR was applied to measure the cytokines expression. Downstream signal transduction components were verified by western blot to evaluate the gene regulations. Mutation of two Loa22 key residues (Asp122 and Arg143) attenuated the affinities for LPGN. rLoa22-LPGN complexes were observed to co-localize with TLR2 and provoked inflammatory responses including CXCL8/IL8, hCCL2/MCP-1, and hTNF-α. Affinity studies suggested that Loa22-LPGN complexes elevated the affinity to TLR2 as compared to Loa22 protein. Downstream signals from TLR2 including p38, ERK, and JNK were regulated under rLoa22-LPGN complexes treatments. This study identified LPGN mediates interactions between Loa22 and TLR2 and induces downstream signals to trigger inflammatory responses. rLoa22-LPGN-TLR2 complexes reveal a novel binding mechanism for the innate immune system.
Sustained, local delivery of the PARP inhibitor talazoparib prevents the development of mammary gland hyperplasia in Brca1-deficient mice
Authors: Zhang Di , Singh Bijay , Moerland Jessica , Mitchell Owen , Lockwood Lizbeth , Carapellucci Sarah , Sridhar Srinivas , Liby Karen T. 
Published: January 2021

AbstractMutations in BRCA genes are the leading cause of hereditary breast cancer. Current options to prevent cancer in these high-risk patients, such as anti-estrogen drugs and radical mastectomy, are limited by lack of efficacy, undesirable toxicities, or physical and emotional challenges. We have previously shown that PARP inhibitors can significantly delay tumor development in BRCA1-deficient mice. Here, we fabricated the PARP inhibitor talazoparib (TLZ) into spacer implants (InCeT-TLZ) for localized and sustained delivery. We hypothesized that this novel formulation will provide an effective chemopreventive strategy with minimal toxicity. TLZ was released gradually over 30 days as implants degraded. InCeT-TLZ significantly decreased proliferation and increased DNA damage in the mammary glands of BRCA1-deficient mice. Notably, the number of mice that developed hyperplasia in the mammary glands was significantly lower with InCeT-TLZ treatment compared to the control group. Meanwhile, InCeT-TLZ was also better tolerated than oral TLZ, without loss of body weight or anemia. This study provides proof of concept for a novel and safe chemopreventive strategy using localized delivery of a PARP inhibitor for high-risk individuals. Future studies will directly evaluate the effects of InCeT-TLZ for preventing tumor development.
The required acoustic parameters simplification of invisibility cloaks and concentrators using the impedance-tunable coordinate transformation
Authors: Cao Jun , Qi Fenghua , Yan Senlin 
Published: January 2021

AbstractTransformation acoustics, as an unconventional theory, provides a powerful tool to design various kinds of acoustic devices with excellent functionalities. However, the required ideal parameters, which are prescribed by the method, are both complex and hard to implement-even using acoustic metamaterials. Furthermore, simplified parameter materials are generally favored in transformation-acoustic design due to its easier realization with artificial structures. In this letter, we propose a coordinate transformation methodology for achieving simplified parameters by tuning the impedance distribution in the geometric limit, where the transformation media parameters can be derived by setting tunable impedance functions in the original space and a combination of suitable linear or nonlinear coordinate transformation. Based on this approach, both two-dimensional acoustic cloak and concentrators are designed with different sets of simplified parameters. Numerical simulations indicate good performance of these devices with minimized scattering at higher frequencies. The proposed method provides more opportunities to realize the designed acoustic devices experimentally, and can also be used for other transformation-acoustic designs including 3D cases.
Berberine-releasing electrospun scaffold induces osteogenic differentiation of DPSCs and accelerates bone repair
Authors: Ma Lan , Yu Yijun , Liu Hanxiao , Sun Weibin , Lin Zitong , Liu Chao , Miao Leiying 
Published: January 2021

AbstractThe repair of skeletal defects in maxillofacial region remains an intractable problem, the rising technology of bone tissue engineering provides a new strategy to solve it. Scaffolds, a crucial element of tissue engineering, must have favorable biocompatibility as well as osteoinductivity. In this study, we prepared berberine/polycaprolactone/collagen (BBR/PCL/COL) scaffolds with different concentrations of berberine (BBR) (25, 50, 75 and 100 μg/mL) through electrospinning. The influence of dosage on scaffold morphology, cell behavior and in vivo bone defect repair were systematically studied. The results indicated that scaffolds could release BBR stably for up to 27 days. Experiments in vitro showed that BBR/PCL/COL scaffolds had appropriate biocompatibility in the concentration of 25–75 μg/mL, and 50 and 75 μg/mL scaffolds could significantly promote osteogenic differentiation of dental pulp stem cells. Scaffold with 50 μg/mL BBR was implanted into the critical bone defect of rats to evaluate the ability of bone repair in vivo. It was found that BBR/PCL/COL scaffold performed more favorable than polycaprolactone/collagen (PCL/COL) scaffold. Overall, our study is the first to evaluate the capability of in vivo bone repair of BBR/PCL/COL electrospun scaffold. The results indicate that BBR/PCL/COL scaffold has prospective potential for tissue engineering applications in bone regeneration therapy.
Sialic acid-binding immunoglobulin-like lectin-15 expression on peritumoral macrophages is a favorable prognostic factor for primary central nervous system lymphoma patients
Authors: Fudaba Hirotaka , Momii Yasutomo , Hirakawa Taisei , Onishi Kouhei , Asou Daigo , Matsushita Wataru , Kawasaki Yukari , Sugita Kenji , Fujiki Minoru 
Published: January 2021

AbstractSialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) is a new immune checkpoint molecule and its role of primary central nervous system lymphoma (PCNSL) tumor microenvironment has been unclear. We explored the Siglec-15 and programed death-ligand 1 (PD-L1) expression in tumor tissues and analyzed the association between the expression of these molecules and overall survival in newly diagnosed PCNSL. A total of 60 patients diagnosed with diffuse large B-cell lymphoma in PCNSL were included in this study. The Siglec-15 and PD-L1 expression on tumor cells, intratumoral macrophages and peritumoral macrophages were immunohistochemically evaluated. The expression of Siglec-15 and PD-L1 was greater in macrophages than in tumor cells. Regarding peritumoral macrophages, the number of Siglec-15-positive samples (n = 24) was greater than the number of PD-L1-positive samples (n = 16). A multivariate Cox analysis showed that the Siglec-15 positivity of peritumoral macrophages and performance of high-dose methotrexate-based chemotherapy were independent predictors of overall survival (hazard ratio: 0.295 and 0.322, respectively). The Kaplan–Meier survival curves showed that patients with Siglec-15-positive peritumoral macrophages had longer overall survival than those with Siglec-15-negative peritumoral macrophages (median overall survival: 3018 days and 746 days, respectively; p = 0.0290). Our findings indicate that the expression of Siglec-15 on peritumoral macrophages induces a favorable outcome in PCNSL patients.
Auditory roughness elicits defense reactions
Authors: Taffou Marine , Suied Clara , Viaud-Delmon Isabelle 
Published: January 2021

AbstractAuditory roughness elicits aversion, and higher activation in cerebral areas involved in threat processing, but its link with defensive behavior is unknown. Defensive behaviors are triggered by intrusions into the space immediately surrounding the body, called peripersonal space (PPS). Integrating multisensory information in PPS is crucial to assure the protection of the body. Here, we assessed the behavioral effects of roughness on auditory-tactile integration, which reflects the monitoring of this multisensory region of space. Healthy human participants had to detect as fast as possible a tactile stimulation delivered on their hand while an irrelevant sound was approaching them from the rear hemifield. The sound was either a simple harmonic sound or a rough sound, processed through binaural rendering so that the virtual sound source was looming towards participants. The rough sound speeded tactile reaction times at a farther distance from the body than the non-rough sound. This indicates that PPS, as estimated here via auditory-tactile integration, is sensitive to auditory roughness. Auditory roughness modifies the behavioral relevance of simple auditory events in relation to the body. Even without emotional or social contextual information, auditory roughness constitutes an innate threat cue that elicits defensive responses.
Direct measurement of vagal tone in rats does not show correlation to HRV
Authors: Marmerstein Joseph T. , McCallum Grant A. , Durand Dominique M. 
Published: January 2021

AbstractThe vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. “Vagal tone” is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension. However, vagal tone has never been directly measured, leading to disagreements in its interpretation and influencing the effectiveness of vagal therapies. Using custom carbon nanotube yarn electrodes, we were able to chronically record neural activity from the left cervical vagus in both anesthetized and non-anesthetized rats. Here we show that tonic vagal activity does not correlate with common HRV metrics with or without anesthesia. Although we found that average vagal activity is increased during inspiration compared to expiration, this respiratory-linked signal was not correlated with HRV either. These results represent a clear advance in neural recording technology but also point to the need for a re-interpretation of the link between HRV and “vagal tone”.