bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anaglyph stereo virtual dissection: a novel inexpensive method for stereoscopic visualisation of intracardiac anatomy on CT angiogram
Authors: Gupta Saurabh Kumar , Gupta Priyanka 
Published: April 2021

AbstractThree-dimensional visualisation is invaluable for evaluating cardiac anatomy. Patient-specific three-dimensional printed models of the heart are useful but require significant infrastructure. The three-dimensional virtual models, derived from 3D echocardiography, computed tomographic (CT) angiography or cardiac magnetic resonance (CMR), permit excellent visualisation of intracardiac anatomy, but viewing on a two-dimensional screen obscures the third dimension. Various forms of extended reality, such as virtual reality and augmented reality, augment the third dimension but only using expensive equipment. Herein, we report a simple technique of anaglyph stereoscopic visualisation of three-dimensional virtual cardiac models. The feasibility of achieving stereovision on a personal computer, using open-source software, and the need for inexpensive anaglyph glasses for viewing make it extremely cost-effective. Further, the retained depth perception of resulting stereo images in electronic and printed format makes sharing with other members of the team easy and effective.
Researching the Politics of Illegal Activities
Authors: Gallien Max 
Published: April 2021

ABSTRACTAlthough an object of increasing interest, researching illegal activities generates a range of methodological challenges for political scientists. Rather than an exhaustive discussion, this article provides a simple framework that structures these challenges. It highlights that illegality is an insufficient guide to method development and needs to be supplemented by an analysis of three dimensions in addition to legality: enforcement, normalization, and ethics. The article explains that beyond providing insight into the feasibility and challenges of different methodologies, examining these dimensions also directly points researchers to key political science questions about illegal activities.
Association of survival with stereotactic body radiation therapy following induction chemotherapy for unresected locally advanced pancreatic cancer
Authors: Ma Sung Jun , Serra Lucas M. , Bartl Austin J. , Han Hye Ri , Fekrmandi Fatemeh , Iovoli Austin J. , Prezzano Kavitha M. , Hermann Gregory M. , Yu Han , Singh Anurag K. 
Published: April 2021

AbstractAim:Induction chemotherapy (iC) followed by concurrent chemoradiation has been shown to improve overall survival (OS) for locally advanced pancreatic cancer (LAPC). However, the survival benefit of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT) following iC remains unclear.Materials and methods:The National Cancer Database (NCDB) was queried for primary stage III, cT4N0-1M0 LAPC (2004–15). Kaplan–Meier analysis, Cox proportional hazards method and propensity score matching were used.Results:Among 872 patients, 738 patients underwent CFRT and 134 patients received SBRT. Median follow-up was 24·3 and 22·9 months for the CFRT and SBRT cohorts, respectively. The use of SBRT showed improved survival in both the multivariate analysis (hazards ratio 0·78, p = 0·025) and 120 propensity-matched pairs (median OS 18·1 versus 15·9 months, p = 0·004) compared to the CFRT.Findings:This NCDB analysis suggests survival benefit with the use of SBRT versus CFRT following iC for the LAPC.
Regulatory Autonomy under the WTO Agreement on Sanitary and Phytosanitary Measures: Implications of Korea–Import Bans, and Testing and Certification Requirements for Radionuclides
Authors: Lee Yong-Shik 
Published: April 2021

AbstractThe recent WTO dispute case, Korea–Import Bans, and Testing and Certification Requirements for Radionuclides, illustrates complex legal issues and significant political implications associated with the regulatory autonomy of a sovereign country under the WTO Agreement on Sanitary and Phytosanitary Measures (SPS Agreement). There has been constant tension between the sovereign right of a WTO member state to determine its own appropriate level of protection (ALOP) and the regulatory constraints imposed under the SPS Agreement to prevent abuse and disguised trade protection. The case emerged from this tension and raises questions on the extent of the regulatory autonomy in the application of an SPS measure. This article addresses these questions and examines the criteria for the qualitative standards for the ALOP, the question that the Appellate Body decision did not fully resolve. The criteria for the qualitative ALOP standards affect the regulatory autonomy significantly under the current SPS rules as they determine the manner and the extent to which a Member may meet the sensitive public interests in the application of an SPS measure. The article proposes a rational basis test to restrain abuse of SPS measures while preserving the regulatory autonomy protected under the SPS Agreement.
Empirical Loss Timescales of Slot Region Electrons due to Plasmaspheric Hiss Based on Van Allen Probes Observations
Authors: Zhu Qi , Cao Xing , Gu Xudong , Ni Binbin , Xiang Zheng , Fu Song , Summers Danny , Hua Man , Lou Yuequn , Ma Xin , Guo Yingjie , Guo Deyu , Zhang Wenxun 
Published: April 2021

AbstractBased on Van Allen Probes observations, in this study we perform a statistical analysis of the spectral intensities of plasmaspheric hiss at L‐shells of 1.8–3.0 in the slot region. Our results show that slot region hiss power intensifies with a strong day‐night asymmetry as the level of substorm activity or L‐shell increases. Using the statistical spectral profiles of plasmaspheric hiss, we calculate the drift‐ and bounce‐averaged electron pitch angle diffusion coefficients and subsequently obtain the resultant electron loss timescales through 1‐D Fokker‐Planck simulations. We find that slot region electron loss timescales vary significantly from <1 day to several years, showing a strong dependence on electron energy, L‐shell and substorm activity. We also construct an empirical model of slot region electron loss timescales due to scattering by plasmaspheric hiss, which agrees well with the 1‐D simulation results and can be readily used in modeling the dynamics of slot region electrons.
Silica optical fiber integrated with two-dimensional materials: towards opto-electro-mechanical technology
Authors: Chen Jin-hui , Xiong Yi-feng , Xu Fei , Lu Yan-qing 
Published: April 2021

AbstractIn recent years, the integration of graphene and related two-dimensional (2D) materials in optical fibers have stimulated significant advances in all-fiber photonics and optoelectronics. The conventional passive silica fiber devices with 2D materials are empowered for enhancing light-matter interactions and are applied for manipulating light beams in respect of their polarization, phase, intensity and frequency, and even realizing the active photo-electric conversion and electro-optic modulation, which paves a new route to the integrated multifunctional all-fiber optoelectronic system. This article reviews the fast-progress field of hybrid 2D-materials-optical-fiber for the opto-electro-mechanical devices. The challenges and opportunities in this field for future development are discussed.
Integrated impedance sensing of liquid sample plug flow enables automated high throughput NMR spectroscopy
Authors: Nassar Omar , Jouda Mazin , Rapp Michael , Mager Dario , Korvink Jan G. , MacKinnon Neil 
Published: April 2021

AbstractA novel approach for automated high throughput NMR spectroscopy with improved mass-sensitivity is accomplished by integrating microfluidic technologies and micro-NMR resonators. A flow system is utilized to transport a sample of interest from outside the NMR magnet through the NMR detector, circumventing the relatively vast dead volume in the supplying tube by loading a series of individual sample plugs separated by an immiscible fluid. This dual-phase flow demands a real-time robust sensing system to track the sample position and velocities and synchronize the NMR acquisition. In this contribution, we describe an NMR probe head that possesses a microfluidic system featuring: (i) a micro saddle coil for NMR spectroscopy and (ii) a pair of interdigitated capacitive sensors flanking the NMR detector for continuous position and velocity monitoring of the plugs with respect to the NMR detector. The system was successfully tested for automating flow-based measurement in a 500 MHz NMR system, enabling high resolution spectroscopy and NMR sensitivity of 2.18 nmol s1/2with the flow sensors in operation. The flow sensors featured sensitivity to an absolute difference of 0.2 in relative permittivity, enabling distinction between most common solvents. It was demonstrated that a fully automated NMR measurement of nine individual 120 μL samples could be done within 3.6 min or effectively 15.3 s per sample.
Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial
Authors: Agarwal Sri Mahavir , Panda Roshni , Costa-Dookhan Kenya A. , MacKenzie Nicole E. , Treen Quinn Casuccio , Caravaggio Fernando , Hashim Eyesha , Leung General , Kirpalani Anish , Matheson Kelly , Chintoh Araba F. , Kramer Caroline K. , Voineskos Aristotle N. , Graff-Guerrero Ariel , Remington Gary J. , Hahn Margaret K. 
Published: April 2021

AbstractPatients with schizophrenia have exceedingly high rates of metabolic comorbidity including type 2 diabetes and lose 15–20 years of life due to cardiovascular diseases, with early accrual of cardiometabolic disease. In this study, thirty overweight or obese (Body Mass Index (BMI) > 25) participants under 40 years old with schizophrenia spectrum disorders and early comorbid prediabetes or type 2 diabetes receiving antipsychotic medications were randomized, in a double-blind fashion, to metformin 1500 mg/day or placebo (2:1 ratio; n = 21 metformin and n = 9 placebo) for 4 months. The primary outcome measures were improvements in glucose homeostasis (HbA1c, fasting glucose) and insulin resistance (Matsuda index—derived from oral glucose tolerance tests and homeostatic model of insulin resistance (HOMA-IR)). Secondary outcome measures included changes in weight, MRI measures of fat mass and distribution, symptom severity, cognition, and hippocampal volume. Twenty-two patients (n = 14 metformin; n = 8 placebo) completed the trial. The metformin group had a significant decrease over time in the HOMA-IR (p = 0.043) and fasting blood glucose (p = 0.007) vs. placebo. There were no differences between treatment groups in the Matsuda index, HbA1c, which could suggest liver-specific effects of metformin. There were no between group differences in other secondary outcome measures, while weight loss in the metformin arm correlated significantly with decreases in subcutaneous, but not visceral or hepatic adipose tissue. Our results show that metformin improved dysglycemia and insulin sensitivity, independent of weight loss, in a young population with prediabetes/diabetes and psychosis spectrum illness, that is at extremely high risk of early cardiovascular mortality. Trial Registration: This protocol was registered with clinicaltrials.gov (NCT02167620).
Radiation enhances the delivery of antisense oligonucleotides and improves chemo-radiation efficacy in brain tumor xenografts
Authors: Ambady Prakash , Wu Yingjen Jeffrey , Kersch Cymon N. , Walker Joshua M. , Holland Samantha , Muldoon Leslie L. , Neuwelt Edward A. 
Published: April 2021

AbstractOverexpression of O6-methylguanine DNA methyltransferase (MGMT) contributes to resistance to chemo-radiation therapy (CRT) in brain tumors. We previously demonstrated that non-ablative radiation improved delivery of anti-MGMT morpholino oligonucleotides (AMONs) to reduce MGMT levels in subcutaneous tumor xenografts. We evaluate this approach to enhance CRT efficacy in rat brain tumor xenograft models. The impact of radiation on targeted delivery was evaluated using fluorescent oligonucleotides (f-ON). In vitro, f-ON was localized to clathrin-coated vesicles, endosomes, and lysosomes using confocal microscopy in T98G glioma cells. In vivo, fluorescence was detected in pre-radiated, but not non-radiated Long Evans (non-tumor bearing) rat brains. Cranial radiation (2 Gy) followed by AMONs (intravenous, 10.5 mg/kg) reduced MGMT expression by 50% in both orthotopic cerebellar D283 medulloblastoma and intracerebral H460 non-small cell lung carcinoma (NSCLC) xenograft models. To evaluate the efficacy, AMONs concurrent with CRT (2 Gy radiation plus oral 20 mg/kg temozolomide ×4 days) reduced tumor volumes in the medulloblastoma model (p = 0.012), and a similar trend was found in the NSCLC brain metastasis model. We provide proof of concept for the use of non-ablative radiation to guide and enhance the delivery of morpholino oligonucleotides into brain tumor xenograft models to reduce MGMT levels and improve CRT efficacy.
Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells
Authors: Bi Yanli , Gong Longyuan , Liu Pengyuan , Xiong Xiufang , Zhao Yongchao 
Published: April 2021

AbstractErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.
TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8+ T cells in conjunction with CEACAM1
Authors: Lake Camille M. , Voss Kelsey , Bauman Bradly M. , Pohida Katherine , Jiang Timothy , Dveksler Gabriela , Snow Andrew L. 
Published: April 2021

AbstractImmune homeostasis depends upon effective clearance of pathogens while simultaneously preventing autoimmunity and immunopathology in the host. Restimulation-induced cell death (RICD) is one such mechanism where by activated T cells receive subsequent antigenic stimulation, reach a critical signal threshold through the T cell receptor (TCR), and commit to apoptosis. Many details of this process remain unclear, including the role of co-stimulatory and co-inhibitory proteins that influence the TCR signaling cascade. Here we characterize the role of T cell immunoglobulin and mucin domain containing 3 (TIM-3) in RICD regulation. TIM-3 protected newly activated CD8+ effector T cells from premature RICD during clonal expansion. Surprisingly, however, we found that TIM-3 potentiated RICD in late-stage effector T cells. The presence of TIM-3 increased proximal TCR signaling and proapoptotic protein expression in late-stage effector T cells, with no consistent signaling effects noted in newly activated cells with or without TIM-3. To better explain these differences in TIM-3 function as T cells aged, we characterized the temporal pattern of TIM-3 expression in effector T cells. We found that TIM-3 was expressed on the surface of newly activated effector T cells, but remained largely intracellular in late-stage effector cells. Consistent with this, TIM-3 required a ligand to prevent early RICD, whereas ligand manipulation had no effects at later stages. Of the known TIM-3 ligands, carcinoembryonic antigen‐related cell adhesion molecule (CEACAM1) showed the greatest difference in surface expression over time and also protected newly activated cells from premature RICD, with no measurable effects in late-stage effectors. Indeed, CEACAM1 enabled TIM-3 surface expression on T cells, implying a co-dependency for these proteins in protecting expanding T cells from premature RICD. Our findings suggest that co-signaling proteins like TIM-3 and CEACAM1 can alter RICD sensitivity at different stages of the effector T cell response, with important implications for checkpoint blockade therapy.
In situ architecture of neuronal α-Synuclein inclusions
Authors: Trinkaus Victoria A. , Riera-Tur Irene , Martínez-Sánchez Antonio , Bäuerlein Felix J. B. , Guo Qiang , Arzberger Thomas , Baumeister Wolfgang , Dudanova Irina , Hipp Mark S. , Hartl F. Ulrich , Fernández-Busnadiego Rubén 
Published: April 2021

AbstractThe molecular architecture of α-Synuclein (α-Syn) inclusions, pathognomonic of various neurodegenerative disorders, remains unclear. α-Syn inclusions were long thought to consist mainly of α-Syn fibrils, but recent reports pointed to intracellular membranes as the major inclusion component. Here, we use cryo-electron tomography (cryo-ET) to image neuronal α-Syn inclusions in situ at molecular resolution. We show that inclusions seeded by α-Syn aggregates produced recombinantly or purified from patient brain consist of α-Syn fibrils crisscrossing a variety of cellular organelles. Using gold-labeled seeds, we find that aggregate seeding is predominantly mediated by small α-Syn fibrils, from which cytoplasmic fibrils grow unidirectionally. Detailed analysis of membrane interactions revealed that α-Syn fibrils do not contact membranes directly, and that α-Syn does not drive membrane clustering. Altogether, we conclusively demonstrate that neuronal α-Syn inclusions consist of α-Syn fibrils intermixed with membranous organelles, and illuminate the mechanism of aggregate seeding and cellular interaction.
Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland
Authors: Lee Hye Kyung , Willi Michaela , Kuhns Tyler , Liu Chengyu , Hennighausen Lothar 
Published: April 2021

AbstractEnhancers are transcription factor platforms that synergize with promoters to control gene expression. Here, we investigate enhancers that activate gene expression several hundred-fold exclusively in the lactating mouse mammary gland. Using ChIP-seq for activating histone marks and transcription factors, we identify two candidate enhancers and one super-enhancer in the Csn1s2b locus. Through experimental mouse genetics, we dissect the lactation-specific distal enhancer bound by the mammary-enriched transcription factors STAT5 and NFIB and the glucocorticoid receptor. While deletions of canonical binding motifs for NFIB and STAT5, individually or combined, have a limited biological impact, a non-canonical STAT5 site is essential for enhancer activity during lactation. In contrast, the intronic enhancer contributes to gene expression only in late pregnancy and early lactation, possibly by interacting with the distal enhancer. A downstream super-enhancer, which physically interacts with the distal enhancer, is required for the functional establishment of the Csn1s2b promoter and gene activation. Lastly, NFIB binding in the promoter region fine-tunes Csn1s2b expression. Our study provides comprehensive insight into the anatomy and biology of regulatory elements that employ the JAK/STAT signaling pathway and preferentially activate gene expression during lactation.
Cell barrier function of resident peritoneal macrophages in post-operative adhesions
Authors: Ito Tomoya , Shintani Yusuke , Fields Laura , Shiraishi Manabu , Podaru Mihai‑Nicolae , Kainuma Satoshi , Yamashita Kizuku , Kobayashi Kazuya , Perretti Mauro , Lewis-McDougall Fiona , Suzuki Ken 
Published: April 2021

AbstractPost-operative adhesions are a leading cause of abdominal surgery-associated morbidity. Exposed fibrin clots on the damaged peritoneum, in which the mesothelial barrier is disrupted, readily adhere to surrounding tissues, resulting in adhesion formation. Here we show that resident F4/80HighCD206−peritoneal macrophages promptly accumulate on the lesion and form a ‘macrophage barrier’ to shield fibrin clots in place of the lost mesothelium in mice. Depletion of this macrophage subset or blockage of CD11b impairs the macrophage barrier and exacerbates adhesions. The macrophage barrier is usually insufficient to fully preclude the adhesion formation; however, it could be augmented by IL-4-based treatment or adoptive transfer of this macrophage subset, resulting in robust prevention of adhesions. By contrast, monocyte-derived recruited peritoneal macrophages are not involved in the macrophage barrier. These results highlight a previously unidentified cell barrier function of a specific macrophage subset, also proposing an innovative approach to prevent post-operative adhesions.
Self-powered ultraflexible photonic skin for continuous bio-signal detection via air-operation-stable polymer light-emitting diodes
Authors: Jinno Hiroaki , Yokota Tomoyuki , Koizumi Mari , Yukita Wakako , Saito Masahiko , Osaka Itaru , Fukuda Kenjiro , Someya Takao 
Published: April 2021

AbstractUltraflexible optical devices have been used extensively in next-generation wearable electronics owing to their excellent conformability to human skins. Long-term health monitoring also requires the integration of ultraflexible optical devices with an energy-harvesting power source; to make devices self-powered. However, system-level integration of ultraflexible optical sensors with power sources is challenging because of insufficient air operational stability of ultraflexible polymer light-emitting diodes. Here we develop an ultraflexible self-powered organic optical system for photoplethysmogram monitoring by combining air-operation-stable polymer light-emitting diodes, organic solar cells, and organic photodetectors. Adopting an inverted structure and a doped polyethylenimine ethoxylated layer, ultraflexible polymer light-emitting diodes retain 70% of the initial luminance even after 11.3 h of operation under air. Also, integrated optical sensors exhibit a high linearity with the light intensity exponent of 0.98 by polymer light-emitting diode. Such self-powered, ultraflexible photoplethysmogram sensors perform monitoring of blood pulse signals as 77 beats per minute.
A compartmental model that predicts the effect of social distancing and vaccination on controlling COVID-19
Authors: Dashtbali Mohammadali , Mirzaie Mehdi 
Published: April 2021

AbstractThe understanding of the interaction between disease dynamics and human behavior is an important and essential point to control infectious. Disease outbreak can be influenced by social distancing and vaccination. In this study, we introduce two compartmental models to derive the epidemic curve and analyze the individual’s behavior in spreading and controlling the COVID-19 epidemic. The first model includes Susceptible, Exposed, Infectious, Hospitalized, Recovered and Death compartments and in the second model, we added a new compartment namely, semi-susceptible individuals that are assumed to be more immune than the susceptible. A comparison of the two models shows that the second model provides a better fit to the daily infected cases from Egypt, Belgium, Japan, Nigeria, Italy, and Germany released by WHO. Finally, we added a vaccinated term to the model to predict how vaccination could control the epidemic. The model was applied on the record data from WHO.