bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Key Climate Variables on Mass Balance of Naimona'nyi Glacier on a North‐Facing Slope in the Western Himalayas
Authors: Zhu Meilin , Yang Wei , Yao Tandong , Tian Lide , Thompson Lonnie G. , Zhao Huabiao
Published: March 2021

Glacier mass changes in the Himalayas impact on sustainable water resources and hazards in downstream regions. However, mass balance variation and its drivers on north‐facing slopes in the Himalayas are not well understood. This study presents the meteorological conditions, energy and mass balance characteristics for Naimona'nyi Glacier on a north‐facing slope in the western Himalayas, based on energy‐mass balance model and high‐altitude measurements from October 2010 to September 2018. The average annual mass balance measured for Naimona'nyi Glacier was −0.39 m water equivalent a−1 and point mass balances below 6,070 m above sea level were always negative. Simulations showed that melt during the ablation season dominated the annual mass balance and the interannual variability in the mass balance, and that variability in melt energy was controlled by albedo during the ablation season. The annual mass balance was found to be significantly correlated with annual precipitation during the 2011–2018 period, which is accounted for by the change in ablation‐season albedo and melt energy. The average mass balance for glaciers in the western Himalayas were higher during the 2010–2019 period than during the 2000–2009 period, partly because of higher annual precipitation during the 2010–2019 period. Over the last 20 years, the increased precipitation in the cold season was driven by a cyclonic circulation anomaly over the northwestern Indian Peninsula, which may be linked to the strengthened North Atlantic Oscillation, and the increased precipitation in the ablation season was driven by an anomaly in the cyclonic circulation over Central India, which may be related to enhanced deep convection over the Indian subcontinent and the enhanced Atlantic multidecadal oscillation.
Locating Rockfalls Using Inter‐Station Ratios of Seismic Energy at Dolomieu Crater, Piton de la Fournaise Volcano
Authors: Kuehnert J. , Mangeney A. , Capdeville Y. , Vilotte J. P. , Stutzmann E. , Chaljub E. , Aissaoui E. , Boissier P. , Brunet C. , Kowalski P. , Lauret F.
Published: March 2021

Rockfalls generate seismic signals that can be used to detect and monitor rockfall activity. Event locations can be estimated on the basis of arrival times, amplitudes, or polarization of these seismic signals. However, surface topography variations can significantly influence seismic wave propagation and hence compromise results. Here, we specifically use the signature of topography on the seismic signal to better constrain the source location. Seismic impulse responses are predicted using Spectral Element based simulation of three‐dimensional wave propagation in realistic geological media. Subsequently, rockfalls are located by minimizing the misfit between simulated and observed inter‐station energy ratios. The method is tested on rockfalls at Dolomieu crater, Piton de la Fournaise volcano, Reunion Island. Both single boulder impacts and distributed granular flows are successfully located, tracking the complete rockfall trajectories by analyzing the signals in sliding time windows. Results from the highest frequency band (here 13–17 Hz) yield the best spatial resolution, making it possible to distinguish detachment positions less than 100 m apart. By taking into account surface topography, both vertical and horizontal signal components can be used. Limitations and the noise robustness of the location method are assessed using synthetic signals. Precise representation of the topography controls the location resolution, which is not significantly affected by the assumed impact direction. Tests on the network geometry reveal best resolution when the seismometers triangulate the source. We conclude that this method can improve the monitoring of rockfall activity in real time once a simulated database for the region of interest is created.
Characterizing Convection Schemes Using Their Responses to Imposed Tendency Perturbations
Authors: Hwong Y. L. , Song S. , Sherwood S. C. , Stirling A. J. , Rio C. , Roehrig R. , Daleu C. L. , Plant R. S. , Fuchs D. , Maher P. , Touzé‐Peiffer L.
Published: March 2021

Convection is usually parameterized in global climate models, and there are often large discrepancies between results obtained with different convection schemes. Conventional methods of comparing convection schemes using observational cases or directly in three‐dimensional (3D) models do not always clearly identify parameterization strengths and weaknesses. In this paper we evaluate the response of parameterizations to various perturbations rather than their behavior under particular strong forcing. We use the linear response function method proposed by Kuang (2010) to compare 12 physical packages in five atmospheric models using single‐column model (SCM) simulations under idealized radiative‐convective equilibrium conditions. The models are forced with anomalous temperature and moisture tendencies. The temperature and moisture departures from equilibrium are compared with published results from a cloud‐resolving model (CRM). Results show that the procedure is capable of isolating the behavior of a convection scheme from other physics schemes. We identify areas of agreement but also substantial differences between convection schemes, some of which can be related to scheme design. Some aspects of the model linear responses are related to their RCE profiles (the relative humidity profile in particular), while others constitute independent diagnostics. All the SCMs show irregularities or discontinuities in behavior that are likely related to threshold‐related mechanisms used in the convection schemes, and which do not appear in the CRM. Our results highlight potential flaws in convection schemes and suggest possible new directions to explore for parameterization evaluation.
Treatment of bilateral sacral insufficiency fractures with sacroplasty in a patient with motor complete tetraplegia
Authors: Petriello Marla A. , Groah Suzanne , Matiana Suman D.
Published: March 2021

Introduction

Osteoporosis is a common secondary complication of spinal cord injury, with fragility fractures typically occurring in the lower body and management often is conservative.

Case presentation

We present a 52-year-old male with chronic complete tetraplegia who presented to the emergency room with unremitting autonomic dysreflexia (AD). He was admitted for medical management of the AD when a source of the AD could not be identified. After an extensive workup, the patient was found to have bilateral sacral insufficiency fractures. He subsequently underwent sacroplasty with immediate and full resolution of AD symptoms and return to full premorbid function within 24 h.

Discussion

People with chronic spinal cord injury (SCI) are at risk for spinal column fragility fractures in addition to lower extremity fractures. Vertebroplasty may be a safe option for treatment of insufficiency fractures in situations where conservative care may put people at risk for significant immobility-associated complications.
N6-methyladenosine modification of circCUX1 confers radioresistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway
Authors: Wu Ping , Fang Xing , Liu Yalan , Tang Yaoyun , Wang Wei , Li Xin , Fan Yuhua
Published: March 2021

Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most common malignant tumors in otolaryngology head and neck surgery and is one of the worst prognostic malignant tumors. Endogenous circular RNA (circRNA) is more stable than mRNA, microRNA (miRNA), and long non-coding RNA (LncRNA) in exosomes, plasma, and urine, and participates in gene expression regulation to perform different functions. Therefore, circRNA is expected to become a biomarker and therapy target for many tumors. However, the expression and function of circRNA regulated by N6-methyladenosine (m6A) are still unclear in HNSCC. In this study, we demonstrated that a specific circRNA, circCUX1, was upregulated in HPSCC patients who are resistant to radiotherapy and predicts poor survival outcome. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circCUX1 and stabilizes its expression. Knockdown circCUX1 promotes the sensitivity of hypopharyngeal cancer cells to radiotherapy. In addition, circCUX1 binds to Caspase1 and inhibits its expression, resulting in a decrease in the release of inflammatory factors, thereby developing tolerance to radiotherapy. Our findings indicate that circCUX1 is a potential therapeutic target for radiotherapy tolerance in HPSCC patients.
CircSPI1 acts as an oncogene in acute myeloid leukemia through antagonizing SPI1 and interacting with microRNAs
Authors: Wang Xiaoling , Jin Peng , Zhang Yi , Wang Kankan
Published: March 2021

PU.1 (encoded by SPI1) is essential for myeloid development, and inhibition of its expression and activity can lead to acute myeloid leukemia (AML). The precise regulation of PU.1 expression is crucial for the development of AML, and the discovery of circular RNAs (circRNAs) can add a new layer of information on regulation. Here, we found that circSPI1, the circular RNA derived from the SPI1 gene, is highly expressed in AML but not in normal counterparts. Unlike SPI1, a tumor suppressor and being lowly expressed in AML, we demonstrate that circSPI1 acts as an oncogene, evidenced by the observation that circSPI1 knockdown induces myeloid differentiation and apoptosis of AML cells. We provide mechanistic evidence for multiple regulatory roles of circSPI1 in AML progression. On one hand, circSPI1 contributes to myeloid differentiation of AML cells by interacting with the translation initiation factor eIF4AIII to antagonize PU.1 expression at the translation level. On the other hand, circSPI1 contributes to proliferation and apoptosis by interacting with miR-1307-3p, miR-382-5p, and miR-767-5p; this role is uncoupled with SPI1. Finally, we illustrate the clinical significance of circSPI1 by showing that circSPI1-regulated genes are associated with the clinical outcome of AML patients. Our data provide new insight into the complex SPI1 gene regulation now involving circSPI1.
Emerging role of RNA modification N6-methyladenosine in immune evasion
Authors: Lou Xin , Wang Juan-Juan , Wei Ya-Qing , Sun Jin-Jin
Published: March 2021

The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at different levels to occur immune evasion, including by N6-methyladenosine (m6A) modification. In this review, we discuss studies revealing the immune evasion mechanism by m6A modification, which underlies the retouching of these signaling networks and the rapid tolerance of innate and adaptive immune molecules during disease. We also focus on the functions of m6A in main chemokines regulation, and their roles in promotive and suppressive immune cell recruitment. We then discuss some of the current challenges in the field and describe future directions for the immunological mechanisms of m6A modification.
Time and classical equations of motion from quantum entanglement via the Page and Wootters mechanism with generalized coherent states
Authors: Foti Caterina , Coppo Alessandro , Barni Giulio , Cuccoli Alessandro , Verrucchi Paola
Published: March 2021

We draw a picture of physical systems that allows us to recognize what “time” is by requiring consistency with the way that time enters the fundamental laws of Physics. Elements of the picture are two non-interacting and yet entangled quantum systems, one of which acting as a clock. The setting is based on the Page and Wootters mechanism, with tools from large-N quantum approaches. Starting from an overall quantum description, we first take the classical limit of the clock only, and then of the clock and the evolving system altogether; we thus derive the Schrödinger equation in the first case, and the Hamilton equations of motion in the second. This work shows that there is not a “quantum time”, possibly opposed to a “classical” one; there is only one time, and it is a manifestation of entanglement.
Photolytic radical persistence due to anoxia in viscous aerosol particles
Authors: Alpert Peter A. , Dou Jing , Corral Arroyo Pablo , Schneider Frederic , Xto Jacinta , Luo Beiping , Peter Thomas , Huthwelker Thomas , Borca Camelia N. , Henzler Katja D. , Schaefer Thomas , Herrmann Hartmut , Raabe Jörg , Watts Benjamin , Krieger Ulrich K. , Ammann Markus
Published: March 2021

In viscous, organic-rich aerosol particles containing iron, sunlight may induce anoxic conditions that stabilize reactive oxygen species (ROS) and carbon-centered radicals (CCRs). In laboratory experiments, we show mass loss, iron oxidation and radical formation and release from photoactive organic particles containing iron. Our results reveal a range of temperature and relative humidity, including ambient conditions, that control ROS build up and CCR persistence in photochemically active, viscous organic particles. We find that radicals can attain high concentrations, altering aerosol chemistry and exacerbating health hazards of aerosol exposure. Our physicochemical kinetic model confirmed these results, implying that oxygen does not penetrate such particles due to the combined effects of fast reaction and slow diffusion near the particle surface, allowing photochemically-produced radicals to be effectively trapped in an anoxic organic matrix.
Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis
Authors: Thulasingam Madhuranayaki , Orellana Laura , Nji Emmanuel , Ahmad Shabbir , Rinaldo-Matthis Agnes , Haeggström Jesper Z.
Published: March 2021

Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C4, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets.
Substantial decrease in CO2 emissions from Chinese inland waters due to global change
Authors: Ran Lishan , Butman David E. , Battin Tom J. , Yang Xiankun , Tian Mingyang , Duvert Clément , Hartmann Jens , Geeraert Naomi , Liu Shaoda
Published: March 2021

Carbon dioxide (CO2) evasion from inland waters is an important component of the global carbon cycle. However, it remains unknown how global change affects CO2 emissions over longer time scales. Here, we present seasonal and annual fluxes of CO2 emissions from streams, rivers, lakes, and reservoirs throughout China and quantify their changes over the past three decades. We found that the CO2 emissions declined from 138 ± 31 Tg C yr−1 in the 1980s to 98 ± 19 Tg C yr−1 in the 2010s. Our results suggest that this unexpected decrease was driven by a combination of environmental alterations, including massive conversion of free-flowing rivers to reservoirs and widespread implementation of reforestation programs. Meanwhile, we found increasing CO2 emissions from the Tibetan Plateau inland waters, likely attributable to increased terrestrial deliveries of organic carbon and expanded surface area due to climate change. We suggest that the CO2 emissions from Chinese inland waters have greatly offset the terrestrial carbon sink and are therefore a key component of China’s carbon budget.
Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection
Authors: Wettstein Lukas , Weil Tatjana , Conzelmann Carina , Müller Janis A. , Groß Rüdiger , Hirschenberger Maximilian , Seidel Alina , Klute Susanne , Zech Fabian , Prelli Bozzo Caterina , Preising Nico , Fois Giorgio , Lochbaum Robin , Knaff Philip Maximilian , Mailänder Volker , Ständker Ludger , Thal Dietmar Rudolf , Schumann Christian , Stenger Steffen , Kleger Alexander , Lochnit Günter , Mayer Benjamin , Ruiz-Blanco Yasser B. , Hoffmann Markus , Sparrer Konstantin M. J. , Pöhlmann Stefan , Sanchez-Garcia Elsa , Kirchhoff Frank , Frick Manfred , Münch Jan
Published: March 2021

SARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of the respiratory tract against SARS-CoV-2 is limited, we generated and screened a peptide/protein library derived from bronchoalveolar lavage for inhibitors of SARS-CoV-2 spike-driven entry. Analysis of antiviral fractions revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. Here, we report that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication in cell lines and primary cells including human airway epithelial cultures. We further demonstrate that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α1AT is an inhibitor of TMPRSS2 and SARS-CoV-2 entry, and may play an important role in the innate immune defense against the novel coronavirus. Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.
Photonic resonator interferometric scattering microscopy
Authors: Li Nantao , Canady Taylor D. , Huang Qinglan , Wang Xing , Fried Glenn A. , Cunningham Brian T.
Published: March 2021

Interferometric scattering microscopy is increasingly employed in biomedical research owing to its extraordinary capability of detecting nano-objects individually through their intrinsic elastic scattering. To significantly improve the signal-to-noise ratio without increasing illumination intensity, we developed photonic resonator interferometric scattering microscopy (PRISM) in which a dielectric photonic crystal (PC) resonator is utilized as the sample substrate. The scattered light is amplified by the PC through resonant near-field enhancement, which then interferes with the <1% transmitted light to create a large intensity contrast. Importantly, the scattered photons assume the wavevectors delineated by PC’s photonic band structure, resulting in the ability to utilize a non-immersion objective without significant loss at illumination density as low as 25 W cm−2. An analytical model of the scattering process is discussed, followed by demonstration of virus and protein detection. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies.
Epigenetic mechanisms in breast cancer therapy and resistance
Authors: Garcia-Martinez Liliana , Zhang Yusheng , Nakata Yuichiro , Chan Ho Lam , Morey Lluis
Published: March 2021

The majority of breast cancers express the estrogen receptor (ERα) and agents targeting this pathway represent the main treatment modality. Endocrine therapy has proven successful in the treatment of hormone-responsive breast cancer since its early adoption in the 1940s as an ablative therapy. Unfortunately, therapeutic resistance arises, leading to disease recurrence and relapse. Recent studies increased our understanding in how changes to the chromatin landscape and deregulation of epigenetic factors orchestrate the resistant phenotype. Here, we will discuss how the epigenome is an integral determinant in hormone therapy response and why epigenetic factors are promising targets for overcoming clinical resistance.
Prediction of stimulus-independent and task-unrelated thought from functional brain networks
Authors: Kucyi Aaron , Esterman Michael , Capella James , Green Allison , Uchida Mai , Biederman Joseph , Gabrieli John D. E. , Valera Eve M. , Whitfield-Gabrieli Susan
Published: March 2021

Neural substrates of “mind wandering” have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering—stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling—dominated by default-frontoparietal control subnetwork interactions—that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of adults with attention-deficit/hyperactivity disorder (ADHD). In three additional resting-state fMRI studies (total n = 1115), including healthy individuals and individuals with ADHD, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales and contexts.
Outcomes of changing systemic therapy in patients with relapsed breast cancer and 1 to 3 brain metastases
Authors: Alhalabi Omar , Soomro Zaid , Sun Ryan , Hasanov Elshad , Albittar Aya , Tripathy Debu , Valero Vicente , Ibrahim Nuhad K.
Published: March 2021

The development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.
Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression
Authors: Mwesigwa Savannah , Williams Lesedi , Retshabile Gaone , Katagirya Eric , Mboowa Gerald , Mlotshwa Busisiwe , Kyobe Samuel , Kateete David P. , Wampande Eddie Mujjwiga , Wayengera Misaki , Mpoloka Sununguko Wata , Mirembe Angella N. , Kasvosve Ishmael , Morapedi Koketso , Kisitu Grace P. , Kekitiinwa Adeodata R. , Anabwani Gabriel , Joloba Moses L. , Matovu Enock , Mulindwa Julius , Noyes Harry , Botha Gerrit ,   Collaborative African Genomics Network (CAfGEN), Tsimako-Johnstone Masego , Katabazi Fred. A. , Kigozi Edgar , Mathuba Keofentse ,   TrypanoGEN Research Group, Brown Chester W. , Mardon Graeme , Matshaba Mogomotsi , Hanchard Neil A.
Published: March 2021

Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%;p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), withAnelloviridaeshowing strong association with LTNP status (p = 3 × 10−4;q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02;q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of theAnelloviridaereads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.
Impact of bronchiolitis guidelines publication on primary care prescriptions in the Italian pediatric population
Authors: Barbieri Elisa , Cantarutti Anna , Cavagnis Sara , Cantarutti Luigi , Baraldi Eugenio , Giaquinto Carlo , Donà Daniele
Published: March 2021

In Italy, two clinical practice guidelines for the diagnosis and treatment of bronchiolitis were published in October 2014 and December 2015. We evaluated prescriptions for bronchiolitis in children aged 0–24 months before (December 2012–December 2014), in between (December 2014–December 2015) and after (December 2015–December 2018) the guidelines publications. Data were retrieved from the Pedianet database; the measured outcomes were prescriptions rates of antibiotics, corticosteroids, β2-agonists, and other respiratory drugs. In 1011 out of 1581 episodes, patients received at least one treatment, with a total of 2003 prescriptions. The rate of treated bronchiolitis decreased from 66% to 57% (p < 0.001) after the publication of the second guideline; the highest reduction was in younger patients (from 57% to 44%, p = 0.013). Overall antibiotic prescriptions rate did not change, with 31.6% of the patients still receiving them. Our results confirm unnecessary non-evidence-based treatments in the primary care setting, with few changes after the guidelines publications.
Crystalline symmetry-protected non-trivial topology in prototype compound BaAl4
Authors: Wang Kefeng , Mori Ryo , Wang Zhijun , Wang Limin , Ma Jonathan Han Son , Latzke Drew W. , Graf David E. , Denlinger Jonathan D. , Campbell Daniel , Bernevig B. Andrei , Lanzara Alessandra , Paglione Johnpierre
Published: March 2021

The BaAl4 prototype crystal structure is the most populous of all structure types, and is the building block for a diverse set of sub-structures including the famous ThCr2Si2 family that hosts high-temperature superconductivity and numerous magnetic and strongly correlated electron systems. The MA4 family of materials (M = Sr, Ba, Eu; A = Al, Ga, In) themselves present an intriguing set of ground states including charge and spin orders, but have largely been considered as uninteresting metals. We predict the exemplary compound BaAl4 to harbor a three-dimensional Dirac spectrum with non-trivial topology and possible nodal lines crossing the Brillouin zone, wherein one pair of semi-Dirac points with linear dispersion along the kz direction and quadratic dispersion along the kx/ky direction resides on the rotational axis with C4v point group symmetry. An extremely large, unsaturating positive magnetoresistance in BaAl4 despite an uncompensated band structure is revealed, and quantum oscillations and angle-resolved photoemission spectroscopy measurements confirm the predicted multiband semimetal structure with pockets of Dirac holes and a Van Hove singularity (VHS) remarkably consistent with the theoretical prediction. We thus present BaAl4 as a topological semimetal, casting its prototype status into a role as a building block for a vast array of topological materials.
Charge density waves in cuprate superconductors beyond the critical doping
Authors: Miao H. , Fabbris G. , Koch R. J. , Mazzone D. G. , Nelson C. S. , Acevedo-Esteves R. , Gu G. D. , Li Y. , Yilimaz T. , Kaznatcheev K. , Vescovo E. , Oda M. , Kurosawa T. , Momono N. , Assefa T. , Robinson I. K. , Bozin E. S. , Tranquada J. M. , Johnson P. D. , Dean M. P. M.
Published: March 2021

The unconventional normal-state properties of the cuprates are often discussed in terms of emergent electronic order that onsets below a putative critical doping of xc ≈ 0.19. Charge density wave (CDW) correlations represent one such order; however, experimental evidence for such order generally spans a limited range of doping that falls short of the critical value xc, leading to questions regarding its essential relevance. Here, we use X-ray diffraction to demonstrate that CDW correlations in La2−xSrxCuO4 persist up to a doping of at least x = 0.21. The correlations show strong changes through the superconducting transition, but no obvious discontinuity through xc ≈ 0.19, despite changes in Fermi surface topology and electronic transport at this doping. These results demonstrate the interaction between CDWs and superconductivity even in overdoped cuprates and prompt a reconsideration of the role of CDW correlations in the high-temperature cuprate phase diagram.
Vitrification of particulated articular cartilage via calculated protocols
Authors: Wu Kezhou , Shardt Nadia , Laouar Leila , Elliott Janet A. W. , Jomha Nadr M.
Published: March 2021

Preserving viable articular cartilage is a promising approach to address the shortage of graft tissue and enable the clinical repair of articular cartilage defects in articulating joints, such as the knee, ankle, and hip. In this study, we developed two 2-step, dual-temperature, multicryoprotectant loading protocols to cryopreserve particulated articular cartilage (cubes ~1 mm3 in size) using a mathematical approach, and we experimentally measured chondrocyte viability, metabolic activity, cell migration, and matrix productivity after implementing the designed loading protocols, vitrification, and warming. We demonstrated that porcine and human articular cartilage cubes can be successfully vitrified and rewarmed, maintaining high cell viability and excellent cellular function. The vitrified particulated articular cartilage was stored for a period of 6 months with no significant deterioration in chondrocyte viability and functionality. Our approach enables high-quality long-term storage of viable articular cartilage that can alleviate the shortage of grafts for use in clinically repairing articular cartilage defects.
Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
Authors: van der Lubbe Joan E. M. , Rosendahl Huber Sietske K. , Vijayan Aneesh , Dekking Liesbeth , van Huizen Ella , Vreugdenhil Jessica , Choi Ying , Baert Miranda R. M. , Feddes-de Boer Karin , Izquierdo Gil Ana , van Heerden Marjolein , Dalebout Tim J. , Myeni Sebenzile K. , Kikkert Marjolein , Snijder Eric J. , de Waal Leon , Stittelaar Koert J. , Tolboom Jeroen T. B. M. , Serroyen Jan , Muchene Leacky , van der Fits Leslie , Rutten Lucy , Langedijk Johannes P. M. , Barouch Dan H. , Schuitemaker Hanneke , Zahn Roland C. , Wegmann Frank
Published: March 2021

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.
Quorum quenching, biological characteristics, and microbial community dynamics as key factors for combating fouling of membrane bioreactors
Authors: Shah Syed Salman Ali , De Simone Luigi , Bruno Giuseppe , Park Hyeona , Lee Kibaek , Fabbricino Massimiliano , Angelidaki Irini , Choo Kwang-Ho
Published: March 2021

Membrane fouling is a major challenge in membrane bioreactors (MBRs) for wastewater treatment. This study investigates the effects of disturbance and solid retention time (SRT) on quorum-quenching (QQ) MBRs relative to antifouling efficacy and microbial community change. The fouling rate increases with the applied disturbance at a short SRT, counteracting the antifouling effect of QQ; however, it decreases with QQ at a long SRT. The microbial community appears to be responsible for such MBR behaviors. Several bacterial species belonging to the biofilm-forming group are dominant after disturbance, resulting in substantive membrane fouling. However, the balance between the bacterial species plays a key role in MBR fouling propensity when stabilized. Koflera flava becomes dominant with QQ, leading to reduced membrane fouling. QQ makes the MBR microbial community more diverse, while lowering its richness. QQ with long SRT would be a favorable operational strategy for effective MBR fouling control.
Cloud icing by mineral dust and impacts to aviation safety
Authors: Nickovic Slobodan , Cvetkovic Bojan , Petković Slavko , Amiridis Vassilis , Pejanović Goran , Solomos Stavros , Marinou Eleni , Nikolic Jugoslav
Published: March 2021

Ice particles in high-altitude cold clouds can obstruct aircraft functioning. Over the last 20 years, there have been more than 150 recorded cases with engine power-loss and damage caused by tiny cloud ice crystals, which are difficult to detect with aircraft radars. Herein, we examine two aircraft accidents for which icing linked to convective weather conditions has been officially reported as the most likely reason for catastrophic consequences. We analyze whether desert mineral dust, known to be very efficient ice nuclei and present along both aircraft routes, could further augment the icing process. Using numerical simulations performed by a coupled atmosphere-dust model with an included parameterization for ice nucleation triggered by dust aerosols, we show that the predicted ice particle number sharply increases at approximate locations and times of accidents where desert dust was brought by convective circulation to the upper troposphere. We propose a new icing parameter which, unlike existing icing indices, for the first time includes in its calculation the predicted dust concentration. This study opens up the opportunity to use integrated atmospheric-dust forecasts as warnings for ice formation enhanced by mineral dust presence.
Compatibility between an overnight fasting and random cholesterol tests in Asians
Authors: Phoon Ian Kwong Yun , Koh Yi Ling Eileen , Guo Xiaoxuan , Usha Sankari , Tan Ngiap Chuan
Published: March 2021

Recent Western guidelines recommend non-fasting lipid profiles to manage dyslipidaemia. We explored its applicability to an Asian population. We determined the differences between an overnight fasting and non-fasting cholesterol profiles of patients with type-2 diabetes mellitus (T2DM) in Singapore. We studied 470 multi-ethnic Asian adult patients with T2DM and dyslipidaemia from 2 primary care clinics in Singapore. Non-fasting blood specimens were collected within 6 h after their last meal and within 14 days of a fasting specimen. The intraclass correlation coefficient (ICC) was used to compare the intraindividual lipid profiles. An ICC value > 0.75 implies good correlation. The mean age and T2DM duration of the study population were 62.5 years and 9.8 years respectively. Their mean non-fasting period was 2.46 h. The mean differences between non-fasting and fasting total cholesterol (TC), high-density lipoprotein (HDL-C), triglyceride (TG), low-density lipoprotein (LDL-C), and non HDL-C were + 0.04 mmol/l, − 0.001 mmol/l, + 0.48 mmol/l, − 0.15 mmol/l, and − 0.05 mmol/l respectively. The ICC (95% CI) for TC, HDL-C, TG, LDL-C and non-HDL-C were 0.820 (0.788–0.847), 0.873 (0.850–0.893), 0.579 (0.516–0.636), 0.764 (0.723–0.799), and 0.825 (0.794–0.852) respectively. The fasting and non-fasting lipid profiles were similar in our local Asian patients with T2DM taking statin. Their non-fasting lipid profile can be used to assess their cholesterol treatment status.
Pretreatment PSA levels affects the completion rate of Ra-223 treatment
Authors: Utsumi Nobuko , Kurosaki Hiromasa , Miura Kosei , Kitoh Hiroki , Akakura Koichiro
Published: March 2021

The aim of this study was to review our initial experience of using radium 223 (Ra-223) for metastatic castration-resistant prostate cancer (CRPC) and to evaluate whether pretreatment PSA levels correlate with completion of Ra-223 treatment. In addition, we examined change ratios of PSA, ALP and BAP after the third administration to evaluate the correlation of these change ratios with completion of the subsequent Ra-223 treatment. Forty patients were enrolled in this retrospective study. Ra-223 treatment was considered completed in patients who received five or six administrations. Patient backgrounds and changes in biomarkers were compared between patient groups (complete vs. incomplete Ra-223 treatment). PSA levels before treatment were significantly lower in the complete compared with the incomplete group (cutoff value; 21.7). ALP and BAP levels had decreased after the third administration in the complete group, compared with baseline levels, while levels in the incomplete group had increased. Significant difference was seen in ALP levels, while was not seen in BAP levels between the two groups. Ra-223 treatment should be considered for CRPC with low PSA levels. Changes in PSA and ALP during Ra-223 treatment might provide markers to identify patients likely to complete Ra-223 treatment, with implications for prognosis.
Low-dose steroids are associated with indeterminate QuantiFERON-TB Gold In-Tube assay results in immunocompetent children
Authors: Kim Kyu Ho , Kang Ji-Man , Ahn Jong Gyun
Published: March 2021

Immunocompromised status can result in indeterminate QuantiFERON-TB Gold In-Tube (QFT-GIT) results, but the association of indeterminate results with immunocompetent status in children is unknown. Therefore, we aimed to identify factors associated with indeterminate QFT-GIT results for immunocompetent children. We conducted a retrospective chart review of children (aged ≤ 18 years) who underwent QFT-GIT between September 2006 and July 2017 at the Severance Hospital, Seoul, South Korea. Of the 2037 QFT-GIT assays included in the present study, 7.7% yielded indeterminate QFT-GIT results. Multivariable logistic regression analysis identified younger age (OR 0.88; 95% CI 0.836–0.927; P < 0.001), elevated white blood cell (WBC) count (OR 1.066; 95% CI 1.020–1.115; P = 0.005), decreased albumin levels (OR 0.505; 95% CI 0.316–0.807; P = 0.004), and low-dose steroid therapy (< 1 mg/kg per day of prednisone or equivalent for < 2 weeks) (OR 76.146; 95% CI 8.940–648.569; P < 0.001) as significant factors influencing indeterminate results. Younger age, high WBC count, low albumin levels, and low-dose steroid therapy were associated with indeterminate QFT-GIT results. Low-dose steroid therapy had the highest OR for the indeterminate results compared to other significant risk factors. Our study suggests that screening for steroid doses is important prior to performing interferon-gamma release assays for immunocompetent children.
Acetylation of ELF5 suppresses breast cancer progression by promoting its degradation and targeting CCND1
Authors: Li Xiahui , Li Shujing , Li Bowen , Li Yanan , Aman Sattout , Xia Kangkai , Yang Yuxi , Ahmad Bashir , Wu Huijian
Published: March 2021

E74-like ETS transcription factor 5 (ELF5) is involved in a wide spectrum of biological processes, e.g., mammogenesis and tumor progression. We have identified a list of p300-interacting proteins in human breast cancer cells. Among these, ELF5 was found to interact with p300 via acetylation, and the potential acetylation sites were identified as K130, K134, K143, K197, K228, and K245. Furthermore, an ELF5-specific deacetylase, SIRT6, was also identified. Acetylation of ELF5 promoted its ubiquitination and degradation, but was also essential for its antiproliferative effect against breast cancer, as overexpression of wild-type ELF5 and sustained acetylation-mimicking ELF5 mutant could inhibit the expression of its target gene CCND1. Taken together, the results demonstrated a novel regulation of ELF5 as well as shedding light on its important role in modulation of breast cancer progression.
Precision medicine: preliminary results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT2) study
Authors: Tsimberidou Apostolia Maria , Hong David S. , Fu Siqing , Karp Daniel D. , Piha-Paul Sarina , Kies Merrill S. , Ravi Vinod , Subbiah Vivek , Patel Sunil M. , Tu Shi-Ming , Janku Filip , Heymach John , Johnson Amber , Cartwright Carrie , Zhao Li , Zhang Jianhua , Berry Donald A. , Vining David J. , Futreal Andrew , Miller Vincent A. , Meric-Bernstam Funda
Published: March 2021

Precision medicine is associated with favorable outcomes in selected patients with cancer. Herein, we report an interim analysis of IMPACT2, an ongoing randomized study evaluating genomic profiling and targeted agents in metastatic cancer. Patients with metastatic cancer underwent tumor genomic profiling (ClinialTrials.gov: NCT02152254), and 69 patients met the criteria for randomization. Tumor board and multidisciplinary review of molecular alterations optimized treatment selection. From 5/2014 to 4/2017, 320 patients (median age, 63 years; men, 47%) had tumor molecular aberrations, and 213 (66.56%) received anticancer therapy. The most frequently mutated genes were TP53 (42%), KRAS (16%), PIK3CA (12%), and CDKN2A (11%). The median OS was 10.9 months (95% CI, 8.8–12.9). OS was shorter in patients with higher tumor mutational burden. Independent factors associated with shorter OS were age ≥60 years, liver metastases, low albumin levels, high LDH levels, and KRAS and TP53 mutations. Outcomes for randomized patients will be reported after completion of the study.
Circulating stromal cells in resectable pancreatic cancer correlates to pathological stage and predicts for poor clinical outcomes
Authors: Gardner Kirby P. , Aldakkak Mohammed , Tang Cha-Mei , Tsai Susan , Adams Daniel L.
Published: March 2021

Pancreatic cancer (PC) is notoriously difficult to diagnosis and properly stage resulting in incorrect primary treatment. Diagnostic and prognostic biomarkers are desperately needed to more accurately stage patients and select proper treatments. Recently, a newly discovered circulating stromal cell, i.e. cancer associated macrophage-like cell (CAML), was found to accurately identify solid cancers and predict for worse prognosis. In this pilot study, blood samples were procured from 63 PC patients prior to start of therapeutic intent. CAMLs were found in 95% of samples tested, with ≥12 CAMLs/7.5 mL and ≥50 µm CAMLs both predicting for advanced pathological stage and progression free survival. These data suggest that CAML assessment prior to treatment of PC predicts patients with under-staged disease and with more aggressive PC less likely to respond to standard of care treatment.
Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer
Authors: Griguolo G. , Serna G. , Pascual T. , Fasani R. , Guardia X. , Chic N. , Paré L. , Pernas S. , Muñoz M. , Oliveira M. , Vidal M. , Llombart-Cussac A. , Cortés J. , Galván P. , Bermejo B. , Martínez N. , López R. , Morales S. , Garau I. , Manso L. , Alarcón J. , Martínez E. , Villagrasa P. , Prat A. , Nuciforo P.
Published: March 2021

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.
Controllable potential barrier for multiple negative-differential-transconductance and its application to multi-valued logic computing
Authors: Seo Seunghwan , Koo Jiwan , Choi Jae-Woong , Heo Keun , Andreev Maksim , Lee Je-Jun , Lee Ju-Hee , Cho Jeong-Ick , Kim Hyeongjun , Yoo Gwangwe , Kang Dong-Ho , Shim Jaewoo , Park Jin-Hong
Published: March 2021

Various studies on multi-valued-logic (MVL) computing, which utilizes more than two logic states, have recently been resumed owing to the demand for greater power saving in the current logic technologies. In particular, unlike old-fashioned researches, extensive efforts have been focused on implementing single devices with multiple threshold voltages via a negative-differential current change phenomenon. In this work, we report a multiple negative-differential-transconductance (NDT) phenomenon, which is achieved through the control of partial gate potential and light power/wavelength in a van-der-Waals (vdW) multi-channel phototransistor. The partial gating formed a controllable potential barrier/well in the vdW channel, enabling control over the collection of carriers and eventually inducing the NDT phenomenon. Especially, the strategy shining lights with different powers/wavelengths facilitated the precise NDT control and the realization of the multiple NDT phenomenon. Finally, the usability of this multiple NDT device as a core device of MVL arithmetic circuits such as MVL inverters/NAND/NOR gates is demonstrated.