bluuebunny/crossref_metadata_2025 huggingface dataset:
Treaty rigidity and domestic democracy: Functions of and constitutional limits to democratic self-binding
Authors: Hohnerlein Jakob
Published: May 2022

International treaties create a layer of law that is particularly hard to change: While modern treaties entail significant constraints on domestic law-making, amendments require a new consensus of state parties. This creates a conflict with a core aspect of democratic constitutions: the power of new majorities to revise the laws made by their predecessors. In particular, several obligations of international economic law, namely regulatory stability promises in investment protection treaties, but also criminalization requirements under the UN drug control conventions face critique for overly diminishing domestic policy space. How can democratic constitutions deal with those tensions? One approach that is common in some countries accepts a power to legislate in violation of treaty obligations. But denying treaties the quality as real law in the domestic sphere risks to undermine the benefits of the instrument without truly solving the democracy concerns. Instead, democratic constitutions can be read to entail certain standards for engaging in treaties, namely (i) procedure-related duties to include denunciation clauses and political reform mechanisms in the treaty, and (ii) the need to establish a substantive justification for treaty constraints on future domestic law-making by legitimate aims of international constitutionalism or co-operation.
Emerging trends: General fine-tuning (gft)
Authors: Ward Church Kenneth , Cai Xingyu , Ying Yibiao , Chen Zeyu , Xun Guangxu , Bian Yuchen
Published: May 2022

This paper describes gft (general fine-tuning), a little language for deep nets, introduced at an ACL-2022 tutorial. gft makes deep nets accessible to a broad audience including non-programmers. It is standard practice in many fields to use statistics packages such as R. One should not need to know how to program in order to fit a regression or classification model and to use the model to make predictions for novel inputs. With gft, fine-tuning and inference are similar to fit and predict in regression and classification. gft demystifies deep nets; no one would suggest that regression-like methods are “intelligent.”
Precise Drift Tracking for In Situ Transmission Electron Microscopy via a Thon-Ring Based Sample Position Measurement
Authors: Zhang Fan , Zhang Xiaoben , Jia Zhenghao , Liu Wei
Published: May 2022

Visualizing how a catalyst behaves during chemical reactions using in situ transmission electron microscopy (TEM) is crucial for understanding the activity origin and guiding performance optimization. However, the sample drifts as temperature changes during in situ reaction, which weakens the resolution and stability of TEM imaging, blocks insights into the dynamic details of catalytic reaction. Herein, a Thon-ring based sample position measurement (TSPM) was developed to track the sample height variation during in situ TEM observation. Drifting characteristics for three commercially available nanochips were studied, showing large biases in aspects of shifting modes, expansion heights, as well as the thermal conduction hysteresis during rapid heating. Particularly, utilizing the TSPM method, for the first time, the gas layer thickness inside a gas-cell nanoreactor was precisely determined, which varies with reaction temperature and gas pressure in a linear manner with coefficients of ~8 nm/°C and ~50 nm/mbar, respectively. Following drift prediction of TSPM, fast oxidation kinetics of a Ni particle was tracked in real time for 12 s at 500°C. This TSPM method is expected to facilitate the functionality of automatic target tracing for in situ microscopy applications when feedback to hardware control of the microscope.
Impact of ovarian vein embolization in recurrent varicose veins of	the lower extremity
Authors: Reinboldt-Jockenhöfer Finja , Traber Jürg , Holzer Liezl Ingrid , von Weymarn Alexander , Dissemond Joachim , Duewell Stefan
Published: May 2022

Summary: Background: The treatment success of catheter-based ovarian vein embolization due to peripheral varicose veins and ovarian vein reflux (OVR) should be investigated in this clinical investagtion. Patients and methods: For this study, 95 female patients were identified over a 5-year period (beginning of 2006 to end of 2011) after catheter-based coil (+/- chemical) embolization of the ovarian vein due to peripheral primary or recurrent varicose veins and proven reflux in the ovarian vein. Treatment success was retrospectively assessed in 2014 by means of a structured telephone interview (n=60), clinical examination (n=56), duplex ultrasound (n=56) and magnetic resonance imaging (n=51) in patients who were willing to participate in the study. Results: After an average of 51.9 months, 95.2% of the 60 included patients were diagnosed with recurrent varicose veins by duplex sonography and 88.1% by clinical examination. In 15.2%, a new intervention was required due to clinical symptoms. The median recurrence-free time was 47.0±5.5 months. A significant improvement by therapy was reported for all subjective symptoms in both pelvis and legs. No significant correlation between radiological findings and complaints or between radiological findings and clinical recurrence was found. Conclusions: The medical history of female patients with peripheral varicose veins should obligatorily include the question of symptoms in the pelvis. An appropriate diagnostic should follow in order to prevent a possible overlook of a pelvic leak point. Only then an individually adapted therapy for symptom relief is possible. Catheter-based ovarian vein embolization is one optional safe procedure that leads to significant improvement of subjective symptoms but does not necessarily prevent recurrent varicose veins.
Erfassung exekutiver Funktionsstörungen mit dem Kölner-Exekutiv-Test
Authors: Scheffels Jannik Florian , Kräling Hannah , Jeschke Michaela , Kalbe Elke , Kessler Josef
Published: May 2022

Zusammenfassung: Exekutive Funktionsstörungen haben eine hohe Prävalenz und treten beispielsweise nach Schädel-Hirn-Traumata, Schlaganfällen oder neurodegenerativen Erkrankungen auf. Obwohl sie oftmals mit Verhaltensänderungen und Emotionserkennungsdefiziten einhergehen, werden diese in der neuropsychologischen Diagnostik meist nicht berücksichtigt. Daher wurde der Kölner-Exekutiv-Test (KEX) entwickelt. Er ist eine Erweiterung bisheriger Verfahren und basiert auf aktuellen Forschungsergebnissen zum Konstrukt „Exekutivfunktionen“. Die einzelnen Untertests – Paarassoziationslernen-5, Tier-Wort-Interferenz-Test, Emotions-Erkennungs-Test, Informant-based Frontal Assessment Questionnaire – wurden zwischen 2014 und 2020 an klinischen und gesunden Stichproben mit 1232 Teilnehmenden an der Uniklinik Köln (Klinik und Poliklinik für Neurologie) erprobt. Diese Arbeit stellt die Untertests des KEX sowie die Ergebnisse der Normierungsstudien vor. Es kann geschlussfolgert werden, dass der KEX ein einfach anwendbares und zeitökonomisches Diagnostikum für eine orientierende Einschätzung zu exekutiven Funktionsstörungen ist.
Preventing Instabilities and Inducing Controlled, Slow‐Slip in Frictionally Unstable Systems
Authors: Stefanou Ioannis , Tzortzopoulos Georgios
Published: May 2022

We propose a theory for preventing instabilities and inducing controlled, slow‐slip in frictionally unstable systems, such as the Generalized‐Burridge‐Knopoff (GBK) model and seismic fault models. We exploit the dependence of friction on pressure and use it as a backdoor for altering the dynamics of the underlying dynamical system. We use the mathematical Theory of Control and, for the first time, we manage to (a) stabilize and restrict chaos in this kind of systems, (b) guarantee slow frictional dissipation and (c) tune the system toward desirable global asymptotic equilibria of lower energy. Our control approach is robust and does not require exact knowledge of the frictional or elastic behavior of the system. Numerical examples of control are given for a Burridge‐Knopoff system and a strike‐slip fault model obeying rate‐and‐state friction. GBK models are known to present Self‐Organized Critical (SOC) behavior. Therefore, the presented methodology shows an additional example of SOC Control. Even though further developments are necessary before any practical application, we expect our methodology to inspire earthquake mitigation strategies regarding anthropogenic and/or natural seismicity.
A 3D Snapshot of Crustal Breakup Deduced From Seismic Analysis of the Tip of the NW South China Sea
Authors: Chao P. , Manatschal G. , Chenin P. , Zhang C. , Ren J. , Peng X. , Zheng J.
Published: May 2022

Based on a high‐resolution seismic reflection data set, we describe and map rift domains at the tip of the V‐shaped NW‐South China Sea (NW‐SCS) Basin. We compare our rift domain map with seismic refraction, magnetic and gravity field data, and previously mapped Continent‐Ocean Boundaries (COB). We also define and map syn‐breakup sedimentary and magmatic sequences across the sediment‐rich NW‐SCS, which enables us to reconstruct the tectono‐stratigraphic evolution of the area. This work enables us to describe and discuss the 3D architecture and nature of the crust at the tip of the NW‐SCS, investigate how extensional and magmatic processes interacted during the breakup, and propose a kinematic model for late rifting, breakup, and finally stalling of the seafloor spreading system. This study provides exceptionally well‐documented insights into the spatial and temporal evolution at the tip of a so‐called “rift propagator,” and enables us to show that breakup in the NW‐SCS may rather correspond to a “retrogrador,” in which the extension zone retreats due to the reorganization of a failing rift system.
Fluid Pressure Changes Recorded by Trace Elements in Quartz
Authors: Raimbourg Hugues , Famin Vincent , Canizarès Aurélien , Le Trong Emmanuel
Published: May 2022

Fluid pressure is a key parameter in earthquake mechanics, controlling seismic failure and plate coupling in convergent zones. Yet fluid pressure is also extremely difficult to quantify at seismogenic depth, which limits our knowledge of the stress state in accretionary prisms. Here, we show that the geochemical record of exhumed hydrothermal quartz veins may be used to place quantitative bounds on fluid pressure variations in subduction zones. The studied veins come from sediments accreted and exhumed by plate convergence in southwestern Japan. Quartz in veins displays growth rims of contrasted bright blue/dark brown cathodoluminescence (CL) colors, high/low Al concentrations, and low/high fluid inclusion abundance. Because Si‐Al substitution (and charge compensation by Li) strongly depends on the rate of quartz precipitation and Si solubility, Al‐Li concentrations must be sensitive to fluid pressure. This is confirmed by fluid inclusions, the density of which, converted into trapping pressures, record fluid pressure drops by up to ∼70 MPa from CL‐brown, Al‐Li‐poor rims to CL‐blue, Al‐Li‐rich quartz rims. CL‐blue rims grow at a fast rate, high Si supersaturation and low fluid pressure whereas CL‐brown rims grow at a slower pace, lower Si supersaturation, and higher fluid pressure. Quartz trace element chemistry thus offers a promising tool to quantify deep fluid pressure variations and their relationships to earthquakes.
An Experimental Model of Unconfined Bubbly Lava Flows: Importance of Localized Bubble Distribution
Authors: Namiki Atsuko , Lev Einat , Birnbaum Janine , Baur Jasper
Published: May 2022

Most lava flows carry bubbles and crystals in suspension. From earlier works, it is known that spherical bubbles increase the effective viscosity while bubbles deformed by rapid flow decrease it. Changes in the spatial distribution of bubbles can lead to variable rheology and flow localization and thus modify the resulting lava flow structure and morphology. To understand the roles of bubble and solid phase crystal distributions, we conducted a series of analog experiments of high bubble fraction suspensions. We poured the analog lava on an inclined slope, observed its shape, calculated the velocity field, and monitored its local thickness. A region of localized rapid flow and low vesicularity, whose thickness is thinner than the surrounding area, develops at the center of the bubbly flows. These features suggest that the locally higher liquid fraction decreases the effective viscosity, increases the fluid density, and accelerates the flow. We also found that a halted particle‐bearing bubbly flow can resume flowing. We interpret this to result from the upward vertical separation of bubbles, which generates a liquid‐rich layer at the bottom of the flow. In our experiment, bubbles are basically spherical and decrease the flow velocity, while our estimate suggests that bubbles in natural lava flows could increase or decrease flow velocity. Downstream decreases in flow velocity stops the bubble deformation and can cause a sudden increase of effective viscosity. The vertical segregation of the liquid phase at the slowed flow front may be a way to generate a cavernous shelly paho’eho’e.
GSK3β palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2–STAT3 axis
Authors: Zhao Chenggang , Yu Huihan , Fan Xiaoqing , Niu Wanxiang , Fan Junqi , Sun Suling , Gong Meiting , Zhao Bing , Fang Zhiyou , Chen Xueran
Published: May 2022

Glioblastoma stem cells (GSCs) are a highly tumorigenic cell subgroup of glioblastoma (GBM). Glycogen synthase kinase 3β (GSK3β) is considered a key hub for promoting malignant phenotypes in GBM. However, the functional relationships between GSK3β and GSCs in GBM are unclear. Here, we found that GSK3β was noted as a substrate for ZDHHC4-mediated palmitoylation at the Cys14 residue, which enhanced GBM temozolomide (TMZ) resistance and GSC self-renewal. Clinically, the expression level of ZDHHC4 was upregulated in GBM, which significantly correlated with tumor grade and poor prognosis. The above phenotypes were based on decreasing p-Ser9 and increasing p-Tyr216 by GSK3β palmitoylation, which further activated the enhancer of the zeste homolog 2 (EZH2)–STAT3 pathway. Notably, STAT3 silencing also inhibited ZDHHC4 expression. This study revealed that GSK3β palmitoylation mediated by ZDHHC4 improved the stemness of TMZ-resistant GBM by activating the EZH2–STAT3 signaling axis, providing a new theoretical basis for further understanding the mechanism of TMZ resistance and recurrence after treatment.
Gas in scattering media absorption spectroscopy as a potential tool in neonatal respiratory care
Authors: Panaviene Jurate , Pacheco Andrea , Schwarz Christoph E. , Grygoryev Konstantin , Andersson-Engels Stefan , Dempsey Eugene M.
Published: May 2022

Gas in scattering media absorption spectroscopy (GASMAS) is a novel optical technology employing near-infrared light. It has a potential use in the medical setting as a monitoring and diagnostic tool by detecting molecular oxygen within gas pockets and thus may be a useful adjunct in respiratory monitoring. GASMAS has potential advantages over other monitoring devices currently used in clinical practice. It is a non-invasive, continuous, non-ionising technology and provides unique information about molecular oxygen content inside the lungs. GASMAS may have a future role in optimising respiratory management of neonates in different clinical scenarios such as monitoring cardiorespiratory transition in the delivery room, assessing surfactant deficiency, and optimising endotracheal tube positioning. This article aims to summarise current evidence exploring GASMAS application in a neonate, discuss possible clinical benefits, and compare with other devices that are currently used in neonatal care.

Impact

This article presents a novel optical technique to measure lung oxygen concentrations that may have important clinical uses.

This review summarises the current literature investigating the concept of optical lung oxygen measurement.

Information from this review can guide researchers in future studies.
Prospects and challenges of dynamic DNA nanostructures in biomedical applications
Authors: Tian Taoran , Li Yanjing , Lin Yunfeng
Published: May 2022

The physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and pH. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal particles. However, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications, including their use as DNA aptamers, ion concentration/pH-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.
Epithelial de-differentiation triggered by co-ordinate epigenetic inactivation of the EHF and CDX1 transcription factors drives colorectal cancer progression
Authors: Luk Ian Y. , Jenkins Laura J. , Schoffer Kael L. , Ng Irvin , Tse Janson W. T. , Mouradov Dmitri , Kaczmarczyk Stanislaw , Nightingale Rebecca , Burrows Allan D. , Anderson Robin L. , Arango Diego , Dopeso Higinio , Croft Larry , Richardson Mark F. , Sieber Oliver M. , Liao Yang , Mooi Jennifer K. , Vukelic Natalia , Reehorst Camilla M. , Afshar-Sterle Shoukat , Whitehall Vicki L. J. , Fennell Lochlan , Abud Helen E. , Tebbutt Niall C. , Phillips Wayne A. , Williams David S. , Shi Wei , Mielke Lisa A. , Ernst Matthias , Dhillon Amardeep S. , Clemons Nicholas J. , Mariadason John M.
Published: May 2022

Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis. Strikingly, EHF and CDX1 were also able to reprogramme non-colonic epithelial cells to express colonic differentiation markers. By contrast, inactivation of EHF and CDX1 in well-differentiated CRC cells triggered tumour de-differentiation. Mechanistically, we demonstrate that EHF physically interacts with CDX1 via its PNT domain, and that these transcription factors co-operatively drive transcription of the colonic differentiation marker, VIL1. Compound genetic deletion of Ehf and Cdx1 in the mouse colon disrupted normal colonic differentiation and significantly enhanced colorectal tumour progression. These findings thus reveal a novel mechanism driving epithelial de-differentiation and tumour progression in CRC.
A genetic engineering strategy for editing near-infrared-II fluorophores
Authors: Tian Rui , Feng Xin , Wei Long , Dai Daoguo , Ma Ying , Pan Haifeng , Ge Shengxiang , Bai Lang , Ke Chaomin , Liu Yanlin , Lang Lixin , Zhu Shoujun , Sun Haitao , Yu Yanbao , Chen Xiaoyuan
Published: May 2022

The second near-infrared (NIR-II) window is a fundamental modality for deep-tissue in vivo imaging. However, it is challenging to synthesize NIR-II probes with high quantum yields (QYs), good biocompatibility, satisfactory pharmacokinetics, and tunable biological properties. Conventional long-wavelength probes, such as inorganic probes (which often contain heavy metal atoms in their scaffolds) and organic dyes (which contain large π-conjugated groups), exhibit poor biosafety, low QYs, and/or uncontrollable pharmacokinetic properties. Herein, we present a bioengineering strategy that can replace the conventional chemical synthesis methods for generating NIR-II contrast agents. We use a genetic engineering technique to obtain a series of albumin fragments and recombinant proteins containing one or multiple domains that form covalent bonds with chloro-containing cyanine dyes. These albumin variants protect the inserted dyes and remarkably enhance their brightness. The albumin variants can also be genetically edited to develop size-tunable complexes with precisely tailored pharmacokinetics. The proteins can also be conjugated to biofunctional molecules without impacting the complexed dyes. This combination of albumin mutants and clinically-used cyanine dyes can help widen the clinical application prospects of NIR-II fluorophores.
Kinetically restrained oxygen reduction to hydrogen peroxide with nearly 100% selectivity
Authors: Chen Jinxing , Ma Qian , Zheng Xiliang , Fang Youxing , Wang Jin , Dong Shaojun
Published: May 2022

Hydrogen peroxide has been synthesized mainly through the electrocatalytic and photocatalytic oxygen reduction reaction in recent years. Herein, we synthesize a single-atom rhodium catalyst (Rh1/NC) to mimic the properties of flavoenzymes for the synthesis of hydrogen peroxide under mild conditions. Rh1/NC dehydrogenates various substrates and catalyzes the reduction of oxygen to hydrogen peroxide. The maximum hydrogen peroxide production rate is 0.48 mol gcatalyst−1 h−1 in the phosphorous acid aerobic oxidation reaction. We find that the selectivity of oxygen reduction to hydrogen peroxide can reach 100%. This is because a single catalytic site of Rh1/NC can only catalyze the removal of two electrons per substrate molecule; thus, the subsequent oxygen can only obtain two electrons to reduce to hydrogen peroxide through the typical two-electron pathway. Similarly, due to the restriction of substrate dehydrogenation, the hydrogen peroxide selectivity in commercial Pt/C-catalyzed enzymatic reactions can be found to reach 75%, which is 30 times higher than that in electrocatalytic oxygen reduction reactions.
Effectiveness of CoronaVac in children 3–5 years of age during the SARS-CoV-2 Omicron outbreak in Chile
Authors: Jara Alejandro , Undurraga Eduardo A. , Zubizarreta José R. , González Cecilia , Acevedo Johanna , Pizarro Alejandra , Vergara Verónica , Soto-Marchant Mario , Gilabert Rosario , Flores Juan Carlos , Suárez Pamela , Leighton Paulina , Eguiguren Pablo , Ríos Juan Carlos , Fernandez Jorge , García-Escorza Heriberto , Araos Rafael
Published: May 2022

The outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac’s inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5–39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6–75.2) against hospitalization and 69.0% (95% CI, 18.6–88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3–5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.
A Fetal Brain magnetic resonance Acquisition Numerical phantom (FaBiAN)
Authors: Lajous Hélène , Roy Christopher W. , Hilbert Tom , de Dumast Priscille , Tourbier Sébastien , Alemán-Gómez Yasser , Yerly Jérôme , Yu Thomas , Kebiri Hamza , Payette Kelly , Ledoux Jean-Baptiste , Meuli Reto , Hagmann Patric , Jakab Andras , Dunet Vincent , Koob Mériam , Kober Tobias , Stuber Matthias , Bach Cuadra Meritxell
Published: May 2022

Accurate characterization of in utero human brain maturation is critical as it involves complex and interconnected structural and functional processes that may influence health later in life. Magnetic resonance imaging is a powerful tool to investigate equivocal neurological patterns during fetal development. However, the number of acquisitions of satisfactory quality available in this cohort of sensitive subjects remains scarce, thus hindering the validation of advanced image processing techniques. Numerical phantoms can mitigate these limitations by providing a controlled environment with a known ground truth. In this work, we present FaBiAN, an open-source Fetal Brain magnetic resonance Acquisition Numerical phantom that simulates clinical T2-weighted fast spin echo sequences of the fetal brain. This unique tool is based on a general, flexible and realistic setup that includes stochastic fetal movements, thus providing images of the fetal brain throughout maturation comparable to clinical acquisitions. We demonstrate its value to evaluate the robustness and optimize the accuracy of an algorithm for super-resolution fetal brain magnetic resonance imaging from simulated motion-corrupted 2D low-resolution series compared to a synthetic high-resolution reference volume. We also show that the images generated can complement clinical datasets to support data-intensive deep learning methods for fetal brain tissue segmentation.
A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients
Authors: Jung Seoyeon , Kim Jaeyeon , Park Jin Hoo , Kim Ki-Yeol , Kim Hyung Jun , Park Wonse
Published: May 2022

Denosumab has been suggested as a first-line therapy for osteoporotic patients. However, a standardized protocol for the prevention of denosumab induced medication-related osteonecrosis of the jaw (MRONJ) has not yet been established. The purpose of this study was to report denosumab induced MRONJ cases, and investigate the factors affecting the occurrence of MRONJ in patients who underwent denosumab and invasive dental treatment (especially tooth extraction) between October 2016 and March 2020. Four of the 98 patients developed MRONJ before and after tooth extraction. The participants were divided into two groups: receiving only denosumab (n = 51) and receiving bisphosphonate as first treatment and denosumab as second treatment (n = 47). There was no significant difference between groups in the occurrence of MRONJ and factors affecting MRONJ. Two out of 4 patients developed MRONJ regardless of invasive treatment after denosumab administration and proceeded with extraction; one patient developed MRONJ after denosumab administration and extraction. The other patient underwent a tooth extraction without osteoporosis treatment, and non-identified MRONJ developed after denosumab administration. MRONJ cases reported in this study show that MRONJ can develop as chronic inflammation without invasive dental treatment; therefore, implementing preventive dental treatment before initiating denosumab treatment is necessary to reduce the occurrence of MRONJ.
Bio-actuated microvalve in microfluidics using sensing and actuating function of Mimosa pudica
Authors: Aishan Yusufu , Funano Shun-ichi , Sato Asako , Ito Yuri , Ota Nobutoshi , Yalikun Yaxiaer , Tanaka Yo
Published: May 2022

Bio-actuators and sensors are increasingly employed in microscale devices for numerous applications. Unlike other artificial devices actuated by living cells or tissues, here we introduce a microvalve system actuated by the stimuli-responsive action plant,Mimosa pudica(sleepy plant). This system realizes the control of the valve to open and close by dropping and recovering responses ofMimosa pudicabranch upon external physical stimulations. The results showed that one matured single uncutMimosa pudicabranch produced average force of 15.82 ± 0.7 mN. This force was sufficient for actuating and keeping the valve open for 8.46 ± 1.33 min in a stimulation-recovering cycle of 30 min. Additionally, two separately cutMimosa pudicabranches were able to keep the valve open for 2.28 ± 0.63 min in a stimulating-recovering cycle of 20min. The pressure resistance and the response time of the valve were 4.2 kPa and 1.4 s, respectively. This demonstration of plant-microfluidics integration encourages exploiting more applications of microfluidic platforms that involve plant science and plant energy harvesting.
Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors
Authors: Iraji Aida , Shareghi-Brojeni Diba , Mojtabavi Somayeh , Faramarzi Mohammad Ali , Akbarzadeh Tahmineh , Saeedi Mina
Published: May 2022

In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.
Multiagent off-screen behavior prediction in football
Authors: Omidshafiei Shayegan , Hennes Daniel , Garnelo Marta , Wang Zhe , Recasens Adria , Tarassov Eugene , Yang Yi , Elie Romuald , Connor Jerome T. , Muller Paul , Mackraz Natalie , Cao Kris , Moreno Pol , Sprechmann Pablo , Hassabis Demis , Graham Ian , Spearman William , Heess Nicolas , Tuyls Karl
Published: May 2022

In multiagent worlds, several decision-making individuals interact while adhering to the dynamics constraints imposed by the environment. These interactions, combined with the potential stochasticity of the agents’ dynamic behaviors, make such systems complex and interesting to study from a decision-making perspective. Significant research has been conducted on learning models for forward-direction estimation of agent behaviors, for example, pedestrian predictions used for collision-avoidance in self-driving cars. In many settings, only sporadic observations of agents may be available in a given trajectory sequence. In football, subsets of players may come in and out of view of broadcast video footage, while unobserved players continue to interact off-screen. In this paper, we study the problem of multiagent time-series imputation in the context of human football play, where available past and future observations of subsets of agents are used to estimate missing observations for other agents. Our approach, called the Graph Imputer, uses past and future information in combination with graph networks and variational autoencoders to enable learning of a distribution of imputed trajectories. We demonstrate our approach on multiagent settings involving players that are partially-observable, using the Graph Imputer to predict the behaviors of off-screen players. To quantitatively evaluate the approach, we conduct experiments on football matches with ground truth trajectory data, using a camera module to simulate the off-screen player state estimation setting. We subsequently use our approach for downstream football analytics under partial observability using the well-established framework of pitch control, which traditionally relies on fully observed data. We illustrate that our method outperforms several state-of-the-art approaches, including those hand-crafted for football, across all considered metrics.
Ultrathin picoscale white light interferometer
Authors: Dahiya Sunil , Tyagi Akansha , Mandal Ankur , Pfeifer Thomas , Singh Kamal P.
Published: May 2022

White light interferometry is a well established technique with diverse precision applications, however, the conventional interferometers such as Michelson, Mach-Zehnder or Linnik are large in size, demand tedious alignment for obtaining white light fringes, require noise-isolation techniques to achieve sub-nanometric stability and importantly, exhibit unbalanced dispersion causing uncertainty in absolute zero delay reference. Here, we demonstrate an ultrathin white light interferometer enabling picometer resolution by exploiting the wavefront division of a broadband incoherent light beam after transmission through a pair of micrometer thin identical glass plates. Spatial overlap between the two diffracted split wavefronts readily produce high-contrast and stable white light fringes, with unambiguous reference to absolute zero path-delay position. The colored fringes evolve when one of the ultrathin plates is rotated to tune the interferometer with picometric resolution over tens of μm range. Our theoretical analysis validates formation of fringes and highlights self-calibration of the interferometer for picoscale measurements. We demonstrate measurement of coherence length of several broadband incoherent sources as small as a few micrometer with picoscale resolution. Furthermore, we propose a versatile double-pass configuration using the ultrathin interferometer enabling a sample cavity for additional applications in probing dynamical properties of matter.
NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59
Authors: Son Sung Wook , Cho Eunho , Cho Hanbyoul , Woo Seon Rang , Lee Hyo-Jung , Oh Se Jin , Kim Suyeon , Kim Jae-Hoon , Chung Eun Joo , Chung Joon-Yong , Kim Min Gyu , Song Kwon-Ho , Kim Tae Woo
Published: May 2022

Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody.
Identification of nontuberculous mycobacteria isolated from household showerheads of patients with nontuberculous mycobacteria
Authors: Choi Ji Yeon , Sim Bo Ra , Park Youngmok , Yong Seung Hyun , Shin Sung Jae , Kang Young Ae
Published: May 2022

This study aimed to examine whether nontuberculous mycobacteria (NTM) inside household showerheads are identical to those in patients with NTM-pulmonary disease (PD) since household water is one of the potential NTM sources. Samples were obtained from 32 household showerheads of patients with NTM-PD recruited through the Pulmonary Outpatient Department at the Severance Hospital between October 2018 and October 2019. All isolates from patients with NTM-PD were diagnosed using a reverse-hybridization line probe assay based on the ropB gene. To determine the mycobacterial compositions, the washing fluids were collected and investigated using multiplex polymerase chain reaction assay and NTM culture; suspected microbial isolates in these fluids and culture were identified using sequencing analysis of 16S rRNA gene. NTM species causing the PD in the patients were Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, and M. fortuitum complex. The mycobacteria isolated from the showerhead were M. lentiflavum, M. gordonae, M. triplex, M. phocaicum, M. mucogenicum, M. florentinum, M. gilvum, M. llatzerense, and M. peregrinum. However, the species identified in the showerheads did not match those of the patients. Despite NTM species in the showerheads, clinical implications in the main pathogenesis associated with the disease in the patients studied were not elucidated.
An animal derivative-free medium enhances Lactobacillus johnsonii LJO02 supernatant selective efficacy against the methicillin (oxacillin)-resistant Staphylococcus aureus virulence through key-metabolites
Authors: Squarzanti Diletta Francesca , Zanetta Paola , Ormelli Margherita , Manfredi Marcello , Barberis Elettra , Vanella Virginia Vita , Amoruso Angela , Pane Marco , Azzimonti Barbara
Published: May 2022

The spread of multidrug-resistant bacteria, such as the skin commensal Staphylococcus aureus, is a worldwide health challenge; new methods to counteract opportunistic pathogen growth and virulence are urgent. We compared the activity of Lacticaseibacillus rhamnosus LR06 (DSM 21981) and Lactobacillus johnsonii LJO02 (DSM 33828) cell-free supernatants (CFSs) produced in the conventional animal derivative-based MRS medium and an innovative animal derivative-free broth (TIL) versus the MDR S. aureus (ATCC 43300). CFS influence was assessed towards the viability, metabolic activity, and ability to form biofilm of the MDR strain through optical density, alamarBlue assay, and crystal violet staining; their content in short-chain fatty acids, lactic acid, and proteins was analysed via high-resolution mass spectrometry and gas chromatography. All CFSs reduce viable and metabolically active S. aureus, being TIL more efficient compared to MRS in stimulating lactic acid bacteria metabolism and decreasing S. aureus biofilm formation. Particularly, the CFS from LJO02 grown in TIL has the best efficacy, revealing a high amount of lactic acid and 59 peculiar proteins; its effectiveness is partially maintained upon trypsin and proteinase K treatments, but not by pepsin and pH basification. Therefore, antagonistic CFSs may represent a strategic prevention approach, with bacteriotherapeutic and bio-repair potential.
Vascular alterations among male elite athletes recovering from SARS-CoV-2 infection
Authors: Bauer Pascal , Kraushaar Lutz , Dörr Oliver , Keranov Stanislav , Nef Holger , Hamm Christian W. , Most Astrid
Published: May 2022

SARS-CoV-2 may affect the cardiovascular system and vascular impairment has been reported in healthy young adults recovering from COVID-19. However, the impact of SARS-CoV-2 infection on the vascular function of elite athletes is unknown. We examined 30 healthy male elite athletes (age 25.8 ± 4.6 years) pre-season and at a 6-month follow-up (182 ± 10 days). Vascular function and central blood pressure were calculated using transfer function-based analysis of peripheral arterial waveforms obtained by oscillometry. We performed a two-way repeated-measures ANOVA on the biomarker data, with SARS-CoV-2 status as the between-groups factor and time as the within-groups factor. Subjects who tested positive for SARS-CoV-2 were studied 18 ± 4 days after their positive testing date at follow-up. Of 30 athletes, 15 tested positive for SARS-CoV-2 after the first examination and prior to the follow-up. None had severe COVID-19 or reported any persisting symptoms. The results of the two-way repeated measures ANOVA revealed that there was no significant main effect of COVID-19 on any of the investigated biomarkers. However, there was a significant interaction between the effects of SARS-CoV-2 exposure and time on augmentation index (Aix) (p = 0.006) and augmentation index normalized to a heart rate of 75 beats per minute (Aix@75), (p = 0.0018). The observation of an interaction effect on Aix and Aix@75 in the absence of any main effect indicates a cross-over interaction. Significant vascular alterations in male elite athletes recovering from COVID-19 were observed that suggest vascular impairment. Whether these alterations affect athletic performance should be evaluated in future studies.
An interpretable deep learning workflow for discovering subvisual abnormalities in CT scans of COVID-19 inpatients and survivors
Authors: Zhou Longxi , Meng Xianglin , Huang Yuxin , Kang Kai , Zhou Juexiao , Chu Yuetan , Li Haoyang , Xie Dexuan , Zhang Jiannan , Yang Weizhen , Bai Na , Zhao Yi , Zhao Mingyan , Wang Guohua , Carin Lawrence , Xiao Xigang , Yu Kaijiang , Qiu Zhaowen , Gao Xin
Published: May 2022

Tremendous efforts have been made to improve diagnosis and treatment of COVID-19, but knowledge on long-term complications is limited. In particular, a large portion of survivors has respiratory complications, but currently, experienced radiologists and state-of-the-art artificial intelligence systems are not able to detect many abnormalities from follow-up computerized tomography (CT) scans of COVID-19 survivors. Here we propose Deep-LungParenchyma-Enhancing (DLPE), a computer-aided detection (CAD) method for detecting and quantifying pulmonary parenchyma lesions on chest CT. Through proposing a number of deep-learning-based segmentation models and assembling them in an interpretable manner, DLPE removes irrelevant tissues from the perspective of pulmonary parenchyma, and calculates the scan-level optimal window, which considerably enhances parenchyma lesions relative to the lung window. Aided by DLPE, radiologists discovered novel and interpretable lesions from COVID-19 inpatients and survivors, which were previously invisible under the lung window. Based on DLPE, we removed the scan-level bias of CT scans, and then extracted precise radiomics from such novel lesions. We further demonstrated that these radiomics have strong predictive power for key COVID-19 clinical metrics on an inpatient cohort of 1,193 CT scans and for sequelae on a survivor cohort of 219 CT scans. Our work sheds light on the development of interpretable medical artificial intelligence and showcases how artificial intelligence can discover medical findings that are beyond sight.
Pre-clinical non-viral vectors exploited forin vivoCRISPR/Cas9 gene editing: an overview
Authors: Rouatbi Nadia , McGlynn Tasneem , Al-Jamal Khuloud T.
Published: May 2022

Non-viral delivery technologies for efficientin vivoClustered Regulatory Interspaced Short Palindromic Repeats (CRISPR/Cas9) gene editing.
Computational study of electron transport in halogen incorporated diindenotetracene compounds: crystal structure, charge transport and optoelectronic properties
Authors: Khatua Rudranarayan , Debata Suryakanti , Sahu Sridhar
Published: May 2022

Anisotropic electron mobility of halogenated diindenotetracene derivatives showing n-type characteristics.
Response of sediment phosphorus partitioning to lanthanum-modified clay amendment and porewater chemistry in a small eutrophic lake
Authors: Neweshy Wessam , Planas Dolors , Tellier Elisabeth , Demers Marie , Marsac Remi , Couture Raoul-Marie
Published: May 2022

Porewater geochemistry in a lanthanum-remediated lake reveal that phosphorus mobility depends on the interplay between carbon and iron.
A functionalized magnetic nanoparticle regulated CRISPR-Cas12a sensor for the ultrasensitive detection of alpha-fetoprotein
Authors: Liu Ya , Chen Yan , Zhang Yue , Zhong Qi , Zhu Xiaoli , Wu Qi
Published: May 2022

We report a functionalized magnetic bead separation platform based on the switching aptamer triggered hybridization chain reaction (SAT-HCR) and the CRISPR-Cas12a sensor for the detection of alpha-fetoprotein (AFP) in the serum of hepatoblastoma patients.
Anticancer therapeutic effect of cerium-based nanoparticles: known and unknown molecular mechanisms
Authors: Amaldoss Maria John Newton , Mehmood Rashid , Yang Jia-Lin , Koshy Pramod , Kumar Naresh , Unnikrishnan Ashwin , Sorrell Charles C.
Published: May 2022

Summary of ROS-dependent and ROS-independent anticancer effects of Ce-based nanoparticles in the cellular environment, categorized according to materials-based and radiation-assisted effects.
Metal–organic cage incorporating thin-film nanocomposite membranes with antifouling properties
Authors: Yuan Yi Di , Zhang Xiaomei , Yang Ziqi , Zhao Dan
Published: May 2022

Incorporation of functional water-stable metal–organic cages (MOCs) in the reverse osmosis membrane changes the membrane morphology and hydrophilicity to achieve better antifouling properties.
Hydration shell model for expeditious and reliable individual hydrogen bond energies in large water clusters
Authors: Ahirwar Mini Bharati , Gurav Nalini D. , Gadre Shridhar R. , Deshmukh Milind M.
Published: May 2022

Molecular tailoring approach-based method for the individual hydrogen bond energy estimation employing shell model.
Pd speciation on black phosphorene in a CO and C2H4 atmosphere: a first-principles investigation
Authors: Liu Xin , Chen Laike , Wu Yong , Zhang Xin , Chambaud Gilberte , Han Yu , Meng Changgong
Published: May 2022

First-principles based thermodynamics calculations predict that atomic dispersion of Pd can be achieved on phosphorene, especially in a CO or C2H4 atmosphere.
[1]Benzothieno[3,2-b][1]benzothiophene-based dyes: effect of the ancillary moiety on mechanochromism and aggregation-induced emission
Authors: Shivaji Babar Suraj , Boddula Rajamouli , Singh Surya Prakash
Published: May 2022

Strategic design of [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivatives (donor–π–acceptor–π–donor) towards AIE, MFC and halo-MFC properties.
Experimental and numerical investigation of NO oxidation on Pt/Al2O3- and NOxstorage on Pt/BaO/Al2O3-catalysts
Authors: Wan Sui , Keller Kevin , Lott Patrick , Shirsath Akash Bhimrao , Tischer Steffen , Häber Thomas , Suntz Rainer , Deutschmann Olaf
Published: May 2022

Effects of temperature and inlet conditions on NO oxidation and NOxstorage, as well as reduced NOxstorage capacity over time – reflected by changes of measured NO concentration, which are reproduced by CFD using detailed reaction mechanisms.