bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid antigen testing as a reactive response to surges in nosocomial SARS-CoV-2 outbreak risk
Authors: Smith David R. M. , Duval Audrey , Zahar Jean Ralph ,   the EMAE-MESuRS Working Group on Nosocomial SARS-CoV-2 Modelling, Hendrickx Niels , Jean Kévin , Jijón Sofía , Oodally Ajmal , Shirreff George , Tamandjou Cynthia , Opatowski Lulla , Temime Laura 
Published: January 2022

AbstractHealthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Antigen rapid diagnostic testing (Ag-RDT) is widely used for population screening, but its health and economic benefits as a reactive response to local surges in outbreak risk are unclear. We simulate SARS-CoV-2 transmission in a long-term care hospital with varying COVID-19 containment measures in place (social distancing, face masks, vaccination). Across scenarios, nosocomial incidence is reduced by up to 40-47% (range of means) with routine symptomatic RT-PCR testing, 59-63% with the addition of a timely round of Ag-RDT screening, and 69-75% with well-timed two-round screening. For the latter, a delay of 4-5 days between the two screening rounds is optimal for transmission prevention. Screening efficacy varies depending on test sensitivity, test type, subpopulations targeted, and community incidence. Efficiency, however, varies primarily depending on underlying outbreak risk, with health-economic benefits scaling by orders of magnitude depending on the COVID-19 containment measures in place.
A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
Authors: Wong Derek P. , Roy Nand K. , Zhang Keman , Anukanth Anusha , Asthana Abhishek , Shirkey-Son Nicole J. , Dunmire Samantha , Jones Bryan J. , Lahr Walker S. , Webber Beau R. , Moriarity Branden S. , Caimi Paolo , Parameswaran Reshmi 
Published: January 2022

AbstractB cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
Towards a generic prototyping approach for therapeutically-relevant peptides and proteins in a cell-free translation system
Authors: Wu Yue , Cui Zhenling , Huang Yen-Hua , de Veer Simon J. , Aralov Andrey V. , Guo Zhong , Moradi Shayli V. , Hinton Alexandra O. , Deuis Jennifer R. , Guo Shaodong , Chen Kai-En , Collins Brett M. , Vetter Irina , Herzig Volker , Jones Alun , Cooper Matthew A. , King Glenn F. , Craik David J. , Alexandrov Kirill , Mureev Sergey 
Published: January 2022

AbstractAdvances in peptide and protein therapeutics increased the need for rapid and cost-effective polypeptide prototyping. While in vitro translation systems are well suited for fast and multiplexed polypeptide prototyping, they suffer from misfolding, aggregation and disulfide-bond scrambling of the translated products. Here we propose that efficient folding of in vitro produced disulfide-rich peptides and proteins can be achieved if performed in an aggregation-free and thermodynamically controlled folding environment. To this end, we modify an E. coli-based in vitro translation system to allow co-translational capture of translated products by affinity matrix. This process reduces protein aggregation and enables productive oxidative folding and recycling of misfolded states under thermodynamic control. In this study we show that the developed approach is likely to be generally applicable for prototyping of a wide variety of disulfide-constrained peptides, macrocyclic peptides with non-native bonds and antibody fragments in amounts sufficient for interaction analysis and biological activity assessment.
MicroRNA-365 regulates human cardiac action potential duration
Authors: Esfandyari Dena , Idrissou Bio Maria Ghéo , Hennis Konstantin , Avramopoulos Petros , Dueck Anne , El-Battrawy Ibrahim , Grüter Laurenz , Meier Melanie Annemarie , Näger Anna Christina , Ramanujam Deepak , Dorn Tatjana , Meitinger Thomas , Hagl Christian , Milting Hendrik , Borggrefe Martin , Fenske Stefanie , Biel Martin , Dendorfer Andreas , Sassi Yassine , Moretti Alessandra , Engelhardt Stefan 
Published: January 2022

AbstractAbnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden cardiac death. Here, we aim to identify microRNAs that regulate the human cardiac action potential and ask whether their manipulation allows for therapeutic modulation of action potential abnormalities. Quantitative analysis of the microRNA targetomes in human cardiac myocytes identifies miR-365 as a primary microRNA to regulate repolarizing ion channels. Action potential recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes show that elevation of miR-365 significantly prolongs action potential duration in myocytes derived from a Short-QT syndrome patient, whereas specific inhibition of miR-365 normalizes pathologically prolonged action potential in Long-QT syndrome myocytes. Transcriptome analyses in these cells at bulk and single-cell level corroborate the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional action potential-regulating genes by this microRNA. Whole-cell patch-clamp experiments confirm miR-365-dependent regulation of repolarizing ionic current Iks. Finally, refractory period measurements in human myocardial slices substantiate the regulatory effect of miR-365 on action potential in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac action potential duration by targeting key factors of cardiac repolarization.
Single-dispersed polyoxometalate clusters embedded on multilayer graphene as a bifunctional electrocatalyst for efficient Li-S batteries
Authors: Lei Jie , Fan Xiao-Xiang , Liu Ting , Xu Pan , Hou Qing , Li Ke , Yuan Ru-Ming , Zheng Ming-Sen , Dong Quan-Feng , Chen Jia-Jia 
Published: January 2022

AbstractThe redox reactions occurring in the Li-S battery positive electrode conceal various and critical electrocatalytic processes, which strongly influence the performances of this electrochemical energy storage system. Here, we report the development of a single-dispersed molecular cluster catalyst composite comprising of a polyoxometalate framework ([Co4(PW9O34)2]10−) and multilayer reduced graphene oxide. Due to the interfacial charge transfer and exposure of unsaturated cobalt sites, the composite demonstrates efficient polysulfides adsorption and reduced activation energy for polysulfides conversion, thus serving as a bifunctional electrocatalyst. When tested in full Li-S coin cell configuration, the composite allows for a long-term Li-S battery cycling with a capacity fading of 0.015% per cycle after 1000 cycles at 2 C (i.e., 3.36 A g−1). An areal capacity of 4.55 mAh cm−2 is also achieved with a sulfur loading of 5.6 mg cm−2 and E/S ratio of 4.5 μL mg−1. Moreover, Li-S single-electrode pouch cells tested with the bifunctional electrocatalyst demonstrate a specific capacity of about 800 mAh g−1 at a sulfur loading of 3.6 mg cm−2 for 100 cycles at 0.2 C (i.e., 336 mA g−1) with E/S ratio of 5 μL mg−1.
Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding
Authors: Gajdos Lukas , Blakeley Matthew P. , Haertlein Michael , Forsyth V. Trevor , Devos Juliette M. , Imberty Anne 
Published: January 2022

AbstractThe opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.
BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1
Authors: Chen Dan , Gervai Judit Z. , Póti Ádám , Németh Eszter , Szeltner Zoltán , Szikriszt Bernadett , Gyüre Zsolt , Zámborszky Judit , Ceccon Marta , d’Adda di Fagagna Fabrizio , Szallasi Zoltan , Richardson Andrea L. , Szüts Dávid 
Published: January 2022

AbstractDefects in BRCA1, BRCA2 and other genes of the homology-dependent DNA repair (HR) pathway cause an elevated rate of mutagenesis, eliciting specific mutation patterns including COSMIC signature SBS3. Using genome sequencing of knock-out cell lines we show that Y family translesion synthesis (TLS) polymerases contribute to the spontaneous generation of base substitution and short insertion/deletion mutations in BRCA1 deficient cells, and that TLS on DNA adducts is increased in BRCA1 and BRCA2 mutants. The inactivation of 53BP1 in BRCA1 mutant cells markedly reduces TLS-specific mutagenesis, and rescues the deficiency of template switch–mediated gene conversions in the immunoglobulin V locus of BRCA1 mutant chicken DT40 cells. 53BP1 also promotes TLS in human cellular extracts in vitro. Our results show that HR deficiency–specific mutagenesis is largely caused by TLS, and suggest a function for 53BP1 in regulating the choice between TLS and error-free template switching in replicative DNA damage bypass.
Probing dark exciton navigation through a local strain landscape in a WSe2 monolayer
Authors: Gelly Ryan J. , Renaud Dylan , Liao Xing , Pingault Benjamin , Bogdanovic Stefan , Scuri Giovanni , Watanabe Kenji , Taniguchi Takashi , Urbaszek Bernhard , Park Hongkun , Lončar Marko 
Published: January 2022

AbstractIn WSe2 monolayers, strain has been used to control the energy of excitons, induce funneling, and realize single-photon sources. Here, we developed a technique for probing the dynamics of free excitons in nanoscale strain landscapes in such monolayers. A nanosculpted tapered optical fiber is used to simultaneously generate strain and probe the near-field optical response of WSe2 monolayers at 5 K. When the monolayer is pushed by the fiber, its lowest energy states shift by as much as 390 meV (>20% of the bandgap of a WSe2 monolayer). Polarization and lifetime measurements of these red-shifting peaks indicate they originate from dark excitons. We conclude free dark excitons are funneled to high-strain regions during their long lifetime and are the principal participants in drift and diffusion at cryogenic temperatures. This insight supports proposals on the origin of single-photon sources in WSe2 and demonstrates a route towards exciton traps for exciton condensation.
Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2
Authors: Gupta Kapil , Toelzer Christine , Williamson Maia Kavanagh , Shoemark Deborah K. , Oliveira A. Sofia F. , Matthews David A. , Almuqrin Abdulaziz , Staufer Oskar , Yadav Sathish K. N. , Borucu Ufuk , Garzoni Frederic , Fitzgerald Daniel , Spatz Joachim , Mulholland Adrian J. , Davidson Andrew D. , Schaffitzel Christiane , Berger Imre 
Published: January 2022

AbstractAs the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.
Ultralow-temperature-driven water-based sorption refrigeration enabled by low-cost zeolite-like porous aluminophosphate
Authors: Liu Zhangli , Xu Jiaxing , Xu Min , Huang Caifeng , Wang Ruzhu , Li Tingxian , Huai Xiulan 
Published: January 2022

AbstractThermally driven water-based sorption refrigeration is considered a promising strategy to realize near-zero-carbon cooling applications by addressing the urgent global climate challenge caused by conventional chlorofluorocarbon (CFC) refrigerants. However, developing cost-effective and high-performance water-sorption porous materials driven by low-temperature thermal energy is still a significant challenge. Here, we propose a zeolite-like aluminophosphate with SFO topology (EMM-8) for water-sorption-driven refrigeration. The EMM-8 is characterized by 12-membered ring channels with large accessible pore volume and exhibits high water uptake of 0.28 g·g−1 at P/P0 = 0.2, low-temperature regeneration of 65 °C, fast adsorption kinetics, remarkable hydrothermal stability, and scalable fabrication. Importantly, the water-sorption-based chiller with EMM-8 shows the potential of achieving a record coefficient of performance (COP) of 0.85 at an ultralow-driven temperature of 63 °C. The working performance makes EMM-8 a practical alternative to realize high-efficient ultra-low-temperature-driven refrigeration.
Selectively tuning ionic thermopower in all-solid-state flexible polymer composites for thermal sensing
Authors: Chi Cheng , An Meng , Qi Xin , Li Yang , Zhang Ruihan , Liu Gongze , Lin Chongjia , Huang He , Dang Hao , Demir Baris , Wang Yan , Ma Weigang , Huang Baoling , Zhang Xing 
Published: January 2022

AbstractThere has been increasing interest in the emerging ionic thermoelectric materials with huge ionic thermopower. However, it’s challenging to selectively tune the thermopower of all-solid-state polymer materials because the transportation of ions in all-solid-state polymers is much more complex than those of liquid-dominated gels. Herein, this work provides all-solid-state polymer materials with a wide tunable thermopower range (+20~−6 mV K−1), which is different from previously reported gels. Moreover, the mechanism of p-n conversion in all-solid-state ionic thermoelectric polymer material at the atomic scale was presented based on the analysis of Eastman entropy changes by molecular dynamics simulation, which provides a general strategy for tuning ionic thermopower and is beneficial to understand the fundamental mechanism of the p-n conversion. Furthermore, a self-powered ionic thermoelectric thermal sensor fabricated by the developed p- and n-type polymers demonstrated high sensitivity and durability, extending the application of ionic thermoelectric materials.
Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes
Authors: Albayram Mehmet Sait , Smith Garrett , Tufan Fatih , Tuna Ibrahim Sacit , Bostancıklıoğlu Mehmet , Zile Michael , Albayram Onder 
Published: January 2022

AbstractMeningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.
Age influences on the molecular presentation of tumours
Authors: Li Constance H. , Haider Syed , Boutros Paul C. 
Published: January 2022

AbstractCancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.
Cosmogenic radionuclides reveal an extreme solar particle storm near a solar minimum 9125 years BP
Authors: Paleari Chiara I. , Mekhaldi Florian , Adolphi Florian , Christl Marcus , Vockenhuber Christof , Gautschi Philip , Beer Jürg , Brehm Nicolas , Erhardt Tobias , Synal Hans-Arno , Wacker Lukas , Wilhelms Frank , Muscheler Raimund 
Published: January 2022

AbstractDuring solar storms, the Sun expels large amounts of energetic particles (SEP) that can react with the Earth’s atmospheric constituents and produce cosmogenic radionuclides such as14C,10Be and36Cl. Here we present10Be and36Cl data measured in ice cores from Greenland and Antarctica. The data consistently show one of the largest10Be and36Cl production peaks detected so far, most likely produced by an extreme SEP event that hit Earth 9125 years BP (before present, i.e., before 1950 CE), i.e., 7176 BCE. Using the36Cl/10Be ratio, we demonstrate that this event was characterized by a very hard energy spectrum and was possibly up to two orders of magnitude larger than any SEP event during the instrumental period. Furthermore, we provide10Be-based evidence that, contrary to expectations, the SEP event occurred near a solar minimum.
Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin
Authors: Pothapragada Shilpa P. , Gupta Praver , Mukherjee Soumi , Das Tamal 
Published: January 2022

AbstractIn epithelia, normal cells recognize and extrude out newly emerged transformed cells by competition. This process is the most fundamental epithelial defence against cancer, whose occasional failure promotes oncogenesis. However, little is known about what factors determine the success or failure of this defence. Here we report that mechanical stiffening of extracellular matrix attenuates the epithelial defence against HRasV12-transformed cells. Using photoconversion labelling, protein tracking, and loss-of-function mutations, we attribute this attenuation to stiffening-induced perinuclear sequestration of a cytoskeletal protein, filamin. On soft matrix mimicking healthy epithelium, filamin exists as a dynamically single population, which moves to the normal cell-transformed cell interface to initiate the extrusion of transformed cells. However, on stiff matrix mimicking fibrotic epithelium, filamin redistributes into two dynamically distinct populations, including a new perinuclear pool that cannot move to the cell-cell interface. A matrix stiffness-dependent differential between filamin-Cdc42 and filamin-perinuclear cytoskeleton interaction controls this distinctive filamin localization and hence, determines the success or failure of epithelial defence on soft versus stiff matrix. Together, our study reveals how pathological matrix stiffening leads to a failed epithelial defence at the initial stage of oncogenesis.
Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy
Authors: Mayer D. , Lever F. , Picconi D. , Metje J. , Alisauskas S. , Calegari F. , Düsterer S. , Ehlert C. , Feifel R. , Niebuhr M. , Manschwetus B. , Kuhlmann M. , Mazza T. , Robinson M. S. , Squibb R. J. , Trabattoni A. , Wallner M. , Saalfrank P. , Wolf T. J. A. , Gühr M. 
Published: January 2022

AbstractThe conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220–250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.
A record thermoelectric efficiency in tellurium-free modules for low-grade waste heat recovery
Authors: Bu Zhonglin , Zhang Xinyue , Hu Yixin , Chen Zhiwei , Lin Siqi , Li Wen , Xiao Chong , Pei Yanzhong 
Published: January 2022

AbstractLow-grade heat accounts for >50% of the total dissipated heat sources in industries. An efficient recovery of low-grade heat into useful electricity not only reduces the consumption of fossil-fuels but also releases the subsequential environmental-crisis. Thermoelectricity offers an ideal solution, yet low-temperature efficient materials have continuously been limited to Bi2Te3-alloys since the discovery in 1950s. Scarcity of tellurium and the strong property anisotropy cause high-cost in both raw-materials and synthesis/processing. Here we demonstrate cheap polycrystalline antimonides for even more efficient thermoelectric waste-heat recovery within 600 K than conventional tellurides. This is enabled by a design of Ni/Fe/Mg3SbBi and Ni/Sb/CdSb contacts for both a prevention of chemical diffusion and a low interfacial resistivity, realizing a record and stable module efficiency at a temperature difference of 270 K. In addition, the raw-material cost to the output power ratio in this work is reduced to be only 1/15 of that of conventional Bi2Te3-modules.