bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-genome comparative analysis at the lineage/sublineage level discloses relationships between Mycobacterium tuberculosis genotype and clinical phenotype
Authors: Negrete-Paz Andrea Monserrat , Vázquez-Marrufo Gerardo , Vázquez-Garcidueñas Ma. Soledad 
Published: September 2021

Background
Human tuberculosis (TB) caused by members of the Mycobacterium tuberculosis complex (MTBC) is the main cause of death among infectious diseases worldwide. Pulmonary TB (PTB) is the most common clinical phenotype of the disease, but some patients develop an extrapulmonary (EPTB) phenotype in which any organ or tissue can be affected. MTBC species include nine phylogenetic lineages, with some appearing globally and others being geographically restricted. EPTB can or not have pulmonary involvement, challenging its diagnosis when lungs are not implicated, thus causing an inadequate treatment. Finding evidence of a specific M. tuberculosis genetic background associated with EPTB is epidemiologically relevant due to the virulent and multidrug-resistant strains isolated from such cases. Until now, the studies conducted to establish associations between M. tuberculosis lineages and PTB/EPTB phenotypes have shown inconsistent results, which are attributed to the strain predominance from specific M. tuberculosis lineages/sublineages in the samples analyzed and the use of low-resolution phylogenetic tools that have impaired sublineage discrimination abilities. The present work elucidates the relationships between the MTBC strain lineages/sublineages and the clinical phenotypes of the disease as well as the antibiotic resistance of the strains.

Methods
To avoid biases, we retrieved the raw genomic reads (RGRs) of all (n = 245) the M. tuberculosis strains worldwide causing EPTB available in databases and an equally representative sample of the RGRs (n = 245) of PTB strains. A multiple alignment was constructed, and a robust maximum likelihood phylogeny based on single-nucleotide polymorphisms was generated, allowing effective strain lineage/sublineage assignment.

Results
A significant Odds Ratio (OR range: 1.8–8.1) association was found between EPTB and the 1.1.1, 1.2.1, 4.1.2.1 and ancestral Beijing sublineages. Additionally, a significant association between PTB with 4.3.1, 4.3.3, and 4.5 and Asian African 2 and Europe/Russia B0/W148 modern Beijing sublineages was found. We also observed a significant association of Lineage 3 strains with multidrug resistance (OR 3.8; 95% CI [1.1–13.6]), as well as between modern Beijing sublineages and antibiotic resistance (OR 4.3; 3.8–8.6). In this work, it was found that intralineage diversity can drive differences in the immune response that triggers the PTB/EPTB phenotype.
Emission Wavelength Tuning via Competing Lattice Expansion and Octahedral Tilting for Efficient Red Perovskite Light‐Emitting Diodes
Authors: Sun Guanwei , Liu Xinyan , Liu Zhe , Liu Denghui , Meng Fanyuan , Li Zhenchao , Chu Linghao , Qiu Weidong , Peng Xiaomei , Xie Wentao , Shen Chenyang , Chen Jiting , Yip Hin‐Lap , Su Shi‐Jian 
Published: September 2021

AbstractThe band‐edge electronic structure of lead halide perovskites (ABX3) is composed of the orbitals of B and X components and can be tuned through the composition and structure of the BX6 octahedron. Although A‐site cations do not directly contribute to near‐edge states, the bandgap of 3D metal halide perovskites can be affected by A‐cations through BX6 octahedron tilting or lattice size variation. Here, as confirmed by the Rietveld refinement results of X‐ray diffraction characterization, the competition between lattice expansion and octahedral tilting is identified for the first time in emission wavelength tuning when introducing a large A‐site cation (C2H5NH3+, EA+) into 1‐naphthylmethylammonium iodide‐passivated CsPbI3 system. The former dominates spectral redshift, while the latter leads to a blueshift of emission peak, which broadens the way to tune the emission wavelength. In addition, excess cations can also passivate the perovskites, leading to a photoluminescence (PL) quantum yield as high as 61%, increased average PL lifetime of 74.7 ns, and a high radiative and non‐radiative recombination ratio of 15.7. Eventually, spectral‐stable deep‐red perovskite light‐emitting diode with a maximum external quantum efficiency of 17.5% is realized, which is one of the highest efficiencies without using any light outcoupling and anti‐solvent techniques.
Identifying Migration Channels and Bottlenecks in Monoclinic NASICON‐Type Solid Electrolytes with Hierarchical Ion‐Transport Algorithms
Authors: Zou Zheyi , Ma Nan , Wang Aiping , Ran Yunbing , Song Tao , He Bing , Ye Anjiang , Mi Penghui , Zhang Liwen , Zhou Hang , Jiao Yao , Liu Jinping , Wang Da , Li Yajie , Avdeev Maxim , Shi Siqi 
Published: September 2021

AbstractMonoclinic natrium superionic conductors (NASICON; Na3Zr2Si2PO12) are well‐known Na‐ion solid electrolytes which have been studied for 40 years. However, due to the low symmetry of the crystal structure, identifying the migration channels of monoclinic NASICON accurately still remains unsolved. Here, a cross‐verified study of Na+ diffusion pathways in monoclinic NASICON by integrating geometric analysis of channels and bottlenecks, bond‐valence energy landscapes analysis, and ab initio molecular dynamics simulations is presented. The diffusion limiting bottlenecks, the anisotropy of conductivity, and the time and temperature dependence of Na+ distribution over the channels are characterized and strategies for improving both bulk and total conductivity of monoclinic NASICON‐type solid electrolytes are proposed. This set of hierarchical ion‐transport algorithms not only shows the efficiency and practicality in revealing the ion transport behavior in monoclinic NASICON‐type materials but also provides guidelines for optimizing their conductive properties that can be readily extended to other solid electrolytes.
Controlling Microring Resonator Extinction Ratio via Metal‐Halide Perovskite Nonlinearity
Authors: Wang Feifan , Zhao Lianfeng , Xiao Yahui , Li Tiantian , Wang Yixiu , Soman Anishkumar , Lee Hwaseob , Kananen Thomas , Hu Xiaoyong , Rand Barry P. , Gu Tingyi 
Published: September 2021

AbstractThe exceptionally high optical nonlinearities, wide bandgap, and homogeneity in solution‐processed metal‐halide perovskite media are utilized as optical nonlinear elements on a silicon photonic platform for low‐power‐active components, such as all‐optical switches, modulators, and lasers. With room temperature back‐end‐of‐line compatible processing, a hybrid metal‐halide perovskite (CH3NH3PbI3) microring resonator (MRR) structure is fabricated on a foundry‐processed low‐loss silicon photonic platform. With in‐plane excitation near the light intensity of 110 W m−2, strong two‐photon absorption and free‐carrier absorption saturation are observed. With 103 field enhancements by MRRs, the photorefractive effect in the metal‐halide perovskite reduces linear absorption, represented by 102 improvement of the MRR's intrinsic quality factor and 20 dB enhancement of the extinction ratio.
Genetically Encoded Protein Thermometer Enables Precise Electrothermal Control of Transgene Expression
Authors: Stefanov Bozhidar‐Adrian , Teixeira Ana P. , Mansouri Maysam , Bertschi Adrian , Krawczyk Krzysztof , Hamri Ghislaine Charpin‐El , Xue Shuai , Fussenegger Martin 
Published: September 2021

AbstractBody temperature is maintained at around 37 °C in humans, but may rise to 40 °C or more during high‐grade fever, which occurs in most adults who are seriously ill. However, endogenous temperature sensors, such as ion channels and heat‐shock promoters, are fully activated only at noxious temperatures above this range, making them unsuitable for medical applications. Here, a genetically encoded protein thermometer (human enhanced gene activation thermometer; HEAT) is designed that can trigger transgene expression in the range of 37–40 °C by linking a mutant coiled‐coil temperature‐responsive protein sensor to a synthetic transcription factor. To validate the construct, a HEAT‐transgenic monoclonal human cell line, FeverSense, is generated and it is confirmed that it works as a fever sensor that can temperature‐ and exposure‐time‐dependently trigger reporter gene expression in vitro and in vivo. For translational proof of concept, microencapsulated designer cells stably expressing a HEAT‐controlled insulin production cassette in a mouse model of type‐1 diabetes are subcutaneously implanted and topical heating patches are used to apply heat corresponding to a warm sensation in humans. Insulin release is induced, restoring normoglycemia. Thus, HEAT appears to be suitable for practical electrothermal control of cell‐based therapy, and may also have potential for next‐generation treatment of fever‐associated medical conditions.
Mechanical Valves for On‐Board Flow Control of Inflatable Robots
Authors: Jin Lishuai , Forte Antonio Elia , Bertoldi Katia 
Published: September 2021

AbstractInflatable robots are becoming increasingly popular, especially in applications where safe interactions are a priority. However, designing multifunctional robots that can operate with a single pressure input is challenging. A potential solution is to couple inflatables with passive valves that can harness the flow characteristics to create functionality. In this study, simple, easy to fabricate, lightweight, and inexpensive mechanical valves are presented that harness viscous flow and snapping arch principles. The mechanical valves can be fully integrated on‐board, enabling the control of the incoming airflow to realize multifunctional robots that operate with a single pressure input, with no need for electronic components, cables, or wires. By means of three robotic demos and guided by a numerical model, the capabilities of the valves are demonstrated and optimal input profiles are identified to achieve prescribed functionalities. The study enriches the array of available mechanical valves for inflatable robots and enables new strategies to realize multifunctional robots with on‐board flow control.
Ocular Delivery of Predatory Bacteria with Cryomicroneedles Against Eye Infection
Authors: Cui Mingyue , Zheng Mengjia , Wiraja Christian , Chew Sharon Wan Ting , Mishra Arti , Mayandi Venkatesh , Lakshminarayanan Rajamani , Xu Chenjie 
Published: September 2021

AbstractThe development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. This work introduces cryomicroneedles (cryoMN) for the ocular delivery of predatory Bdellovibrio bacteriovorus (B. bacteriovorus) bacteria. The cryoMN patches are prepared by freezing B. bacteriovorus containing a cryoprotectant medium in a microneedle template. The viability of B. bacteriovorus in cryoMNs remains above 80% as found in long‐term storage studies, and they successfully impede the growth of gram‐negative bacteria in vitro or in a rodent eye infection model. The infection is significantly relieved by nearly six times through 2.5 days of treatment without substantial effects on the cornea thickness and morphology. This approach represents the safe and efficient delivery of new class of antimicrobial armamentarium to otherwise impermeable ocular surface and opens up new avenues for the treatment of ocular surface disorders.
Mammary Tumor Organoid Culture in Non‐Adhesive Alginate for Luminal Mechanics and High‐Throughput Drug Screening
Authors: Fang Guocheng , Lu Hongxu , Rodriguez de la Fuente Laura , Law Andrew M. K. , Lin Gungun , Jin Dayong , Gallego‐Ortega David 
Published: September 2021

AbstractMammary tumor organoids have become a promising in vitro model for drug screening and personalized medicine. However, the dependency on the basement membrane extract (BME) as the growth matrices limits their comprehensive application. In this work, mouse mammary tumor organoids are established by encapsulating tumor pieces in non‐adhesive alginate. High‐throughput generation of organoids in alginate microbeads is achieved utilizing microfluidic droplet technology. Tumor pieces within the alginate microbeads developed both luminal‐ and solid‐like structures and displayed a high similarity to the original fresh tumor in cellular phenotypes and lineages. The mechanical forces of the luminal organoids in the alginate capsules are analyzed with the theory of the thick‐wall pressure vessel (TWPV) model. The luminal pressure of the organoids increase with the lumen growth and can reach 2 kPa after two weeks’ culture. Finally, the mammary tumor organoids are treated with doxorubicin and latrunculin A to evaluate their application as a drug screening platform. It is found that the drug response is related to the luminal size and pressures of organoids. This high‐throughput culture for mammary tumor organoids may present a promising tool for preclinical drug target validation and personalized medicine.
A Framework of Paracellular Transport via Nanoparticles‐Induced Endothelial Leakiness
Authors: Lee Myeongsang , Ni Nengyi , Tang Huayuan , Li Yuhuan , Wei Wei , Kakinen Aleksandr , Wan Xulin , Davis Thomas P. , Song Yang , Leong David Tai , Ding Feng , Ke Pu Chun 
Published: September 2021

AbstractNanomaterial‐induced endothelial leakiness (NanoEL) is an interfacial phenomenon denoting the paracellular transport of nanoparticles that is pertinent to nanotoxicology, nanomedicine and biomedical engineering. While the NanoEL phenomenon is complementary to the enhanced permeability and retention effect in terms of their common applicability to delineating the permeability and behavior of nanoparticles in tumoral environments, these two effects significantly differ in scope, origin, and manifestation. In the current study, the descriptors are fully examined of the NanoEL phenomenon elicited by generic citrate‐coated gold nanoparticles (AuNPs) of changing size and concentration, from microscopic gap formation and actin reorganization down to molecular signaling pathways and nanoscale interactions of AuNPs with VE‐cadherin and its intra/extracellular cofactors. Employing synergistic in silico methodologies, for the first time the molecular and statistical mechanics of cadherin pair disruption, especially in response to AuNPs of the smallest size and highest concentration are revealed. This study marks a major advancement toward establishing a comprehensive NanoEL framework for complementing the understanding of the transcytotic pathway and for guiding the design and application of future nanomedicines harnessing the myriad functions of the mammalian vasculature.
Development and Applications of Double Diels‐Alder Reaction in Organic Synthesis
Authors: Mali Ghanshyam , Chauhan Amar Nath Singh , Chavan Kailas Arjun , Erande Rohan D. 
Published: September 2021

AbstractThe class of Double Diels‐Alder (DDA) reactions leading the targets concisely where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods. After the tremendous development and discoveries in various Diels‐Alder reactions including its key role applications in many natural products syntheses, the DDA reaction is considered as a growing branch of Diels‐Alder reaction where two consecutive [4+2] cycloadditions trigger the streamlined construction of polycyclic and macrocyclic architectures. In light of the ever‐increasing importance of DDA reactions in chemical sciences, we review the comprehensive studies and recent advances in DDA reactions in organic synthesis. This review summarizes key achievements of DDA for the preparation of macrocyclic, bicyclic, heterocyclic, and polycyclic structures documented since its revelation in 1980 to 2020. Emphasis is put on the synthesis of various structural classes based on the selectivity of the DDA reaction.
A Catalyst/Oxidant/Base Free Benzylic Csp3−H Alkoxylation of toluidines via Electro‐oxidative Csp3−O‐Coupling with Alcohols
Authors: Chowdhury Sushobhan , Pandey Shubham 
Published: September 2021

AbstractFunctionalization of Csp3−H bond meets various challenges owing to their well‐known inertness. The task becomes even more challenging for carbon‐heteroatom coupling e. g., Csp3−O coupling. Herein we report an electrochemical approach for the direct regioselctive cross‐dehydrogenative hetero‐coupling of benzylic Csp3−H bonds of toluidines with alcohols at room temperature under external catalyst, oxidant and base‐free condition. The developed protocol utilizes benzylic substrates as the limiting reagent for the site‐selective coupling and demonstrates wide substrate scope with respect to both the coupling partners synthesizing corresponding benzylic ethers in moderate to excellent yields.
Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease
Authors: Chatterjee Pratishtha , Pedrini Steve , Ashton Nicholas J. , Tegg Michelle , Goozee Kathryn , Singh Abhay K. , Karikari Thomas K. , Simrén Joel , Vanmechelen Eugeen , Armstrong Nicola J. , Hone Eugene , Asih Prita R. , Taddei Kevin , Doré Vincent , Villemagne Victor L. , Sohrabi Hamid R. , Zetterberg Henrik , Masters Colin L. , Blennow Kaj , Martins Ralph N. 
Published: September 2021

AbstractIntroductionThis study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t‐tau), phosphorylated tau (p‐tau181 and p‐tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).MethodsPlasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) of brain amyloidosis.ResultsPlasma GFAP, t‐tau, p‐tau181, and p‐tau231 concentrations were higher in Aβ+ CU compared with Aβ− CU cross‐sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ− CU; however, no statistically significant differences were observed between the AUCs of GFAP, p‐tau181, and p‐tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t‐tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p‐tau181 in Aβ+ CU and increased NFL in Aβ− CU, over a 12‐month duration. GFAP, p‐tau181, p‐tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.DiscussionThese findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p‐tau for preclinical AD.
Asymmetric Synthesis of 2,2‐Difluorotetrahydrofurans through Palladium‐Catalyzed Formal [3+2] Cycloaddition
Authors: Liu Jun , Yu Longhui , Zheng Changwu , Zhao Gang 
Published: September 2021

AbstractThe asymmetric synthesis of 2,2‐difluorinated tetrahydrofurans was accomplished via enantioselective formal [3+2] cycloaddition catalyzed by palladium. The asymmetric reaction between gem‐difluoroalkenes and racemic vinyl epoxides or vinylethylene carbonates resulted in the formation of enantioenriched 2,2‐difluorotetrahydrofurans with an enantioselectivity up to 98 %. Notably, the reaction used the readily available (R)‐BINAP as the ligand at a low loading and yielded a wide variety of difluorinated products in moderate to high yields. Both chiral diastereomers could be obtained in a single sequence.
Chemical vapor deposition graphene transfer onto asymmetric PMMA support
Authors: Vivas Vinícius Henrique , Flores Marcelo Costa , Jesus Wander Pereira , Ferlauto André Santarosa , Da Cunha Thiago Henrique Rodrigues , De Souza Figueiredo Katia Cecília 
Published: September 2021

AbstractGraphene is a promising material for membrane applications. However, the graphene production with large specific area and good structural quality is a challenge. Therefore, the production and characterization of composite membranes with graphene grown by chemical vapor deposition (CVD) over a porous polymethylmethacrylate (PMMA) substrate was investigated. The experimental strategy consisted in applying CVD‐graphene on a PMMA surface using PMMA‐assisted graphene wet transfer. The proposed methodology resulted in large‐area membranes with 2 cm diameter. The samples were characterized by Raman spectroscopy, indicating the presence of graphene in good quality and relative structural integrity. The analysis by scanning electron microscopy revealed the formation of a microporous support with an asymmetric structure. The gas permeation measurements of graphene/PMMA membranes showed a permeability reduction of 81.9% for CO2 and 83.7% for N2. The contribution of PMMA to flow resistance was 2% and 11% for CO2 and N2, respectively, and the contribution of graphene was 98% and 89% for CO2 and N2. Therefore, this research presents a potential advance in transferring graphene to porous support, and the impermeability process of membranes composed of graphene/PMMA, a fundamental step for the development of graphene membranes before the production of controlled‐sized pores.
New Insights into Structural Evolution of LiNiO2 Revealed by Operando Neutron Diffraction
Authors: Chien Po‐Hsiu , Wu Xianyang , Song Bohang , Yang Zhijie , Waters Crystal K. , Everett Michelle S. , Lin Feng , Du Zhijia , Liu Jue 
Published: September 2021

AbstractLiNiO2 (LNO) represents the end member in the compositional space of the LiNi1‐x‐yMnxCoyO2 (as x and y approach zero) cathode system. Despite its high theoretical specific capacity (275 mAh/g), LNO suffers from phase transitions with large volume change and unfavorable reactions upon electrochemical cycling, which restricts its practical use in the application of lithium‐ion batteries. While the contributing factor to the structural instability is commonly linked to the undesired volume collapse associated with the H2‐H3 phase transition, detailed analysis of structural evolution following the entire route of phase transitions (H1‐M‐H2‐H3) in real time under battery operating conditions remains a challenging task. In this work, we employ operando neutron diffraction to study the structural changes (crystal lattice, Li/Ni−O bond length, O−Ni−O bond angles, and LiO2/NiO2 layer thickness) of LNO cathode in a home‐built LixNiO2||graphite full cell during Li+ de‐/intercalation. In particular, the anomalous increase(decrease) of Ni−O(Li−O) bond length at high SOC (>∼85 %) in the H3 phase is discussed in the context of O2− (2p)→Ni4+(3d) negative charge transfer.