bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breath and plasma metabolomics to assess inflammation in acute stroke
Authors: Ahmed Waqar , White Iain R. , Wilkinson Maxim , Johnson Craig F. , Rattray Nicholas , Kishore Amit K. , Goodacre Royston , Smith Craig J. , Fowler Stephen J. 
Published: November 2021

AbstractInflammation is strongly implicated in both injury and repair processes occurring after stroke. In this exploratory study we assessed the feasibility of repeated sampling of exhaled volatile organic compounds and performed an untargeted metabolomic analysis of plasma collected at multiple time periods after stroke. Metabolic profiles were compared with the time course of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Serial breath sampling was well-tolerated by all patients and the measurement appears feasible in this group. We found that exhaled decanal tracks CRP and IL-6 levels post-stroke and correlates with several metabolic pathways associated with a post-stroke inflammatory response. This suggests that measurement of breath and blood metabolites could facilitate development of novel therapeutic and diagnostic strategies. Results are discussed in relation to the utility of breath analysis in stroke care, such as in monitoring recovery and complications including stroke associated infection.
Multifaceted phytogenic silver nanoparticles by an insectivorous plant Drosera spatulata Labill var. bakoensis and its potential therapeutic applications
Authors: Gaddam Susmila Aparna , Kotakadi Venkata Subbaiah , Subramanyam Gunasekhar Kalavakunta , Penchalaneni Josthna , Challagundla Varadarajulu Naidu , DVR Sai Gopal , Pasupuleti Visweswara Rao 
Published: November 2021

AbstractThe current investigation highlights the green synthesis of silver nanoparticles (AgNPs) by the insectivorous plant Drosera spatulata Labill var. bakoensis, which is the first of its kind. The biosynthesized nanoparticles revealed a UV visible surface plasmon resonance (SPR) band at 427 nm. The natural phytoconstituents which reduce the monovalent silver were identified by FTIR. The particle size of the Ds-AgNPs was detected by the Nanoparticle size analyzer confirms that the average size of nanoparticles was around 23 ± 2 nm. Ds-AgNPs exhibit high stability because of its high negative zeta potential (− 34.1 mV). AFM studies also revealed that the Ds-AgNPs were spherical in shape and average size ranges from 10 to 20 ± 5 nm. TEM analysis also revealed that the average size of Ds-AgNPs was also around 21 ± 4 nm and the shape is roughly spherical and well dispersed. The crystal nature of Ds-AgNPs was detected as a face-centered cube by the XRD analysis. Furthermore, studies on antibacterial and antifungal activities manifested outstanding antimicrobial activities of Ds-AgNPs compared with standard antibiotic Amoxyclav. In addition, demonstration of superior free radical scavenging efficacy coupled with potential in vitro cytotoxic significance on Human colon cancer cell lines (HT-29) suggests that the Ds-AgNPs attain excellent multifunctional therapeutic applications.
Adaptation strategies and collective dynamics of extraction in networked commons of bistable resources
Authors: Schauf Andrew , Oh Poong 
Published: November 2021

AbstractWhen populations share common-pool resources (CPRs), individuals decide how much effort to invest towards resource extraction and how to allocate this effort among available resources. We investigate these dual aspects of individual choice in networked games where resources undergo regime shifts between discrete quality states (viable or depleted) depending on collective extraction levels. We study the patterns of extraction that emerge on various network types when agents are free to vary extraction from each CPR separately to maximize their short-term payoffs. Using these results as a basis for comparison, we then investigate how results are altered if agents fix one aspect of adaptation (magnitude or allocation) while letting the other vary. We consider two constrained adaptation strategies: uniform adaptation, whereby agents adjust their extraction levels from all CPRs by the same amount, and reallocation, whereby agents selectively shift effort from lower- to higher-quality resources. A preference for uniform adaptation increases collective wealth on degree-heterogeneous agent-resource networks. Further, low-degree agents retain preferences for these constrained strategies under reinforcement learning. Empirical studies have indicated that some CPR appropriators ignore—while others emphasize—allocation aspects of adaptation; our results demonstrate that structural patterns of resource access can determine which behavior is more advantageous.
Dirac semimetal phase and switching of band inversion in XMg2Bi2 (X = Ba and Sr)
Authors: Takane Daichi , Kubota Yuya , Nakayama Kosuke , Kawakami Tappei , Yamauchi Kunihiko , Souma Seigo , Kato Takemi , Sugawara Katsuaki , Ideta Shin-ichiro , Tanaka Kiyohisa , Kitamura Miho , Horiba Koji , Kumigashira Hiroshi , Oguchi Tamio , Takahashi Takashi , Segawa Kouji , Sato Takafumi 
Published: November 2021

AbstractTopological Dirac semimetals (TDSs) offer an excellent opportunity to realize outstanding physical properties distinct from those of topological insulators. Since TDSs verified so far have their own problems such as high reactivity in the atmosphere and difficulty in controlling topological phases via chemical substitution, it is highly desirable to find a new material platform of TDSs. By angle-resolved photoemission spectroscopy combined with first-principles band-structure calculations, we show that ternary compound BaMg2Bi2 is a TDS with a simple Dirac-band crossing around the Brillouin-zone center protected by the C3 symmetry of crystal. We also found that isostructural SrMg2Bi2 is an ordinary insulator characterized by the absence of band inversion due to the reduction of spin–orbit coupling. Thus, XMg2Bi2 (X = Sr, Ba, etc.) serves as a useful platform to study the interplay among crystal symmetry, spin–orbit coupling, and topological phase transition around the TDS phase.
Tunable control of CAR T cell activity through tetracycline mediated disruption of protein–protein interaction
Authors: Hotblack Alastair , Kokalaki Evangelia K. , Palton Morgan J. , Cheung Gordon Weng-Kit , Williams Iwan P. , Manzoor Somayya , Grothier Thomas I. , Piapi Alice , Fiaccadori Valeria , Wawrzyniecka Patrycja , Roddy Harriet A. , Agliardi Giulia , Roddie Claire , Onuoha Shimobi , Thomas Simon , Cordoba Shaun , Pule Martin 
Published: November 2021

AbstractChimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an “off-switch” by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule.
Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials
Authors: Kiss Szabolcs , Gede Noémi , Hegyi Péter , Nagy Bettina , Deák Rita , Dembrovszky Fanni , Bunduc Stefania , Erőss Bálint , Leiner Tamás , Szakács Zsolt , Alizadeh Hussain 
Published: November 2021

AbstractDaratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33–5.61)] and sCR [OR = 2.29 (CI 1.49–3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39–0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76–10.66)] and sCR [OR = 3.08 (CI 2.00–4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37–0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.
Local, multimodal intralesional therapy renders distant brain metastases susceptible to PD-L1 blockade in a preclinical model of triple-negative breast cancer
Authors: Yokoi Toshihiro , Oba Takaaki , Kajihara Ryutaro , Abrams Scott I. , Ito Fumito 
Published: November 2021

AbstractDespite recent progress in therapeutic strategies, prognosis of metastatic triple-negative breast cancer (TNBC) remains dismal. Evidence suggests that the induction and activation of tumor-residing conventional type-1 dendritic cells (cDC1s) is critical for the generation of CD8+ T cells that mediate the regression of mammary tumors and potentiate anti-PD-1/PD-L1 therapeutic efficacy. However, it remains unknown whether this strategy is effective against metastatic TNBC, which is poorly responsive to immunotherapy. Here, using a mouse model of TNBC, we established orthotopic mammary tumors and brain metastases, and treated mammary tumors with in situ immunomodulation (ISIM) consisting of intratumoral injections of Flt3L to mobilize cDC1s, local irradiation to induce immunogenic tumor cell death, and TLR3/CD40 stimulation to activate cDC1s. ISIM treatment of the mammary tumor increased circulating T cells with effector phenotypes, and infiltration of CD8+ T cells into the metastatic brain lesions, resulting in delayed progression of brain metastases and improved survival. Furthermore, although anti-PD-L1 therapy alone was ineffective against brain metastases, ISIM overcame resistance to anti-PD-L1 therapy, which rendered these tumor-bearing mice responsive to anti-PD-L1 therapy and further improved survival. Collectively, these results illustrate the therapeutic potential of multimodal intralesional therapy for patients with unresectable and metastatic TNBC.
Expression analyses in Ginkgo biloba provide new insights into the evolution and development of the seed
Authors: Zumajo-Cardona Cecilia , Little Damon P. , Stevenson Dennis , Ambrose Barbara A. 
Published: November 2021

AbstractAlthough the seed is a key morphological innovation, its origin remains unknown and molecular data outside angiosperms is still limited. Ginkgo biloba, with a unique place in plant evolution, being one of the first extant gymnosperms where seeds evolved, can testify to the evolution and development of the seed. Initially, to better understand the development of the ovules in Ginkgo biloba ovules, we performed spatio-temporal expression analyses in seeds at early developing stages, of six candidate gene homologues known in angiosperms: WUSCHEL, AINTEGUMENTA, BELL1, KANADI, UNICORN, and C3HDZip. Surprisingly, the expression patterns of most these ovule homologues indicate that they are not wholly conserved between angiosperms and Ginkgo biloba. Consistent with previous studies on early diverging seedless plant lineages, ferns, lycophytes, and bryophytes, many of these candidate genes are mainly expressed in mega- and micro-sporangia. Through in-depth comparative transcriptome analyses of Ginkgo biloba developing ovules, pollen cones, and megagametophytes we have been able to identify novel genes, likely involved in ovule development. Finally, our expression analyses support the synangial or neo-synangial hypotheses for the origin of the seed, where the sporangium developmental network was likely co-opted and restricted during integument evolution.
Last glacial temperature reconstructions using coupled isotopic analyses of fossil snails and stalagmites from archaeological caves in Okinawa, Japan
Authors: Asami Ryuji , Hondo Rikuto , Uemura Ryu , Fujita Masaki , Yamasaki Shinji , Shen Chuan-Chou , Wu Chung-Che , Jiang Xiuyang , Takayanagi Hideko , Shinjo Ryuichi , Kano Akihiro , Iryu Yasufumi 
Published: November 2021

AbstractWe applied a new geoarchaeological method with two carbonate archives, which are fossil snails from Sakitari Cave and stalagmites from Gyokusen Cave, on Okinawa Island, Japan, to reconstruct surface air temperature changes over the northwestern Pacific since the last glacial period. Oxygen isotope ratios (δ18O) of modern and fossil freshwater snail shells were determined to infer seasonal temperature variations. The observational and analytical data confirm that δ18O values of fluid inclusion waters in the stalagmite can be regarded as those of spring waters at the sites where snails lived. Our results indicate that the annual mean, summer, and winter air temperatures were lower by 6–7 °C at ca. 23 thousand years ago (ka) and 4–5 °C at ca. 16–13 ka than those of the present day. Our reconstruction implies that surface air cooling was possibly two times greater than that of seawater around the Ryukyu Islands during the Last Glacial Maximum, which potentially enhanced the development of the East Asian summer monsoon during the last deglaciation. Considering the potential uncertainties in the temperature estimations, the climatic interpretations of this study are not necessarily definitive due to the limited number of samples. Nevertheless, our new geoarchaeological approach using coupled δ18O determinations of fossil snails and stalagmite fluid inclusion waters will be useful for reconstructing snapshots of seasonally resolved time series of air temperatures during the Quaternary.
Gene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching and function
Authors: Barbuti Peter A. , Ohnmacht Jochen , Santos Bruno F. R. , Antony Paul M. , Massart François , Cruciani Gérald , Dording Claire M. , Pavelka Lukas , Casadei Nicolas , Kwon Yong-Jun , Krüger Rejko 
Published: November 2021

AbstractParkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the alpha-synuclein protein causing an autosomal-dominant form of PD. There are limited studies assessing pathogenic SNCA mutations in patient-derived isogenic cell models. Here we provide a functional assessment of dopaminergic neurons derived from a patient harbouring the p.A30P SNCA mutation. Using two clonal gene-corrected isogenic cell lines we identified image-based phenotypes showing impaired neuritic processes. The pathological neurons displayed impaired neuronal activity, reduced mitochondrial respiration, an energy deficit, vulnerability to rotenone, and transcriptional alterations in lipid metabolism. Our data describes for the first time the mutation-only effect of the p.A30P SNCA mutation on neuronal function, supporting the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease-modifying compound screenings and drug discovery strategies.
Diagnostic odyssey of acute disseminated encephalomyelitis in children
Authors: Takahashi Yoko , Hayakawa Itaru , Abe Yuichi 
Published: November 2021

AbstractWe aimed to determine whether acute disseminated encephalomyelitis (ADEM) diagnosis in children is delayed, and if so, to identify the clinical risk factors of delayed diagnosis. Standardised data were collected from children with ADEM from 2003 to 2020. Overall diagnostic delay (time between symptom onset and ADEM diagnosis), physicians’ delay (between the first medical visit and ADEM diagnosis), and patients’ delay (between symptom onset and the first medical visit) were analysed. Thirty ADEM patients were identified, including 16 (54%) with neurological deficits at discharge. Overall, physicians’, and patients’ delays were 9 (interquartile range [IQR] 6–20.5), 5.5 (IQR 3–14), and 4 (IQR 2–8) days, respectively. Overall delay was significantly associated with physicians’ delay, but not with patients’ delay. There were 61 misdiagnoses among 25 (83%) patients, while 5 (17%) were diagnosed correctly at the first visit. The misdiagnoses of common respiratory and gastrointestinal infection and aseptic meningitis were associated with overall and/or physicians’ delay. Later onset of specific neurological features suggestive of ADEM was associated with all three diagnostic delays. A unique diagnostic odyssey exists in ADEM. Several clinical risk factors were associated with the diagnostic delay.
Epidemiologic trends in cancer-related emergency department utilization in Korea from 2015 to 2019
Authors: Lee Sun Young , Ro Young Sun , Shin Sang Do , Moon Sungwoo 
Published: November 2021

AbstractIt is inevitable for cancer patients to visit the emergency department (ED) for symptoms of cancer itself and various treatment-related complications. As the prevalence of cancer increases along with cancer survival rates, the number of ED visits of cancer patients may increase. This study aimed to investigate the epidemiologic trends and characteristics of cancer-related ED visits. A cross-sectional study was conducted for all ED visits nationwide between 2015 and 2019. The characteristics of cancer- and non-cancer-related ED visits were compared, and the cancer type and primary reason for ED visits were investigated for cancer-related ED visits. The age- and sex-standardized incidence rate per 100,000 population was calculated. Among 44,983,523 ED visits for 5 years, 1,372,119 (3.1%) were cancer-related. Among cancer-related ED visits, 54.8% led to hospitalization including 5.1% in ICU, and 9.5% died in the hospital. The age- and sex-standardized incidence rates of cancer-related ED visits per 100,000 population increased from 521.8 in 2015 to 642.2 in 2019 (p-for-trends, < 0.01), and rates of cancer-related hospital admission via ED were 309.0 in 2015 and 336.6 in 2019 (p-for-trends, 0.75). The most common cancer types were lung cancer (14.7%), liver cancer (13.1%), and colorectal cancer (11.5%). The most common primary reasons of cancer-related ED visits were pneumonia (3.6%), gastroenteritis (2.7%), fever (2.6%), abdominal pain (2.4%), and ileus (2.1%). Cancer-related ED visits accounted for 3.1% of all ED visits, with 1.37 million cases over five years. The incidence rate of cancer-related ED visits has increased year by year, with high hospitalization and mortality rates, and the burden of cancer-related ED visits will continue to increase as the prevalence increases.
Elastic deformation plays a non-negligible role in Greenland’s outlet glacier flow
Authors: Christmann Julia , Helm Veit , Khan Shfaqat Abbas , Kleiner Thomas , Müller Ralf , Morlighem Mathieu , Neckel Niklas , Rückamp Martin , Steinhage Daniel , Zeising Ole , Humbert Angelika 
Published: November 2021

AbstractFuture projections of global mean sea level change are uncertain, partly because of our limited understanding of the dynamics of Greenland’s outlet glaciers. Here we study Nioghalvfjerdsbræ, an outlet glacier of the Northeast Greenland Ice Stream that holds 1.1 m sea-level equivalent of ice. We use GPS observations and numerical modelling to investigate the role of tides as well as the elastic contribution to glacier flow. We find that ocean tides alter the basal lubrication of the glacier up to 10 km inland of the grounding line, and that their influence is best described by a viscoelastic rather than a viscous model. Further inland, sliding is the dominant mechanism of fast glacier motion, and the ice flow induces persistent elastic strain. We conclude that elastic deformation plays a role in glacier flow, particularly in areas of steep topographic changes and fast ice velocities.
Real-time kinetic studies of Mycobacterium tuberculosis LexA-DNA interaction
Authors: Chatterjee Chitral , Majumdar Soneya , Deshpande Sachin , Pant Deepak , Matheshwaran Saravanan 
Published: November 2021

Transcriptional repressor, LexA, regulates the “SOS” response, an indispensable bacterial DNA damage repair machinery. Compared to its E.coli ortholog, LexA from Mycobacterium tuberculosis (Mtb) possesses a unique N-terminal extension of additional 24 amino acids in its DNA binding domain (DBD) and 18 amino acids insertion at its hinge region that connects the DBD to the C-terminal dimerization/autoproteolysis domain. Despite the importance of LexA in “SOS” regulation, Mtb LexA remains poorly characterized and the functional importance of its additional amino acids remained elusive. In addition, the lack of data on kinetic parameters of Mtb LexA-DNA interaction prompted us to perform kinetic analyses of Mtb LexA and its deletion variants using Bio-layer Interferometry (BLI). Mtb LexA is seen to bind to different “SOS” boxes, DNA sequences present in the operator regions of damage-inducible genes, with comparable nanomolar affinity. Deletion of 18 amino acids from the linker region is found to affect DNA binding unlike the deletion of the N-terminal stretch of extra 24 amino acids. The conserved RKG motif has been found to be critical for DNA binding. Overall, this study provides insights into the kinetics of the interaction between Mtb LexA and its target “SOS” boxes. The kinetic parameters obtained for DNA binding of Mtb LexA would be instrumental to clearly understand the mechanism of “SOS” regulation and activation in Mtb.
A PUF‐based lightweight authentication and key agreement protocol for smart UAV networks
Authors: Zhang Li , Xu Jianbo , Obaidat Mohammad S. , Li Xiong , Vijayakumar Pandi 
Published: November 2021

AbstractWith the advancement of information technology and the reduction of costs, the application of unmanned aerial vehicle (UAV) has gradually expanded from the military field to the industrial field and civilian field. It brings great convenience to people in surveillance, detection, transportation, emergency rescue etc. However, UAVs usually work in harsh natural environments, and their communication security confronts various challenges. Due to UAVs' limited resources, such as computing capability, storage space, and energy, traditional security protection schemes based on complex cryptographic algorithms are not suitable for UAV systems directly. Therefore, a two‐stage lightweight identity authentication and key agreement protocol for UAV is proposed in this paper. The entire process only uses hash and XOR operations, which significantly improves the authentication efficiency. Simultaneously, the physical unclonable function (PUF) is introduced and embedded into the UAV hardware to ensure UAV network communication security when a UAV suffers a physical capture attack. In the paper, the security of the proposed protocol is proved with Burrows–Abadi–Needham (BAN) logic, Real‐or‐Random (ROR) model, and AVISPA simulation tools. An informal security analysis is also provided to illustrate that the protocol satisfies the security requirements of UAV networks. Finally, the protocol is compared with other existing protocols regarding function properties, computation cost, and communication cost, which shows that the proposed protocol has effectiveness and practicality.