bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thein vitroactivity of delafloxacin and comparator agents against bacterial pathogens isolated from patients with cancer
Authors: Gerges Bahgat , Rolston Kenneth , Shelburne Samuel A , Rosenblatt Joel , Prince Randall , Raad Issam 
Published: March 2023

AbstractBackgroundFluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the in vitro activity of delafloxacin and selected comparators against 560 bacterial pathogens isolated exclusively from patients with cancer.MethodsAntimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer.ResultsDelafloxacin was more active than ciprofloxacin and levofloxacin against Staphylococcus aureus and CoNS. Overall, 63% of staphylococcal isolates were susceptible to delafloxacin, 37% to ciprofloxacin and 39% to levofloxacin. Activity of delafloxacin against most Enterobacterales was similar to that of ciprofloxacin and levofloxacin. Escherichia coli and MDR Pseudomonas aeruginosa isolates had low susceptibility rates to the three tested fluoroquinolones. In time-kill studies delafloxacin and levofloxacin decreased the bacterial load to 3.0 log10 in 8 and 13 h, respectively, using 8 × MIC.ConclusionsDelafloxacin is more active than ciprofloxacin and levofloxacin against S. aureus but has substantial gaps in coverage against GNB. Resistance to all three fluoroquinolones could be high among leading GNB such as E. coli and P. aeruginosa, particularly in cancer centres where these agents are widely used as prophylactic agents.
Integrating economic considerations into cutpoint selection may help align clinical decision support toward value-based healthcare
Authors: Parsons Rex , Blythe Robin , Cramb Susanna M , McPhail Steven M 
Published: March 2023

AbstractObjectiveClinical prediction models providing binary categorizations for clinical decision support require the selection of a probability threshold, or “cutpoint,” to classify individuals. Existing cutpoint selection approaches typically optimize test-specific metrics, including sensitivity and specificity, but overlook the consequences of correct or incorrect classification. We introduce a new cutpoint selection approach considering downstream consequences using net monetary benefit (NMB) and through simulations compared it with alternative approaches in 2 use-cases: (i) preventing intensive care unit readmission and (ii) preventing inpatient falls.Materials and methodsParameter estimates for costs and effectiveness from prior studies were included in Monte Carlo simulations. For each use-case, we simulated the expected NMB resulting from the model-guided decision using a range of cutpoint selection approaches, including our new value-optimizing approach. Sensitivity analyses applied alternative event rates, model discrimination, and calibration performance.ResultsThe proposed approach that considered expected downstream consequences was frequently NMB-maximizing compared with other methods. Sensitivity analysis demonstrated that it was or closely tracked the optimal strategy under a range of scenarios. Under scenarios of relatively low event rates and discrimination that may be considered realistic for intensive care (prevalence = 0.025, area under the receiver operating characteristic curve [AUC] = 0.70) and falls (prevalence = 0.036, AUC = 0.70), our proposed cutpoint method was either the best or similar to the best of the compared methods regarding NMB, and was robust to model miscalibration.DiscussionOur results highlight the potential value of conditioning cutpoints on the implementation setting, particularly for rare and costly events, which are often the target of prediction model development research.ConclusionsThis study proposes a cutpoint selection method that may optimize clinical decision support systems toward value-based care.
Jie Geng Tang reverses cisplatin resistance through the Nrf2 pathway in lung cancer
Authors: Zhao Jing , Hou Manting , Ding Kaixin , Li Shixiong , Li Hui , Zhang Xili , Bai Zhaofang , Liu Wenlong 
Published: March 2023

Abstract

Objectives
Jie Geng Tang (JGT) is an ancient traditional Chinese herbal decoction that exhibits various pharmacological activities, however, is poorly understood in the sensitivity of lung cancer to chemotherapy. Here, we explored the effect of JGT on sensitizing cisplatin (DDP)-resistant A549 cells (A549/DDP).

Methods
Cell viability was assessed using cell counting kit-8 assay. Flow cytometry was applied to detected cell apoptosis, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. Western blotting and qRT-PCR were performed to determine protein and mRNA levels.

Key findings
The results demonstrated that DDP co-treatment with JGT significantly increased the cytotoxicity of A549/DDP cells and exhibited efficacy in suppressing the migration and proliferation. The rate of apoptosis was increased by co-treatment with DDP and JGT, along with a higher rate of Bax/Bcl-2, and increased loss of MMP. Furthermore, the combination promoted ROS accumulation and increased γ-H2AX levels. Moreover, Nrf2 levels were suppressed in a dose- and time-dependent manner, Nrf2 stability was reduced following treatment with JGT. Notably, the combination induced inhibition of the Nrf2/ARE pathway at the mRNA and protein levels.

Conclusions
Collectively, these results indicate that co-treatment with JGT and DDP can be considered a combinational approach to treating DDP resistance.
The Best Developed Man in Great Britain and Ireland? Eugen Sandow and the Commercialization of Eugenics in Twentieth-Century Britain
Authors: Heffernan Conor 
Published: March 2023

Abstract
In 1901 Eugen Sandow, a strong man performer turned health authority, hosted a competition in the Royal Albert Hall to determine the ‘best developed man in Great Britain and Ireland’. At the contest, members of the public, the military, and the scientific community watched as Sandow and his judges compared men’s physiques. Typically depicted by historians as a pivotal step in the development of bodybuilding as a sport, this article repositions Sandow’s contest as a public manifestation of British eugenics and concerns about physical deterioration. Welcoming a thousand competitors in its qualifying rounds, Sandow’s contest was advertised with reference to perfecting the British male body and stemming the tide of British degeneration. When the outbreak of the Second South African War in 1899 delayed the contest’s finale, Sandow’s marketers redoubled efforts to depict the contest as an antidote to the physical deterioration of British troops said to have become evident in the conflict. Here it is argued that Sandow simultaneously magnified, and profited, from a broader British eugenic concern about the male body. His competition served as a strong reminder for how widespread such concerns were in late Victorian and early Edwardian Britain and, more importantly, how they could be commercialized.
A rare occurrence of Anaplasma-associated peritonitis
Authors: Bush Valerie , Chaudhary Jitendra , Manu Devarajan , Hyman Charles 
Published: March 2023

Abstract
Anaplasmosis or human granulocytic anaplasmosis is a tick-borne illness caused by the bacteria, Anaplasma phagocytophilum, resulting from an infected tick bite. Examination of a blood smear within the first week of exposure may show microcolonies of anaplasmae (morulae) in the cytoplasm of neutrophils that are highly suggestive of anaplasmosis but not definitive. We present the first case describing Anaplasma-related peritonitis and morulae in peritoneal fluid granulocytes in a peritoneal dialysis patient who developed anaplasmosis.
Effectiveness of diphenyl diselenide against experimental sporotrichosis caused by Sporothrix brasiliensis
Authors: Munhoz Lívia Silveira , Poester Vanice Rodrigues , Benelli Jéssica Louise , Melo Aryse Martins , Trápaga Mariana Rodrigues , Nogueira Cristina Wayne , Zeni Gilson , Flores Mariana Martins , Stevens David A , Xavier Melissa Orzechowski 
Published: March 2023

Abstract
Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (P &lt; .001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.
A biotic habitable zone: impacts of adaptation in biotic temperature regulation
Authors: Nicholson A E , Mayne N J 
Published: March 2023

ABSTRACTThe search for biosignatures necessitates developing our understanding of life under different conditions. If life can influence the climate evolution of its planet then understanding the behaviour of life-climate feedbacks under extreme conditions is key to determine the ‘edges’ of the habitable zone. Additionally understanding the behaviour of a temperature limited biosphere will help towards formulating biosignature predictions for alien life living under conditions very different to those on Earth. Towards this aim, we extend the ‘ExoGaia Model’ – an abstract model of microbial life living on a highly simplified zero-dimensional planet. Via their metabolisms, microbes influence the atmospheric composition and therefore the temperature of the planet and emergent feedback loops allow microbes to regulate their climate and maintain long-term habitability. Here, we adapt the ExoGaia model to include temperature adaptation of the microbes by allowing different species to have different temperature ‘preferences’. We find that rather than adapting towards the planet’s abiotic conditions the biosphere tends to more strongly influence the climate of its planet, suggesting that the surface temperature of an inhabited planet might be significantly different from that predicted using abiotic models. We find that the success rate for microbial establishment on planets is improved when adaptation is allowed. However, planetary abiotic context is important for determining whether overall survival prospects for life will be improved or degraded. These results indicate the necessity to develop an understanding of life living under different limiting regimes to form predictions for the boundaries of the habitable zone.
Tentative detection of titanium oxide in the atmosphere of WASP-69 b with a 4m ground-based telescope
Authors: Ouyang Qinglin , Wang Wei , Zhai Meng , Chen Guo , Rojo Patricio , Liu Yujuan , Zhao Fei , Huang Jia-Sheng , Zhao Gang 
Published: March 2023

ABSTRACT
Transiting planets provide unique opportunities for the atmospheric characterization of exoplanets as they can reveal composition and the temperature structures at the day–night terminator regions in planetary atmospheres, and help understand the atmospheric process and formation environments of exoplanets. Here, we present the optical transmission spectroscopic study of an inflated Saturn-mass planet WASP-69 b, obtained by the 4m ground-based telescope Southern Astrophysical Research Telescope (SOAR). We obtain spectroscopic transit light curves in 20 passbands from 502 to 890 nm, and fit them using Gaussian processes and an analytical transit model to obtain independent transit depths for each. The derived transmission spectrum of WASP-69 b shows a slope with absorption depth increasing towards blue wavelengths, indicating a Rayleigh scattering in the atmosphere consistent with previous works. The retrieval analysis yields a tentative detection of TiO absorption feature in the transmission spectrum. We present the first results from the SOAR telescope to characterize exoplanetary atmospheres proving its capability and precision for hot Jupiters around bright stars in an area dominated by results from large ground-based telescopes or space telescopes.
A sub-Neptune transiting the young field star HD 18599  at 40 pc
Authors: de Leon J P , Livingston J H , Jenkins J S , Vines J I , Wittenmyer R A , Clark J T , Winn J I M , Addison B , Ballard S , Bayliss D , Beichman C , Benneke B , Berardo D A , Bowler B P , Brown T , Bryant E M , Christiansen J , Ciardi D , Collins K A , Collins K I , Crossfield I , Deming D , Dragomir D , Dressing C D , Fukui A , Gan T , Giacalone S , Gill S , Gorjian V , González Alvarez E , Hesse K , Horner J , Howell S B , Jenkins J M , Kane S R , Kendall A , Kielkopf J F , Kreidberg L , Latham D W , Liu H , Lund M B , Matson R , Matthews E , Mengel M W , Morales F , Mori M , Narita N , Nishiumi T , Okumura J , Plavchan P , Quinn S , Rabus M , Ricker G , Rudat A , Schlieder J , Schwarz R P , Seager S , Shporer A , Smith A M S , Stassun K , Tamura M , Tan T G , Tinney C , Vanderspek R , Werner M W , West R G , Wright D , Zhang H , Zhou G 
Published: March 2023

ABSTRACT
Transiting exoplanets orbiting young nearby stars are ideal laboratories for testing theories of planet formation and evolution. However, to date only a handful of stars with age &lt;1 Gyr have been found to host transiting exoplanets. Here we present the discovery and validation of a sub-Neptune around HD 18599 , a young (300 Myr), nearby (d = 40 pc) K star. We validate the transiting planet candidate as a bona fide planet using data from the TESS , Spitzer , and Gaia  missions, ground-based photometry from IRSF , LCO , PEST , and NGTS , speckle imaging from Gemini, and spectroscopy from CHIRON , NRES , FEROS , and Minerva-Australis . The planet has an orbital period of 4.13 d , and a radius of 2.7 R⊕ . The RV data yields a 3-σ mass upper limit of 30.5 M⊕  which is explained by either a massive companion or the large observed jitter typical for a young star. The brightness of the host star (V∼9 mag) makes it conducive to detailed characterization via Doppler mass measurement which will provide a rare view into the interior structure of young planets.
A dual-purpose polymerase engineered for direct sequencing of pseudouridine and queuosine
Authors: Huber Luisa B , Kaur Navpreet , Henkel Melanie , Marchand Virginie , Motorin Yuri , Ehrenhofer-Murray Ann E , Marx Andreas 
Published: March 2023

Abstract
More than 170 posttranscriptional RNA modifications are so far known on both coding and noncoding RNA species. Within this group, pseudouridine (Ψ) and queuosine (Q) represent conserved RNA modifications with fundamental functional roles in regulating translation. Current detection methods of these modifications, which both are reverse transcription (RT)-silent, are mostly based on the chemical treatment of RNA prior to analysis. To overcome the drawbacks associated with indirect detection strategies, we have engineered an RT-active DNA polymerase variant called RT-KTq I614Y that produces error RT signatures specific for Ψ or Q without prior chemical treatment of the RNA samples. Combining this polymerase with next-generation sequencing techniques allows the direct identification of Ψ and Q sites of untreated RNA samples using a single enzymatic tool.
Rolling circle extension-assisted loop-mediated isothermal amplification (Rol-LAMP) method for locus-specific and visible detection of RNA N6-methyladenosine
Authors: Li Jiexin , Zhou Jiawang , Xia Yan , Rui Yalan , Yang Xianyuan , Xie Guoyou , Jiang Guanmin , Wang Hongsheng 
Published: March 2023

Abstract
N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic mRNAs. Currently available detection methods for locus-specific m6A marks rely on RT-qPCR, radioactive methods, or high-throughput sequencing. Here, we develop a non-qPCR, ultrasensitive, isothermal, and naked-eye visible method for m6A detection based on rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP), named m6A-Rol-LAMP, to verify putative m6A sites in transcripts obtained from the high-throughput data. When padlock probes hybridize to the potential m6A sites on targets, they are converted to circular form by DNA ligase in the absence of m6A modification, while m6A modification hinders the sealing of padlock probes. Subsequently, Bst DNA polymerase-mediated RCA and LAMP allow the amplification of the circular padlock probe to achieve the locus-specific detection of m6A. Following optimization and validation, m6A-Rol-LAMP can ultra-sensitively and quantitatively determine the existence of m6A modification on a specific target site as low as 100 amol under isothermal conditions. Detections of m6A can be performed on rRNA, mRNA, lincRNA, lncRNA and pre-miRNA from biological samples with naked-eye observations after dye incubation. Together, we provide a powerful tool for locus-specific detection of m6A, which can simply, quickly, sensitively, specifically, and visually determine putative m6A modification on RNA.
ATXN3 controls DNA replication and transcription by regulating chromatin structure
Authors: Hernández-Carralero Esperanza , Cabrera Elisa , Rodríguez-Torres Gara , Hernández-Reyes Yeray , Singh Abhay N , Santa-María Cristina , Fernández-Justel José Miguel , Janssens Roel C , Marteijn Jurgen A , Evert Bernd O , Mailand Niels , Gómez María , Ramadan Kristijan , Smits Veronique A J , Freire Raimundo 
Published: March 2023

Abstract
The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.
Locating, tracing and sequencing multiple expanded genetic letters in complex DNA context via a bridge-base approach
Authors: Wang Honglei , Zhu Wuyuan , Wang Chao , Li Xiaohuan , Wang Luying , Huo Bianbian , Mei Hui , Zhu Anlian , Zhang Guisheng , Li Lingjun 
Published: March 2023

Abstract
A panel of unnatural base pairs is developed to expand genetic alphabets. One or more unnatural base pairs (UBPs) can be inserted to enlarge the capacity, diversity, and functionality of canonical DNA, so monitoring the multiple-UBPs-containing DNA by simple and convenient approaches is essential. Herein, we report a bridge-base approach to repurpose the capability of determining TPT3-NaM UBPs. The success of this approach depends on the design of isoTAT that can simultaneously pair with NaM and G as a bridge base, as well as the discovering of the transformation of NaM to A in absence of its complementary base. TPT3-NaM can be transferred to C–G or A–T by simple PCR assays with high read-through ratios and low sequence-dependent properties, permitting for the first time to dually locate the multiple sites of TPT3-NaM pairs. Then we show the unprecedented capacity of this approach to trace accurate changes and retention ratios of multiple TPT3-NaM UPBs during in vivo replications. In addition, the method can also be applied to identify multiple-site DNA lesions, transferring TPT3-NaM makers to different natural bases. Taken together, our work presents the first general and convenient approach capable of locating, tracing, and sequencing site- and number-unlimited TPT3-NaM pairs.
Influence of Tobacco Variety and Curing on Free Radical Production in Cigarette Smoke
Authors: Bitzer Zachary T , Mocniak Leanne E , Trushin Neil , Smith Michael , Richie John P 
Published: March 2023

Abstract

Introduction
Cigarette smoke contains highly reactive free radicals thought to play an important role in tobacco smoke-induced harm. Previously, large variations in free radical and toxicant output have been observed in commercial cigarettes. These variations are likely because of cigarette design features (paper, filter, and additives), tobacco variety (burley, bright, oriental, etc.), and tobacco curing methods (air, sun, flue, and fire). Previous reports show that tobacco varieties and curing methods influence the production of tobacco smoke constituents like the tobacco-specific carcinogen nicotine-derived nitrosamine ketone (NNK).

Aims and Methods
We evaluated free radical, nicotine, and NNK production in cigarette smoke from cigarettes produced with 15 different types of tobacco. Gas-phase free radicals were captured by spin trapping with N-tert-butyl-α-phenylnitrone and particulate-phase radicals were captured on a Cambridge Filter pad (CFP). Both types of radicals were analyzed using electron paramagnetic resonance spectroscopy. Nicotine and NNK were extracted from the CFP and analyzed by gas chromatography flame ionization detection and liquid chromatography-mass spectrometry, respectively.

Results
Gas-phase radicals varied nearly 8-fold among tobacco types with Saint James Perique tobacco producing the highest levels (42 ± 7 nmol/g) and Canadian Virginia tobacco-producing the lowest levels (5 ± 2 nmol/g). Nicotine and NNK levels in smoke varied 14-fold and 192-fold, respectively, by type. Gas-phase free radicals were highly correlated with NNK levels (r = 0.92, p &lt; .0001) and appeared to be most impacted by tobacco curing method.

Conclusions
Altogether, these data suggest that tobacco types used in cigarette production may serve as a target for regulation to reduce harm from cigarette smoking.

Implications
Variations in cigarette free radical and NNK levels vary based on the tobacco variety and curing method. Reducing the ratio of high-producing free radical and NNK tobacco types offer a potential tool for regulators and producers looking to reduce toxicant output from cigarettes.