bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended Induction and Prognostic Indicators of Response in Patients Treated with Mirikizumab with Moderately to Severely Active Ulcerative Colitis in the LUCENT Trials
Authors: D’Haens Geert , Higgins Peter D R , Peyrin-Biroulet Laurent , Sands Bruce E , Lee Scott , Moses Richard E , Redondo Isabel , Escobar Rodrigo , Hunter Gibble Theresa , Keohane Anthony , Morris Nathan , Zhang Xin , Arora Vipin , Kobayashi Taku 
Published: January 2024

Abstract

Background
Efficacy and safety of mirikizumab, a p19-targeted anti-interleukin-23 monoclonal antibody, for moderately to severely active ulcerative colitis was demonstrated previously. We evaluated clinical response, baseline characteristics, and clinical status in patients not responding by 12 weeks (W) of induction who then received extended induction treatment.

Method
Patients unresponsive to 300 mg of intravenous (IV) mirikizumab every 4 weeks by W12 received 3 additional 300 mg IV doses every 4 weeks. Week-4 responders received 200 mg mirikizumab every 4 weeks subcutaneously until W52. Patients responding by W12 but subsequently losing response received rescue therapy with 300 mg IV for 3 doses every 4 weeks. Logistic regression modelling was performed for patients not achieving W12 clinical response to assess baseline characteristics and W12 efficacy parameters and potential prognostic factors of clinical response at W24.

Results
Of patients not achieving clinical response during induction, 53.7% achieved response following extended induction. After 52W, 72.2%, 43.1%, and 36.1% of patients achieved clinical response, endoscopic, and clinical remission, respectively. Of induction responders who subsequently lost response, 63.2% and 36.8% achieved symptomatic response and remission, respectively, after receiving rescue therapy No prior biologic or tofacitinib treatment, no immunomodulators at baseline, age older than 40 years, and W12 modified Mayo Score improvement were positively associated with a response to extended induction. The safety profile was similar to initial induction, with 38.3% treatment emergent adverse events, mostly mild.

Conclusion
With “extended induction,” total of 80.3% mirikizumab-treated patients achieved clinical response by W24. Potential prognostic factors determining response include disease severity, disease phenotype, C-reactive protein, and previous biologic therapy.
Clinical evaluation of the impact of mediastinal tumour size on the subxiphoid approach video-assisted thoracoscopic surgery
Authors: Tang Muhu , Liu Jiacong , Shuai Yongfeng , Wang Luming , Huang Xuhua , Lv Wang , Lin Xu , Zhu Linhai , Hu Jian 
Published: January 2024

Abstract

OBJECTIVES
The application of video-assisted thoracoscopic surgery (VATS) for relatively large mediastinal tumours (≥5.0 cm) has been a subject of debate, and few studies have investigated the subxiphoid approach VATS in different tumour size categories. The study aims to compare the efficacy of the subxiphoid approach VATS for achieving curative outcomes based on tumour size categories (&lt;3.0, 3.0–4.9 and 5.0–10.0 cm).

METHODS
A total of 165 patients with anterior mediastinal tumours who underwent surgery at our hospital between January 2018 and July 2022 were consecutively enrolled, categorized according to tumour size—group A (&lt;3.0 cm): 58, group B (3.0–4.9 cm): 70 and group C (5.0–10.0 cm): 37. Clinical baseline data, intraoperative and postoperative outcomes, and postoperative complications were analysed.

RESULTS
The study revealed significant differences in operation time among the 3 groups (group A: 103.4 ± 36.1, group B: 106.4 ± 35.2, group C: 127.4 ± 44.8; P &lt; 0.05) as well as in the volume of drainage (group A: 273.3 ± 162.0, group B: 411.9 ± 342.6, group C: 509.7 ± 543.7; P &lt; 0.05). However, no differences were seen in blood loss, drainage duration, postoperative hospital stay and duration of postoperative oral analgesics. Additionally, the incidence of postoperative complications did not exhibit significant differences across these groups.

CONCLUSIONS
Subxiphoid approach VATS is considered a feasible and safe surgical method for large-sized anterior mediastinal tumours (5.0–10.0 cm) with no invasion to the surrounding tissues and organs.
Reaction dynamics and early-time behaviour of chemical decontamination
Authors: Murphy S , Vynnycky M , Mitchell S L , O’Kiely D 
Published: January 2024

Abstract
When a hazardous chemical soaks into a porous material such as a concrete floor, it can be difficult to remove. One approach is chemical decontamination, where a cleanser is added to react with and neutralise the contaminating agent. The goal of this paper is to investigate the reaction dynamics and the factors that affect the efficacy of the decontamination procedure. We consider a one-dimensional porous medium initially saturated with an oil-based agent. An aqueous cleanser is applied at the surface, so the two chemicals are immiscible and a boundary forms between them. A neutralising reaction takes place at this boundary in which cleanser and agent are consumed and reaction products are created. This is a Stefan problem, and the boundary between the cleanser and agent moves as the reaction proceeds. Reaction products formed at the interface may dissolve in one or both liquids. This may temporarily prevent cleanser and/or agent from reaching the reaction site, so diffusion of the chemical species, in particular the diffusion of product from the interface, plays a key role. The scenario described above was considered previously by Dalwadi et al. (2017, Mathematical modelling of chemical agent removal by reaction with an immiscible cleanser. SIAM J. Appl. Math., 77, 1937–1961) in the limit where the depth of the porous medium is large compared to the length scale over which concentrations vary inside the medium. Here, we present results that are valid for any ratio between these length scales and an analysis of agent removal times for various dimensionless parameter regimes. We also highlight the emergence of a boundary layer associated with diffusion in the oil phase for early times, where the thickness of the boundary layer is directly proportional to the square root of the time variable.
A bubble model for the gating of Kv channels
Authors: Song Zilong , Eisenberg Robert , Xu Shixin , Huang Huaxiong 
Published: January 2024

Abstract
Voltage-gated K$_{\mathrm{v}}$ channels play fundamental roles in many biological processes, such as the generation of the action potential. The gating mechanism of K$_{\mathrm{v}}$ channels is characterized experimentally by single-channel recordings and ensemble properties of the channel currents. In this work, we propose a bubble model coupled with a Poisson–Nernst–Planck (PNP) system to capture the key characteristics, particularly the delay in the opening of channels. The coupled PNP system is solved numerically by a finite-difference method and the solution is compared with an analytical approximation. We hypothesize that the stochastic behaviour of the gating phenomenon is due to randomness of the bubble and channel sizes. The predicted ensemble average of the currents under various applied voltage across the channels is consistent with experimental observations, and the Cole–Moore delay is captured by varying the holding potential.
In Vivo Evolution of a Klebsiella pneumoniae Capsule Defect With wcaJ Mutation Promotes Complement-Mediated Opsonophagocytosis During Recurrent Infection
Authors: Bain William , Ahn Brian , Peñaloza Hernán F , McElheny Christi L , Tolman Nathanial , van der Geest Rick , Gonzalez-Ferrer Shekina , Chen Nathalie , An Xiaojing , Hosuru Ria , Tabary Mohammadreza , Papke Erin , Kohli Naina , Farooq Nauman , Bachman William , Olonisakin Tolani F , Xiong Zeyu , Griffith Marissa P , Sullivan Mara , Franks Jonathan , Mustapha Mustapha M , Iovleva Alina , Suber Tomeka , Shanks Robert Q , Ferreira Viviana P , Stolz Donna B , Van Tyne Daria , Doi Yohei , Lee Janet S 
Published: January 2024

Abstract

Background
Klebsiella pneumoniae carbapenemase–producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection.

Methods
We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model.

Results
We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice.

Conclusions
Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence.
Microbiome in a ground-based analog cabin of China Space Station during a 50-day human occupation
Authors: Zhang Ying , Li Zhidong , Peng Yuan , Guo Zimu , Wang Hong , Wei Tao , Shakir Yasmeen , Jiang Guohua , Deng Yulin 
Published: January 2024

Abstract
Dead-corner areas in space station that untouched by the clean-up campaign often experience microorganisms outbreaks, but the microbiome of these areas has never been studied. In this study, the microbiome in a ground-based analog ``Tianhe'' core module of China Space Station was first investigated during a 50-day three-crew occupation. Dead-corner areas were receiving attention by adopting a new sampling method. Results indicate that the astronauts occupation did not affect the dominant bacteria community, but affected a small proportion. Due to the frequent activity of astronauts in the work and sleep areas, the biomarkers in these two areas are common human skin surface and gut microorganisms, respectively. For areas that astronaut rarely visits, the biomarkers in which are common environmental microbial groups. Fluorescence counting showed that 70.12–84.78% of bacteria were alive, with a quantity of 104–105 cells/100 cm2. With the occupation time extension, the number of microorganisms increased. At the same sampling time, there was no significant bioburden difference in various locations. The cultivable bioburden ranged from 101 to 104 colony forming unit (CFU)/100 cm2, which are the following eight genera Penicillium, Microsphaeropsis, Stachybotrys, Humicola, Cladosporium, Bacillus, Planomicrobium, and Acinetobacter. Chryseomicrobium genus may be a key focus for future microbial prevention and control work.
Use of genotypic HIV DNA testing: a DELPHI-type consensus
Authors: Andre-Garnier Elisabeth , Bocket Laurence , Bourlet Thomas , Hocqueloux Laurent , Lepiller Quentin , Maillard Anne , Reigadas Sandrine , Barriere Guillaume , Durand François , Montes Brigitte , Stefic Karl , Marcelin Anne-Geneviève 
Published: January 2024

Abstract

Objectives
As many disparities in the clinical use of HIV DNA sequencing are observed, a DELPHI-type consensus was initiated in France to homogenize use, techniques and interpretation of results.

Methods
Based on a literature review and clinical experience, a steering committee (SC) of eight virologists and one infectious disease specialist formulated statements. Statements were submitted to an independent and anonymous electronic vote of virologists and HIV clinicians in France, between October 2022 and December 2022.

Results
The SC developed 20 statements grouped into six categories: clinical situations for the use of HIV DNA genotyping; techniques for performing HIV DNA genotyping; consideration of apolipoprotein B mRNA editing enzyme (APOBEC) mutations; genotyping results reporting; recycling of antiretrovirals; and availability of HIV DNA genotyping tests and delays. Twenty-one virologists and 47 clinicians participated in two voting rounds and 18/20 (90%) assertions reached a ‘strong’ consensus. For example, that prior genotyping on HIV DNA is useful for clinical decision-making when considering switching to some long-acting regimens or to reduce the number of antiretroviral agents in virologically suppressed patients for whom RNA data are unavailable/not exploitable/not sufficiently informative. Two statements achieved no consensus: reporting any detected viral minority population for discussion in multidisciplinary meetings (virologists), and possible risk of virological failure when using a second-generation InSTI plus lamivudine or emtricitabine regimen in patients with undetectable viral load within ≥1 year and in the presence of a documented M184V mutation within the last 5 years (clinicians).

Conclusions
This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing.
Comparing human and animal antimicrobial usage: a critical appraisal of the indicators used is needed
Authors: Sanders Pim , van Geijlswijk Ingeborg , Bonten Marc , Mughini-Gras Lapo , van Hout Jobke , Heederik Dick 
Published: January 2024

Abstract
Comparisons between antimicrobial usage (AMU) in humans and food-producing animals are regularly made. The accuracy of such comparisons depends on the indicators used to quantify AMU. Indicators for AMU quantitatively relate use data (the numerator) to population data (the denominator). The denominator should be a proxy for the population at risk in a certain period when comparing the exposure of different populations to antimicrobials. Denominators based on numbers of animals slaughtered, such as the commonly used population correction unit, do not consider the time at risk of antimicrobial treatment. Production-based indicators underestimate animal AMU. Additionally, production-based indicators are fundamentally different from indicators used to quantify human AMU. Using such indicators to compare human and animal AMU therefore leads to biased results. More caution should be taken in selecting the indicator to quantify AMU when comparing AMU in food-producing animals and humans.
Bacillus subtilis NBRI-W9 simultaneously activates SAR and ISR against Fusarium chlamydosporum NBRI-FOL7 to increase wilt resistance in tomato
Authors: Yadav Udit , Anand Vandana , Kumar Sanjeev , Verma Isha , Anshu Anshu , Pandey Ishan Alok , Kumar Manoj , Behera Sandip Kumar , Srivastava Suchi , Singh Poonam C 
Published: January 2024

Abstract

Aims
The study aimed to determine the pathogenicity of Fusarium species currently prevalent in tomato fields having history of chemical fungicide applications and determine the bio-efficacy of Bacillus subtilis NBRI-W9 as a potent biological control agent.

Methods and results
Fusarium was isolated from surface-sterilized infected tomato plants collected from fields. Pathogenicity of 30 Fusarium isolates was determined by in vitro and in vivo assays. Following Koch’s postulates, F. chlamydosporum (FOL7) was identified as a virulent pathogen. The biological control of FOL 7 by B. subtilis NBRI-W9 (W9) and the colonization potential of W9 were established using spontaneous rifampicin-resistant mutants. W9 showed 82% inhibition of FOL7 on a dual-culture plate and colonization levels in tomato plants of ∼5.5, ∼3.3, and ∼2.2 log10 CFU/g in root, stem, and leaf tissue, respectively. Antagonistic activity was shown by scanning electron microscopy (SEM) and cell-wall-degradative enzymes. W9 reduced FOL7 infection in net-house and field experiments by 60% and 41%, respectively. Biochemical investigation, defence enzymes, defence gene expression analysis, SEM, and field studies provide evidence of hyperparasitism and induced resistance as the mode of biological control. The study also demonstrates that the potent biocontrol agent W9, isolated from Piper, can colonize tomato plants, control fungal disease by inducing induced systemic resistance (ISR) and systemic acquired resistance (SAR) simultaneously, and increase crop yield by 21.58% under field conditions.

Conclusions
This study concludes that F. chlamydosporum (NBRI-FOL7) is a potent, fungicide-resistant pathogen causing wilt in tomatoes. NBRI-W9 controlled FOL7 through mycoparasitism and simultaneously activated ISR and SAR in plants, providing an attractive tool for disease control that acts at multiple levels.
Production improvement of an antioxidant in cariogenic Streptococcus mutans UA140
Authors: Li Shuyu , Zhang Yuwei , Zong Jianfa , Liu Yufeng , Tang Yue , Lu Jincai , Chen Yihua 
Published: January 2024

Abstract

Aims
This study aimed to improve the production of mutantioxidin, an antioxidant encoded by a biosynthetic gene cluster (mao) in Streptococcus mutans UA140, through a series of optimization methods.

Method and results
Through the construction of mao knockout strain S. mutans UA140∆mao, we identified mutantioxidin as the antioxidant encoded by mao and verified its antioxidant activity through a reactive oxygen species (ROS) tolerance assay. By optimizing the culture medium and fermentation time, 72 h of fermentation in chemically defined medium (CDM) medium was determined as the optimal fermentation conditions. Based on two promoters commonly used in Streptococcus (ldhp and xylS1p), eight promoter refactoring strains were constructed, nevertheless all showed impaired antioxidant production. In-frame deletion and complementation experiments demonstrated the positive regulatory role of mao1 and mao2, on mao. Afterward, the mao1 and mao2, overexpression strain S. mutans UA140/pDL278:: mao1mao2, were constructed, in which the production of mutantioxidin was improved significantly.

Conclusions
In this study, through a combination of varied strategies such as optimization of fermentation conditions and overexpression of regulatory genes, production of mutantioxidin was increased by 10.5 times ultimately.
Differential consumption of malic acid and fructose in apple musts by Pichia kudriavzevii strains
Authors: Mazzucco María Belén , Rodríguez María Eugenia , Catalina Caballero Adriana , Ariel Lopes Christian 
Published: January 2024

Abstract

Aims
To assess the capability of Pichia kudriavzevii strains isolated from wine, cider, and natural environments in North Patagonia to produce ciders with reduced malic acid levels.

Methods and results
Fermentation kinetics and malic acid consumption were assessed in synthetic media and in regional acidic apple musts. All P. kudriavzevii strains degraded malic acid and grew in synthetic media with malic acid as the sole carbon source. Among these strains, those isolated from cider exhibited higher fermentative capacity, mainly due to increased fructose utilization; however, a low capacity to consume sucrose present in the must was also observed for all strains. The NPCC1651 cider strain stood out for its malic acid consumption ability in high-malic acid Granny Smith apple must. Additionally, this strain produced high levels of glycerol as well as acceptable levels of acetic acid. On the other hand, Saccharomyces cerevisiae ÑIF8 reference strain isolated from Patagonian wine completely consumed reducing sugars and sucrose and showed an important capacity for malic acid consumption in apple must fermentations.

Conclusions
Pichia kudriavzevii NPCC1651 strain isolated from cider evidenced interesting features for the consumption of malic acid and fructose in ciders.
Screening of astaxanthin-overproducing Xanthophyllomyces dendrorhous strains via iterative ARTP mutagenesis and cell sorting by flow cytometry
Authors: Ding Ruirui , Huang Ruilin , Su Hang , Li Jiawen , Li Fuli , Wang Shi'an 
Published: January 2024

Abstract

Aims
The astaxanthin-producing yeast Xanthophyllomyces dendrorhous is widely used in aquaculture. Due to the production of carotenoid, this yeast shows visible color; however, high-throughput approaches for identification of astaxanthin-overproducing strains remain rare.

Methods and results
This study verified an effective approach to identify astaxanthin-overproducing mutants of X. dendrorhous by flow cytometry (FCM) and cell sorting. First, the mutant libraries were generated by atmospheric and room-temperature plasma (ARTP) mutagenesis. Second, a highly direct correlation between the concentrations of intracellular astaxanthin and the levels of emitting fluorescence was constructed by testing a variety of astaxanthin-contained populations via FCM and cell sorting. Third, iterative cell sorting efficiently improves the identification of astaxanthin-overproducing strains. Finally, two mutants producing 4.96 mg astaxanthin g−1 DCW (dry cell weight) and 5.30 mg astaxanthin g−1 DCW were obtained, which were 25.3% and 33.8% higher than that of the original strain, respectively.

Conclusions
This study demonstrated that iterative ARTP mutagenesis along with cell sorting by FCM is effective for identifying astaxanthin-overproduction strains.
Biometric contrastive learning for data-efficient deep learning from electrocardiographic images
Authors: Sangha Veer , Khunte Akshay , Holste Gregory , Mortazavi Bobak J , Wang Zhangyang , Oikonomou Evangelos K , Khera Rohan 
Published: January 2024

Abstract

Objective
Artificial intelligence (AI) detects heart disease from images of electrocardiograms (ECGs). However, traditional supervised learning is limited by the need for large amounts of labeled data. We report the development of Biometric Contrastive Learning (BCL), a self-supervised pretraining approach for label-efficient deep learning on ECG images.

Materials and Methods
Using pairs of ECGs from 78 288 individuals from Yale (2000-2015), we trained a convolutional neural network to identify temporally separated ECG pairs that varied in layouts from the same patient. We fine-tuned BCL-pretrained models to detect atrial fibrillation (AF), gender, and LVEF &lt; 40%, using ECGs from 2015 to 2021. We externally tested the models in cohorts from Germany and the United States. We compared BCL with ImageNet initialization and general-purpose self-supervised contrastive learning for images (simCLR).

Results
While with 100% labeled training data, BCL performed similarly to other approaches for detecting AF/Gender/LVEF &lt; 40% with an AUROC of 0.98/0.90/0.90 in the held-out test sets, it consistently outperformed other methods with smaller proportions of labeled data, reaching equivalent performance at 50% of data. With 0.1% data, BCL achieved AUROC of 0.88/0.79/0.75, compared with 0.51/0.52/0.60 (ImageNet) and 0.61/0.53/0.49 (simCLR). In external validation, BCL outperformed other methods even at 100% labeled training data, with an AUROC of 0.88/0.88 for Gender and LVEF &lt; 40% compared with 0.83/0.83 (ImageNet) and 0.84/0.83 (simCLR).

Discussion and Conclusion
A pretraining strategy that leverages biometric signatures of different ECGs from the same patient enhances the efficiency of developing AI models for ECG images. This represents a major advance in detecting disorders from ECG images with limited labeled data.