bluuebunny/crossref_metadata_2025_split huggingface dataset:
A modular plasmid toolkit applied in marine bacteria reveals functional insights during bacteria-stimulated metamorphosis
Authors: Alker Amanda T. , Farrell Morgan V. , Aspiras Alpher E. , Dunbar Tiffany L. , Fedoriouk Andriy , Jones Jeffrey E. , Mikhail Sama R. , Salcedo Gabriella Y. , Moore Bradley S. , Shikuma Nicholas J. 
Published: August 2023

ABSTRACT

A conspicuous roadblock to studying marine bacteria for fundamental research and biotechnology is a lack of modular synthetic biology tools for their genetic manipulation. Here, we applied, and generated new parts for, a modular plasmid toolkit to study marine bacteria in the context of symbioses and host-microbe interactions. To demonstrate the utility of this plasmid system, we genetically manipulated the marine bacterium
Pseudoalteromonas luteoviolacea
, which stimulates the metamorphosis of the model tubeworm,
Hydroides elegans
. Using these tools, we quantified constitutive and native promoter expression, developed reporter strains that enable the imaging of host-bacteria interactions, and used CRISPR interference (CRISPRi) to knock down a secondary metabolite and a host-associated gene. We demonstrate the broader utility of this modular system for testing the genetic tractability of marine bacteria that are known to be associated with diverse host-microbe symbioses. These efforts resulted in the successful conjugation of 12 marine strains from the Alphaproteobacteria and Gammaproteobacteria classes. Altogether, the present study demonstrates how synthetic biology strategies enable the investigation of marine microbes and marine host-microbe symbioses with potential implications for environmental restoration and biotechnology.

IMPORTANCE

Marine Proteobacteria are attractive targets for genetic engineering due to their ability to produce a diversity of bioactive metabolites and their involvement in host-microbe symbioses. Modular cloning toolkits have become a standard for engineering model microbes, such as
Escherichia coli
, because they enable innumerable mix-and-match DNA assembly and engineering options. However, such modular tools have not yet been applied to most marine bacterial species. In this work, we adapt a modular plasmid toolkit for use in a set of 12 marine bacteria from the Gammaproteobacteria and Alphaproteobacteria classes. We demonstrate the utility of this genetic toolkit by engineering a marine
Pseudoalteromonas
bacterium to study their association with its host animal
Hydroides elegans
. This work provides a proof of concept that modular genetic tools can be applied to diverse marine bacteria to address basic science questions and for biotechnology innovations.
Draft genome of the
Ogataea polymorpha
type strain CBS 4732
Authors: Collins Joseph H. , Young Eric M. 
Published: August 2023

ABSTRACT

The methylotrophic yeast
Ogataea polymorpha
is of significant biotechnological interest, particularly in high-temperature fermentations and for recombinant protein production. Here, we present a high-quality genome assembly for the
O. polymorpha
type strain CBS 4732.
Exceptional age constraint on a fossiliferous sedimentary succession preceding the Cretaceous Thermal Maximum
Authors: Tucker Ryan T. , Crowley James L. , Mohr Michael T. , Renaut Ray K. , Makovicky Peter J. , Zanno Lindsay E. 
Published: August 2023

Abstract
Understanding the effects of climatic upheavals during the Early to Late Cretaceous transition is essential for characterizing the tempo of tectonically driven landscape modification and biological interchange; yet, current chronostratigraphic frameworks are too imprecise, even on regional scales, to address many outstanding questions. This includes the Mussentuchit Member of the uppermost Cedar Mountain Formation, central Utah (southwestern United States), which could provide crucial insights into these impacts within the Western Interior Basin of North America yet remains imprecisely constrained. Here, we present high-precision U-Pb zircon dates from four primary ash beds distributed across ~50 km in central Utah that better constrain the timing of deposition of the Mussentuchit Member and the age of entombed fossils. Ages for ash beds are interpreted through a combination of Bayesian depositional age estimation and stratigraphic age modeling, resulting in posterior ages from 99.490 + 0.057/–0.050 to 98.905 + 0.158/–0.183 Ma. The age model predicts probabilistic ages for fossil localities between the ashes, including new ages for Moros intrepidus, Siats meekerorum, and several undescribed ornithischian dinosaur species of key interest for understanding the timing of faunal turnover in western North America. This new geochronology for the Mussentuchit Member offers unprecedented temporal insights into a volatile interval in Earth’s history.
Out-of-hospital multimodal seizure detection: a pilot study
Authors: Nielsen Jonas Munch , Kristinsdóttir Ástrós Eir , Zibrandtsen Ivan Chrilles , Masulli Paolo , Ballegaard Martin , Andersen Tobias Søren , Kjær Troels Wesenberg 
Published: August 2023

BackgroundOut-of-hospital seizure detection aims to provide clinicians and patients with objective seizure documentation in efforts to improve the clinical management of epilepsy. In-patient studies have found that combining different modalities helps improve the seizure detection accuracy. In this study, the objective was to evaluate the viability of out-of-hospital seizure detection using wearable ECG, accelerometry and behind-the-ear electroencephalography (EEG). Furthermore, we examined the signal quality of out-of-hospital EEG recordings.MethodsSeventeen patients were monitored for up to 5 days. A support vector machine based seizure detection algorithm was applied using both in-patient seizures and out-of-hospital electrographic seizures in one patient. To assess the content of noise in the EEG signal, we compared the root-mean-square (RMS) of the recordings to a reference threshold derived from manually categorised segments of EEG recordings.ResultsIn total 1427 hours of continuous EEG was recorded. In one patient, we identified 15 electrographic focal impaired awareness seizures with a motor component. After training our algorithm on in-patient data, we found a sensitivity of 91% and a false alarm rate (FAR) of 18/24 hours for the detection of out-of-hospital seizures using a combination of EEG and ECG recordings. We estimated that 30.1% of the recorded EEG signal was physiological EEG, with an RMS value within the reference threshold.ConclusionWe found that detection of out-of-hospital focal impaired awareness seizures with a motor component is possible and that applying multiple modalities improves the diagnostic accuracy compared with unimodal EEG. However, significant challenges remain regarding a high FAR and that only 30.1% of the EEG data represented usable signal.
Antitetanus toxoid antibodies in mothers and neonates: a single-centre study from Uganda
Authors: Mugagga Nicholas , Bagaya Bernard Ssentalo , Nantongo Mary , Muwanda Fahad , Mukunya David , Musaba Milton W , Nakimuli Annette Olivia , Musooko Moses , Sekikubo Musa 
Published: August 2023

BackgroundNeonatal mortality due to tetanus persists in Uganda despite the mandatory vaccination of pregnant mothers. Maternal antibodies wane within a year. Uganda’s maternal vaccination guidelines do not specify the timing or frequency of tetanus shots, contributing to suboptimal transfer of tetanus antibodies to neonates. We aimed to determine the prevalence and factors associated with protective tetanus antibodies among newborns at Kawempe National Referral Hospital.MethodsWe conducted a cross-sectional study among 293 mother-newborn pairs. At delivery, neonatal cord and maternal venous blood were collected and titred for antitetanus antibodies using a quantitative ELISA kit. The primary outcome of the study was the proportion of newborn babies with tetanus antibodies ≥0.1 IU/mL. Associated factors were determined using generalised linear models for the Poisson family with a log link and robust variance estimation.ResultsA total of 258/293 (88.1%) newborns had protective antibody titres. Factors associated with adequate protective antibodies in the newborn included: high (≥0.1 IU/mL) maternal antibody titres, first antenatal visit ≥12 weeks of gestation and receiving a tetanus toxoid (TT) shot ≥28 weeks of gestation. However, number of doses received before current pregnancy was not associated with adequate protective antibody titres.ConclusionThere is a high prevalence of adequate protective levels of antibodies among TT-vaccinated mothers. Maternal titres and a third trimester TT dose correlate with adequate levels of protective anti-TT antibodies among newborns. A third trimester TT dose is recommended.
Deep learning with test-time augmentation for radial endobronchial ultrasound image differentiation: a multicentre verification study
Authors: Yu Kai-Lun , Tseng Yi-Shiuan , Yang Han-Ching , Liu Chia-Jung , Kuo Po-Chih , Lee Meng-Rui , Huang Chun-Ta , Kuo Lu-Cheng , Wang Jann-Yuan , Ho Chao-Chi , Shih Jin-Yuan , Yu Chong-Jen 
Published: August 2023

PurposeDespite the importance of radial endobronchial ultrasound (rEBUS) in transbronchial biopsy, researchers have yet to apply artificial intelligence to the analysis of rEBUS images.Materials and methodsThis study developed a convolutional neural network (CNN) to differentiate between malignant and benign tumours in rEBUS images. This study retrospectively collected rEBUS images from medical centres in Taiwan, including 769 from National Taiwan University Hospital Hsin-Chu Branch, Hsinchu Hospital for model training (615 images) and internal validation (154 images) as well as 300 from National Taiwan University Hospital (NTUH-TPE) and 92 images were obtained from National Taiwan University Hospital Hsin-Chu Branch, Biomedical Park Hospital (NTUH-BIO) for external validation. Further assessments of the model were performed using image augmentation in the training phase and test-time augmentation (TTA).ResultsUsing the internal validation dataset, the results were as follows: area under the curve (AUC) (0.88 (95% CI 0.83 to 0.92)), sensitivity (0.80 (95% CI 0.73 to 0.88)), specificity (0.75 (95% CI 0.66 to 0.83)). Using the NTUH-TPE external validation dataset, the results were as follows: AUC (0.76 (95% CI 0.71 to 0.80)), sensitivity (0.58 (95% CI 0.50 to 0.65)), specificity (0.92 (95% CI 0.88 to 0.97)). Using the NTUH-BIO external validation dataset, the results were as follows: AUC (0.72 (95% CI 0.64 to 0.82)), sensitivity (0.71 (95% CI 0.55 to 0.86)), specificity (0.76 (95% CI 0.64 to 0.87)). After fine-tuning, the AUC values for the external validation cohorts were as follows: NTUH-TPE (0.78) and NTUH-BIO (0.82). Our findings also demonstrated the feasibility of the model in differentiating between lung cancer subtypes, as indicated by the following AUC values: adenocarcinoma (0.70; 95% CI 0.64 to 0.76), squamous cell carcinoma (0.64; 95% CI 0.54 to 0.74) and small cell lung cancer (0.52; 95% CI 0.32 to 0.72).ConclusionsOur results demonstrate the feasibility of the proposed CNN-based algorithm in differentiating between malignant and benign lesions in rEBUS images.
Health systems research in burn care: an evidence gap map
Authors: Keshri Vikash Ranjan , Peden Margaret , Singh Pratishtha , Norton Robyn , Abimbola Seye , Jagnoor Jagnoor 
Published: August 2023

BackgroundBurn injury is associated with significant mortality and disability. Resilient and responsive health systems are needed for optimal response and care for people who sustain burn injuries. However, the extent of health systems research (HSR) in burn care is unknown. This review aimed to systematically map the global HSR related to burn care.MethodsAn evidence gap map (EGM) was developed based on the World Health Organization health systems framework. All major medical, health and injury databases were searched. A standard method was used to develop the EGM.ResultsA total of 6586 articles were screened, and the full text of 206 articles was reviewed, of which 106 met the inclusion criteria. Most included studies were cross-sectional (61%) and were conducted in hospitals (71%) with patients (48%) or healthcare providers (29%) as participants. Most studies were conducted in high-income countries, while only 13% were conducted in low-and middle-income countries, accounting for 60% of burns mortality burden globally. The most common health systems areas of focus were service delivery (53%), health workforce (33%) and technology (19%). Studies on health policy, governance and leadership were absent, and there were only 14 qualitative studies.ConclusionsMajor evidence gaps exist for an integrated health systems response to burns care. There is an inequity between the burden of burn injuries and HSR. Strengthening research capacity will facilitate evidence-informed health systems and policy reforms to sustainably improve access to affordable, equitable and optimal burn care and outcomes.
Bans on tobacco display, advertising and vending machines in the Netherlands: impact on visibility of tobacco and compliance of retailers
Authors: Borowiecki Mateusz , van Deelen Tessa R D , van den Putte Bas , Kunst Anton E , Kuipers Mirte A G 
Published: August 2023

Introduction
Visibility of tobacco products at retail tobacco outlets is associated with smoking initiation. To address this, across 2020–2022 the Netherlands banned tobacco product displays, advertisements and vending machines in the retail environment. Tobacco/vape specialist shops were exempted. This study assessed the impact of these policies on tobacco visibility in the retail environment and retailer compliance.

Methods
We conducted observational audits of all tobacco outlets in four Dutch cities (Amsterdam, Haarlem, Eindhoven and Zwolle) between 2019 and 2022 (before and after policy implementation), assessing visibility of tobacco products and advertisements, compliance and remaining sources of tobacco visibility (after implementation). We described results by location and outlet type.

Results
The number of tobacco outlets with any tobacco advertising or product visibility declined from 530 to 267 (−50%). Among outlets not exempt from the ban, the number with visibility declined from 449 to 172 (−62%), with lower postban visibility in petrol stations (12%) and supermarkets (6%) than small shops (47%). Visibility among tobacco/vape shops increased by 17%. Tobacco product displays remained the main source of visibility. 93% of tobacco vending machines were removed. Maps showed that non-compliance is concentrated in Amsterdam’s city centre and more evenly distributed in other cities.

Conclusion
The bans on tobacco display and tobacco advertising halved the visibility of tobacco in the retail environment, and the vending machine ban practically eradicated vending machines. To further reduce tobacco visibility, violations in small shops should be addressed and tobacco visibility should be regulated in currently exempt tobacco specialist shops.
Overspinning a rotating black hole in semiclassical gravity with type-A trace anomaly
Authors: Jiang Jie , Zhang Ming 
Published: August 2023

AbstractRecently, Fernandes discovered an analytic solution for rotating black holes in semiclassical gravity induced by the trace anomaly. These solutions exhibit some distinctive characteristics, including a non-spherically symmetric event horizon, the absence of circularity conditions, and violations of the Kerr bound. As a crucial assumption to uphold causality in spacetime, we investigate the validity of the weak cosmic censorship conjecture (WCCC) within this class of solutions with type-A trace anomaly by introducing a test particle on the equatorial plane. Our study reveals three distinct mechanisms that can potentially destroy the event horizon, leading to a violation of the WCCC. Our findings indicate that, with the exception of extremal Kerr, static extremal, and static singular black holes, the WCCC may be violated under the first-order perturbation of the test particle. These results suggest the need for further exploration of modifications to the behavior of the test particle under quantum effects in order to address the violation of the WCCC in this system.
Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model
Authors: Zhang Weiwei , Zhao Min , Pu Zhichen , Yin Qin , Shui Yinping 
Published: August 2023

Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were stimulated with LPS+ATP to build the in vitro model. CA significantly alleviated inflammation and oxidative stress in both the in vivo and in vitro models of ALI through the inhibition of NLR family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. In addition, CA attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis in the in vivo and in vitro models of ALI by suppressing the production of reactive oxygen species (ROS) via inhibiting the Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. CA inhibited the interaction between Akt at T308 and phosphoinositide-dependent kinase-1 (PDPK1) at S549, thus promoting the phosphorylation of the Akt protein. Furthermore, CA directly targeted the PDPK1 protein and accelerated PDPK1 ubiquitination, indicating that 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP, and 223-ASP might be responsible for the interaction between PDPK1 and CA. In conclusion, CA from Lettuce alleviated NLRP3-mediated pyroptosis in the ALI model through ROS-induced mitochondrial damage by activating Akt/Nrf2 pathway via PDPK1 ubiquitination. The present study suggests that CA might be a potential therapeutic drug to treat or prevent ALI in pneumonia or COVID-19.
Exploring natural hydrogen hotspots: a review and soil-gas survey design for identifying seepage
Authors: Langhi Laurent , Strand Julian 
Published: August 2023

Exploration for natural hydrogen seepages has grown rapidly, with surface seepages being seen as a primary indication of an underlying resource. While soil gas sampling has proven successful in detecting hydrogen in the soil, current understanding of hydrogen in the subsurface remains incomplete, with various potential sources of origin.
This paper presents a selected review of published hydrogen hotspots around the world, examining their distribution with respect to two main features commonly associated with natural seepages: sub-circular depressions (SCD) and fault zones. Based on the findings, the paper proposes a conceptual soil-gas survey design for efficiently identifying potential hydrogen hotspots. The proposed scheme is tested on a SCD and a fault zone located in Western Australia. The study findings near the Perth Basin and the Yilgarn Craton highlight the presence of anthropogenic artifacts in hydrogen measurement, necessitating further investigation to constrain the possible sources of hydrogen generation.
The study of the SCD in the Perth Basin supports the development of a statistical understanding of hydrogen distribution around surface features associated with hydrogen hotspots. Such a framework can guide soil-gas surveys and target areas with a higher likelihood of detecting natural hydrogen seepage. By addressing these points, prospective areas for natural hydrogen seepage can be better identified and evaluated, ultimately contributing to the development of hydrogen as a sustainable energy resource.

Thematic collection:
This article is part of the Hydrogen as a future energy source collection available at:
https://www.lyellcollection.org/topic/collections/hydrogen
Tumor Microenvironment Modifications Induced by Afatinib in Squamous Cell Carcinoma of the Head and Neck: A Window-of-Opportunity Study (EORTC-90111–24111)
Authors: Beyaert Simon P. , Loriot Axelle E. , Huyghe Nicolas D. , Goebbels Rose-Marie , Mendola Antonella , Govaerts Anne-Sophie , Fortpied Catherine , Baldin Pamela , Licitra Lisa F. , Lalami Yassine , Clement Paul M. , Machiels Jean-Pascal H. , Schmitz Sandra 
Published: August 2023

Abstract

Purpose:
The EORTC-90111–24111 phase II window study evaluated afatinib versus no preoperative treatment in patients with primary squamous cell carcinoma of the head and neck (HNSCC). We investigated afatinib-induced tumor and microenvironment modifications by comparing pre- and posttreatment tumor biopsies.

Patients and Methods:
Thirty treatment-naïve patients with primary HNSCC were randomized. Twenty-five patients received afatinib for 14 days before surgery (40 mg 1×/day) and 5 patients were attributed to the control arm. Biopsies were taken at work-up and during surgery. Good quality RNA samples were used for omics analyses. The control arm was enlarged by samples coming from our previous similar window study.

Results:
IHC analyses of afatinib-treated tumor biopsies showed a decrease in pEGFR (P ≤ 0.05) and pERK (P ≤ 0.05); and an increase in CD3+ (P ≤ 0.01) and CD8+ (P ≤ 0.01) T-cell infiltration, and in CD3+ (P ≤ 0.05) T-cell density. RNA sequencing analyses of afatinib-treated tumor samples showed upregulation of inflammatory genes and increased expression scores of signatures predictive of response to programmed cell death protein 1 blockade (P ≤ 0.05). In posttreatment biopsies of afatinib-treated patients, two clusters were observed. Cluster 1 showed a higher expression of markers and gene sets implicated in epithelial-to-mesenchymal transition (EMT) and activation of cancer-associated fibroblasts (CAF) compared with cluster 2 and controls.

Conclusions:
Short-term treatment with afatinib in primary HNSCC induces CD3+ and CD8+ tumor infiltration and, in some patients, EMT and CAF activation. These results open perspectives to overcome resistance mechanisms to anti-HER therapy and to potentiate the activity of immune checkpoint inhibitors.
The New NCI Precision Medicine Trials
Authors: Harris Lyndsay N. , Blanke Charles D. , Erba Harry P. , Ford James M. , Gray Robert J. , LeBlanc Michael L. , Hu-Lieskovan Siwen , Litzow Mark R. , Luger Selina M. , Meric-Bernstam Funda , O'Dwyer Peter J. , Othus Megan K.D. , Politi Katerina , Shepherd Lois E. , Allegra Carmen J. , Chen Helen X. , Ivy S. Percy , Korde Larissa A. , Little Richard F. , McShane Lisa M. , Moscow Jeffrey A. , Patton David R. , Thurin Magdalena , Yee Laura M. , Doroshow James H. 
Published: August 2023

Abstract
Basket, umbrella, and platform trial designs (master protocols) have emerged over the last decade to study precision medicine approaches in oncology. First-generation trials like NCI-MATCH (Molecular Analysis for Therapy Choice) have proven the principle that studying targeted therapies on a large scale is feasible both from the laboratory and clinical perspectives. However, single-agent targeted therapies have shown limited ability to control metastatic disease, despite careful matching of drug to target. As such, newer approaches employing combinations of targeted therapy, or targeted therapy with standard therapies, need to be considered. The NCI has recently embarked on three second-generation precision medicine trials to address this need: ComboMATCH, iMATCH, and myeloMATCH. The design of these trials and necessary infrastructure are discussed in the following perspective.