bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Stress State in an Axially Loaded Beam Using Modal Data
Authors: Gosavi Hrishikesh , Malladi Vijaya V. N. Sriram 
Published: November 2023

Abstract
Residual stresses are found to play a vital role in the dynamic behavior of the beam. These stresses are sometimes induced unintentionally due to manufacturing processes where temperate plays a role, while at other times, beams are subjected to stresses to alter their dynamic behavior for a particular application. Owing to the ubiquitous presence of the stressed beam, the estimation of its stress state becomes imperative to prevent structural failures. This study employs an approach to estimate the stress state of a beam from the natural frequencies and mode shapes. Using the modal data, the wave-numbers are calculated, and hence a dispersion relation is established. Modal analysis for a beam subjected to axial load is performed in a standard finite element software package, and the natural frequencies and the mode shapes are extracted. The analysis is performed for different values of loads, both compressive and tensile. The dispersion relation for the load cases is calculated, and the relationship between the wave-number, natural frequency, and load value is established using a curve-fitting approach. It was found that the discussed approach estimated the load value accurately. The discussed approach can be utilized to estimate the buckling of structures and stress states in a beam directly from the experimental data of the axially loaded beam.
A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing
Authors: Miranda Samantha Wellington , Greenberg E. Peter 
Published: November 2023

ABSTRACT

Many bacterial species communicate and cooperate with kin using a form of cell-cell signaling called quorum sensing. Sensitivity and selectivity are fundamental properties of quorum sensing, and of cell signaling more generally, as they dictate the ability of cells to accurately detect and interpret signals. In this study, we investigate the impact of signal sensitivity on gene regulation and on bacterial fitness using two variants of the LasR quorum sensing receptor in the opportunistic pathogen
Pseudomonas aeruginosa
. Our studies reinforce that altering LasR signal-binding residues tends to result in decreased signal selectivity. We also find that LasR hyper-sensitivity results in earlier and stronger expression of LasR-regulated genes, whereas hypo-sensitivity results in delayed transcription from both LasR- and RhlR-regulated promoters. Furthermore, strains expressing either the hyper- or hypo-sensitive LasR polypeptide exhibit reduced production of pyocyanin, a key antimicrobial that impacts intra- and interspecies competition as well as pathogenicity. These changes to gene expression underscore the complex regulatory network by which
P. aeruginosa
controls group behaviors. Ultimately, altered signal sensitivity results in a fitness defect for LasR hyper-sensitive cells during kin competition against wild-type
P. aeruginosa
and for hypo-sensitive cells during interspecies competition against the opportunistic pathogen
Burkholderia multivorans
. Our findings highlight the delicate balance between group behaviors regulated by quorum sensing and bacterial fitness and contribute to a better understanding of the evolutionary pressures that may tune sensitivity in cell-cell signaling.

IMPORTANCE

Quorum sensing (QS) is a widespread form of cell-cell signaling that regulates group behaviors important for competition and cooperation within bacterial communities. The QS systems from different bacterial species have diverse properties, but the functional consequences of this diversity are largely unknown. Taking advantage of hyper- and hypo-sensitive QS receptor variants in the opportunistic pathogen
Pseudomonas aeruginosa
, we examine the costs and benefits of altered signal sensitivity. We find that the sensitivity of a model QS receptor, LasR, impacts the timing and level of quorum gene expression, and fitness during intra- and interspecies competition. These findings suggest competition with kin and with other bacterial species work together to tune signal sensitivity.
Profiling whole-tissue metabolic reprogramming during cutaneous poxvirus infection and clearance
Authors: Pei Luxin , Overdahl Kirsten E. , Shannon John P. , Hornick Katherine M. , Jarmusch Alan K. , Hickman Heather D. 
Published: November 2023

ABSTRACT

Vaccinia virus (VACV) infection induces prominent changes in host cell metabolism. Little is known about the global metabolic reprogramming that takes place in whole tissue during viral infection. Here, we performed a longitudinal metabolomics study in VACV-infected mouse skin to investigate metabolic changes in the tissue during infection. We assessed metabolites in homogenized skin of the ear pinnae over time in the presence or absence of antigen-specific T cells using untargeted mass spectrometry. VACV infection induced several significant metabolic changes in the tissue, including in the levels of nucleic acid metabolites (reflecting the impact of viral replication on the skin metabolome). Furthermore, monocyte- and antiviral T cell-produced metabolites, such as itaconic acid and glutamine, were significantly increased following infection, highlighting the immune response’s contribution to the global skin metabolome. Additional RNA-Seq of infected skin tissue recapitulated metabolic changes identified by metabolomics analysis. Overall, our study reveals the metabolic balance of viral replication and the antiviral immune response in the skin, elucidating metabolic pathways that could contribute to cutaneous poxvirus control
in vivo
.

IMPORTANCE

Human poxvirus infections have caused significant public health burdens both historically and recently during the unprecedented global Mpox virus outbreak. Although vaccinia virus (VACV) infection of mice is a commonly used model to explore the anti-poxvirus immune response, little is known about the metabolic changes that occur
in vivo
during infection. We hypothesized that the metabolome of VACV-infected skin would reflect the increased energetic requirements of both virus-infected cells and immune cells recruited to sites of infection. Therefore, we profiled whole VACV-infected skin using untargeted mass spectrometry to define the metabolome during infection, complementing these experiments with flow cytometry and transcriptomics. We identified specific metabolites, including nucleotides, itaconic acid, and glutamine, that were differentially expressed during VACV infection. Together, this study offers insight into both virus-specific and immune-mediated metabolic pathways that could contribute to the clearance of cutaneous poxvirus infection.
Genome sequences of Mx1, the first
Myxococcus
phage isolated, and Mx4, a generalized transducing myxophage
Authors: López-Rojo Alfonso , Jackson Simon A. , Bernal-Bernal Diego , Galbis-Martínez Marisa , Fineran Peter C. , Elías-Arnanz Montserrat 
Published: November 2023

ABSTRACT

Myxococcus xanthus
is the best-studied member of the phylum Myxococcota, but the bacteriophages infecting it and their characterization remain limited. Here, we present complete genomes of Mx1, the first
Myxococcus
phage isolated, and of an Mx4 derivative widely used for generalized transduction, both unclassified Caudoviricetes with long, contractile tails.
Identification of an anti-CRISPR protein that inhibits the CRISPR-Cas type I-B system in
Clostridioides difficile
Authors: Muzyukina Polina , Shkaruta Anton , Guzman Noemi M. , Andreani Jessica , Borges Adair L. , Bondy-Denomy Joseph , Maikova Anna , Semenova Ekaterina , Severinov Konstantin , Soutourina Olga 
Published: November 2023

ABSTRACT

CRISPR-Cas systems provide prokaryotic hosts with adaptive immunity against mobile genetic elements. Many bacteriophages encode anti-CRISPR (Acr) proteins that inhibit host defense. The identification of Acr proteins is challenging due to their small size and high sequence diversity, and only a limited number has been characterized to date. In this study, we report the discovery of a novel Acr protein, AcrIB2, encoded by the φCD38-2
Clostridioides difficile
phage that efficiently inhibits interference by the type I-B CRISPR-Cas system of the host and likely acts as a DNA mimic. Most
C. difficile
strains contain two
cas
operons, one encoding a full set of interference and adaptation proteins and another encoding interference proteins only. Unexpectedly, we demonstrate that only the partial operon is required for interference and is subject to inhibition by AcrIB2.

IMPORTANCE

Clostridioides difficile
is the widespread anaerobic spore-forming bacterium that is a major cause of potentially lethal nosocomial infections associated with antibiotic therapy worldwide. Due to the increase in severe forms associated with a strong inflammatory response and higher recurrence rates, a current imperative is to develop synergistic and alternative treatments for
C. difficile
infections. In particular, phage therapy is regarded as a potential substitute for existing antimicrobial treatments. However, it faces challenges because
C. difficile
has highly active CRISPR-Cas immunity, which may be a specific adaptation to phage-rich and highly crowded gut environment. To overcome this defense,
C. difficile
phages must employ anti-CRISPR mechanisms. Here, we present the first anti-CRISPR protein that inhibits the CRISPR-Cas defense system in this pathogen. Our work offers insights into the interactions between
C. difficile
and its phages, paving the way for future CRISPR-based applications and development of effective phage therapy strategies combined with the engineering of virulent
C. difficile
infecting phages.
Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity
Authors: Martínez-Arribas Blanca , Annang Frederick , Díaz-González Rosario , Pérez-Moreno Guiomar , Martín Jesús , Mackenzie Thomas A. , Castillo Francisco , Reyes Fernando , Genilloud Olga , Ruiz-Pérez Luis Miguel , Vicente Francisca , Ramos María C. , González-Pacanowska Dolores 
Published: November 2023

ABSTRACT
Human coronaviruses cause respiratory tract infections and are of great importance due to the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Human betacoronavirus OC43 (HCoV-OC43) is an adequate surrogate for SARS-CoV-2 because it infects the human respiratory system, presents a comparable biology, and is transmitted in a similar way. Its use is advantageous since it only requires biosafety level 2 infrastructure that minimizes costs and biosafety-associated limitations. In this report, we describe a high-throughput screening platform to identify compounds that inhibit the propagation of HCoV-OC43. Optimization of assays, based on inhibition of the cytopathic effect and virus immunodetection with a specific antibody, has provided a robust methodology for the screening of a selection of microbial natural product extracts from the Fundación MEDINA collection. Using this approach, a subset of 1,280 extracts has been explored. Of these, upon hit confirmation and early liquid chromatography mass spectrometry (LC-MS) dereplication, 10 extracts that contain potential new compounds were identified. In addition, we report on the novel antiviral activity of some previously described natural products whose presence in bioactive extracts was confirmed by LC-MS analysis.

IMPORTANCE
The COVID-19 pandemic has revealed the lack of effective treatments against betacoronaviruses and the urgent need for new broad-spectrum antivirals. Natural products are a valuable source of bioactive compounds with pharmaceutical potential that may lead to the discovery of new antiviral agents. Specifically, compared to conventional synthetic molecules, microbial natural extracts possess a unique and vast chemical diversity and are amenable to large-scale production. The implementation of a high-throughput screening platform using the betacoronavirus OC43 in a human cell line infection model has provided proof of concept of the approach and has allowed for the rapid and efficient evaluation of 1,280 microbial extracts. The identification of several active compounds validates the potential of the platform for the search for new compounds with antiviral capacity.
Spatiotemporal analysis of SARS-CoV-2 infection reveals an expansive wave of monocyte-derived macrophages associated with vascular damage and virus clearance in hamster lungs
Authors: Bagato Ola , Balkema-Buschmann Anne , Todt Daniel , Weber Saskia , Gömer André , Qu Bingqian , Miskey Csaba , Ivics Zoltan , Mettenleiter Thomas C. , Finke Stefan , Brown Richard J. P. , Breithaupt Angele , Ushakov Dmitry S. 
Published: November 2023

ABSTRACT
Lung immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for the ability to deal with infection. Using light sheet fluorescence microscopy of hamster lung slices in combination with virological, immunohistochemical, and RNA sequencing analyses, we show a wave of monocyte-derived macrophage (MDM) infiltration and the antiviral response which follows the spread of SARS-CoV-2 through the lungs and lead to virus elimination. These innate immune processes are related to the onset of necrotizing inflammatory and remodeling responses, which manifest as extensive cell death, vascular damage, and cell proliferation. We show that MDM appear in parallel with virus clearance and endothelial injury. Prothrombotic factor upregulation, tissue repair, and alveolar cell proliferation result in tissue remodeling, which is followed by fibrosis despite a decrease in inflammatory and antiviral activities. Although the lung tissue integrity is repaired, longer-term alterations of the lung arise as an outcome of concurrent tissue damage and regeneration processes.

IMPORTANCE
We present the first study of the 3D kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the early host response in a large lung volume using a combination of tissue imaging and transcriptomics. This approach allowed us to make a number of important findings:

Spatially restricted antiviral response is shown, including the formation of monocytic macrophage clusters and upregulation of the major histocompatibility complex II in infected epithelial cells.

The monocyte-derived macrophages are linked to SARS-CoV-2 clearance, and the appearance of these cells is associated with post-infection endothelial damage; thus, we shed light on the role of these cells in infected tissue.

An early onset of tissue repair occurring simultaneously with inflammatory and necrotizing processes provides the basis for longer-term alterations in the lungs.
Combination of computed tomography measurements and flexible video bronchoscope guidance for accurate placement of the right-sided double-lumen tube: a randomised controlled trial
Authors: Li Jian , Qian Yingcong , Lei Yishan , Huo Wenwen , Xu Mingzhu , Zhang Yuanyuan , Ji Qiuyuan , Yang Jianping , Liu Huayue , Hou Yongheng 
Published: November 2023

ObjectiveTo compare the modified strategy for the right-sided double-lumen tube (R-DLT) placement using a combination of CT measurements and flexible video bronchoscopy guidance with traditional bronchoscopy technique.Trial design, setting and participantsDouble-blind, parallel randomised control trial at a tertiary care medical centre in China. 100 patients undergoing video-assisted thoracoscopic surgery and requiring R-DLT were randomly allocated to the control group and the intervention group.InterventionThe control group used the traditional bronchoscopy-guided technique. In the intervention group, the length and anteroposterior diameter of the right main bronchus (RMB) were measured on CT images to select the side and size of the Rüsch tube, and then a black depth marker was placed on the tube according to the difference between the length of the RMB and the bronchial cuff. Under the guidance of bronchoscopy, the depth marker should be placed parallel to the tracheal carina and a characteristic white line on the tube should be parallel to the midline of the tracheal carina.Main outcomesThe primary endpoint was the positioning of right upper lobe (RUL) ventilatory slot and RUL bronchial orifice. The secondary endpoints included intubation data and perioperative adverse events.ResultsCompared with the control group, our modified strategy significantly increased the optimal and acceptable position rate (76% vs 98%, respectively; p<0.039), decreased the replacement rate (80% vs 94%; p=0.042), shortened the intubation time (101.4±7.3 s vs 75.2±8.1 s; p=0.019) and reduced the incidence of transient hypoxaemia (25% vs 6%; p=0.022), subglottic resistance (20% vs 6%; p=0.037), tracheobronchial injury (35% vs 13%; p=0.037) and postoperative RUL collapse (15% vs 2%; p=0.059).ConclusionThis study demonstrates the superiority of our strategy and provides a new viable method for R-DLT placement.Trial registration numberChinese Clinical Trial Registry (ChiCTR1900021676).
Burden, determinants, consequences and care of multimorbidity in rural and urbanising Telangana, India: protocol for a mixed-methods study within the APCAPS cohort
Authors: Lieber Judith , Banjara Santosh Kumar , Mallinson Poppy Alice Carson , Mahajan Hemant , Bhogadi Santhi , Addanki Srivalli , Birk Nick , Song Wenbo , Shah Anoop SV , Kurmi Om , Iyer Gowri , Kamalakannan Sureshkumar , Kishore Galla Raghu , Sadanand Shilpa , Dasi Teena , Kulkarni Bharati , Kinra Sanjay 
Published: November 2023

IntroductionThe epidemiological and demographic transitions are leading to a rising burden of multimorbidity (co-occurrence of two or more chronic conditions) worldwide. Evidence on the burden, determinants, consequences and care of multimorbidity in rural and urbanising India is limited, partly due to a lack of longitudinal and objectively measured data on chronic health conditions. We will conduct a mixed-methods study nested in the prospective Andhra Pradesh Children and Parents’ Study (APCAPS) cohort to develop a data resource for understanding the epidemiology of multimorbidity in rural and urbanising India and developing interventions to improve the prevention and care of multimorbidity.Methods and analysisWe aim to recruit 2100 APCAPS cohort members aged 45+ who have clinical and lifestyle data collected during a previous cohort follow-up (2010–2012). We will screen for locally prevalent non-communicable, infectious and mental health conditions, alongside cognitive impairments, disabilities and frailty, using a combination of self-reported clinical diagnosis, symptom-based questionnaires, physical examinations and biochemical assays. We will conduct in-depth interviews with people with varying multimorbidity clusters, their informal carers and local healthcare providers. Deidentified data will be made available to external researchers.Ethics and disseminationThe study has received approval from the ethics committees of the National Institute of Nutrition and Indian Institute of Public Health Hyderabad, India and the London School of Hygiene and Tropical Medicine, UK. Meta-data and data collection instruments will be published on the APCAPS website alongside details of existing APCAPS data and the data access process (www.lshtm.ac.uk/research/centres-projects-groups/apcaps).
Longitudinal outcome monitoring in patients with chronic gastroduodenal symptoms investigated using the Gastric Alimetry system: study protocol
Authors: Varghese Chris , Dachs Nicky , Schamberg Gabriel , McCool Kiel , Law Mikaela , Xu William , Calder Stefan , Foong Daphne , Ho Vincent , Daker Charlotte , Andrews Christopher N , Gharibans Armen A , O'Grady Gregory 
Published: November 2023

IntroductionThe Gastric Alimetry platform offers a multimodal assessment of gastric function through body surface gastric mapping (BSGM) and concurrent symptom-tracking via a validated App. We aim to perform a longitudinal cohort study to examine the impact of Gastric Alimetry, and changes in clinical management on patient symptoms, quality of life and psychological health.Methods and analysisThis is a prospective multicentre longitudinal observational cohort study of participants with chronic gastroduodenal symptoms. Consecutive participants undergoing Gastric Alimetry will be invited to participate. Quality of life will be assessed via EuroQol-5D and the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score. Gastrointestinal symptoms will be assessed via the Patient Assessment of Upper Gastrointestinal Symptom Severity index, and the Gastroparesis Cardinal Symptom Index. Psychometrics will be assessed, including anxiety via the General Anxiety Disorder-7, perceived stress using the Perceived Stress Scale 4, and depression via the Patient Health Questionnaire 9. Clinical parameters including diagnoses, investigations and treatments (medication and procedures) will also be captured. Assessments will be made the week after the BSGM test, at 30 days, 90 days, 180 days and 360 days thereafter. The primary outcome is feasibility of longitudinal follow-up of a cohort that have undergone Gastric Alimetry testing; from which patients’ continuum of care can be characterised. Secondary outcomes include changes in patient-reported symptoms, quality of life and psychometrics (anxiety, stress and depression). Inferential causal analyses will be performed at the within patient level to explore causal associations between treatment changes and clinical outcomes. The impact of Gastric Alimetry on clinical management will also be captured.Ethics and disseminationThe protocol has been approved in Aotearoa New Zealand by the Auckland Health Research Ethics Committee. Results will be submitted for conference presentation and peer-reviewed publication.
Chronic kidney disease and functional impairment in a longitudinal study of older adults in China
Authors: Duan Xiaoyu , Wang Lingdian , Wei Wei , Wang Zhifeng , Zhang Xiaoli , Liu Jianjun , Ding Degang 
Published: November 2023

ObjectivesTo examine the associations of chronic kidney disease (CKD) with dynamic functional impairment among older Chinese adults.DesignThis was a prospective longitudinal study.SettingData were derived from the Chinese Longitudinal Healthy Longevity Study.ParticipantsAll adults aged ≥60 years were potentially eligible. This study included 2970 participants.Primary outcome measuresCKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Functional performances included instrumental activities of daily living (IADL) and basic activities of daily living (BADL), which were measured using six daily activities, including eating, dressing, transferring, using the toilet, bathing and continence, and eight daily activities, including visiting neighbours, shopping, cooking, washing clothes, walking 1 km, lifting 5 kg, crouching and standing up three times and taking public transportation, respectively.ResultsThis study included 2970 participants, including 988 (33.60%) participants with CKD. Participants with CKD had higher IADL scores than those without CKD (β=0.895, 95% CI: 0.761 to 1.029). Furthermore, there was a significant linear trend in the association of CKD severity with the IADL score (p<0.001). Similarly, CKD was significantly associated with higher BADL scores (β=0.067, 95% CI: 0.017 to 0.118). However, only participants with moderate and advanced CKD had a higher BADL score (β=0.088 and 0.152, 95% CI: 0.006 to 0.171 and 0.019 to 0.286, respectively).ConclusionsCKD was associated with worse functional impairment. Furthermore, there was a significant linear trend in the association of the severity of CKD with the IADL score. However, only participants with moderate and advanced CKD had higher BADL scores.