bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study
Authors: Taniguchi Jumpei , Jo Taisuke , Aso Shotaro , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo 
Published: May 2024

AbstractBackground and ObjectivePyrazinamide (PZA) is the standard first‐line treatment for tuberculosis (TB); however, its safety in elderly patients has not been thoroughly investigated.MethodsThis retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for TB between July 2010 and March 2022. Patients were categorized into HRE (isoniazid, rifampicin and ethambutol) and HREZ (isoniazid, rifampicin, ethambutol and PZA) groups. Primary outcomes included in‐hospital mortality and overall adverse events (characterized by a composite of hepatotoxicity, gout attack, allergic reactions and gastrointestinal intolerance). Secondary outcomes included the length of hospital stay, 90‐day readmission and use of drugs related to the primary outcome adverse events. Data were analysed using propensity score matching; we also conducted a subgroup analysis for those aged ≥75 years.ResultsAmong 19,930 eligible patients, 8924 received HRE and 11,006 received HREZ. Propensity score matching created 3578 matched pairs with a mean age of approximately 80 years. Compared with the HRE group, the HREZ group demonstrated a higher proportion of overall adverse events (3.1% vs. 4.7%; p < 0.001), allergic reactions (1.4% vs. 2.5%; p < 0.001) and antihistamine use (21.9% vs. 27.6%; p < 0.001). No significant differences were observed regarding in‐hospital mortality, hepatotoxicity or length of hospital stay between the groups. Subgroup analysis for those aged ≥75 years showed consistent results.ConclusionMedical practitioners may consider adding PZA to an initial treatment regimen even in elderly patients with TB.
Research gaps and priorities for quantitative microbial risk assessment (QMRA)
Authors: Hamilton Kerry A. , Ciol Harrison Joanna , Mitchell Jade , Weir Mark , Verhougstraete Marc , Haas Charles N. , Nejadhashemi A. Pouyan , Libarkin Julie , Gim Aw Tiong , Bibby Kyle , Bivins Aaron , Brown Joe , Dean Kara , Dunbar Gwyneth , Eisenberg Joseph N. S. , Emelko Monica , Gerrity Daniel , Gurian Patrick L. , Hartnett Emma , Jahne Michael , Jones Rachael M. , Julian Timothy R. , Li Hongwan , Li Yanbin , Gibson Jacqueline MacDonald , Medema Gertjan , Meschke J. Scott , Mraz Alexis , Murphy Heather , Oryang David , Owusu‐Ansah Emmanuel de‐Graft Johnson , Pasek Emily , Pradhan Abani K. , Razzolini Maria Tereza Pepe , Ryan Michael O. , Schoen Mary , Smeets Patrick W. M. H. , Soller Jeffrey , Solo‐Gabriele Helena , Williams Clinton , Wilson Amanda M. , Zimmer‐Faust Amy , Alja'fari Jumana , Rose Joan B. 
Published: May 2024

AbstractThe coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose–response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co‐exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source‐to‐outcome continuum. Cross‐cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies.
Occurrence of Coxiella burnetii in wild lagomorphs and their ticks in Spanish Mediterranean ecosystems
Authors: Castro‐Scholten Sabrina , Caballero‐Gómez Javier , Martínez Remigio , Nadales‐Martín Borja J. , Cano‐Terriza David , Jiménez‐Martín Débora , Remesar Susana , Jiménez‐Ruiz Saúl , Gómez‐Guillamón Félix , García‐Bocanegra Ignacio 
Published: May 2024

AbstractBackgroundCoxiella burnetii, the causative agent of Q fever, is a zoonotic multi‐host vector‐borne pathogen of major public health importance. Although the European Food Safety Authority has recently made the monitoring of this bacterium in wildlife a priority, the role of wild lagomorphs in the transmission and maintenance of C. burnetii is poorly understood.AimsThe aims of this study were to determine the prevalence and risk factors associated with C. burnetii circulation in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis) and to assess the presence of this pathogen in ticks that feed on them in Mediterranean ecosystems in Spain, the country with the highest number of reported cases of Q fever in Europe.MethodsA total of 574 spleen samples were collected from 453 wild rabbits and 121 Iberian hares, and 513 ticks (processed in 120 pools) between the 2017/2018 and 2021/2022 hunting seasons.ResultsC. burnetii DNA was detected in 103 (17.9%; 95% CI: 14.8–21.1) of the 574 wild lagomorphs tested. By species, prevalence was 16.3% (74/453; 95% CI: 12.9–19.7) in the European wild rabbit and 24.0% (29/121; 95% CI: 16.4–31.6) in the Iberian hare. At least one positive lagomorph was found on 47.9% of the 96 hunting estates sampled and in every hunting season since 2018/2019. Two risk factors associated with C. burnetii infection were as follows: outbreak of myxomatosis on the hunting estate in the month prior to sampling and high tick abundance observed by gamekeepers on the hunting estate. C. burnetii DNA was also found in 33 of the 120 (27.5%; 95% CI: 19.5–35.5) tick pools tested. The pathogen was detected in 66.7% (4/6), 29.2% (26/89) and 21.4% (3/14) of Haemaphysalis hispanica, Rhipicephalus pusillus and Hyalomma lusitanicum pools respectively.ConclusionsThis study provides new epidemiological data on C. burnetii in European wild rabbits and is the first survey on this zoonotic pathogen performed in Iberian hares. Our results indicate widespread endemic circulation of C. burnetii and highlight the importance of both wild lagomorph species as natural reservoirs of this zoonotic bacterium in Mediterranean ecosystems in southern Spain, which may be of public and animal health concern. The high prevalence and wide diversity of positive tick species suggest the possible role of ticks in the epidemiological cycle of C. burnetii, with the potential risk of transmission to sympatric species, including humans.
Design and Effect Evaluation of a Hydrogen–Natural Gas Mixing Device at Jingbian Compressor Station
Authors: Liu Wu , Zhou Haonan , Huang Bin , Lu Pengfei 
Published: May 2024

Abstract
Hydrogen gas is an environmentally friendly alternative energy source with zero emissions, making it highly valuable for replacing fossil fuels and reducing carbon emissions. One effective method of transporting hydrogen gas is by injecting it into existing natural gas pipelines. In this research, we focus on the Jingbian compressor station. This station is used for hydrogenation, blending hydrogen with the natural gas flowing through the pipelines. We propose a suitable process for hydrogen blending and design a mixing device to facilitate this process. To evaluate the mixing effect of the blended gas, we conducted numerical simulations to analyze the velocity and concentration distribution along the continuous section of the hydrogen blending pipeline. The results indicated that achieving a hydrogen branch length of 1/2 the diameter of the natural gas main pipe and a hydrogen flowrate of 10% resulted in a nonuniformity of hydrogen concentration at L = 30D of less than 0.05. Furthermore, when the hydrogen concentration was set at 3%, 10%, and 30%, the hydrogen concentration in the cross section of the pipe gradually approached the expected concentration as the mixed gas flowed. It is worth noting that during transportation of hydrogen-containing natural gas to the outlet, the velocity distribution on the cross section remained asymmetric, potentially leading to measurement errors. However, the use of a flow conditioner resulted in a further reduction in hydrogen nonuniformity and minimized velocity fluctuations, resulting in a small and uniformly distributed flow, which is advantageous for accurate measurement and transportation purposes.
Study of Buffeting Excitation Acting on Coil Tube Bundles in Cross Flow
Authors: Wang Yue , Guo Shuang , Chen Xiaodong , Tan Wei 
Published: May 2024

Abstract
The amplitudes induced by random excitation forces on the tubes bring continuous friction between the tube and supports, which results in gradual failure of the tubes due to fretting wear. Therefore, it is very important to determine the envelope lines of the random excitation force spectrum for the coil tube. To the authors' knowledge, there are no published studies on the normalized force spectrum of coil tubes. In this paper, a simplified three-layer experimental model was established. The robustness of the numerical method was demonstrated by comparing the experimental and simulated results, including the vibration response and the fluid excitation force spectrum. Then, a semi-empirical equation for predicting the dominant frequency of turbulent buffeting was constructed by employing the threshold envelope method. Through the observation of time-history and root-mean-square (RMS) data, it was found that the pitch diameter ratio between adjacent tube layers, a, had the greatest influence on the force coefficients. The smaller a is, the larger the force coefficients are. The pitch diameter ratio in the same layer, b, and helix angle, α, had little effect on the force coefficients. With the increase of α, the flow instability in the shell-side flow enhanced and the fluctuation of force coefficients became larger. Finally, the mechanisms of the tube position, Reynolds number (Re), and bundle structure on the normalized force spectrum were studied. The normalized envelope force spectrum for coil tubes was proposed as the guidelines to predict and evaluate the random excitation force acting on the tubes.
A New Type of S–N Equation and Its Application to Multi-Axial Fatigue Life Prediction
Authors: Xiangqiao Yan 
Published: May 2024

Abstract
The S–N equation is one of the most important equations in fatigue model investigation. A majority of fatigue models, including multi-axial fatigue model and mean effect models, are established on the basis of the S–N equation. Obviously, an accuracy of the S–N equation is very important. Taking into account that the S–N equation is, in fact, an empirical one in which the material constants are determined by numerical fitting fatigue experimental data, in this study, the S–N equation can be improved, by further processing these fatigue experimental data, to present a new type of S–N equation that is more accurate than the S–N equation. The new type of S–N equation is called a similar S–N equation in this study. By using a large number of experimental data of metallic materials reported in the literature, an accuracy of the similar S–N equation has been proven.
Path Forward: Materials Data Modernization for ASME Codes and Standards in the Artificial Intelligence Era
Authors: Ren Weiju 
Published: May 2024

Abstract
Development of the ASME Materials Properties Database was initiated in the early 2010s to support the ASME Codes and Standards. As information technologies advance at an accelerated pace with the artificial intelligence era on the horizon, the ASME Materials Properties Database must be further modernized from a database to a knowledgebase to ride the wave of digital information revolution and effectively support the ASME Codes and Standards in the new era. This paper is intended to provide an overview of the ASME Materials Properties Database and discuss a roadmap for its future development to facilitate understanding of and participation from different sectors of the Codes and Standards community. It first reviews the basic concepts of data, information, knowledge, database, and database system as well as the pros and cons in different types of data management and then discusses the path forward for a desired evolution of the database into a self-explanatory and machine-readable knowledgebase that is consistent with human cognitive processes for the Codes and Standards development and, furthermore, provides resources for data processing and analysis to reach an eventual goal of streamlining the Codes and Standards development from the initial inquiry, throughout data submission, analysis, …, to Codes and Standards rule establishment for final publication.
Mean Stress Correction of S45C Carbon Steel Based on Crack Growth Concept (Proposal of Non-Closure Model)
Authors: Kamaya Masayuki 
Published: May 2024

Abstract
Influence of the tensile mean stress on fatigue life and fatigue limit was investigated for carbon steel. Uni-axial fatigue tests were conducted under stress and strain-controlled conditions at room temperature. The fatigue life and fatigue limit were reduced by applying the mean stress for the same stress amplitude. The fatigue life exhibited a better correlation with the strain range than with the stress amplitude. Increase in strain range caused by applying the mean stress correlated well with the decrease in the fatigue life. It was proposed that the mean stress effect on the fatigue life was brought about by the change in crack growth rate caused by applying the mean stress. The mean stress enhanced crack opening and accelerated the crack growth. The reduction in the fatigue limit was also brought about by the same effect. It was shown that the effective strain range considering crack closure effect gave good prediction of fatigue life and fatigue limit with and without the mean stress.
Mobile-CRISPRi as a powerful tool for modulating
Vibrio
gene expression
Authors: Geyman Logan J. , Tanner Madeline P. , Rosario-Meléndez Natalia , Peters Jason M. , Mandel Mark J. , van Kessel Julia C. 
Published: May 2024

ABSTRACT

CRISPRi (Clustered Regularly Interspaced Palindromic Repeats interference) is a gene knockdown method that uses a deactivated Cas9 protein (dCas9) that binds a specific gene target locus dictated by an encoded guide RNA (sgRNA) to block transcription. Mobile-CRISPRi is a suite of modular vectors that enable CRISPRi knockdowns in diverse bacteria by integrating IPTG-inducible
dcas9
and
sgRNA
genes into the genome using Tn
7
transposition. Here, we show that the Mobile-CRISPRi system functions robustly and specifically in multiple
Vibrio
species:
Vibrio cholerae
,
Vibrio fischeri
,
Vibrio vulnificus
,
Vibrio parahaemolyticus
, and
Vibrio campbellii
. We demonstrate efficacy by targeting both essential and non-essential genes that function to produce defined, measurable phenotypes: bioluminescence, quorum sensing, cell division, and growth arrest. We anticipate that Mobile-CRISPRi will be used in
Vibrio
species to systematically probe gene function and essentiality in various behaviors and native environments.

IMPORTANCE

The genetic manipulation of bacterial genomes is an invaluable tool in experimental microbiology. The development of CRISPRi (Clustered Regularly Interspaced Palindromic Repeats interference) tools has revolutionized genetics in many organisms, including bacteria. Here, we optimized the use of Mobile-CRISPRi in five
Vibrio
species, each of which has significant impacts on marine environments and organisms that include squid, shrimp, shellfish, finfish, corals, and multiple of which pose direct threats to human health. The Mobile-CRISPRi technology is easily adaptable, moveable from strain to strain, and enables researchers to selectively turn off gene expression. Our experiments demonstrate Mobile-CRISPRi is effective and robust at repressing gene expression of both essential and non-essential genes in
Vibrio
species.
An
Azospirillum brasilense
chemoreceptor that mediates nitrate chemotaxis has conditional roles in the colonization of plant roots
Authors: Ganusova Elena E. , Russell Matthew H. , Patel Siddhi , Seats Terry , Alexandre Gladys 
Published: May 2024

ABSTRACT

Motile plant-associated bacteria use chemotaxis and dedicated chemoreceptors to navigate gradients in their surroundings and to colonize host plant surfaces. Here, we characterize a chemoreceptor that we named Tlp2 in the soil alphaproteobacterium
Azospirillum brasilense
. We show that the Tlp2 ligand-binding domain is related to the 4-helix bundle family and is conserved in chemoreceptors found in the genomes of many soil- and sediment-dwelling alphaproteobacteria. The promoter of
tlp2
is regulated in an NtrC- and RpoN-dependent manner and is most upregulated under conditions of nitrogen fixation or in the presence of nitrate. Using fluorescently tagged Tlp2 (Tlp2-YFP), we show that this chemoreceptor is present in low abundance in chemotaxis-signaling clusters and is prone to degradation. We also obtained evidence that the presence of ammonium rapidly disrupts Tlp2-YFP localization. Behavioral experiments using a strain lacking Tlp2 and variants of Tlp2 lacking conserved arginine residues suggest that Tlp2 mediates chemotaxis in gradients of nitrate and nitrite, with the R159 residue being essential for Tlp2 function. We also provide evidence that Tlp2 is essential for root surface colonization of some plants (teff, red clover, and cowpea) but not others (wheat, sorghum, alfalfa, and pea). These results highlight the selective role of nitrate sensing and chemotaxis in plant root surface colonization and illustrate the relative contribution of chemoreceptors to chemotaxis and root surface colonization.

IMPORTANCE
Bacterial chemotaxis mediates host-microbe associations, including the association of beneficial bacteria with the roots of host plants. Dedicated chemoreceptors specify sensory preferences during chemotaxis. Here, we show that a chemoreceptor mediating chemotaxis to nitrate is important in the beneficial soil bacterium colonization of some but not all plant hosts tested. Nitrate is the preferred nitrogen source for plant nutrition, and plants sense and tightly control nitrate transport, resulting in varying nitrate uptake rates depending on the plant and its physiological state. Nitrate is thus a limiting nutrient in the rhizosphere. Chemotaxis and dedicated chemoreceptors for nitrate likely provide motile bacteria with a competitive advantage to access this nutrient in the rhizosphere.
Immune restoration by TIGIT blockade is insufficient to control chronic SIV infection
Authors: Webb Gabriela M. , Pessoa Cleiton T. , McCullen Allyson J. , Hwang Joseph M. , Humkey Matthew C. , Thormin-Odum Raymond , Kukula Kaitlyn A. , Smedley Jeremy , Fischer Miranda , Sciurba Joseph , Bochart Rachele M. , Shriver-Munsch Christine , Ndhlovu Lishomwa C. , Sacha Jonah B. 
Published: May 2024

ABSTRACT

TIGIT is a negative immune checkpoint receptor associated with T cell exhaustion in cancer and HIV. TIGIT upregulation in virus-specific CD8
+
T cells and NK cells during HIV/SIV infection results in dysfunctional effector capabilities.
In vitro
studies targeting TIGIT on CD8
+
T cells suggest TIGIT blockade as a viable strategy to restore SIV-specific T cell responses. Here, we extend these studies
in vivo
using TIGIT blockage in nonhuman primates in an effort to reverse T cell and NK cell exhaustion in the setting of SIV infection. We demonstrate that
in vivo
administration of a humanized anti-TIGIT monoclonal antibody (mAb) is well tolerated in both cynomolgus macaques and rhesus macaques. Despite sustained plasma concentrations of anti-TIGIT mAb, we observed no consistent improvement in NK or T cell cytolytic capacity. TIGIT blockade minimally enhanced T cell proliferation and virus-specific T cell responses in both magnitude and breadth though plasma viral loads in treated animals remained stable indicating that anti-TIGIT mAb treatment alone was insufficient to increase anti-SIV CD8
+
T cell function. The enhancement of virus-specific T cell proliferative responses observed
in vitro
with single or dual blockade of TIGIT and/or PD-1 highlights TIGIT as a potential target to reverse T cell dysfunction. Our studies, however, reveal that targeting the TIGIT pathway alone may be insufficient in the setting of viremia and that combining immune checkpoint blockade with other immunotherapeutics may be a future path forward for improved viral control or elimination of HIV.

IMPORTANCE
Upregulation of the immune checkpoint receptor TIGIT is associated with HIV-mediated T cell dysfunction and correlates with HIV disease progression. Compelling evidence exists for targeting immune checkpoint receptor pathways that would potentially enhance immunity and refocus effector cell efforts toward viral clearance. In this report, we investigate TIGIT blockade as an immunotherapeutic approach to reverse immune exhaustion during chronic SIV/SHIV infection in a nonhuman primate model of HIV infection. We show that interfering with the TIGIT signaling axis alone is insufficient to improve viral control despite modest improvement in T cell immunity. Our data substantiate the use of targeting multiple immune checkpoint receptors to promote synergy and ultimately eliminate HIV-infected cells.
Patterns of cytotoxic T-cell densities in immunogenic endometrial cancers reveal a potential mechanism for differences in immunotherapy efficacy
Authors: Ryan Neil , Glaire Mark , Walker Thomas , ter Haar Natalja , Ijsselsteijn Marieke , Bolton James , de Miranda Noel , Evans Gareth , Church David N , Bosse Tjalling , Crosbie Emma 
Published: May 2024

ObjectiveTo explore the impact of molecular subtype in endometrial cancer (EC) on CD8+T cell densities. Furthermore, this work will test the assumption that all mismatch repair deficient (MMRd) tumours are immunologically similar which would enable current trial data to be generalised to all MMRd ECs.Methods and analysisAll tumours were characterised into the four clinical molecular subtypes. For analysis, theTP53mutant and no-specific molecular profile tumours were grouped together and described as the low mutational burden (LMB) cohort. CD8+T cell counts were taken from four regions of interest which sampled the tumour-stromal interface and the tumour core. CD8+T cell counts were analysed as mean averages.ResultsIn total, 607 ECs contributed to the analysis. CD8+T cell counts in confirmed Lynch syndrome (LS) ECs were significantly higher thanMLH1-methylated ECs in all tumour locations excluding the tumour stroma. Confirmed LS and path_POLEECs had significantly higher CD8+T cell counts across all tumour locations when compared with LMB ECs. There were limited significant differences in CD8+T cell counts between path_POLEversus confirmed LS ECs. There was no significant difference in the CD8+T cells counts and gene (MLH1,MSH2,MSH6,PMS2) in which the LS pathogenic variant was found; however, this analysis was limited by small numbers.ConclusionThese data indicate that CD8+T cell numbers and distribution is not equal betweenMLH1-methylated and confirmed LS ECs. This is relevant when interpreting current trial data looking to the application of checkpoint inhibition treatments in MMRd cancers.