bluuebunny/crossref_metadata_2025 huggingface dataset:
Scientists, censorship, and suppression: A combined comparative‐processual analysis of U.S. cases involving chemical and climate change expertise
Authors: Hess David J.
Published: June 2024

Although scientific research is often crucial for efforts to achieve improved environmental regulation for industrial products and processes, scientists who document or publicize research on possible risks can face suppression or censorship by industry, government, and other actors. This study contributes to the sociology of science by examining the challenges and responses of environmental scientists in the U.S. in two research areas: toxic chemicals and climate change. Drawing on comparative and processual methods applied to a small‐N, unique data set of cases, the study conducts formal coding of variables for contextual conditions and four general categories of the suppression sequence: triggering circumstances and actions, suppression actions, responses, and outcomes. The first stage of the analysis identifies significant relationships between contextual conditions and the suppression sequence, such as the different forms of suppression that government employees and university professors face. The second stage identifies three composite processual sequences: employment risk for government scientists, records attacks for both government and university scientists, and reputation attacks on university scientists. Together, the two types of analysis advance research by identifying novel relationships in a more systematic way than is accomplished with the standard approach of one or a few cases. The approach also examines the benefits of a mode of comparative analysis that can be more readily connected with theory testing via process tracing at the case level. The practical issue of responding to suppression or censorship is considered, which could be of value to environmental scientists and their partners.
Tryptophan intrinsic fluorescence from wound healing correlates with re‐epithelialization in a rabbit model
Authors: Duran‐Padilla Marco , Serrano‐Loyola Raul , Perez‐Garcia Adolfo , Carrillo‐Betancourt Rodolfo , Campos‐García Rojas Cuauhtemoc , Reyes‐Alberto Miguel , Franco Walfre , Hernandez‐Ruiz Joselin , Gutierrez‐Herrera Enoch
Published: June 2024

Background

Wound healing monitoring and timely decision‐making are critical for wound classification. Tryptophan (Tr) intrinsic fluorescence, detected at 295/340 nm, provides a noninvasive approach for wound assessment. Our previous work demonstrated that this autofluorescence is associated with keratinocytes in a highly proliferative state in vitro.

Objective

We investigated the correlation between Tr fluorescence and key wound healing parameters, including re‐epithelialization, fibrosis, neovascularization, and acute and chronic inflammation, using a rabbit model.

Methods

Seven rabbits underwent wound healing assessment over a 15‐day period. We employed histological analysis from central and marginal biopsies, and UV fluorescence imaging captured by a monochromatic near‐UV sensitive camera equipped with a passband optical filter (340 nm/12 nm). Excitation was achieved using a 295 nm LEDs ring lamp. Normalized fluorescence values were correlated with histological measurements using Pearson correlation.

Results

The UV fluorescence strongly exhibited a strong correlation with re‐epithelization (r = 0.8) at the wound edge, with peak intensity observed between the sixth and ninth days. Notably, wound‐healing dynamics differed between the wound center and edge, primarily attributed to variations in re‐epithelialization, neovascularization, and chronic inflammation.

Conclusion

Our findings highlight the presence of autofluorescence at 295/340 nm during wound healing, demonstrating a robust association with re‐epithelialization. This excitation/emission signal holds promise as a valuable noninvasive strategy for monitoring wound closure, re‐epithelialization, and other biological processes where Tr plays a pivotal role.
The effects of immigrant generational status on the likelihood of misreporting turnout
Authors: Qi Dan
Published: June 2024

Objective

This article explores the effects of immigrant generational status on the likelihood of misreporting turnout. I contend that varied levels of immigrant status affect individuals’ misreporting turnout in different ways due to social desirability and assimilation level concerns.

Methods

Using data from 2016 and 2020 Cooperative Election Study data sets, which include questions on respondents’ immigrant status and voting behavior variables, this study analyzes the effect of varied levels of immigrant status on misreporting turnout.

Results

The analysis shows that there is a decreased likelihood of misreporting turnout as individuals move farther away from their immigrant generation in both the 2016 and 2020 elections. In other words, first‐generation immigrants are most likely to misreport turnout. Second‐ and third‐generation immigrants are less likely to misreport turnout than the first generations but are still significantly more likely to misreport their turnout than those who are not immigrants or who do not have immigrant parents or grandparents.

Conclusion

The findings generally support the expectation. The levels of immigrant status affect individuals’ misreporting turnout in different ways.
A personalised delisting strategy enables successful kidney transplantation in highly sensitised patients with preformed donor‐specific anti HLA antibodies
Authors: García‐Jiménez Sandra , Paz‐Artal Estela , Trujillo Hernando , Polanco Natalia , Castro María J. , Del Rey Manuel J. , Alfocea Ángel , Morales Enrique , González Esther , Andrés Amado , Mancebo Esther
Published: June 2024

This study investigates kidney transplant outcomes in highly sensitised patients after implementing a delisting strategy aimed at enabling transplantation despite preformed donor‐specific antibodies (preDSA), with the goal of reducing acute antibody‐mediated rejection (aAMR) risk. Fifty‐three sensitised recipients underwent kidney transplant after delisting prohibited HLA antigens, focusing initially in low MFI antibodies (<5000), except for anti‐HLA‐DQ. If insufficient, higher MFI antibodies were permitted, especially for those without an immunogenic eplet pattern assigned. Delisting of Complement‐fixing antibodies (C1q+) was consistently avoided. Comparison cohorts included 53 sensitised recipients without DSA (SwoDSA) and 53 non‐sensitised (NS). The average waiting time prior to delisting was 4.4 ± 1.8 years, with a reduction in cPRA from 99.7 ± 0.5 to 98.1 ± 0.7, followed by transplantation within 7.2 ± 8.0 months (analysed in 34 patients). Rejection rates were similar among preDSA, SwoDSA, and NS groups (16%, 8%, and 11%, respectively; p = 0.46). However, aAMR was higher in the preDSA group (12%, 4%, and 2%, respectively; p = 0.073), only presented in recipients with DSA of MFI >5000. The highest MFI DSA were against HLA‐DP (Median: 10796 MFI), with 50% of preDSA aAMR cases due to anti‐DP antibodies (n = 3). Graft survival rates at 1 and 5 years in preDSA group were 94%, and 67%, comparable to SwoDSA (94%, and 70%; p = 0.69), being significantly higher in the NS group (p = 0.002). The five‐year recipient survival rate was 89%, comparable to SwoDSA and NS groups (p = 0.79). A delisting strategy enables safe kidney transplant in highly sensitised patients with preDSA, with a slight increase in aAMR and comparable graft and patient survivals to non‐DSA cohorts.
Characterisation of the novel HLA‐B*38:01:01:18 allele by next‐generation sequencing
Authors: Kouniaki Diamanto , Kitsiou Vasiliki , Tsirogianni Alexandra
Published: June 2024

HLA‐B*38:01:01:18 differs from the HLA‐B*38:01:01:01 allele by one nucleotide substitution in the 5′UTR.
Characterisation of the novel HLA‐B*18:243 allele using short‐ and long‐read sequencing technologies
Authors: Secco Danielle , Cunha Mayara , Andrade Gabriela , Vianna Romulo , Porto Luís Cristóvão
Published: June 2024

The novel HLA‐B*18:243 allele, first described in a potential bone marrow donor from Brazil.
The VSSL scale: A brief instructor tool for assessing students' perceived value of software to learning statistics
Authors: Alter Udi , Dang Carmen , Kunicki Zachary J. , Counsell Alyssa
Published: June 2024

The biggest difference in statistical training from previous decades is the increased use of software. However, little research examines how software impacts learning statistics. Assessing the value of software to statistical learning demands appropriate, valid, and reliable measures. The present study expands the arsenal of tools by reporting on the psychometric properties of the Value of Software to Statistical Learning (VSSL) scale in an undergraduate student sample. We propose a brief measure with strong psychometric support to assess students' perceived value of software in an educational setting. We provide data from a course using SPSS, given its wide use and popularity in the social sciences. However, the VSSL is adaptable to any statistical software, and we provide instructions for customizing it to suit alternative packages. Recommendations for administering, scoring, and interpreting the VSSL are provided to aid statistics instructors and education researchers understand how software influences students' statistical learning.
Suppression of plant immunity by Verticillium dahliae effector Vd6317 through AtNAC53 association
Authors: Liu Lisen , Li Jianing , Wang Zhaohan , Zhou Haodan , Wang Ye , Qin Wenqiang , Duan Hongying , Zhao Hang , Ge Xiaoyang
Published: June 2024

Verticillium dahliae, a soil‐borne fungal pathogen, compromises host innate immunity by secreting a plethora of effectors, thereby facilitating host colonization and causing substantial yield and quality losses. The mechanisms underlying the modulation of cotton immunity by V. dahliae effectors are predominantly unexplored. In this study, we identified that the V. dahliae effector Vd6317 inhibits plant cell death triggered by Vd424Y and enhances PVX viral infection in Nicotiana benthamiana. Attenuation of Vd6317 significantly decreased the virulence of V. dahliae, whereas ectopic expression of Vd6317 in Arabidopsis and cotton enhanced susceptibility to V. dahliae infection, underscoring Vd6317's critical role in pathogenicity. We observed that Vd6317 targeted the Arabidopsis immune regulator AtNAC53, thereby impeding its transcriptional activity on the defense‐associated gene AtUGT74E2. Arabidopsis nac53 and ugt74e2 mutants exhibited heightened sensitivity to V. dahliae compared to wild‐type plants. A mutation at the conserved residue 193L of Vd6317 abrogated its interaction with AtNAC53 and reduced the virulence of V. dahliae, which was partially attributable to a reduction in Vd6317 protein stability. Our findings unveil a hitherto unrecognized regulatory mechanism by which the V. dahliae effector Vd6317 directly inhibits the plant transcription factor AtNAC53 activity to suppress the expression of AtUGT74E2 and plant defense.
An Experimental Investigation on Novel Segmented Omni Wheeled Hybrid Mobile Robot to Assess Obstacle Climbing Capability
Authors: Nagaraja Prashanth , Joharapuram Sudheer Reddy , Malenahalli Ganesh Bindusagar , Herai Matt Basavaraj , Umesh Nikhil , Madrahalli Chidanandamurthy Kiran
Published: June 2024

This article introduces a novel quadrupedal hybrid mobile robot with a segmented omni wheel design capable of climbing obstacles of height greater than its wheel radius. The unique wheel design comprises two parallel coaxial 240-deg segmented omni wheels per leg with independent offset angle control. The transformation from wheel to leg mode and vice versa can be seamlessly achieved by controlling the offset angle between the segmented omni wheels. A series of experiments are carried out to evaluate the robot's performance for obstacle climbing capability utilizing various wheel end effector designs, and a comparative analysis is presented. The results indicate that the obstacle climbing capability of segmented omni wheel design with zero offset angle is improved by 40.7% compared to standard wheel, and the unique wheel design configuration facilitates seamless staircase climbing capability without any complex control scheme. In addition, statistical studies using the Taguchi method and analysis of variance (ANOVA) are performed on the experimental findings. A linear regression model to predict power consumption has been developed, and the significant factors influencing the robot's power consumption and stability are presented.
A C-3 Clamp for Improved Connection Between Catheter Tube and Barbed Connector Together With Its Evaluation Using a Maximum Pull-Off Force Method
Authors: Ceco Irma , Yanez Leonardo Zamora , Scott Peter , Li Mo , Slocum Alexander , Fuenfer Michael
Published: June 2024

The majority of hospitalized patients require the insertion of a catheter as part of their medical treatment. For catheters to be connected to external devices, barbed connectors are often employed. If this connection is ever disrupted, a direct channel from the environment to the patient's internal body may be introduced, leading to a life-threatening emergency. Current methods of securing catheter tubes to connectors have various limitations that have prevented their widespread adoption in medical settings, ranging from low ease of use to poor geometric compatibility. The authors present a device, called the Catheter Connector Clamp (C-3), shown in Fig. 1 that will securely clamp multisize catheter tubes to existing barbed connectors to increase the security and repeatability of the connection. The authors also propose a method for comparing the effectiveness of current catheter connection solutions to their C-3 design using maximum pull-off force. On silicone medical tubing, the C-3 clamp performed more than twice as well as friction alone (2.09 times more), and 25% better than the hospital gold-standard taped connection.
Characterization of Resistance-Welded Hybrid Sandwich Sheets With Additively Manufactured Core Structure
Authors: Rosenthal Stephan , Dardaei Joghan Hamed , Hahn Marlon , Tekkaya A. Erman
Published: June 2024

Production of additively manufactured sandwich sheets is limited to small sizes. In the newly introduced process route, additively manufactured core structures are joined with large rolled face sheets by resistance welding, and the formability of the hybrid sandwich sheets is investigated. The necessity of developing the humps to improve the quality of resistance welding is initially investigated. Two different core structures, namely honeycomb and hollow sphere, are selected, and electrical-thermal coupled simulations with the abaqus software are performed to study the temperature distribution during resistance welding without and with hump. The strength of the joints for the fabricated sandwich sheets is verified by a quasi-static shear test. It is experimentally proven that the sandwich sheets without a hump in the core structure are not fully joined, and desired temperature localization is possible only by applying the hump. This is because the hump reduces the contact area, which leads to an increase in current density at the point where the resistance ratios are changed. This leads to higher temperatures in the intended joining zone. Different hump geometries for the core structure are designed, fabricated, and joined to the face sheets under different process parameters. The spot contact yields up to 50% higher shear strength than the linear or area contact. The free air-bending results show that the double weld is essential for successful subsequent bending. It is also concluded that increasing the resistance welding time by more than 120 ms does not affect the joining strength of hybrid sheets.
​Antropología de la Educación en Contextos Marginados: Un Enfoque Transformador y Participativo
Authors: Santaolalla Rueda Pablo
Published: June 2024

La identidad y cómo la educación y otros instrumentos culturales la generan o modifican han sido cuestionados desde los primeros trabajos sobre el activismo social. Esto ha llevado a la necesidad de una “antropología de la educación en la que teoría, investigación, práctica y justicia social estén unidas” (McCarty y Lomawaima, 2002). Se destaca la importancia no solo de cómo son las cosas, sino de cómo pueden ser transformadas. Este enfoque cambiará el panorama general y los procesos educativos actuales. Históricamente, la atención se ha centrado en los estados, las relaciones entre culturas, países, grupos y clases, y cómo estos factores influyen en los estudiantes. En el ámbito de la Antropología de la Educación (AE), el enfoque ha sido las personas y no los centros educativos. En la Psicología y Pedagogía, el interés se centra en los procesos de aprendizaje y enseñanza, aunque en realidad el foco ha sido en la persona estudiante. En el nuevo milenio, la AE se centra en los centros educativos con un objetivo claro. Este texto pretende acercarse a la repercusión de la Antropología de la Educación en el conocimiento científico y el análisis de los procesos educativos en escuelas situadas en contextos de opresión y marginación, así como la necesidad de metodologías transformadoras para el futuro.
The perception and production of Korean stops in second dialect acquisition
Authors: Lee Hyunjung , Kong Eun Jong , Holliday Jeffrey J.
Published: June 2024

This study investigated the acoustic cue weighting of the Korean stop contrast in the perception and production of speakers who moved from a nonstandard dialect region to the standard dialect region, Seoul. Through comparing these mobile speakers with data from nonmobile speakers in Seoul and their home region, it was found that the speakers shifted their cue weighting in perception and production to some degree, but also retained some subphonemic features of their home dialect in production. The implications of these results for the role of dialect prestige and awareness in second dialect acquisition are discussed.
Hamstring Injuries, From the Clinic to the Field: A Narrative Review Discussing Exercise Transfer
Authors: Vicens-Bordas Jordi , Sarand Ali Parvaneh , Beato Marco , Buhmann Robert
Published: June 2024

Purpose: The optimal approach to hamstring training is heavily debated. Eccentric exercises reduce injury risk; however, it is argued that these exercises transfer poorly to improved hamstring function during sprinting. Some argue that other exercises, such as isometric exercises, result in better transfer to running gait and should be used when training to improve performance and reduce injury risk. Given the performance requirements of the hamstrings during the terminal swing phase, where they are exposed to high strain, exercises should aim to improve the torque production during this phase. This should improve the hamstrings’ ability to resist overlengthening consequently, improving performance and limiting strain injury. Most hamstring training studies fail to assess running kinematics postintervention. Of the limited evidence available, only eccentric exercises demonstrate changes in swing-phase kinematics following training. Studies of other exercise modalities investigate effects on markers of performance and injury risk but do not investigate changes in running kinematics. Conclusions: Despite being inconsistent with principles of transfer, current evidence suggests that eccentric exercises result in transfer to swing-phase kinematics. Other exercise modalities may be effective, but the effect of these exercises on running kinematics is unknown.
Physiological and transcriptomic response to methyl-coenzyme M reductase limitation in
Methanosarcina acetivorans
Authors: Chadwick Grayson L. , Dury Gavin A. , Nayak Dipti D.
Published: June 2024

Methyl-coenzyme M reductase (MCR) catalyzes the final step of methanogenesis, the microbial metabolism responsible for nearly all biological methane emissions to the atmosphere. Decades of biochemical and structural research studies have generated detailed insights into MCR function
in vitro
, yet very little is known about the interplay between MCR and methanogen physiology. For instance, while it is routinely stated that MCR catalyzes the rate-limiting step of methanogenesis, this has not been categorically tested. In this study, to gain a more direct understanding of MCR’s control on the growth of
Methanosarcina acetivorans,
we generate a strain with an inducible
mcr
operon on the chromosome, allowing for careful control of MCR expression. We show that MCR is not growth rate-limiting in substrate-replete batch cultures. However, through careful titration of MCR expression, growth-limiting state(s) can be obtained. Transcriptomic analysis of
M. acetivorans
experiencing MCR limitation reveals a global response with hundreds of differentially expressed genes across diverse functional categories. Notably, MCR limitation leads to strong induction of methylsulfide methyltransferases, likely due to insufficient recycling of metabolic intermediates. In addition, the
mcr
operon is not transcriptionally regulated, i.e., it is constitutively expressed, suggesting that the overabundance of MCR might be beneficial when cells experience nutrient limitation or stressful conditions. Altogether, we show that there is a wide range of cellular MCR concentrations that can sustain optimal growth, suggesting that other factors such as anabolic reactions might be rate-limiting for methanogenic growth.

IMPORTANCE

Methane is a potent greenhouse gas that has contributed to ca. 25% of global warming in the post-industrial era. Atmospheric methane is primarily of biogenic origin, mostly produced by microorganisms called methanogens. Methyl-coenzyme M reductase (MCR) catalyzes methane formatio in methanogens. Even though MCR comprises ca. 10% of the cellular proteome, it is hypothesized to be growth-limiting during methanogenesis. In this study, we show that
Methanosarcina acetivorans
cells grown in substrate–replicate batch cultures produce more MCR than its cellular demand for optimal growth. The tools outlined in this study can be used to refine metabolic models of methanogenesis and assay lesions in MCR in a higher-throughput manner than isolation and biochemical characterization of pure protein.
Mouse and human immune responses share neutralization epitopes of HAstV-VA1
Authors: Ramírez-Bello Inci , López Tomás , Espinosa Rafaela , Ghosh Anisa , Green Kassidy , Riaño-Umbarila Lidia , Gaspar-Castillo Carlos , Aguilera-Flores Catalina , Alpuche-Aranda Celia M. , López Susana , DuBois Rebecca M. , Arias Carlos F.
Published: June 2024

Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in human astroviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient’s immunotherapy. In agreement with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, suggesting that both mouse and human antibody responses target shared neutralization epitopes. The isolated Nt-MAbs reported in this work will help to characterize the functional domains of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

IMPORTANCE

Human astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. In this work high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1 were isolated and characterized. The proposed binding sites for these antibodies and for neutralizing antibodies against classical HAstVs suggest that there are at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will help to define the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.
Define SNP thresholds for delineation of tuberculosis transmissions using whole-genome sequencing
Authors: Xiao Yu-Xin , Chan Tai-Hua , Liu Kuang-Hung , Jou Ruwen
Published: June 2024

For facilitating tuberculosis (TB) control, we used a whole-genome sequencing (WGS)-based approach to delineate transmission networks in a country with an intermediate burden of TB. A cluster was defined as
Mycobacterium tuberculosis
isolates with identical genotypes, and an outbreak was defined as clustered cases with epidemiological links (epi-links). To refine a cluster predefined using space oligonucleotide typing and mycobacterial interspersed repetitive unit variable tandem repeat typing, we analyzed one pansusceptible TB (C1) and three multidrug-resistant (MDR)-TB (C2-C4) clusters from different scenarios. Pansusceptible TB cluster (C1) consisting of 28 cases had ≤5 single nucleotide polymorphisms (SNPs) difference between their isolates. C1 was a definite outbreak, with cases attending the same junior high school in 2012. Three MDR-TB clusters (C2-C4) with distinct genotypes were identified, each consisting of 12–22 cases. Some of the cases had either ≤5 or ≤15 SNPs difference with clear or probable epi-links. Of note, even though WGS could effectively assist TB contact tracing, we still observed missing epi-links in some cases within the same cluster. Our results showed that thresholds of ≤5 and ≤15 SNPs difference between isolates were used to categorize definite and probable TB transmission, respectively. Furthermore, a higher SNP threshold might be required to define an MDR-TB outbreak. WGS still needs to be combined with classical epidemiological methods for improving outbreak investigations. Importantly, different SNP thresholds have to be applied to define outbreaks.

IMPORTANCE

TB is a chronic disease. Depending on host factors and TB burden, clusters of cases may continue to increase for several years. Conventional genotyping methods overestimate TB transmission, hampering precise detection of outbreaks and comprehensive surveillance. WGS can be used to obtain SNP information of
M. tuberculosis
to improve discriminative limitations of conventional methods and to strengthen delineation of transmission networks. It is important to define the country-specific SNP thresholds for investigation of transmission. This study demonstrated the use of thresholds of ≤5 and ≤15 SNPs difference between isolates to categorize definite and probable transmission, respectively. Different SNP thresholds should be applied while a higher cutoff was required to define an MDR-TB outbreak. The utilization of SNP thresholds proves to be crucial for guiding public health interventions, eliminating the need for unnecessary public health actions, and potentially uncovering undisclosed TB transmissions.
A
Mycobacterium ulcerans
vaccine pilot trial using an accurate low-dose challenge
Authors: Muhi Stephen , Porter Jessica L. , Stinear Timothy P.
Published: June 2024

A
Mycobacterium ulcerans
human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate
M. ulcerans
JKD8049 in naïve and
Mycobacterium bovis
bacille Calmette–Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of
M. ulcerans
[95% confidence interval (CI) 17–22 CFU] with a mean time to visible lesion of 86 days (95% CI 79–92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days (
P
= 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this
in vivo
model and highlights both the promise and the problems with trying to induce protective immunity against
M. ulcerans
.

IMPORTANCE

In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of
Mycobacterium ulcerans
JKD8049 (our proposed CHIM strain). We also demonstrate that
Mycobacterium bovis
bacille Calmette–Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible.
Changing epidemiology and antimicrobial resistance of bacteria causing bacteremia in Taiwan: 2002–2020
Authors: Huang Ying-Chi , Kuo Shu-Chen , Fang Chi-Tai , Lauderdale Tsai-Ling
Published: June 2024

Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July–September as part of the TSAR program. The three most common bacteremia agents were
Escherichia coli
(31%),
Staphylococcus aureus
(13.6%), and
Klebsiella pneumoniae
(12.7%) overall. However, there was a steady increase in the proportions of
E. coli
and
Enterococcus faecium
isolated from bacteremia cases (both
P
< 0.001), while the proportions of
Acinetobacter
spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among
E. coli
and
K. pneumoniae
, while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in
E. coli
. Of concern is the alarming increase in vancomycin resistance among
E. faecium
, rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant
S. aureus
has remained stable at 51.2% overall. In conclusion,
E. coli
, with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of
E. faecium
in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade.

IMPORTANCE

AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002–2020 TSAR program. The study highlights an alarming increase in the proportion of
E. faecium
causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions.
Enrichment of Terbium(III) under synergistic effect of biosorption and biomineralization by
Bacillus
sp. DW015 and
Sporosarcina pasteurii
Authors: Bian Zijun , Dong Wei , Li Xi , Song Yuexin , Huang Huihong , Hong Kemin , Hu Kaijian
Published: June 2024

Biosorption and biomineralization are commonly used for the immobilization of metal ions. Biosorption is commonly used as a green method to enrich rare earth ions from wastewater. However, little attention has been paid to the facilitating role of biomineralization in the enrichment of rare earth ions. In this study, a strain of
Bacillus
sp. DW015, isolated from ion adsorption type rare earth ores and a urease-producing strain
Sporosarcina pasteurii
were used to enrich rare earth elements (REEs) from an aqueous solution. The results indicate that biomineralization accelerates the enrichment of Terbium(III) compared to biosorption alone. Kinetic analysis suggests that the main mode of action of DW015 was biosorption, following pseudo-second-order kinetics (
R
2
= 0.998). The biomineralization of DW015 did not significantly contribute to the enrichment of Tb(III), whereas excessive biomineralization of
S. pasteurii
led to a decrease in the enrichment of Tb(III). A synergistic system of biosorption and biomineralization was established by combining the two bacteria, with the optimal mixed bacteria (
S. pasteurii
:DW015) ratio being 1:19. This study provides fundamental support for the synergistic effect of biosorption and biomineralization and offers a new reference for future microbial-based enrichment methods.

IMPORTANCE

A weak microbially induced calcium carbonate precipitation (MICP) promotes the enrichment of Tb(III) by bacteria, while a strong MICP leads to the release of Tb(III). However, existing explanations cannot elucidate these mechanisms. In this study, the morphology of the bioprecipitation and the degree of Tb(III) enrichment were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The data revealed that MICP could drive stable attachment of Tb(III) onto the cell surface, forming a Tb-CaCO
3
mixed solid phase. Excessive rapid rate of calcite generation could disrupt the Tb(III) adsorption equilibrium, leading to the release of Tb(III). Therefore, in order for Tb(III) to be stably embedded in calcite, it is necessary to have a sufficient number of adsorption sites on the bacteria and to regulate the rate of MICP. This study provides theoretical support for the process design of MICP for the enrichment of rare earth ions.
Modulation of riboflavin biosynthesis and utilization in mycobacteria
Authors: Chengalroyen Melissa D. , Mehaffy Carolina , Lucas Megan , Bauer Niel , Raphela Mabule L. , Oketade Nurudeen , Warner Digby F. , Lewinsohn Deborah A. , Lewinsohn David M. , Dobos Karen M. , Mizrahi Valerie
Published: June 2024

Riboflavin (vitamin B
2
) is the precursor of the flavin coenzymes, FAD and FMN, which play a central role in cellular redox metabolism. While humans must obtain riboflavin from dietary sources, certain microbes, including
Mycobacterium tuberculosis
(Mtb), can biosynthesize riboflavin
de novo
. Riboflavin precursors have also been implicated in the activation of mucosal-associated invariant T (MAIT) cells which recognize metabolites derived from the riboflavin biosynthesis pathway complexed to the MHC-I-like molecule, MR1. To investigate the biosynthesis and function of riboflavin and its pathway intermediates in mycobacterial metabolism and physiology, we constructed conditional knockdowns (hypomorphs) in riboflavin biosynthesis and utilization genes in
Mycobacterium smegmatis
(Msm) and Mtb by inducible CRISPR interference. Using this comprehensive panel of hypomorphs, we analyzed the impact of gene silencing on viability, on the transcription of (other) riboflavin pathway genes, on the levels of the pathway proteins, and on riboflavin itself. Our results revealed that (i) despite lacking a canonical transporter, both Msm and Mtb assimilate exogenous riboflavin when supplied at high concentration; (ii) there is functional redundancy in lumazine synthase activity in Msm; (iii) silencing of
ribA2
or
ribF
is profoundly bactericidal in Mtb; and (iv) in Msm,
ribA2
silencing results in concomitant knockdown of other pathway genes coupled with RibA2 and riboflavin depletion and is also bactericidal. In addition to their use in genetic validation of potential drug targets for tuberculosis, this collection of hypomorphs provides a useful resource for future studies investigating the role of pathway intermediates in MAIT cell recognition of mycobacteria.

IMPORTANCE

The pathway for biosynthesis and utilization of riboflavin, precursor of the essential coenzymes, FMN and FAD, is of particular interest in the flavin-rich pathogen,
Mycobacterium tuberculosis
(Mtb), for two important reasons: (i) the pathway includes potential tuberculosis (TB) drug targets and (ii) intermediates from the riboflavin biosynthesis pathway provide ligands for mucosal-associated invariant T (MAIT) cells, which have been implicated in TB pathogenesis. However, the riboflavin pathway is poorly understood in mycobacteria, which lack canonical mechanisms to transport this vitamin and to regulate flavin coenzyme homeostasis. By conditionally disrupting each step of the pathway and assessing the impact on mycobacterial viability and on the levels of the pathway proteins as well as riboflavin, our work provides genetic validation of the riboflavin pathway as a target for TB drug discovery and offers a resource for further exploring the association between riboflavin biosynthesis, MAIT cell activation, and TB infection and disease.
Central role of the
ramAR
locus in the multidrug resistance in ESBL
-Enterobacterales
Authors: Gravey François , Michel Alice , Langlois Bénédicte , Gérard Mattéo , Galopin Sébastien , Gakuba Clément , Du Cheyron Damien , Fazilleau Laura , Brossier David , Guérin François , Giard Jean-Christophe , Le Hello Simon
Published: June 2024

The aim of this study was to evaluate the proportion of resistance to a temocillin, tigecycline, ciprofloxacin, and chloramphenicol phenotype called t2c2 that resulted from mutations within the
ramAR
locus among extended-spectrum β-lactamases
-Enterobacterales
(ESBL-E) isolated in three intensive care units for 3 years in a French university hospital. Two parallel approaches were performed on all 443 ESBL-E included: (i) the minimal inhibitory concentrations of temocillin, tigecycline, ciprofloxacin, and chloramphenicol were determined and (ii) the genomes obtained from the Illumina sequencing platform were analyzed to determine multilocus sequence types, resistomes, and diversity of several
tetR
-associated genes including
ramAR
operon. Among the 443 ESBL-E strains included, isolates of
Escherichia coli
(
n
= 194),
Klebsiella pneumoniae
(
n
= 122), and
Enterobacter cloacae
complex (
Ecc
) (
n
= 127) were found. Thirty-one ESBL-E strains (7%), 16
K
.
pneumoniae
(13.1%), and 15
Ecc
(11.8%) presented the t2c2 phenotype in addition to their ESBL profile, whereas no
E. coli
presented these resistances. The t2c2 phenotype was invariably reversible by the addition of Phe-Arg-β-naphthylamide, indicating a role of resistance-nodulation-division pumps in these observations. Mutations associated with the t2c2 phenotype were restricted to RamR, the
ramAR
intergenic region (IR), and AcrR. Mutations in RamR consisted of C- or N-terminal deletions and amino acid substitutions inside its DNA-binding domain or within key sites of protein–substrate interactions. The
ramAR
IR showed nucleotide substitutions involved in the RamR DNA-binding domain. This diversity of sequences suggested that RamR and the
ramAR
IR represent major genetic events for bacterial antimicrobial resistance.

IMPORTANCE

Morbimortality caused by infectious diseases is very high among patients hospitalized in intensive care units (ICUs). A part of these outcomes can be explained by antibiotic resistance, which delays the appropriate therapy. The transferable antibiotic resistance gene is a well-known mechanism to explain the high rate of multidrug resistance (MDR) bacteria in ICUs. This study describes the prevalence of chromosomal mutations, which led to additional antibiotic resistance among MDR bacteria. More than 12% of
Klebsiella pneumoniae
and
Enterobacter cloacae
complex strains presented mutations within the
ramAR
locus associated with a dysregulation of an efflux pump called AcrAB-TolC and a porin: OmpF. These dysregulations led to an increase in antibiotic output notably tigecycline, ciprofloxacin, and chloramphenicol associated with a decrease of input for beta-lactam, especially temocillin. Mutations within transcriptional regulators such as
ramAR
locus played a major role in antibiotic resistance dissemination and need to be further explored.
Clostridium sporogenes
increases fat accumulation in mice by enhancing energy absorption and adipogenesis
Authors: Du Lei , Wang Jing , Qiu Xiaoyu , Wang Qi , Peng Han , Huang Jinxiu , Yang Feiyun , Liu Zuohua , Qi Renli
Published: June 2024

Gut bacteria belonging to the
Clostridium
family play a pivotal role in regulating host energy balance and metabolic homeostasis. As a commensal bacterium,
Clostridium sporogenes
has been implicated in modulating host energy homeostasis, albeit the underlying mechanism remains elusive. Therefore, this study aimed to investigate the impact of
C. sporogenes
supplementation on various physiological parameters, intestinal morphology, particularly adipose tissue accumulation, and glucolipid metabolism in mice. The findings reveal that mice supplemented with
C. sporogenes
for 6 weeks exhibited a notable increase in body weight, fat mass, adipocyte size, and serum triglyceride (TG) levels. Notably, the increased fat accumulation is observed despite consistent feed intake in treated mice. Mechanistically,
C. sporogenes
supplementation significantly improved the structure integrity of intestinal villi and enhanced energy absorption efficiency while reducing excretion of carbohydrates and fatty acids in feces. This was accompanied by upregulation of glucose and fatty acid transporter expression. Furthermore, supplementation with
C. sporogenes
promoted adipogenesis in both liver and adipose tissues, as evidenced by increased levels of hepatic pyruvate, acetyl-CoA, and TG, along with elevated expression levels of genes associated with lipid synthesis. Regarding the microbiological aspect,
C. sporogenes
supplementation correlated with an increased abundance of
Clostridium
genus bacteria and enhanced carbohydrate enzyme activity. In summary,
C. sporogenes
supplementation significantly promotes fat accumulation in mice by augmenting energy absorption and adipogenesis, possibly mediated by the expansion of
Clostridium
bacteria population with robust glycolipid metabolic ability.

IMPORTANCE

The
Clostridia
clusters have been implicated in energy metabolism, the specific species and underlying mechanisms remain unclear. This present study is the first to report
Clostridium sporogenes
is able to affect fat accumulation and glycolipid metabolism. We indicated that gavage of
C. sporogenes
promoted the adipogenesis and fat accumulation in mice by not only increasing the abundance of
Clostridium
bacteria but by also enhancing the metabolic absorption of carbohydrates and fatty acids significantly. Obviously, changes of gut microbiota caused by the
C. sporogenes
, especially the significant increase of
Clostridium
bacteria, contributed to the fat accumulation of mice. In addition, the enhancement of
Clostridium
genus bacteria remarkably improved the synthesis of hepatic pyruvate, acetyl-CoA, and triglyceride levels, as well as reduced the excretion of fecal carbohydrates, short-chain fatty acids, and free fatty acids remarkably. These findings will help us to understand the relationship of specific bacteria and host energy homeostasis.
Magnetosonic Solitary Waves
Authors: Ignatov A. M.
Published: June 2024

The set of equations is obtained that describes the nonlinear three-dimensional dynamics of magnetosonic waves. Plane solitary waves propagating at a small angle to the guiding magnetic field have been studied. Three-dimensional spatially localized waves have been qualitatively studied.
Breast cancer symptom profile longitudinal changes: data mining study
Authors: Fathian Mohammad , Akbari Farzane
Published: June 2024

Objectives

Identifying stable co-occurring symptoms in breast cancer (BC) patients during chemotherapy can improve symptom management and the treatment process. This study examines symptom cluster stability in Iranian BC patients receiving chemotherapy and evaluates stability across three-time points within each cluster.

Methods

This study collected data from three-time points: initial chemotherapy commencement, 2½ months postdiagnosis, and 5 months postdiagnosis. The research used exploratory factor analysis (EFA) in combination with hierarchical cluster analysis (HCA) and K means clustering to address research questions.

Results

In the initial clustering step, EFA identified five clusters with high consistency across three-time points. The first cluster showed depression, anxiety and irritability, while the second cluster was characterised by sexual interest and pain. The third cluster was associated with diarrhoea and vomiting. In the second step, we obtained the HCA item output and two clusters of K means clustering that recorded depression and anxiety symptoms over time. Vomiting, dry mouth, sexual interest, worrying and numbness were observed during the first and second points, but the frequency has decreased since then.

Conclusions

Cancer’s psychological and physiological symptoms, including depression, anxiety, digestive and hormonal issues, remain stable throughout the disease. Palliative care centres can improve patients’ quality of life and treatment process by addressing persistent symptoms.