bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferable GeSn ribbon photodetectors for high-speed short-wave infrared photonic applications
Authors: Zhao Haochen , Park Suho , Lin Guangyang , Zhang Yuying , Zhama Tuofu , Samanta Chandan , Chang Lorry , Zhu Xiaofeng , Feng Xu , Díaz-Aponte Kevin O. , Cong Lin , Zeng Yuping
Published: June 2024

We experimentally demonstrate a low-cost transfer process of GeSn ribbons to insulating substrates for short-wave infrared (SWIR) sensing/imaging applications. By releasing the original compressive GeSn layer to nearly fully relaxed state GeSn ribbons, the room-temperature spectral response of the photodetector is further extended to 3.2 μm, which can cover the entire SWIR range. Compared with the as-grown GeSn reference photodetectors, the fabricated GeSn ribbon photodetectors have a fivefold improvement in the light-to-dark current ratio, which can improve the detectivity for high-performance photodetection. The transient performance of a GeSn ribbon photodetector is investigated with a rise time of about 40 μs, which exceeds the response time of most GeSn (Ge)-related devices. In addition, this transfer process can be applied on various substrates, making it a versatile technology that can be used for various applications ranging from optoelectronics to large-area electronics. These results provide insightful guidance for the development of low-cost and high-speed SWIR photodetectors based on Sn-containing group IV low-dimensional structures.
Upgrading of the modified Knudsen equation and its verification for calculating the gas flow rate through cylindrical tubes
Authors: Yoshida Hajime
Published: June 2024

The modified Knudsen equation was developed to calculate the gas flow rate through a cylindrical tube with arbitrary length-to-diameter ratio in any flow regime including molecular flow, viscous laminar flow, turbulent flow, critical flow, subcritical flow, and their intermediates in our laboratory. Here, it is upgraded for better agreement with literature data, and the upgraded version is compared with 83 literature sources including 31 gas flow equations to verify its reliability. For Kn > 10−5, the modified Knudsen equation mostly agrees with the literature data to within 20%, except for orifice flows with pd/pu ≈ 1.
Spaced Use of Social Media Apps Among Motor Practice Trials Impacts Performance Without Influencing Mental Fatigue and Motor Learning
Authors: Leal Marina Gonçalves , Luz José Eduardo dos Martírios , Santos Ana Kariele da Silva , Costa Cicero Luciano Alves , Bandeira Paulo Felipe Ribeiro , Meira Cassio de Miranda , Bonuzzi Giordano Marcio Gatinho
Published: June 2024

We aimed to investigate the impact of smartphone use during intertrial intervals within a distributed practice regime on mental fatigue, performance, and learning of a balance motor skill. One hundred and thirty-six participants were randomly divided into two groups: the smartphone use group (SMARTPHONE) and the control group (CONTROL). The SMARTPHONE accessed social media during the rest periods within a distributed practice of a balance task, whereas the CONTROL rested passively during the rest periods. The participants practiced the toe-touch task. The participants underwent a pretest consisting of one trial. Subsequently, the participants were engaged in practice, completing six trials interspersed with 2-min intervals of either rest or smartphone use. Following the practice phase, a posttest was conducted, and after 24 hr, we administered a retention test and a transfer test. The number of touches and the number of errors (contacting the ground with the free leg to regain balance) were performance measures. We evaluated the participants’ mental fatigue after the practice session using a visual analog scale. The groups demonstrated similar mental fatigue after practice. Our results suggest that using social media on smartphones during rest periods within a distributed practice impairs performance but not motor learning.
Sex-dependent regulation of vertebrate somatic growth and aging by germ cells
Authors: Abe Kota , Ino Hikaru , Niwa Tomomi , Semmy Daniel , Takaochi Ayami , Nishimura Takashi , Mogi Chihiro , Uenaka Maki , Ishii Masaru , Tanaka Kaori , Ohkawa Yasuyuki , Ishitani Tohru
Published: June 2024

The function of germ cells in somatic growth and aging has been demonstrated in invertebrate models but remains unclear in vertebrates. We demonstrated sex-dependent somatic regulation by germ cells in the short-lived vertebrate model
Nothobranchius furzeri
. In females, germ cell removal shortened life span, decreased estrogen, and increased insulin-like growth factor 1 (IGF-1) signaling. In contrast, germ cell removal in males improved their health with increased vitamin D signaling. Body size increased in both sexes but was caused by different signaling pathways, i.e., IGF-1 and vitamin D in females and males, respectively. Thus, vertebrate germ cells regulate somatic growth and aging through different pathways of the endocrine system, depending on the sex, which may underlie the sexual difference in reproductive strategies.
TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends
Authors: Bettin Nicole , Querido Emmanuelle , Gialdini Irene , Grupelli Glenda Paola , Goretti Elena , Cantarelli Marta , Andolfato Marta , Soror Eslam , Sontacchi Alessandra , Jurikova Katarina , Chartrand Pascal , Cusanelli Emilio
Published: June 2024

The function of TERRA in the regulation of telomerase in human cells is still debated. While TERRA interacts with telomerase, how it regulates telomerase function remains unknown. Here, we show that TERRA colocalizes with the telomerase RNA subunit hTR in the nucleoplasm and at telomeres during different phases of the cell cycle. We report that TERRA transcripts relocate away from chromosome ends during telomere lengthening, leading to a reduced number of telomeric TERRA-hTR molecules and consequent increase in “TERRA-free” telomerase molecules at telomeres. Using live-cell imaging and super-resolution microscopy, we show that upon transcription, TERRA relocates from its telomere of origin to long chromosome ends. Furthermore, TERRA depletion by antisense oligonucleotides promoted hTR localization to telomeres, leading to increased residence time and extended half-life of hTR molecules at telomeres. Overall, our findings indicate that telomeric TERRA transcripts inhibit telomere elongation by telomerase acting in trans, impairing telomerase access to telomeres that are different from their chromosome end of origin.
Does coevolution in refugia drive mimicry in bumble bees? Insights from a South Asian mimicry group
Authors: Cui Jixiang , Chen Yuxin , Hines Heather M. , Ma Ling , Yang Wanhu , Wang Chao , Liu Shanlin , Li Hu , Cai Wanzhi , Da Wa , Williams Paul , Tian Li
Published: June 2024

Müllerian mimicry was proposed to be an example of a coevolved mutualism promoted by population isolation in glacial refugia. This, however, has not been well supported in butterfly models. Here, we use genomic data to test this theory while examining the population genetics behind mimetic diversification in a pair of co-mimetic bumble bees,
Bombus breviceps
Smith and
Bombus trifasciatus
Smith. In both lineages, populations were structured by geography but not as much by color pattern, suggesting sharing of color alleles across regions of restricted gene flow and formation of mimicry complexes in the absence of genetic differentiation. Demographic analyses showed mismatches between historical effective population size changes and glacial cycles, and niche modeling revealed only mild habitat retraction during glaciation. Moreover, mimetic subpopulations of the same color form in the two lineages only in some cases exhibit similar population history and genetic divergence. Therefore, the current study supports a more complex history in this comimicry than a simple refugium-coevolution model.
Discovering the gene-brain-behavior link in autism via generative machine learning
Authors: Kundu Shinjini , Sair Haris , Sherr Elliott H. , Mukherjee Pratik , Rohde Gustavo K.
Published: June 2024

Autism is traditionally diagnosed behaviorally but has a strong genetic basis. A genetics-first approach could transform understanding and treatment of autism. However, isolating the gene-brain-behavior relationship from confounding sources of variability is a challenge. We demonstrate a novel technique, 3D transport-based morphometry (TBM), to extract the structural brain changes linked to genetic copy number variation (CNV) at the 16p11.2 region. We identified two distinct endophenotypes. In data from the Simons Variation in Individuals Project, detection of these endophenotypes enabled 89 to 95% test accuracy in predicting 16p11.2 CNV from brain images alone. Then, TBM enabled direct visualization of the endophenotypes driving accurate prediction, revealing dose-dependent brain changes among deletion and duplication carriers. These endophenotypes are sensitive to articulation disorders and explain a portion of the intelligence quotient variability. Genetic stratification combined with TBM could reveal new brain endophenotypes in many neurodevelopmental disorders, accelerating precision medicine, and understanding of human neurodiversity.
Wireless, customizable coaxially shielded coils for magnetic resonance imaging
Authors: Wu Ke , Zhu Xia , Anderson Stephan W. , Zhang Xin
Published: June 2024

Anatomy-specific radio frequency receive coil arrays routinely adopted in magnetic resonance imaging (MRI) for signal acquisition are commonly burdened by their bulky, fixed, and rigid configurations, which may impose patient discomfort, bothersome positioning, and suboptimal sensitivity in certain situations. Herein, leveraging coaxial cables’ inherent flexibility and electric field confining property, we present wireless, ultralightweight, coaxially shielded, passive detuning MRI coils achieving a signal-to-noise ratio comparable to or surpassing that of commercially available cutting-edge receive coil arrays with the potential for improved patient comfort, ease of implementation, and substantially reduced costs. The proposed coils demonstrate versatility by functioning both independently in form-fitting configurations, closely adapting to relatively small anatomical sites, and collectively by inductively coupling together as metamaterials, allowing for extension of the field of view of their coverage to encompass larger anatomical regions without compromising coil sensitivity. The wireless, coaxially shielded MRI coils reported herein pave the way toward next-generation MRI coils.
Genes required for survival and proliferation of
Mycoplasma bovis
in association with host cells
Authors: Premachandre Chintha K. , Vaz Paola K. , Sharma Shukriti , Kanci Condello Anna , Browning Glenn F. , Wawegama Nadeeka K.
Published: June 2024

Mycoplasma bovis
is an important emerging pathogen of cattle and bison, but our understanding of the genetic basis of its interactions with its host is limited. The aim of this study was to identify genes of
M. bovis
required for interaction and survival in association with host cells. One hundred transposon-induced mutants of the type strain PG45 were assessed for their capacity to survive and proliferate in Madin-Darby bovine kidney cell cultures. The growth of 19 mutants was completely abrogated, and 47 mutants had a prolonged doubling time compared to the parent strain. All these mutants had a similar growth pattern to the parent strain PG45 in the axenic media. Thirteen genes previously classified as dispensable for the axenic growth of
M. bovis
were found to be essential for the growth of
M. bovis
in association with host cells. In most of the mutants with a growth-deficient phenotype, the transposon was inserted into a gene involved in transportation or metabolism. This included genes coding for ABC transporters, proteins related to carbohydrate, nucleotide and protein metabolism, and membrane proteins essential for attachment. It is likely that these genes are essential not only
in vitro
but also for the survival of
M. bovis
in infected animals.

IMPORTANCE

Mycoplasma bovis
causes chronic bronchopneumonia, mastitis, arthritis, keratoconjunctivitis, and reproductive tract disease in cattle around the globe and is an emerging pathogen in bison. Control of mycoplasma infections is difficult in the absence of appropriate antimicrobial treatment or effective vaccines. A comprehensive understanding of host-pathogen interactions and virulence factors is important to implement more effective control methods against
M. bovis
. Recent studies of other mycoplasmas with
in vitro
cell culture models have identified essential virulence genes of mycoplasmas. Our study has identified genes of
M. bovis
required for survival in association with host cells, which will pave the way to a better understanding of host-pathogen interactions and the role of specific genes in the pathogenesis of disease caused by
M. bovis
.
In vivo
efficacy of phage cocktails against carbapenem resistance
Acinetobacter baumannii
in the rat pneumonia model
Authors: Li Shibin , Wei Bingdong , Xu Le , Cong Cong , Murtaza Bilal , Wang Lili , Li Xiaoyu , Li Jibin , Xu Mu , Yin Jiajun , Xu Yongping
Published: June 2024

Acinetobacter baumannii
, an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant
A. baumannii
, has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two
A. baumannii
phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and
in vitro
bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study underscore the potential of phages for future development as a treatment strategy and offer compelling evidence regarding immune system dynamics throughout the treatment process.

IMPORTANCE

Due to the growing problem of multi-drug-resistant bacteria, the use of phages is being considered as an alternative to antibiotics, and the genetic safety and application stability of phages determine the potential of phage application. The absence of drug resistance genes and virulence genes in the phage genome can ensure the safety of phage application, and the fact that phage can remain active in a wide range of temperatures and pH is also necessary for application. In addition, the effect evaluation of preclinical studies is especially important for clinical application. By simulating the immune response situation during the treatment process through mammalian models, the changes in animal immunity can be observed, and the effect of phage therapy can be further evaluated. Our study provides compelling evidence that phages hold promise for further development as therapeutic agents for
Acinetobacter baumannii
infections.
The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6
Authors: Sun Kunfeng , Bose Dipayan , Singh Rajnish Kumar , Pei Yonggang , Robertson Erle S.
Published: June 2024

Most mature B-cell malignancies originate from the malignant transformation of germinal center (GC) B cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is BCL6, a key regulator of this process. We now demonstrate that BCL6 protein levels were dramatically decreased in Epstein-Barr virus (EBV)-positive lymphoblastoid cell lines and Burkitt’s lymphoma cell lines. Notably, BCL6 degradation was significantly enhanced in the presence of both EBNA3C and FBXO11. Furthermore, the amino-terminal domain of EBNA3C, which contains residues 50–100, interacts directly with FBXO11. The expression of EBNA3C and FBXO11 resulted in a significant induction of cell proliferation. Furthermore, BCL6 protein expression levels were regulated by EBNA3C via the Skp Cullin Fbox (SCF)
FBXO11
complex, which mediated its ubiquitylation, and knockdown of FBXO11 suppressed the transformation of lymphoblastoid cell lines. These data provide new insights into the function of EBNA3C in B-cell transformation during GC reaction and raise the possibility of developing new targeted therapies against EBV-associated cancers.

IMPORTANCE

The novel revelation in our study involves the suppression of BCL6 expression by the essential Epstein-Barr virus (EBV) antigen EBNA3C, shedding new light on our current comprehension of how EBV contributes to lymphomagenesis by impeding the germinal center reaction. It is crucial to note that while several EBV latent proteins are expressed in infected cells, the collaborative mechanisms among these proteins in regulating B-cell development or inducing B-cell lymphoma require additional investigation. Nonetheless, our findings carry significance for the development of emerging strategies aimed at addressing EBV-associated cancers.
Complete genome sequence of Indonesian probiotic strain
Lactiplantibacillus plantarum
subsp.
plantarum
Dad-13
Authors: Sutriswati Rahayu Endang , Suroto Dian Anggraini , Mariyatun Mariyatun , Pramesi Putrika Citta
Published: June 2024

Previous studies have investigated the probiotic properties of
L. plantarum
subsp.
plantarum
Dad-13. Nevertheless, genomic sequence data from previous studies were not yet available to support each probiotic characteristic. This study focused on the complete genome sequence of the strain to validate its role in specific probiotic properties.
Draft genome sequence of carbapenems-resistant
Acinetobacter baumannii
Hakim RU_CBWP strain isolated from a pond surface water in Bangladesh
Authors: Khan Muhib Ullah , Romance M. , Polash Md. Arif-Uz-Zaman , Zahan Nusrat , Ali Md. Sumon , Raihan Jafor , Sarker Subir , Haque Md. Hakimul
Published: June 2024

We have revealed the genomic sequence of
Acinetobacter baumannii
strain Hakim RU_CBWP isolated from pond surface water. Our assembled genome covers 3.787 Mb with 45.5629× coverage, showcasing an average GC content of 38.60%. This genome contains two CRISPR arrays, 17 prophages, 22 antibiotic resistance genes, and 20 virulence factor genes.
Oligomycin-producing
Streptomyces
sp. newly isolated from Swiss soils efficiently protect
Arabidopsis thaliana
against
Botrytis cinerea
Authors: Louviot Fanny , Abdelrahman Ola , Abou-Mansour Eliane , L'Haridon Floriane , Allard Pierre-Marie , Falquet Laurent , Weisskopf Laure
Published: June 2024

Botrytis cinerea
is a necrotrophic phytopathogen able to attack more than 200 different plant species causing strong yield losses worldwide. Many synthetic fungicides have been developed to control this disease, resulting in the rise of fungicide-resistance
B. cinerea
strains. The aim of this study was to identify
Streptomyces
strains showing antagonistic activity against
B. cinerea
to contribute to plant protection in an environmentally friendly way. We isolated 15 Actinomycete strains from 9 different Swiss soils. The culture filtrates of three isolates showing antifungal activity inhibited spore germination and delayed mycelial growth of
B. cinerea
. Infection experiments showed that
Arabidopsis thaliana
plants were more resistant to this pathogen after leaf treatment with the
Streptomyces
filtrates. Bioassay-guided isolation of the active compounds revealed the presence of germicidins A and B as well as of oligomycins A, B, and E. While germicidins were mostly inactive, oligomycin B reduced the mycelial growth of
B. cinerea
significantly. Moreover, all three oligomycins inhibited this fungus’ spore germination, suggesting that these molecules might contribute to the
Streptomyces
’s ability to protect plants against infection by the broad host-pathogen
Botrytis cinerea
.

IMPORTANCE

This study reports the isolation of new
Streptomyces
strains with strong plant-protective potential mediated by their production of specialized metabolites. Using the broad host range pathogenic fungus
Botrytis cinerea
, we demonstrate that the cell-free filtrate of selected
Streptomyces
isolates efficiently inhibits different developmental stages of the fungus, including mycelial growth and the epidemiologically relevant spore germination. Beyond
in vitro
experiments, the strains and their metabolites also efficiently protected plants against the disease caused by this pathogen. This work further identifies oligomycins as active compounds involved in the observed antifungal activity of the strains. This work shows that we can harness the natural ability of soil-borne microbes and of their metabolites to efficiently fight other microbes responsible for significant crop losses. This opens the way to the development of environmentally friendly health protection measures for crops of agronomical relevance, based on these newly isolated strains or their metabolic extracts containing oligomycins.
A metabolomics perspective on clorobiocin biosynthesis: discovery of bromobiocin and novel derivatives through LC-MS
E
-based molecular networking
Authors: Janzing Niklas B. M. , Niehoff Maurice , Sander Wolfram , Senges Christoph H. R. , Schäkermann Sina , Bandow Julia E.
Published: June 2024

Clorobiocin is a well-known, highly effective inhibitor of DNA gyrase belonging to the aminocoumarin antibiotics. To identify potentially novel derivatives of this natural product, we conducted an untargeted investigation of clorobiocin biosynthesis in the known producer
Streptomyces roseochromogenes
DS 12.976 using LC-MS
E
, molecular networking, and analysis of fragmentation spectra. Previously undescribed clorobiocin derivatives uncovered in this study include bromobiocin, a variant halogenated with bromine instead of chlorine, hydroxylated clorobiocin, carrying an additional hydroxyl group on its 5-methyl-pyrrole 2-carboxyl moiety, and two other derivatives with modifications on their 3-dimethylallyl 4-hydroxybenzoate moieties. Furthermore, we identified several compounds not previously considered clorobiocin pathway products, which provide new insights into the clorobiocin biosynthetic pathway. By supplementing the medium with different concentrations of potassium bromide, we confirmed that the clorobiocin halogenase can utilize bromine instead of chlorine. The reaction, however, is impeded such that non-halogenated clorobiocin derivatives accumulate. Preliminary assays indicate that the antibacterial activity of bromobioin against
Bacillus subtilis
and efflux-impaired
Escherichia coli
matches that of clorobiocin. Our findings emphasize that yet unexplored compounds can be discovered from established strains and biosynthetic gene clusters by means of metabolomics analysis and highlight the utility of LC-MS
E
-based methods to contribute to unraveling natural product biosynthetic pathways.

IMPORTANCE

The aminocoumarin clorobiocin is a well-known gyrase inhibitor produced by the gram-positive bacterium
Streptomyces roseochromogenes
DS 12.976. To gain a deeper understanding of the biosynthetic pathway of this complex composite of three chemically distinct entities and the product spectrum, we chose a metabolite-centric approach. Employing high-resolution LC-MS
E
analysis, we investigated the pathway products in extracted culture supernatants of the natural producer. Novel pathway products were identified that expand our understanding of three aspects of the biosynthetic pathway, namely the modification of the noviose, transfer and methylation of the pyrrole 2-carboxyl moiety, and halogenation. For the first time, brominated products were detected. Their levels and the levels of non-halogenated products increased in medium supplemented with KBr. Based on the presented data, we propose that the enzyme promiscuity contributes to a broad product spectrum.
Transcriptional responses of brain endothelium to
Plasmodium falciparum
patient-derived isolates
in vitro
Authors: Askonas Caroline , Storm Janet , Camarda Grazia , Craig Alister , Pain Arnab
Published: June 2024

A hallmark of cerebral malaria (CM) is sequestration of
Plasmodium falciparum
-infected erythrocytes (IE) within the brain microvasculature. Binding of IE to endothelium reduces microvascular flow and, combined with an inflammatory response, perturbs endothelial barrier function, resulting in breakdown of the blood-brain barrier (BBB). Cytoadherence leads to activation of the endothelium and alters a range of cell processes affecting signaling pathways, receptor expression, coagulation, and disruption of BBB integrity. Here, we investigated whether CM-derived parasites elicit differential effects on human brain microvascular endothelial cells (HBMECs), as compared to uncomplicated malaria (UM)-derived parasites. Patient-derived IE from UM and CM clinical cases, as well as non-binding skeleton-binding protein 1 knockout parasites, were overlaid onto tumour necrosis factor (TNF)-activated HBMECs. Gene expression analysis of endothelial responses was performed using probe-based assays of a panel of genes involved in inflammation, apoptosis, endothelial barrier function, and prostacyclin synthesis pathway. We observed a significant effect on endothelial transcriptional responses in the presence of IE, yet there was no significant correlation between HBMEC responses and type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and level of IE binding to HBMECs, as we detected the same change in endothelial responses when employing both binding and non-binding parasites. Our results suggest that interaction of IE with endothelial cells in this co-culture model induces some endothelial responses that are independent of clinical origin and independent of the expression of the major variant antigen
Plasmodium falciparum
erythrocyte membrane protein 1 on the IE surface.

IMPORTANCE

Cerebral malaria (CM) is the most prevalent and deadly complication of severe
Plasmodium falciparum
infection. A hallmark of this disease is sequestration of
P. falciparum
-infected erythrocytes (IE) in brain microvasculature that ultimately results in breakdown of the blood-brain barrier. Here, we compared the effect of
P. falciparum
parasites derived from uncomplicated malaria (UM) and CM cases on the relative gene expression of human brain microvascular endothelial cells (HBMECs) for a panel of genes. We observed a significant effect on the endothelial transcriptional response in the presence of IE, yet there is no significant correlation between HBMEC responses and the type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and the level of IE binding to HBMECs. Our results suggest that interaction of IE with endothelial cells induces endothelial responses that are independent of clinical origin and not entirely driven by surface
Plasmodium falciparum
erythrocyte membrane protein 1 expression.
Efficacy of rifapentine and other rifamycins against
Coxiella burnetii in vitro
Authors: Miller Halie K. , Kersh Gilbert J.
Published: June 2024

Since 1999, doxycycline and hydroxychloroquine have been the recommended treatment for chronic Q fever, a life-threatening disease caused by the bacterial pathogen,
Coxiella burnetii
. Despite the duration of its use, the treatment is not ideal due to the lengthy treatment time, high mortality rate, resistant strains, and the potential for contraindicated usage. A literature search was conducted to identify studies that screened large panels of drugs against
C. burnetii
to identify novel targets with potential efficacy against
C. burnetii
. Twelve candidate antimicrobials approved for use in humans by the US Food and Drug Administration were selected and minimum inhibitory concentrations (MICs) were determined against the low virulence strain Nine Mile phase II. Rifabutin and rifaximin were the best performing antibiotics tested with MICs of ≤0.01 µg mL
−1
. Further screening of these top candidates was conducted alongside two drugs from the same class, rifampin, well-characterized
,
and rifapentine, not previously reported against
C. burnetii
. These were screened against virulent strains of
C. burnetii
representing three clinically relevant genotypes. Rifapentine was the most effective in the human monocytic leukemia cell line, THP-1, with a MIC ≤0.01 µg mL
−1
. In the human kidney epithelial cell line, A-498, efficacy of rifapentine, rifampin, and rifabutin varied across
C. burnetii
strains with MICs between ≤0.001 and 0.01 µg mL
−1
. Rifampin, rifabutin, and rifapentine were all bactericidal against
C. burnetii
; however, rifabutin and rifapentine demonstrated impressive bactericidal activity as low as 0.1 µg mL
−1
and should be further explored as alternative Q fever treatments given their efficacy
in vitro
.

IMPORTANCE

This work will help inform investigators and physicians about potential alternative antimicrobial therapies targeting the causative agent of Q fever,
Coxiella burnetii
. Chronic Q fever is difficult to treat, and alternative antimicrobials are needed. This manuscript explores the efficacy of rifamycin antibiotics against virulent strains of
C. burnetii
representing three clinically relevant genotypes
in vitro
. Importantly, this study determines the susceptibility of
C. burnetii
to rifapentine, which has not been previously reported. Evaluation of the bactericidal activity of the rifamycins reveals that rifabutin and rifapentine are bactericidal at low concentrations, which is unusual for antibiotics against
C. burnetii
.
Genomic and phenotypic studies among
Clostridioides difficile
isolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea
Authors: Meléndez-Sánchez D. , Hernández Laura , Ares Miguel , Méndez Tenorio A. , Flores-Luna Lourdes , Torres Javier , Camorlinga-Ponce M.
Published: June 2024

Clostridioides difficile
(
C. difficile
) is widely distributed in the intestinal tract of humans, animals, and in the environment. It is the most common cause of diarrhea associated with the use of antimicrobials in humans and among the most common healthcare-associated infections worldwide. Its pathogenesis is mainly due to the production of toxin A (TcdA), toxin B (TcdB), and a binary toxin (CDT), whose genetic variants may be associated with disease severity. We studied genetic diversity in 39
C
.
difficile
isolates from adults and children attended at two Mexican hospitals, using different gene and genome typing methods and investigated their association with
in vitro
expression of toxins. Whole-genome sequencing in 39 toxigenic
C. difficile
isolates were used for multilocus sequence typing,
tcdA
, and
tcdB
typing sequence type, and phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity in cell-culture assays. Clustering of strains by genome-wide phylogeny matched clade classification, forming different subclusters within each clade. The toxin profile
tcdA+/tcdB+/cdt+
and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which TcdA2 and TcdB2 were more prevalent. Prevalent clades and toxin subtypes in strains from children differed from those in adult strains. Toxin gene expression or cytotoxicity was not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity among
C. difficile
isolates from patients with healthcare-associated diarrhea.

IMPORTANCE

Clostridioides difficile
is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical
C. difficile
isolates. Most isolates presented a
tcdA+/ tcdB+/cdt
+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of
C. difficile
better and find markers for better clinical use
Health consequences of the Urmia Lake crisis: the baseline study protocol
Authors: Sadeghi-Bazargani Homayoun , Saadatkhah Mortaza , Farahbakhsh Mostafa , Sarraf Behrouz Sari , Abbasnezhad Ommolbanin , Mohebbi Iraj , Mohammadi Gholamhassan , EntezarMahdi Rasoul , Pourasghar Faramarz
Published: June 2024

Introduction

Climate change may affect human health due to various mechanisms including overexposure to environmental pollution or dispersed particles. Lake Urmia (LU) drying in recent years has turned into a crisis with particle distribution as its main manifest. It is told that this crisis may affect the health of neighbouring residents. In this paper, we elaborate on a research protocol developed to assess the potential health consequences of LU drying (LUD) by investigating the distribution of physical and mental health conditions/disorders among residents of LU’s surrounding provinces with different exposure levels to LUD outcomes.

Methods and analysis

The target population of this study is the residents of the LU basin from East Azerbaijan and West Azerbaijan provinces of Iran. A total of 803 households and 2783 people are studied in 86 clusters. Cluster sampling is applied. The weighting of the samples is based on a satellite map of the density of suspended particles such that people living in areas with higher risk have a higher chance of selection. Various types of measurements are done in three major groups including self-reported health, clinical interview/examination and paraclinical assays.

Ethics and dissemination

In this project, all procedures are in accordance with the ethical standards of the Ethics Committee of Tabriz University of Medical Sciences. Moreover, an informed consent letter is obtained from all participants included in the study. The results from this study will be disseminated in international journals and implemented in the primary care guidelines and national policy documents on managing the potential health consequences of LUD.
Early provision of clinical information with an ‘opt in’ approach improves patient experience in tonsillectomy referrals
Authors: Philp Nichola , Maqsood Raeesah , Joshyulla-Prasanna Adithya , van der Meer Robert Bauke , Douglas Catriona M , Wood Margaret , Rymaszewski Lech
Published: June 2024

Patients referred by their general practitioner (GP) with a definite diagnosis, for example, recurrent sore throat for consideration of tonsillectomy in adults, may wait for months without receiving any further clinical information from the hospital until their outpatient consultation. Prompt provision of condition-specific information after referral has received little attention despite considerable potential to enhance patients’ understanding, thereby relieving uncertainty and anxiety, and facilitating shared decision-making.

This study aimed to report the experience of patients with recurrent tonsillitis who had been sent a booklet outlining the benefits and risks of tonsillectomy immediately after GP referral.

Greater Glasgow and Clyde Health Board received 218 referrals of patients aged 16–40 to discuss tonsillectomy between January and August 2022. Every patient was sent a 16-page booklet by post and given the choice to opt in for a consultation.

165 (76%) patients opted in, and 53 (24%) did not. Feedback was obtained from 143 patients (66%) from both groups. 99% found the information booklet easy to understand, 97% would recommend it to a friend with recurrent tonsillitis, 93% felt their questions had been answered and 92% believed it helped them to decide whether to proceed with tonsillectomy. Socioeconomic deprivation did not influence the outcome.

In conclusion, most patients found provision of clinical information immediately after vetting of the referral to be beneficial, irrespective of whether they opted in for a consultation. This concept has broad applicability across all specialties, and the principles can be readily adopted and adapted by clinicians and managers in local units.
Evaluating the participation of junior members and patient and healthcare professionals representatives in EULAR task forces: results from an international survey
Authors: Juge Pierre-Antoine , Kragstrup Tue Wenzel , Perez-Garcia Luis Fernando , Frãzao-Mateus Elsa , Makri Souzi , Boyd Peter , Primdahl Jette , Ferreira Ricardo J O , Vliet Vlieland Theodora P M , Ndosi Mwidimi , Kiltz Uta , Landewé Robert , Lauper Kim , de Hooge Manouk
Published: June 2024

Objective

European Alliance of Associations for Rheumatology (EULAR) task forces (TF) requires participation of ≥2 junior members, a health professional in rheumatology (HPR) and two patient research partners for the development of recommendations or points to consider. In this study, participation of these junior and representative members was compared with the one of traditional TF members (convenor, methodologist, fellow and expert TF members).

Methods

An online survey was developed and emailed to previous EULAR TF members. The survey comprised multiple-choice, open-ended and 0–100 rating scale (fully disagree to fully agree) questions.

Results

In total, 77 responded, 48 (62%) women. In total, 46 (60%) had participated as a junior or representative TF member. Most junior/representative members reported they felt unprepared for their first TF (10/14, 71%). Compared with traditional members, junior/representative members expressed a significantly higher level of uncertainty about their roles within the TF (median score 23 (IQR 7.0–52.0) vs 7 (IQR 0.0–21.0)), and junior/representative members felt less engaged by the convenor (54% vs 71%). Primary factors that facilitated interaction within a TF were experience, expertise and preparation (54%), a supportive atmosphere (42%) and a clear role (12%).

Conclusion

Juniors, patients and HPR experience various challenges when participating in a EULAR TF. These challenges differ from and are generally less pronounced than those experienced by traditional TF members. The convenor should introduce the participants to the tasks, emphasise the value of their contributions and how to prepare accordingly for the TF meeting.
Factors Associated with Poor Mental Health in Patients with Axial Spondyloarthritis: Results from the International Map of Axial Spondyloarthritis (IMAS)
Authors: Garrido-Cumbrera Marco , Navarro-Compán Victoria , Poddubnyy Denis , Sommerfleck Fernando , Makri Souzi , Correa-Fernández José , Akerkar Shashank , Lowe Jo , Karam Elie , Bundy Christine
Published: June 2024

Background

This study aims to assess the prevalence of poor mental health in axial spondyloarthritis (axSpA) and its associated factors in a large sample of patients from the International Map of Axial Spondyloarthritis (IMAS) study from around the globe.

Methods

IMAS is a cross-sectional online survey (2017–2022) that includes 5557 unselected patients with axSpA worldwide. Mental health was evaluated by the 12-item General Health Questionnaire (GHQ-12) and the cut-off point for poor mental health was set at 3. Logistic regression analysis was used to evaluate relationships between the investigated factors and poor mental health (GHQ-12≥3) in patients with axSpA (n=4335).

Results

Of 5351 patients, the mean of GHQ-12 was 4.7 and 59.4% were having poor mental health, being 69.9% in South Africa, 63.7% in Latin America, 60.8% in Europe, 54.3% in North America and 51.8% in Asia. Overall, 40.5% and 37.2% of patients experienced anxiety and depression. The factors associated with poor mental health were younger age (OR=0.99), female gender (OR=1.16), being on sick leave or unemployed (OR=1.63), non-physical activity (OR=1.22), smoking (OR=1.20), higher Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] (OR=1.42), functional limitation (OR=1.02) and shorter symptoms duration (OR=0.98).

Conclusions

Globally, 6 in 10 patients with axSpA had poor mental health, with a higher proportion in South Africa and lower in Asia. The factors associated with poor mental health include domains such as younger age, female gender, employment difficulties, harmful habits, disease burden and symptom duration. A holistic management approach to axSpA should encompass both physical and mental health.
Using benthic recruitment densities to forecast fisheries recruitment of American lobster in Atlantic Canada
Authors: White Lydia M. , Sainte-Marie Bernard , Lawton Peter , Rochette Rémy
Published: June 2024

There is limited understanding of the mechanisms underlying the marked spatial and temporal trends in landings of American lobster in Canada since the mid-1980s, and little ability to forecast changes. We built an individual-based model for three Lobster Fishing Areas (LFAs) in Canada that uses the annual density of benthic recruits in nursery grounds to generate an index of exploited biomass 6 to 10 years in the future, using von Bertalanffy growth equations complemented with inter-individual variability in growth, and regional maturity ogives and spawning probabilities to allow exclusion of ovigerous females from the exploitable biomass. We found significant positive relationships between the modelled biomass index and fisheries landings in all three LFAs. Out-of-sample validation in two LFAs (longer time series) using 1-year and 6-year reduced data sets revealed mean annual prediction errors of 11.4% and 11.2%, and 23.7% and 51.7%, respectively. Our findings strongly suggest benthic recruitment indices could help make strategic decisions concerning lobster fishing activities, and they argue for the continued and expanded monitoring of lobster benthic recruitment in Canada.
LHCb potential to discover long-lived new physics particles with lifetimes above 100 ps
Authors: Gorkavenko Volodymyr , Jashal Brij Kishor , Kholoimov Valerii , Kyselov Yehor , Mendoza Diego , Ovchynnikov Maksym , Oyanguren Arantza , Svintozelskyi Volodymyr , Zhuo Jiahui
Published: June 2024

For years, it has been believed that the main LHC detectors can play only a limited role of a lifetime frontier experiment exploring the parameter space of long-lived particles (LLPs)—hypothetical particles with tiny couplings to the Standard Model. This paper demonstrates that the LHCb experiment may become a powerful lifetime frontier experiment if it uses the new algorithm reconstructing tracks that do not allow hits in the LHCb vertex tracker. In particular, for many LLP scenarios, LHCb may be as sensitive as the proposed experiments beyond the main LHC detectors for various LLP models, including heavy neutral leptons, dark scalars, dark photons, and axion-like particles.
On the study of interaction phenomena to the (2+1)-dimensional Korteweg–de Vries–Sawada–Kotera–Ramani equation
Authors: Younas Usman , Sulaiman Tukur A. , Ismael Hajar F. , Murad Muhammad Amin S.
Published: June 2024

The (2+1)-dimensional Korteweg–de Vries–Sawada–Kotera–Ramani equation which consists of the KdV equation and the SK equation is the subject of investigation in this study. The studied equation has rich physical meaning in nonlinear waves. The KdV- type equations hold great importance as a prototypical representation of an infinite-dimensional system that is completely integrable and exactly solvable in the context of nonlinearity. The KdV equation is utilized to describe shallow water waves in a density-stratified ocean, which exhibit weak and nonlinear interactions with long internal waves. The Hirota bilinear method has been used with the support of various test functions. For the purpose of analyzing the governing equation, numerous solutions are secured, including breathers and two-wave solutions. Breather waves refer to solitary waves that exhibit both partial localization and periodic structure in either space or time. Breathers serve crucial functions in nonlinear physics and have been observed in various physical domains, including optics, hydrodynamics, and quantized superfluidity. To visually represent the results, a range of graphs with unique shapes are generated in accordance with the specified parameter values. The computational intricacies and outcomes underscore the technique’s efficacy, simplicity and transparency, demonstrating its suitability for numerous types of static and dynamic nonlinear equations pertaining to evolutionary phenomena in computational physics, in addition to other research and practical domains. The physical properties of solutions and the collision-related components of various nonlinear physical processes are illustrated with these results.
DFT and TDDFT study of Al(III), Ga(III), In(III) porphyrazinates and their perhalogenated derivatives
Authors: Vyalkin Dmitriy A. , Eroshin Alexey V. , Otlyotov Arseniy A. , Minenkov Yury , Finogenov Daniil N. , Zhabanov Yuriy A. , Stuzhin Pavel A.
Published: June 2024

The effect of perhalogenation (F, Cl) of porphyrazine macrocycle on the molecular structure, electronic and spectral properties of AlIII, GaIII and InIII complexes bearing axial pentafluorophenoxy (C6F5O) group was investigated by DFT and TDDFT methods. Interactions between the axial pentafluorophenoxy group and porphyrazine core were carried out using the Symmetry-Adapted Perturbation Theory (SAPT0) method. According to the calculation results, the nature of the metal atom and peripheral halogenation slightly affect the geometry parameters. Analysis of the simulated spectra showed a bathochromic shift of the Q-band for perchlorinated complexes which correlates with narrowing of the HOMO-LUMO gap.
Imino(dialkylamino)isoindolines: Structures and dynamic behavior
Authors: Bore Joan , Chen Wei-Yuan , Nemykin Victor N. , Ziegler Christopher J.
Published: June 2024

In 1956, Elvidge and coworkers investigated the synthesis of a series of isoindoline compounds derived from phthalonitrile. They produced a series of secondary amine-modified isoindolines known as the imino(dialkylamino)isoindolines, and in this report, we revisit this chemistry. In addition to confirming the previously observed reactivity, we structurally characterized three examples and observed a double bond character between the isoindoline carbon atom and the secondary nitrogen atom position. This results in a rotational barrier about this bond, which we observed by NMR spectroscopy and probed using computational methods. The barriers are comparable to those seen in bis-substituted amides.