bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA stability is regulated by both RNA polyadenylation and ATP levels, linking RNA and energy metabolisms in
Escherichia coli
Authors: Roux Charlotte , Ramos-Hue Marvin , Audonnet Marjorie , Duviau Marie-Pierre , Nouaille Sébastien , Carpousis Agamemnon J. , Laguerre Sandrine , Hajnsdorf Eliane , Cocaign-Bousquet Muriel , Girbal Laurence
Published: November 2024

The post-transcriptional process of RNA polyadenylation sits at the crossroads of energy metabolism and RNA metabolism. RNA polyadenylation is catalyzed by poly(A) polymerases, which use ATP as a substrate to add adenine to the 3′ end of RNAs, which can alter their stability. In
Escherichia coli,
RNA polyadenylation mediated by the major poly(A) polymerase was previously shown to facilitate degradation of individual RNAs. In this study, we performed the first genome-wide study of RNA stability in the absence of PAP I. Inactivation of the
pcnB
gene coding for PAP I led to the stabilization of more than a thousand of
E. coli
RNAs in the form of full-length functional molecules or non-functional fragments. The absence of PAP I altered the energy metabolism, with an almost 20% reduction in ATP levels. To better understand how RNA and energy metabolisms are interconnected, we investigated the role of ATP levels in regulating RNA stability. When we lowered intracellular ATP levels below 0.5 mM, many RNAs were stabilized, demonstrating the causal link between ATP levels and RNA stability for the first time in
E. coli
. Above this concentration, changes in ATP levels had no impact on RNA stability. We also demonstrated that some RNAs were stabilized when PAP I was inactivated by low ATP availability. These results clearly demonstrate that PAP I mediates an energy-dependent RNA stabilization, which may contribute to cell energy homeostasis under energy-limited conditions.

IMPORTANCE

Poly(A) polymerases are prime targets for understanding the interactions between RNA polyadenylation, RNA stability, and cellular energy. These enzymes catalyze the process of RNA polyadenylation, which involves ATP hydrolysis and addition of poly(A) tails to the 3′ end of RNAs. 3′ end poly(A) extensions potentially facilitate RNA degradation in bacteria. In this study, we inactivated the
pcnB
gene encoding PAP I, the major poly(A) polymerase in
E. coli
, and investigated the effects on RNA stability and energy levels. Our results show for the first time in
E. coli
a genome-wide RNA stabilization in the absence of PAP I associated with a decrease in ATP levels. We provide the first evidence in
E. coli
of a link between ATP levels and RNA stabilization and demonstrate that this is mediated in some cases by PAP I. PAP I-mediated RNA stabilization at low ATP levels could be a means of energy conservation under energy-limited conditions.
Coatomer complex I is required for the transport of SARS-CoV-2 progeny virions from the endoplasmic reticulum-Golgi intermediate compartment
Authors: Hirabayashi Ai , Muramoto Yukiko , Takenaga Toru , Tsunoda Yugo , Wakazaki Mayumi , Sato Mayuko , Fujita-Fujiharu Yoko , Nomura Norimichi , Yamauchi Koji , Onishi Chiho , Nakano Masahiro , Toyooka Kiminori , Noda Takeshi
Published: November 2024

SARS-CoV-2 undergoes budding within the lumen of the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), and the progeny virions are delivered to the cell surface via vesicular transport. However, the molecular mechanisms remain poorly understood. Using three-dimensional electron microscopic analysis, such as array tomography and electron tomography, we found that virion-transporting vesicles possessed protein coats on their membrane and demonstrated that the protein coat was coatomer complex I (COPI). During the later stages of SARS-CoV-2 infection, we observed a notable alteration in the distribution of COPI and ERGIC throughout the cytoplasm, suggesting their potential involvement in virus replication. Depletion of COPB2, a key component of COPI, led to the confinement of SARS-CoV-2 progeny virions within the ERGIC at the perinuclear region. While the expression levels of viral proteins within cells were comparable, this depletion significantly reduced the efficiency of virion release, leading to the significant reduction of viral replication. Hence, our findings suggest COPI as a critical player in facilitating the transport of SARS-CoV-2 progeny virions from the ERGIC. Thus, COPI could be a promising target for the development of antivirals against SARS-CoV-2.

IMPORTANCE

SARS-CoV-2 virions are synthesized within the ERGIC and are transported to the cell surface via vesicular transport for release. However, the precise mechanisms remain unclear. Through various electron microscopic techniques, we identified the presence of COPI on virion-transporting vesicles. Alterations in the distribution of COPI and ERGIC in SARS-CoV-2 infected cells are evident, suggesting their involvement in virus replication. When COPB2, a component of COPI, is depleted, progeny virions become trapped within the ERGIC, leading to a reduction in the efficiency of virion release. These findings highlight COPI’s crucial role in mediating SARS-CoV-2 vesicular transport from the ERGIC and suggest it as a potential antiviral target.
A whole-genome metagenomic approach to explore the gut microbiome of inflammatory bowel disease patients in Bangladesh
Authors: Siam Md. Hasanul Banna , Mondol Spencer Mark , Shakil Md. Shahriar Kabir , Islam Md. Rafiul , Islam Israt , Saha Otun , Amiruzzaman  , Datta Raj , Ahmed Toufiq , Gomes Donald James , Rahaman Md. Mizanur
Published: November 2024

In this study, we analyzed the gut microbiome of four Bangladeshi
inflammatory bowel disease patients, identifying
Segatella
copri
as the most prevalent, followed by
Phocaeicola
vulgatus
,
Bacteroides xylanisolvens
,
Bacteroides fragilis
,
Bacteroides
thetaiotaomicron
,
Bacteroides ovatus
,
Bacteroides uniformis
,
Phocaeicola
dorei
, and many other species. Firmicutes, Proteobacteria,
Bacteroidetes, and Actinobacteria were the major phyla detected.
Site-selective modifications by lipid A phosphoethanolamine transferases linked to colistin resistance and bacterial fitness
Authors: Schumann Anna , Gaballa Ahmed , Yang Hyojik , Yu Di , Ernst Robert K. , Wiedmann Martin
Published: November 2024

Genes encoding lipid A modifying phosphoethanolamine transferases (PETs) are genetically diverse and can confer resistance to colistin and antimicrobial peptides. To better understand the functional diversity of PETs, we characterized three canonical mobile colistin resistance (
mcr
) alleles (
mcr-1
,
-3
,
-9
), one intrinsic
pet
(
eptA
), and two
mcr
-like genes (
petB
,
petC
) in
Escherichia coli
. Using an isogenic expression system, we show that
mcr-1
and
mcr-3
confer similar phenotypes of decreased colistin susceptibility with low fitness costs.
mcr-9
, which is phylogenetically closely related to
mcr-3
, and
eptA
only provide fitness advantages in the presence of sub-inhibitory concentrations of colistin and significantly reduce fitness in media without colistin. PET-B and PET-C were phenotypically distinct from bonafide PETs; neither impacted colistin susceptibility nor caused considerable fitness cost. Strikingly, we found for the first time that different PETs selectively modify different phosphates of lipid A; MCR-1, MCR-3, and PET-C selectively modify the 4′-phosphate, whereas MCR-9 and EptA modify the 1-phosphate. However, 4′-phosphate modifications facilitated by MCR-1 and -3 are associated with lowered colistin susceptibility and low toxicity. Our results suggest that PETs have a wide phenotypic diversity and that increased colistin resistance is associated with specific lipid A modification patterns that have been largely unexplored thus far.

IMPORTANCE

Rising levels of resistance to increasing numbers of antimicrobials have led to the revival of last resort antibiotic colistin. Unfortunately, resistance to colistin is also spreading in the form of
mcr
genes, making it essential to (i) improve the identification of resistant bacteria to allow clinicians to prescribe effective drug regimens and (ii) develop new combination therapies effective at targeting resistant bacteria. Our results demonstrate that PETs, including MCR variants, are site-selective in
Escherichia coli
and that site-selectivity correlates with the level of susceptibility and fitness costs conferred by certain PETs. Site selectivity associated with a given PET may not only help predict colistin resistance phenotypes but may also provide an avenue to (i) improve drug regimens and (ii) develop new combination therapies to better combat colistin-resistant bacteria.
Direct prion neuroinvasion following inhalation into the nasal cavity
Authors: Kincaid Anthony E. , Clouse Melissa D. , Magrum Shawn M. , Bartz Jason C.
Published: November 2024

Inhalation of prions into the nasal cavity is an efficient route of infection. Following inhalation of infectious prions, animals develop disease with a similar incubation period compared with per os exposure, but with greater efficiency. To identify the reason for this increased efficiency, we identified neural structures that uniquely innervate the nasal cavity and neural structures known to mediate neuroinvasion following oral infection and used immunohistochemistry to determine the temporal and spatial accumulation of prions from hamster tissue sections containing cell bodies and axons at 2-week intervals following prion exposure. Prions were identified in the trigeminal ganglion, the spinal trigeminal tract in the brainstem, the intermediolateral cell column of the thoracic spinal cord, and the dorsal motor nucleus of the vagus/solitary nucleus complex months prior to detection of prions in the olfactory bulb or superior cervical ganglion. These results indicate that the trigeminal nerve, but not the olfactory nerve or sympathetic nerves, are involved in neuroinvasion following inhalation of prions into the nasal cavity. The detection of prions in the intermediolateral cell column of the thoracic spinal cord and dorsal motor nucleus of the vagus nerve 14 weeks following inhalation is consistent with inoculum crossing the alimentary wall and infecting the enteric nervous system via this route of infection. Neuroinvasion via the trigeminal nerve, in combination with entry into the central nervous system via autonomic innervation of the enteric nervous system, may contribute to increased efficiency of nasal cavity exposure to prions compared with per os exposure in hamsters.

IMPORTANCE

Inhalation of prions into the nasal cavity is thought to be a route of infection in naturally acquired prion diseases. Experimental studies indicate that inhalation of prions is up to two orders of magnitude more efficient compared with ingestion. The mechanisms underlying this observation are poorly understood. We found a previously unreported direct route of neuroinvasion from the nasal cavity to the nervous system. Importantly, the peripheral ganglia involved may be a useful tissue to sample for prion diagnostics. Overall, identification of a new route of neuroinvasion following prion infection may provide an anatomical basis to explain the increased efficiency of infection following prion inhalation.
Antimicrobial resistance, virulence gene profiles, and molecular epidemiology of enterococcal isolates from patients with urinary tract infections in Shanghai, China
Authors: Wu Weiyi , Xiao Shuzhen , Han Lizhong , Wu Qiong
Published: November 2024

Urinary tract infections (UTIs) are among the most prevalent infectious diseases, yet there is still limited understanding of the epidemiology of Enterococcal strains isolated from UTI patients in Shanghai. This study aims to elucidate the antimicrobial resistance profiles, virulence gene carriage, and molecular epidemiology of selected Enterococcal strains from UTI patients in Shanghai. A cohort of 80
Enterococcus faecalis
and 40
Enterococcus faecium
clinical isolates were randomly selected from UTI patients from October 2022 to March 2023. No vancomycin-resistant strains were identified based on minimum inhibitory concentration (MIC) testing. However, five strains of linezolid-resistant
E. faecalis
were identified, all of which were confirmed to be
optrA
-positive through whole-genome sequencing (WGS), with ST300 being reported as the first instance of this ST type in China. Polymerase chain reaction (PCR) assays were employed to ascertain the presence of virulence genes and multi-locus sequence type (MLST). In
E. faecalis
, the most common virulence genes were
asal
(75%),
gelE
(65%),
esp
(52.5%), and
cylA
(47.5%). In contrast,
E. faecium
primarily exhibited
esp
(65%) and
hyl
(12.5%). Among the
E. faecalis
strains, 21 distinct MLST types were identified, with ST16 and ST179 prevailing. Conversely,
E. faecium
exhibited only five MLST types, with ST78 being predominant. The prevalence of
E. faecalis
CC16 and
E. faecium
CC17 further complicates the treatment landscape for Enterococcal UTIs.

IMPORTANCE

This study highlighted the critical need to understand Enterococcal strains causing UTIs in Shanghai, given their high prevalence. By assessing antimicrobial resistance profiles, virulence gene presence, and molecular epidemiology, the research offered valuable insights into the local epidemiology of
Enterococcus faecalis
and
Enterococcus. faecium
. Identifying linezolid-resistant strains, all of which carry the
optrA
gene, including the first report of ST300 in China and recognizing dominant MLST types, such as ST16 and ST179 for
E. faecalis
and ST78 for
E. faecium
, are vital for guiding treatment and addressing the challenges these infections present. The data emphasize the need for ongoing surveillance and customized therapeutic approaches to combat emerging resistance and virulence factors in Enterococcal UTIs.
ITS amplicon sequencing revealed that rare taxa of tea rhizosphere fungi are closely related to the environment and provide feedback on tea tree diseases
Authors: Zhao Yuanqi , Ran Weiwei , Xu Wenming , Song Yuehua
Published: November 2024

The rhizospheres of plants and soil microorganisms are intricately interconnected. Tea trees are cultivated extensively on the karst plateau of Guizhou Province, China; however, the understanding of the interactions among fungal communities, community taxa, and diseases impacting tea tree in the soil rhizosphere is limited. Our aim is to offer insights for the advancement of modern agriculture in ecologically fragile karst tea gardens, as well as microbiomics concepts for green and sustainable environmental development. This study utilized the internal transcribed spacer high-throughput sequencing technology to explore the symbiotic relationship between rhizosphere fungi and plant disease feedback in multiple tea estates across the Guizhou Plateau. The ecological preferences and environmental thresholds of fungi were investigated via environmental variables. Furthermore, a correlation was established between different taxa and individual soil functions. Research has indicated that tea leaf blight disrupts symbiotic connections among fungal groups. For various taxa, we found that numerous taxa consistently maintained core positions within the community, whereas rare taxa were able to stabilize due to a high proportion of positive effects. Additionally, abundant taxa presented a wider range of environmental feedback, whereas the rare taxon diversity presented a stronger positive association with the soil Z score. This study contributes to our understanding of the importance of rare taxa in plant rhizosphere soil processes. Emphasis should be placed on the role of rare taxa in pest and disease control within green agriculture while also strengthening systematic development and biogeographical research related to rare taxa in this region.

IMPORTANCE

In this study, based on internal transcribed spacer high-throughput sequencing, fungal communities in the rhizosphere soil of tea trees and their interactions with the environment in karst areas were reported, and the symbiotic relationships of different fungal taxa and their feedback to the environment were described in detail by using the knowledge of microbial ecology. On this basis, it was found that tea tree diseases affect the symbiotic relationships of fungal taxa. At the same time, we found that rare taxa have stronger cooperative relationships in response to environmental changes and explored their participation in soil processes based on fungal trait sets. This study will provide basic data for the development of modern agriculture in tea gardens and theoretical basis for the sustainable prevention and control of tea tree diseases.
Multiomics comparative analysis of feces AMRGs of Duroc pigs and Tibetan and the effect of fecal microbiota transplantation on AMRGs upon antibiotic exposure
Authors: Wang Tao , Luo Yuheng , Kong Xiangfeng , Fang Ling , Zhu Liping , Yu Bing , Zheng Ping , Huang Zhiqing , Mao Xiangbing , Jie Yu , Luo Junqiu , Yan Hui , He Jun
Published: November 2024

Fecal matter is recognized as both a reservoir and a transmission source for various antimicrobial resistance genes (AMRGs). However, the transcriptional activity of AMRGs in swine feces is not well understood. In addition, the effect of fecal microbiota transplantation (FMT) on the excretion of AMRGs has rarely been reported. Our study explored the diversity, abundance, transcriptional activity, and bacterial hosts of AMRGs in Tibetan and Duroc pig feces using metagenomic and metatranscriptomic sequencing technologies. We discovered a significantly higher genomic abundance of AMRGs in the feces of Duroc pigs compared to Tibetan pigs (
P <
0.001), although the transcript levels did not show a significant difference. The results showed that the core composition of AMRGs in pig feces varied considerably, with the most transcriptionally active AMRGs being
oqxB
,
tetQ
,
Bla1
,
dfrA1
, and
amrB
. Furthermore, the
Firmicutes
phylum is the main host of AMRGs. By transplanting fecal flora from Tibetan and Duroc pigs into the intestines of Duroc Landrace Yorkshire (DLY) piglets after acute antibiotic exposure, we found that only Tibetan pig fecal flora significantly reduced AMRGs in the feces of DLY piglets (
P <
0.05). The effectiveness of Tibetan pig fecal microorganisms in removing AMRGs from DLY pig feces was mainly influenced by microbial communities, especially the
Bacteroidota
phylum. These findings offer valuable insights for the prevention and control of AMRG pollution.

IMPORTANCE

To the best of our knowledge, this study represents the first comprehensive analysis of antimicrobial resistance gene (AMRGs) expression in the fecal microbiota of Tibetan and Duroc pigs, employing an integrated metagenomic and metatranscriptomic approach. Our findings indicate a higher risk of AMRGs transmission in the feces of Duroc pigs compared to Tibetan pigs. Given the escalating antimicrobial resistance crisis, novel therapeutic interventions are imperative to mitigate gut colonization by pathogens and AMRGs. In this regard, we investigated the impact of fecal microbiota from Tibetan and Duroc pig sources on AMRGs excretion in Duroc Landrace Yorkshire (DLY) piglets’ feces following acute antibiotic exposure. Remarkably, only fecal microbiota sourced from Tibetan pigs exhibited a reduction in AMRGs excretion in DLY piglets’ feces. This underscores the significance of evaluating the presence of AMRGs within donor fecal microbiota for effective AMRGs decolonization strategies.
The prevalence of
optrA
-carrying
Enterococci
in the vaginal micro-ecology of pregnant women in late pregnancy
Authors: Xie Yanjun , Xu Fangyi , Dong Huali , Mao Jianfeng , Zhang Chuanling
Published: November 2024

The colonization of
Enterococcus
in the female vagina leads to neonatal and pediatric enterococcal septicemia. Linezolid (LZD) is a kind of mainstream drug for treating multidrug-resistant Gram-positive infections.
OptrA
is the main LZD-resistance gene at
Enterococci
in human isolates. It is essential to explore the prevalence of
optrA
-carrying
Enterococcus
in vaginal secretions of late pregnant women and the drug resistance of
optrA
. From May to June 2023, this study recruited 340 volunteers in late pregnancy (35–40 weeks of pregnancy) to provide non-repetitive vaginal discharge samples. Luria-Bertani broth and florfenicol (10 µg/mL) were used to enrich bacteria.
Enterococci
was identified through time-of-flight mass spectrometry. Additionally, antimicrobial susceptibility, polymerase chain reaction, and next-generation sequencing assays were applied to this study. Fifty-four
optrA
-carrying
Enterococcus
strains were obtained, the proportion of the whole vagina of late pregnant women was 15.88% (54 out of 340), and
Enterococcus faecalis
account the highest proportion. All
optrA
-carrying
Enterococcus
were resistant to at least three drugs. Tetracycline, chloramphenicol, erythromycin, and LZD have higher bacterial resistance rates. Genetic environment analysis revealed that IS
1216E
,
fexA
, and
erm
(A) may synergistically exert multidrug resistance with
optrA
. It is necessary to strengthen the surveillance of
optrA
-carrying
Enterococcus
in pregnant women. This study provides scientific support for controlling hospital infections and managing antibiotic-resistant bacteria, and provides a scientific basis for rational clinical medication.

IMPORTANCE

The disruption of cervicovaginal microbiota homeostasis is considered a key factor in causing imbalance in the microenvironment, leading to inflammation, transmission of infections, and illness.
Enterococcus
is considered a major cause of healthcare-related infections globally. It has resistance to multiple antimicrobial drugs, which pose significant challenges for clinical treatment. Therefore, it is crucial to assess the prevalence of
optrA
-carrying
Enterococcus
in vaginal secretions of late pregnant women and the drug resistance of
optrA
. This study detected 15.88% of
optrA
-carried
Enterococci
in 340 pregnant women. Furthermore, we found that
optrA
-carrying
Enterococcus
strains are highly resistant to tetracycline, chloramphenicol, erythromycin, and Linezolid. Additionally, genetic environment analysis revealed that
IS1216E
,
fexA
, and
erm
(A) may synergistically exert multidrug resistance with
optrA
. This study provides scientific support for controlling hospital infections and managing antibiotic-resistant bacteria and provides a scientific basis for rational clinical medication.
New pneumococcal serotype 20C is a WciG O-acetyltransferase deficient variant of canonical serotype 20B
Authors: Yu Jigui , Ravenscroft Neil , Davey Peter , Liyanage Roshan , Lorenz Oliver , Kuttel Michelle M. , Lo Stephanie W. , Ganaie Feroze A. , Nahm Moon H.
Published: November 2024

The polysaccharide (PS) capsule of
Streptococcus pneumoniae
(pneumococcus) is the immunodominant surface structure that shields the bacteria from the host immune system. Since the capsule is the primary target of currently available pneumococcal vaccines, anti-capsular antibodies are highly protective but serotype-specific. Pneumococci may evade host or vaccine-induced immunity as a result of variation in capsule structure mediated via multiple mechanisms, such as the loss or gain of O-acetylation. Previous biochemical studies of serogroup 20 isolates have identified two subtypes—20A and 20B, whose capsule PS differs in the WhaF-mediated glucose side chain. Herein, we characterize a newly discovered capsule type, 20C, that differs from serotype 20B via the inactivation of capsule O-acetyltransferase gene,
wciG
. Structural analysis demonstrated that 20C and 20B share an identical repeat unit [→3)-α-D-Glc
p
NAc-[β-D-Gal
f
-(1→4)][α-D-Glc
p
-(1→6)]-(1→P→6)-α-D-Glc
p
-(1→6)- β-D-Glc
p
-(1→3)-β-D-Gal
f
5,6Ac
2
-(1→3)-β-D-Glc
p
-(1→], except for the absence of WciG-mediated O
-
acetyl group at terminal galactofuranose (β-D-Gal
f
). We confirmed that deletion of the
wciG
gene in a 20B strain resulted in the expression of the 20C capsule. Serotype 20C is serologically indistinguishable from the canonical 20A and 20B using conventional serotyping antibodies, but serogroup 20 subtypes can be distinguished by sequencing of
cps
genes—
whaF
,
wciG
, and
wcjE
. While genetic screening suggests 20C to be globally less prevalent, a new variant was identified which appears to have both
wciG
and
whaF
genes inactive, potentially indicating it to be a new serotype. Consequently, genome-based serotyping/bioinformatic tools must scrutinize all
cps
genes for mutations that might inactivate/modify
cps
-encoded enzymes, ensuring effective tracking of emerging capsule variants in response to ongoing vaccination efforts.

IMPORTANCE

Streptococcus pneumoniae
(pneumococcus) is a significant human pathogen known for producing a wide array of antigenically and structurally diverse capsule types, a fact that poses a serious challenge to the effectiveness of vaccines targeting pneumococcal capsule polysaccharide (PS). Herein, we provide a comprehensive analysis-genetic, antigenic, and biochemical of a newly identified capsule type, 20C, which differs from the canonical serotype 20B due to the inactivation of the capsule O-acetyltransferase gene,
wciG
. Our findings highlight how pneumococci can alter their capsule PS structure and immunological characteristics through minor genetic modifications. Since the appearance of new capsule types can directly affect pneumococcal conjugate vaccine (PCV) implementation, a deeper understanding of capsule PS at the genetic, immunological, and biochemical levels is critical for the development of future diagnostic tools and vaccines.
Modulation of Azithromycin Activity against Single-Species and Binary Biofilms of Staphylococcus aureus and Kytococcus schroeteri by Norepinephrine
Authors: Diuvenji E. V. , Soloviev I. D. , Sukhacheva M. V. , Nevolina E. D. , Ovcharova M. A. , Loginova N. A. , Mosolova A. M. , Mart’yanov S. V. , Plakunov V. K. , Gannesen A. V.
Published: November 2024

The effect of norepinephrine as a compound modulating the activity of the antibiotic azithromycin on single-species and binary biofilms of members of the human microbiota, Staphylococcus aureus and Kytococcus schroeteri, was studied in various model systems. At the concentration of 3.55 µM, the hormone was shown to be able, depending on the cultivation system and incubation time, of both enhancing and weakening the effects of azithromycin at subinhibitory concentrations (0.001 and 4 µg/mL). In the case of rapidly formed biofilms, norepinephrine weakened the inhibitory effect of the antibiotic, while in the presence of the full stage of adhesion the hormone, on the contrary, enhanced the inhibitory effect. Interaction between two microorganisms in the community was no less important, since the presence of K. schroeteri in the community changed the effect of azithromycin (4 μg/mL) in combination with norepinephrine on S. aureus. It was shown that azithromycin and norepinephrine, as well as their combinations, were able to change the expression of the genes coding resistance not only to macrolides (increased expression of the mrx gene by a combination of 4 μg/mL azithromycin and 3.55 μM norepinephrine), but also to fluoroquinolones (decreased expression of the arlR gene and increased one of mdtK).
Herpetic encephalitis with autoimmune recurrence following cerebral aneurysm clipping
Authors: Moniz Dionísio Joana , Santos Mariana , Seromenho-Santos Alexandra , Reizinho Carla
Published: November 2024

A man in his late 60s with well-controlled HIV underwent an uneventful surgical clipping of an unruptured intracranial aneurism. Postoperatively, he developed fever, seizures and an altered mental status. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, high protein count and a positive herpes simplex virus (HSV)-2 PCR. Acyclovir was started. Brain MRI showed right hemisphere T2/FLAIR-weighted anterior temporal cortical and subcortical hyperintensities. After 2 months, he developed psychosis, an upper limb tremor and pyramidal tract dysfunction. A new brain MRI revealed a new right frontal white matter lesion, extending to the corpus callosum. Anti-N-methyl-D-aspartate receptor (NMDAR) antibodies were positive in CSF, while there was no evidence of active HSV infection. Methylprednisolone and IVIg were started, and a significant clinical improvement was achieved.

If an unknown inflammatory process occurs after surgery, herpetic encephalitis should be considered, and treatment should be initiated precociously. Since herpetic encephalitis can trigger an anti-NMDAR encephalitis, this autoimmune complication must be considered.
Medial sural artery perforator flap following orbital exenteration
Authors: ALNafisee Daniah , Cave Taylor , Chang Brent A
Published: November 2024

An extended orbital exenteration defect in a male in his mid-80s was successfully reconstructed with a medial sural artery perforator flap. To our knowledge, this flap has not been described in the literature for such defects until now. While it may require meticulous intramuscular perforator dissection, it provides several advantages; it is thin, pliable, has a long pedicle of large calibre facilitating microanastomosis and provides adequate coverage where the amount of chimeric muscle can easily be tailored to the defect’s surface area and volume. In addition, its robust vascular supply can withstand volume changes post radiation therapy. Two years after surgery, the patient has healed well with an excellent functional outcome.
Focal dermal hypoplasia (Goltz syndrome) with concurrent growth hormone deficiency and response to therapy
Authors: Divyasri Namburi , Javid Juveria , Kunnuru Sumana , Anne Beatrice
Published: November 2024

A toddler presented with failure to thrive and dysmorphic features since birth. On examination, she was found to have a cleft lip, syndactyly, hypopigmented patchy skin lesions and patchy alopecia. The baseline haematological evaluation was normal. Given the syndromic features, whole exome sequencing was performed and revealed a heterozygous pathogenic variant in exon 8 of the PORCN gene, associated with focal dermal hypoplasia. Despite adequate nutrition, no significant improvement was observed in height and weight. Further evaluation revealed growth hormone deficiency and the patient was initiated on growth hormone therapy. She displayed a good response to treatment on follow-up visits. Goltz syndrome is a rare form of ectodermal dysplasia and its association with growth hormone deficiency is exceedingly rare. Here, we report a case of focal dermal hypoplasia associated with growth hormone deficiency and its subsequent response to therapy.
Remission of longstanding metastatic paraganglioma in a patient after use of zoledronic acid
Authors: Schutte Justin , Mardani Mahta , Weilbaecher Katherine , Prasad Vikas , Chrisinger John S A , Trikalinos Nikolaos A
Published: November 2024

A patient with a long history of bone predominant, metastatic paraganglioma who had multiple episodes of progressive disease despite prior treatments demonstrated a remarkable disease response to zoledronic acid. After 1 year of treatment, there was a complete resolution of lymphadenopathy and disappearance of all somatostatin receptor avid lesions by positron emission tomography-CT and radiopharmaceutical Gallium Ga 68 Dotatate. Stability of disease was further demonstrated by CT over several years. The patient continues on surveillance.
The effects of literacy on health in Gypsies, Roma and Travellers (GRT): a systematic review and narrative synthesis
Authors: Dunn Montgomery , Turner-Moss Eleanor J C , Carpenter Beverley , Speed Ewen , Dixon Kathryn Charlotte , Blumenfeld Tanya
Published: November 2024

Introduction

Gypsies, Roma and Travellers (GRT) frequently experience poorer health outcomes than the general population and represent the most socially and economically disadvantaged individuals in many countries. In general, GRT in OECD (Organisation for Economic Co-operation and Development) countries have lower rates of literacy than the general population. Although ‘health literacy’ has been examined before, the link between low functional literacy and its effects on health has not yet been explored.

Methods

Searches were conducted on five large English-language databases for research papers since 2008. Grey literature was included as the number of eligible papers was small. This was complimented by citation ‘chaining’. Study findings of qualitative papers were extracted, codes were devised and then analysed thematically. A narrative synthesis was reported, supplemented by the quantitative findings.

Results

15 studies (and two substudies) were analysed. Four strongly overlapping themes were developed: (1) The context of culturally inadequate healthcare systems, (2) psychological impact and disempowerment, (3) intersectional, contextual factors and the unique needs of GRT and (4) considerations for health information resources for GRT patients with low literacy.

Conclusion

Although low literacy in GRT groups is a well-recognised issue, this is the first systematic review to analyse the link between low literacy and its effects on health outcomes for GRT. The wide range of socioeconomic and cultural factors present in GRT communities, combined with low literacy, act synergistically to worsen the physical and mental health of GRT groups in different ways than that seen in members of the general population with similar low literacy levels. National intervention is required to improve the literacy of GRT children and adults. There is a clear need to develop policies and processes that facilitate a better understanding of literacy levels and how they interact with other social determinants of GRT health among healthcare professionals.

Registration number

CRD42023468449.
Understanding the demographic and socioeconomic determinants of morbidity in Eastern Uganda: a retrospective analysis of the Iganga-Mayuge health and demographic surveillance data
Authors: Cygu Steve Bicko , Nabukeera Betty , English Lindsey , Babirye Shakira , Gyezaho Collins , Ng'etich Maureen , Ochola Michael , Amadi David , Odero Henry Owoko , Banturaki Grace , Kadengye Damazo Twebaze , Kiragga Agnes , Kajungu Dan
Published: November 2024

Introduction

Understanding the determinants of disease burden is imperative in enhancing population health outcomes. This study uses data from the Iganga-Mayuge Health and Demographic Surveillance Site, to understand demographic and socioeconomic factors influencing morbidity.

Methods

We analysed secondary data from 2018 to 2023. We employed graphs and tables to present morbidity patterns across different sociodemographic factors and applied mixed-effects multinomial multivariate logistic regression model to understand the correlates of morbidity.

Results

The findings reveal a predominant prevalence of malaria, lower respiratory tract infections, coryza, gastric acid-related and urinary tract infections, collectively constituting 83% of diagnosed diseases. Noteworthy demographic variations, particularly gender and age, significantly impact disease distribution, revealing higher diagnosis rates among females. Additionally, socioeconomic factors, including education and wealth status, contribute to discernible differences in disease burden.

Conclusion

This research provides crucial insights into the implications of demographic and socioeconomic factors on disease burden in Uganda. The results contribute to evidence-based policy-making, highlighting the necessity for targeted interventions addressing specific health challenges encountered by diverse populations. The study advocates for continuous assessment of the epidemiological landscape to inform more tailored and effective health strategies, ultimately enhancing resilience in disease control efforts.
Association of child weight and adverse outcomes following antibiotic prescriptions in children: a national data study in Wales, UK
Authors: Opatola Ayodele Vincent , Seaborne Mike J , Kennedy Jonathan , Hughes Dyfrig , Laing Hamish , Owen Rhiannon K , Tuthill David , Bracchi Robert , Brophy Sinead
Published: November 2024

Objective

To examine if the weight of a child determines adverse events following oral antibiotics prescription.

Design

Population respective cohort using linked general practice (GP), hospital data and linkage with the Welsh Demographic Service for demographic information. Data linkage was performed using Wales health data, extracted from the SAIL (Secure Anonymised Information Linkage) databank.

Inclusion

Children (0–12 years) prescribed oral antibiotics by their GP in Wales.

Exposure

Antibiotic prescription (penicillins, cephalosporins, macrolides, dihydropyrimidines, nitroimidazoles, nitrofurans, lincosamides).

Outcome

Adverse event as defined by; patients’ death within 5 days, records of emergency admission within 5 days and GP records of adverse drug reactions or prescription of another antibiotic within 14 days.

Analysis

Logistic regression of adverse events versus no adverse events at follow-up time.

Results

There were 139 571 prescriptions of the selected antibiotics and 71 541 children (51.39% male) included with follow-up data of which there were 25 445 (18.23% of all prescriptions) children experienced adverse outcomes. There was higher odds of adverse events for lower weight children and those who were younger, female, of Asian origin or deprived.

Conclusion

The findings support the hypothesis that smaller children for their age (eg, low weight, female, Asian) are more likely to experience adverse events following antibiotics prescription. This work suggests child weight, in addition to age, should be used when prescribing antibiotics to children in primary care.
Large-scale observational study of AI-based patient and surgical material verification system in ophthalmology: real-world evaluation in 37 529 cases
Authors: Tabuchi Hitoshi , Ishitobi Naofumi , Deguchi Hodaka , Nakaniida Yuta , Tanaka Hayato , Akada Masahiro , Tanabe Mao
Published: November 2024

Background

Surgical errors in ophthalmology can have devastating consequences. We developed an artificial intelligence (AI)-based surgical safety system to prevent errors in patient identification, surgical laterality and intraocular lens (IOL) selection. This study aimed to evaluate its effectiveness in real-world ophthalmic surgical settings.

Methods

In this retrospective observational before-and-after implementation study, we analysed 37 529 ophthalmic surgeries (18 767 pre-implementation, 18 762 post implementation) performed at Tsukazaki Hospital, Japan, between 1 March 2019 and 31 March 2024. The AI system, integrated with the WHO surgical safety checklist, was implemented for patient identification, surgical laterality verification and IOL authentication.

Results

Post implementation, five medical errors (0.027%) occurred, with four in non-authenticated cases (where the AI system was not fully implemented or properly used), compared with one (0.0053%) pre-implementation (p=0.125). Of the four non-authenticated errors, two were laterality errors during the initial implementation period and two were IOL implantation errors involving unlearned IOLs (7.3% of cases) due to delayed AI updates. The AI system identified 30 near misses (0.16%) post implementation, vs 9 (0.048%) pre-implementation (p=0.00067), surgical laterality errors/near misses occurred at 0.039% (7/18 762) and IOL recognition at 0.29% (28/9713). The system achieved>99% implementation after 3 months. Authentication performance metrics showed high efficiency: facial recognition (1.13 attempts, 11.8 s), surgical laterality (1.05 attempts, 3.10 s) and IOL recognition (1.15 attempts, 8.57 s). Cost–benefit analysis revealed potential benefits ranging from US$181 946.94 to US$2 769 129.12 in conservative and intermediate scenarios, respectively.

Conclusions

The AI-based surgical safety system significantly increased near miss detection and showed potential economic benefits. However, errors in non-authenticated cases underscore the importance of consistent system use and integration with existing safety protocols. These findings emphasise that while AI can enhance surgical safety, its effectiveness depends on proper implementation and continuous refinement.
Bendamustine–rituximab elicits dual tumoricidal and immunomodulatory responses via cGAS–STING activation in diffuse large B-cell lymphoma
Authors: Xiao Ruipei , Zhao Wenli , Lin Wei , Xiao Yudian , Ren Jie , Zhou Yang , Meng Wei , Bi Enguang , Jiang Ling
Published: November 2024

Background

Bendamustine–rituximab (BR) therapy stands out as a promising alternative for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating notable efficacy when conventional regimens pose challenges. Despite its clinical success, the intricate mechanisms underlying BR therapy have remained elusive.

Methods

DLBCL cell lines were used to investigate the mechanism of BR therapy in vitro. RNA-seq and Western blot were used to explore the target pathways of BR therapy. STING was knocked out using Crispr-cas9 and inhibited using H-151 to investigate its role in BR therapy. Bulk RNA-seq and single-cell RNA-seq data from patients were analyzed to investigate the association between STING and pyroptosis pathways, validated using STING downregulated cells. Flow cytometry, transwell experiments and co-culture experiments were performed to investigate the inflammatory phenotype of DLBCL cells after BR treatment and its effect on T-cell recruitment and activation.

Results

This study elucidates that BR elicits direct tumoricidal effects by promoting apoptosis and inducing cell cycle arrest. The synergistic impact with rituximab is further potentiated by complement addition, demonstrating the pivotal role of in vivo antibody-dependent cellular cytotoxicity. Moreover, our investigation reveals that, through a cGAS–STING-dependent pathway, prolonged exposure to BR induces pyroptosis in DLBCL cells. Activation of the cGAS–STING pathway by BR therapy triggers the release of inflammatory factors and upregulates major histocompatibility complex molecules, shaping an immunologically hot tumor microenvironment.

Conclusions

This unique dual influence not only directly targets DLBCL cells but also engages the patient’s immune system, paving the way for innovative combination therapies. The study provides comprehensive insights into the multifaceted actions of BR in DLBCL, offering a foundation for refined and personalized treatment strategies in elderly patients.
Endovascular therapy versus medical management in isolated anterior cerebral artery acute ischemic stroke: a multinational multicenter propensity score-weighted study
Authors: Salim Hamza Adel , Pulli Benjamin , Yedavalli Vivek , Milhem Fathi , Musmar Basel , Adeeb Nimer , Lakhani Dhairya A , Essibayi Muhammed Amir , Heit Jeremy Josef , Faizy Tobias D , El Naamani Kareem , Henninger Nils , Sundararajan Sri Hari , Kuhn Anna Luisa , Khalife Jane , Ghozy Sherief , Scarcia Luca , Yeo Leonard LL , Tan Benjamin YQ , Regenhardt Robert W , Cancelliere Nicole M , Rouchaud Aymeric , Fiehler Jens , Sheth Sunil A , Puri Ajit S , Dyzmann Christian , Colasurdo Marco , Renieri Leonardo , Filipe João Pedro , Harker Pablo , Radu Răzvan Alexandru , Abdalkader Mohamad , Klein Piers , Marotta Thomas R , Spears Julian , Ota Takahiro , Mowla Ashkan , Jabbour Pascal , Biswas Arundhati , Clarençon Frédéric , Siegler James E , Nguyen Thanh N , Varela Ricardo , Baker Amanda , Altschul David , Gonzalez Nestor , Möhlenbruch Markus A , Costalat Vincent , Gory Benjamin , Stracke Paul , Hecker Constantin , Marnat Gaultier , Shaikh Hamza , Griessenauer Christoph J , Liebeskind David S , Pedicelli Alessandro , Alexandre Andrea Maria , Tancredi Illario , Kalsoum Erwah , Lubicz Boris , Patel Aman B , Mendes Pereira Vitor , Wintermark Max , Guenego Adrien , Dmytriw Adam A
Published: November 2024

Background

Isolated anterior cerebral artery occlusions (ACAo) in patients with acute ischemic stroke present significant challenges due to their rarity. The efficacy and safety of endovascular therapy (EVT) in comparison with best medical therapy (BMT) for ACAo remains unclear. This study aimed to assess the outcomes of these treatments.

Methods

This multinational, multicenter study analyzed data from the MAD-MT registry. Data were collected retrospectively from 37 sites across North America, Asia, and Europe. Inverse probability of treatment weighting (IPTW) was applied to balance confounding variables. The primary outcome was functional independence (modified Rankin Scale (mRS) scores of 0–2) at 90 days. Secondary outcomes included excellent outcomes (mRS 0–1), mortality at 90 days, and NIH Stroke Scale (NIHSS) score on day 1 post treatment.

Results

Of the 108 patients, 36 received BMT and 72 underwent EVT. The median age was 75 years, and 56% were male. At 90 days, 40% of patients achieved mRS 0–2, with no significant difference between EVT and BMT (38% vs 45%, p=0.46). Procedural success (mTICI 2b-3) was 91% in the EVT group, with a sICH rate of 2.9%. IPTW-adjusted analysis showed no significant difference between EVT and BMT for functional independence (OR 1.17, 95% CI 0.23 to 6.02, p=0.85), mortality (25% vs 21%, p=0.71) or day 1 NIHSS scores (Beta 2.2, 95% CI −0.51 to 4.8, p=0.11).

Conclusions

EVT showed high procedural success but did not significantly improve functional outcomes or mortality compared with BMT in patients with ACAo. Further randomized trials are needed to clarify EVT’s role in ACAo.
Reappraisal of reliability of a slope through hybridisation of regional and site-specific soil shear strength information
Authors: Lo M.K. , Leung Y.F. , Chan C.L. , Sze E.H.Y.
Published: November 2024

Uncertainty in soil parameters is usually characterised by probability density functions (PDFs), with the influence on system performance represented through the probability of failure. Difficulties in selecting representative PDFs for a project often arise from scarcity of site-specific information, even with ample previous knowledge and test data of similar soil types in the region. This paper proposes an approach to rationally assimilate regional and site-specific information. A newly-compiled regional database of shear strength information for saprolitic soils in Hong Kong is presented, based on results of multi-stage consolidated-undrained triaxial tests. A hierarchical Bayesian model is fitted to the regional database, followed by a Bayesian updating model that produces posterior predictive distributions of shear strength parameters. The posterior estimates incorporate site-specific features into regional information, leading to profound impacts on the evaluation of failure probability for a slope case. To further illustrate the significance of data hybridisation, four semi-hypothetical scenarios are created using the same slope geometry, by assuming that distributions of shear strength parameters are completely known at the site. With the proposed approach, the estimated failure probability approaches the true value with increasing amount of site-specific data, and is more robust than adopting regional data or site data alone.
Non-Kerr constraints using binary black hole inspirals considering phase modifications up to 4 PN order
Authors: Das Debtroy , Shashank Swarnim , Bambi Cosimo
Published: November 2024

The gravitational field around an astrophysical black hole (BH) is thought to be described by the Kerr spacetime, which is a solution of the Einstein equation. Signatures of binary black hole (BBH) coalescence in gravitational waves (GW) follow the Kerr spacetime as the theoretical foundation. Hence, any possible deviations from the Kerr spacetime around BHs serve as a test of the nature of gravity in the strong-field regime and of the predictions of General Relativity. In our study, we perform a theory-agnostic test of the Kerr hypothesis using BBH inspirals from the third Gravitational-wave Transient Catalog (GWTC-3). Considering the Johannsen metric, we compute the leading-order deviation to the emitted GW in the frequency domain. Our results provide constraints on two deformation parameters ($$\alpha _{13}$$

α
13

and $$\epsilon _3$$

ϵ
3

) and demonstrate the degeneracy between these two non-Kerr parameters.