bluuebunny/crossref_metadata_2025 huggingface dataset:
The emergence of metronidazole-resistant
Prevotella bivia
harboring
nimK
gene in Japan
Authors: Ito Yukitaka , Hashimoto Yusuke , Suzuki Masato , Kaneko Naomi , Yoshida Mieko , Nakayama Haruo , Tomita Haruyoshi
Published: August 2024

We present the identification and characterization of the complete genome of metronidazole (MTZ)-resistant
Prevotella bivia
strain TOH-2715 [minimum inhibitory concentration (MIC): 8 mg/L], isolated from the urine of an elderly Japanese woman, as well as details of its mobile genetic elements (MGEs) containing antimicrobial resistance (AMR) genes and its relationship with other bacterial species determined using whole-genome sequencing (WGS) data. TOH-2715 possessed two chromosomes with putative MGEs containing AMR genes. Two AMR-related MGE regions were present in chromosome 2. MGE-region 1 (7,821 bp) included Tn
6456
, where
nimK
was located, and MGE-region 2 (58.8 Kbp) included the integrative and conjugative element (ICE), where
tet
(Q) and
ermF
were located. The genetic structure of the ICE of TOH-2715 was similar to that of CTn
DOT
-family transposons, where
ermF
and
tet
(Q) are located. A search of public databases revealed that
nimK
was present in
Prevotella
spp., including
P. bivia
, and was partially composed of a Tn
6456
-like element lacking the efflux transporter gene
qacE
and the Crp/Fnr family transcriptional regulator gene in some cases. Core ICE gene analysis showed that ICEs similar to that of TOH-2715 were present in
Prevotella
spp. and
Bacteroides
spp., suggesting horizontal gene transfer among anaerobes. This is the report of WGS analysis of an MTZ-resistant clinical strain of
P. bivia
(TOH-2715) with Tn
6456
encoding
nimK
. Other submitted genomes have described the presence of
nimK
, but none of them have described MTZ resistance. Additionally, we described putative MGE regions containing the AMR gene within the genus
Prevotella
and among anaerobes, raising concerns about the future spread of
nimK
among anaerobes.

IMPORTANCE

Metronidazole (MTZ) is an important antimicrobial agent in anaerobic infections and is widely used in clinical settings. The rate of MTZ resistance in anaerobic bacteria has been increasing in recent years, and the
nim
gene (nitro-imidazole reductase) is one of the resistance mechanisms.
Prevotella bivia
is found in humans in the urinary tract and vagina and is known to cause infections in some cases. One of the
nim
genes,
nimK
, has recently been discovered in this species of bacteria, but there are no reports of antimicrobial resistance (AMR)-related regions in its whole genome level. In this study, we analyzed the AMR region of
nimK
-positive
P. bivia
derived from clinical specimens based on comparisons with other anaerobic genomes.
P. bivia
was found to be engaged in horizontal gene transfer with other anaerobic bacteria, and the future spread of the
nimK
gene is a concern.
Calcium-binding protein TgpCaBP regulates calcium storage of the zoonotic parasite
Toxoplasma gondii
Authors: Sun Weisong , Jiang Ning , Li Qilong , Liu Yize , Zhang Yiwei , Chen Ran , Feng Ying , Sang Xiaoyu , Long Shaojun , Chen Qijun
Published: August 2024

Toxoplasma gondii
, the causative parasite of toxoplasmosis, is an apicomplexan parasite that infects warm-blooded mammals. The ability of the calcium-binding proteins (CBPs) to transport large amounts of Ca
2+
appears to be critical for the biological activity of
T. gondii
. However, the functions of some members of the CBP family have not yet been deciphered. Here, we characterized a putative CBP of
T. gondii
, TgpCaBP (TGME49_229480), which is composed of four EF-hand motifs with Ca
2+
-binding capability. TgpCaBP was localized in the cytosol and ER of
T. gondii
, and parasites lacking the
TgpCaBP
gene exhibited diminished abilities in cell invasion, intracellular growth, egress, and motility. These phenomena were due to the abnormalities in intracellular Ca
2+
efflux and ER Ca
2+
storage, and the reduction in motility was associated with a decrease in the discharge of secretory proteins. Therefore, we propose that TgpCaBP is a Ca
2+
transporter and signaling molecule involved in Ca
2+
regulation and parasitization in the hosts.

IMPORTANCE

Ca
2+
signaling is essential in the development of
T. gondii
. In this study, we identified a calcium-binding protein in
T. gondii
, named TgpCaBP, which actively regulates intracellular Ca
2+
levels in the parasite. Deletion of the gene coding for TgpCaBP caused serious deficits in the parasite’s ability to maintain a stable intracellular calcium environment, which also impaired the secretory protein discharged from the parasite, and its capacity of gliding motility, cell invasion, intracellular growth, and egress from host cells. In summary, we have identified a novel calcium-binding protein, TgpCaBP, in the zoonotic parasite
T. gondii
, which is a potential therapeutic target for toxoplasmosis.
Three prolonged outbreaks of metallo-β-lactamase-producing
Pseudomonas aeruginosa
in an Upper Austrian hospital, 2017–2023
Authors: Cabal Adriana , Hörtenhuber Anna , Salaheddin Yarub , Stöger Anna , Springer Burkhard , Bletz Stefan , Mellmann Alexander , Hyden Patrick , Hartl Rainer , Weinberger Johannes , Conzemius Rick , Hell Markus , Daza-Prieto Beatriz , Lippert Kathrin , Steindl Georg , Köberl-Jelovcan Sandra , Ruppitsch Werner
Published: August 2024

In spring 2022, an increase in metallo-β-lactamase-producing
Pseudomonas aeruginosa
(MBL-Pa) infections was detected in a hospital in Upper Austria. To identify the source of infection and to stop further transmissions, an epidemiological outbreak investigation including whole-genome sequencing (WGS)-based typing was conducted. The final case definition included cases admitted to the hospital between 2020 and 2023 with an MBL-Pa in one of the three genomic clusters identified. In addition, the investigation was extended to include historical cases from 2017. Core genome multilocus sequence typing was performed to assess the genetic relatedness between the isolates. Fifty-four clinical
P. aeruginosa
isolates and eight
P. aeruginosa
isolates from the hospital environment were obtained. All but nine isolates grouped into one of three genomic clusters (ST235/
bla
VIM-1
, ST111/
bla
VIM-2
, or ST621/
bla
IMP-13
), which were considered to be distinct, prolonged outbreaks involving 47 out of 52 cases. The most likely source of infection for cluster 1 (ST111/
bla
VIM-2
) and cluster 2 (ST235/
bla
VIM-1
) was sinks in the intensive care unit (ICU) washroom. Cluster 3 clone (ST621/
bla
IMP-13
) could have originated in the urology ward in 2020 and then spread to the ICU years later. However, the nosocomial origin of this clone could not be proven. In March 2023, following the implementation of control measures (gowning, patient isolation, screening, and daily disinfection), no further MLB-Pa was detected, and the outbreaks were considered to be over. As ICUs play an important role in the transmission of
P. aeruginosa
, emphasis should be placed on genomic surveillance, infection prevention, and control in such wards.

IMPORTANCE

The significance of our work lies in the successful resolution of three prolonged outbreaks of MBL-Pa infections in a hospital in Upper Austria. Through a comprehensive epidemiological investigation coupled with WGS-based typing of
P. aeruginosa
isolates, the study identified three distinct genomic clusters responsible for prolonged outbreaks involving 47 cases. The investigation pinpointed sinks in the ICU washroom as the likely source of infection for two of the clusters. The study demonstrates the effectiveness of control measures such as hand hygiene, gowning, patient isolation, screening, and disinfection in stopping further transmission and bringing the outbreaks to a close. This underscores the critical role of genomic surveillance and control measures, particularly in high-risk settings like ICUs, in reducing nosocomial transmission of MBL-Pa infections.
Dynamic interplay of immune response, metabolome, and microbiota in cows during high-grain feeding: insights from multi-omics analysis
Authors: Castillo-Lopez Ezequias , Ricci Sara , Rivera-Chacon Raul , Sener-Aydemir Arife , Pacífico Cátia , Reisinger Nicole , Schwartz-Zimmermann Heidi E. , Berthiller Franz , Kreuzer-Redmer Susanne , Zebeli Qendrim
Published: August 2024

This study explores the dynamics of immune gene expression, ruminal metabolome, and gut microbiota in cows due to the duration of high-grain feeding, shedding light on host response and microbial dynamics in parallel. Cows consumed forage for a week, then gradually transitioned to a high-grain diet, which they consumed for 4 weeks. Immune response was evaluated in ruminal papillae by expression of genes related to the nuclear factor-kappaB (NFkB) pathway and correlated with the microbiota. Rumen metabolome was evaluated with high-performance liquid chromatography coupled with mass spectrometry and anion-exchange chromatography. Rumen and fecal microbiota were evaluated with 16S rRNA gene amplicon sequencing. In the rumen, expression of inflammation-associated genes increased with the duration on high grain, indicating activation of pro-inflammatory cascades; microbial diversity decreased with a high-grain diet but stabilized after week 3 on high grain. Changes in microbial relative abundance and metabolite enrichment were observed throughout the 4 weeks on high grain, with increments in propionogenic taxa (i.e.,
Succinivibrionaceae
). Metabolite enrichment analysis showed that at the start of high-grain feeding, simple carbohydrates were enriched; then, these were substituted by their fermentation products. There were correlations between certain ruminal bacterial taxa (i.e.,
Ruminococcaceae
UCG-005) and expression of genes of the NFkB pathway, suggesting the influence of these taxa on host immune response. In feces, microbial diversity and several
Ruminococcaceae
members initially declined but recovered by weeks 3 and 4. Overall, despite the stabilization of microbial diversity, changes in microbial relative abundance and proinflammatory genes were observed throughout high-grain feeding, suggesting that cows need more than 4 weeks to fully adjust once consuming a high-grain diet.

IMPORTANCE

Despite the stepwise diet transition typically assumed to serve for animal adaptation, expression of signaling receptors, mediators, and downstream targets of nuclear factor-kappaB pathway were found throughout the 4 weeks on high grain, which correlated with changes in the rumen microbial profile. In addition, although microbial diversity recovered in the feces and stabilized in the rumen in week 3 on high grain, we observed changes in microbial relative abundance throughout the 4 weeks on high grain, suggesting that cows need more than 4 weeks to adjust once consuming this diet. Findings are particularly important to consider when planning experiments involving dietary changes.
Real-time flow cytometry to assess qualitative and quantitative responses of oral pathobionts during exposure to antiseptics
Authors: Chatzigiannidou I. , Heyse J. , Props R. , Rubbens P. , Mermans F. , Teughels W. , Van de Wiele T. , Boon N.
Published: August 2024

Antiseptics are widely used in oral healthcare to prevent or treat oral diseases, such as gingivitis and periodontitis. However, the incidence of bacteria being tolerant to standard antiseptics has sharply increased over the last few years. This stresses the urgency for surveillance against tolerant organisms, as well as the discovery of novel antimicrobials. Traditionally, susceptibility to antimicrobials is assessed by broth micro-dilution or disk diffusion assays, both of which are time-consuming, labor-intensive, and provide limited information on the mode of action of the antimicrobials. The abovementioned limitations highlight the need for the development of new methods to monitor and further understand antimicrobial susceptibility. In this study, we used real-time flow cytometry, combined with membrane permeability staining, as a quick and sensitive technology to study the quantitative and qualitative responses of two oral pathobionts to different concentrations of chlorhexidine (CHX), cetylpyridinium chloride (CPC), or triclosan. Apart from the real-time monitoring of cell damage, we further applied a phenotypic fingerprinting method to differentiate between the bacterial subpopulations that arose due to treatment. We quantified the pathobiont damage rate of different antiseptics at different concentrations within 15 minutes of exposure and identified the conditions under which the bacteria were most susceptible. Moreover, we detected species-specific and treatment-specific phenotypic subpopulations. This proves that real-time flow cytometry can provide information on the susceptibility of different microorganisms in a short time frame while differentiating between antiseptics and thus could be a valuable tool in the discovery of novel antimicrobial compound, while at the same time deciphering their mode of action.

IMPORTANCE

With increasing evidence that microorganisms are becoming more tolerant to standard antimicrobials, faster and more accessible antimicrobial susceptibility testing methods are needed. However, traditional susceptibility assays are laborious and time-consuming. To overcome the abovementioned limitations, we introduce a novel approach to define antimicrobial susceptibility in a much shorter time frame with the use of real-time flow cytometry. Furthermore, phenotypic fingerprinting analysis can be applied on the data to study the way antiseptics affect the bacterial cell morphology over time and, thus, gain information on the mode of action of a certain compound.
Orthologs of
Plasmodium
ICM1 are dispensable for Ca
2+
mobilization in
Toxoplasma gondii
Authors: Cabral Gabriel , Ren Bingjian , Bisio Hugo , Otey Dawson , Soldati-Favre Dominique , Brown Kevin M.
Published: August 2024

Apicomplexan parasites mobilize ionic calcium (Ca
2+
) from intracellular stores to promote microneme secretion and facilitate motile processes including gliding motility, invasion, and egress. Recently, a multipass transmembrane protein, ICM1, was found to be
i
mportant for
c
alcium
m
obilization in
Plasmodium falciparum
and
P. berghei
. Comparative genomics and phylogenetics have revealed putative ICM orthologs in
Toxoplasma gondii
and other apicomplexans.
T. gondii
possesses two ICM-like proteins, which we have named TgICM1-L (TGGT1_305470) and TgICM2-L (TGGT1_309910). TgICM1-L and TgICM2-L localized to undefined puncta within the parasite cytosol. TgICM1-L and TgICM2-L are individually dispensable in tachyzoites, suggesting a potential compensatory relationship between the two proteins may exist. Surprisingly, mutants lacking both TgICM1-L and TgICM2-L are fully viable, exhibiting no obvious defects in growth, microneme secretion, invasion, or egress. Furthermore, loss of TgICM1-L, TgICM2-L, or both does not impair the parasite’s ability to mobilize Ca
2+
. These findings suggest that additional proteins may participate in Ca
2+
mobilization or import in Apicomplexa, reducing the dependence on ICM-like proteins in
T. gondii
. Collectively, these results highlight similar yet distinct mechanisms of Ca
2+
mobilization between
T. gondii
and
Plasmodium
.

IMPORTANCE

Ca
2+
signaling plays a crucial role in governing apicomplexan motility; yet, the mechanisms underlying Ca
2+
mobilization from intracellular stores in these parasites remain unclear. In
Plasmodium
, the necessity of ICM1 for Ca
2+
mobilization raises the question of whether this mechanism is conserved in other apicomplexans. Investigation into the orthologs of
Plasmodium
ICM1 in
T. gondii
revealed a differing requirement for ICM proteins between the two parasites. This study suggests that
T. gondii
employs ICM-independent mechanisms to regulate Ca
2+
homeostasis and mobilization. Proteins involved in Ca
2+
signaling in apicomplexans represent promising targets for therapeutic development.
New species, new records, and common species of
Diderma
(Physarales,
Didymiaceae
) from China
Authors: Li Xuefei , Tuo Yonglan , Hu Jiajun , Li You , Dai Dan , Sossah Frederick Leo , Wang Jiajia , Guo Yanfang , Liu Shuyan , Ma Haixia , Zhang Bo , Li Xiao , Li Yu
Published: August 2024

Myxomycetes are fungus-like organisms that play a significant role in ecological processes, however, their taxonomic diversity and distribution in China are poorly understood.
Diderma
is an important genus within the Class Myxogastria that has received little attention in China. This study provides new insights into the geographic range of
Diderma
species in China and identifies previously unreported and newly recorded species. Our results reveal that the geographic distribution of
Diderma
species in China is more diverse than previously thought, with four previously unreported species found in Liaoning, Hubei, Sichuan, and Gansu provinces. In addition, we describe five new
Diderma
species that are distinct from previously known species, namely
Diderma annuliferum
,
Diderma gansuense
,
Diderma roseum
,
Diderma jilinense
, and
Diderma flexocapillitium
. We identified these species using a combination of morphological characterization, DNA sequencing, and phylogenetic analysis. Our findings have important implications for understanding Myxomycete biodiversity in China and can inform future research on the ecology, biogeography, and evolution of these fascinating organisms. Specifically, our study highlights the need for continued exploration of underrepresented areas to gain a more comprehensive understanding of the diversity and distribution of Myxomycetes in China.

IMPORTANCE

The discovery of five new
Diderma
species and the revelation of their diverse distribution expand our understanding of Myxomycete diversity and provide a foundation for future studies on the ecology and biogeography of these organisms. These findings contribute to our knowledge of microbial diversity and have practical implications for conserving underrepresented areas and maintaining healthy ecosystems.
Development of a triplex RT-qPCR assay for simultaneous quantification of Japanese encephalitis, Murray Valley encephalitis, and West Nile viruses for environmental surveillance
Authors: Liu Yawen , Smith Wendy J , Gebrewold Metasebia , Simpson Stuart L. , Wang Xinhong , Ahmed Warish
Published: August 2024

The co-circulation of mosquito-borne Japanese encephalitis virus (JEV), Murray Valley encephalitis virus (MVEV), and West Nile virus (WNV) has impacted human and animal health in multiple countries worldwide. To facilitate early warnings and surveillance of the presence of these viral infectious agents in the environment, a triplex reverse transcription-quantitative PCR (RT-qPCR) was developed for simultaneous quantification of JEV, MVEV, and WNV in potential hotspots such as piggery and urban wastewater and environmental water samples. The performance of the developed triplex RT-qPCR assay was compared with that of simplex counterparts, all using the same primer and probe sequences. The quantifiable results showed a concordance rate of 93.9%–100% (Cohen’s kappa) between the triplex and simplex assays. The mean concentrations of exogenous JEV, MVEV, and WNV using the triplex and simplex RT-qPCR assays were remarkably similar in piggery/urban wastewater and environmental water samples. However, the impacts of the matrix effects (i.e., sample composition and PCR inhibition) of environmental water samples on the accurate quantification of these viruses need to be considered. Taken together, this newly developed triplex RT-qPCR assay of JEV, MVEV, and WNV will allow for a more rapid and cost-efficient sample analysis and data interpretation. The application of the triplex assay for environmental surveillance may be a valuable tool to complement the existing disease and mosquito surveillance approaches used to safeguard the health of both humans and animals.

IMPORTANCE

The co-circulation of mosquito-borne Japanese encephalitis virus (JEV), Murray Valley encephalitis virus (MVEV), and West Nile virus (WNV) poses significant threats to human and animal health globally. In this study, a triplex RT-qPCR assay was developed for simultaneous quantification of these viruses in wastewater and environmental water samples. Results demonstrated high concordance and sensitivity of the newly developed triplex RT-qPCR assay compared to simplex assays, indicating its efficacy for environmental surveillance. This cost-effective and rapid assay offers a vital tool for timely monitoring of mosquito-borne viruses in environmental samples, enhancing our ability to mitigate potential outbreaks and safeguard public health.
Clinical value of guideline recommended molecular targets and genome targeted cancer therapies: cross sectional study
Authors: Tibau Ariadna , Hwang Thomas J , Avorn Jerry , Kesselheim Aaron S
Published: August 2024

Objective

To assess the clinical benefit and actionability of molecular targets for genome targeted cancer drugs recommended for clinical practice by the National Comprehensive Cancer Network (NCCN).

Design

Cross sectional study.

Participants/setting

Genome targeted cancer drugs recommended by NCCN guidelines in the advanced setting.

Main outcome measures

Molecular target actionability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit of genome targeted oncology therapies was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets at ESCAT category level I associated with studies showing substantial clinical benefit by ESMO-MCBS (grades 4-5) were designated as high benefit, and those linked to studies achieving an ESMO-MCBS grade of 3 were categorized as being of promising but unproven benefit.

Results

411 recommendations related to 74 genome targeted drugs targeting 50 driver alterations were examined. Most recommendations (346/411; 84%) were associated with clinical trials of various phases, but 16% (65/411) relied on only case reports or pre-clinical studies. However, clinical trials mostly comprised phase I or phase II (271/346; 78%), single arm (262/346; 76%) studies. The primary endpoint assessed in most trials was overall response rate (271/346; 78%) rather than survival. ESCAT tier I targetability encompassed 60% (246/411) of target recommendations, 35% (142/411) were classified as tier II or III, and 6% (23/411) had their relevance yet to be determined (tiers IV to X). When ESMO-MCBS was applied to 267 scorable trials, only 12% (32/267) showed substantial clinical benefit (grades 4-5) and 45% (121/267) were grade 3. When both frameworks were combined, 12% (32/267) of trials supported a determination of high benefit and 33% (88/267) indicated promising but unproven benefit. Of the 118 interventions endorsed by NCCN authors as preferred, 62 (53%) applied to treatments with high or promising but unproven benefit.

Conclusion

According to the ESCAT and ESMO-MCBS frameworks, about one eighth of genome based treatments for solid cancer were rated as likely to offer a high benefit to patients, whereas around a third were identified as offering a promising but unproven substantial benefit. Ensuring that NCCN recommendations are aligned with expected clinical benefits is crucial for promoting informed, evidence based, genomic guided treatment decisions.
Mainstreaming genetics into Italian prenatal care: exploring the future implementation of non-invasive prenatal testing (NIPT) in the Italian National Healthcare System using stakeholder interviews
Authors: Sesa Giulia , Czabanowska Katarzyna , Kok Kristiaan , Vrijenhoek Terry
Published: August 2024

Introduction

Non-invasive prenatal testing (NIPT) has revolutionised the way prenatal testing is performed globally. Italy is one of the European countries considering incorporating NIPT nationwide into the publicly funded healthcare system. Given the extensive autonomy granted to the private sector, that not all technological applications result in equal benefits, and that only a few Italian regions currently offer NIPT through the public healthcare system free of charge, it is crucial to consider how to implement such a technology in the Italian public healthcare sector.

Methods

A qualitative study consisting of 12 semistructured interviews was performed. The study population included gynaecologists, geneticists, bioethicists, health economists and public health professionals. Non-probability sampling techniques were used to recruit the study’s participants. Content analysis was employed to analyse the data.

Results

From the interviews, it emerged that a contingent implementation of NIPT for major chromosomal aneuploidies screening seems the most cost-effective and logical in the Italian context. No consensus was reached on fetal sex and sex chromosome aneuploidies screening. Most interviewees disagreed with making whole-genome/whole-exome sequencing available through the public sector. The high appreciation of NIPT, its potential to advance fundamental objectives of healthcare systems and its compatibility with the Italian prenatal testing culture are among the factors that may facilitate the transition of NIPT from the private to the public sector. Mainstreaming NIPT in the public healthcare system is challenged by its high costs, current offer, lack of prioritisation and regional differences.

Conclusions

While transitions take time and are challenging to achieve, this study shows that the current prenatal testing structure and practice would only need modest adjustments to accommodate NIPT, offering hope for the future. Future studies could expand this research by involving a broad range of stakeholders and investigating the effects of various NIPT implementation strategies presently employed across Italian regions.
Sphenopalatine ganglion (SPG) block for symptomatic relief of acute migraine
Authors: Jaconelli Tom , Crane Steven
Published: August 2024

A shortcut review of the literature was conducted to examine whether administering a sphenopalatine ganglion (SPG) block provides symptomatic relief in adult patients with acute migraine. 381 papers were found of which 4 included data on patients relevant to the specific clinical question, these are discussed in the paper. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. The clinical bottom line is that to date there is not enough evidence that a SPG block is likely to provide sustained symptomatic relief of acute migraine in the emergency setting. Further work is needed to establish if it can provide benefit for this patient group.
Prevalence of intracerebral thrombus detected by optical coherence tomography in patients with posterior circulation stroke or transient ischemic attack
Authors: Xu Ran , Yang Bin , Wang Tao , Zhang Xiao , Li Tianhua , Feng Yao , Guo Xiaofan , Jia Jinzhu , Ma Yan , Dmytriw Adam A , Jia Haibo , Jiao Liqun
Published: August 2024

Background

The incidence of thrombosis in patients with intracranial atherosclerotic stenosis (ICAS) remains unclear. Optical coherence tomography (OCT) has the potential to explore the vessel wall structure of posterior-circulation ICAS because of its relatively straight anatomical structure compared with that of the anterior cerebral arteries. This study aimed to determine the prevalence and characteristics of thrombosis in the posterior-circulation ICAS using OCT.

Methods

This prospective study was conducted on 135 patients with posterior-circulation arterial stenosis who underwent OCT. All patients were symptomatic and had a severely stenotic lesion (70–99%) in the vetebrobasilar artery. The enrolled patients were classified according to the presence of in situ thrombus as defined by OCT. Clinical data and OCT characteristics were compared.

Results

Eighty-two patients diagnosed with posterior-circulation ICAS were enrolled. In situ thrombi were identified in 34 patients. Clinically, patients with in situ thrombus were more prone to cerebral infarctions than transient ischemic attacks. The percentage area of stenosis in the non-thrombus group was significantly lower than that in the thrombus group. The thrombus burden, mean flow area, mean thrombus area, maximum lipid arc, and mean lumen area were significantly different among white, red, and mixed thrombi.

Conclusions

We achieved in vivo vessel wall structural analysis of posterior-circulation ICAS with the largest sample size. We also revealed the true incidence of in situ thrombosis and potential corresponding clinical events of posterior-circulation ICAS for the first time.
Arrhythmia in patients with systemic sclerosis: incidence, risk factors and impact on mortality in a Swedish register-based study
Authors: Bairkdar Majd , Dong Zihan , Andell Pontus , Hesselstrand Roger , Holmqvist Marie
Published: August 2024

Objectives

The objectives of this study are to study the risk of developing cardiac arrhythmia and its subtypes over time in patients with systemic sclerosis (SSc), to assess potential risk factors for arrhythmia in SSc and to explore whether arrhythmia is associated with mortality.

Methods

We used nationwide Swedish registers to identify patients with incident SSc 2004–2019 and matched general population comparators (1:10). The primary outcome was incident arrhythmia. Follow-up started at the date of SSc diagnosis and ended at the primary outcome, death, emigration or 31 December 2019. We estimated the incidence of arrhythmia overall and stratified by subtype and explored the relative risk in relation to time since diagnosis using flexible parametric models. We used Cox regression to study risk factors for arrhythmia and the association of arrhythmia with mortality.

Results

We identified 1565 patients and 16 009 comparators. The overall incidence of arrhythmia was 255 (95% CI 221 to 295) and 119 (95% CI 112 to 127) per 10 000 person years in patients with SSc and comparators, respectively, corresponding to an IRR of 2.1 (95% CI 1.8 to 2.5). The greatest hazard difference between patients with SSc compared with the comparators was seen in the first year of follow-up (HR for arrhythmia 3.0; 95% CI 2.3 to 3.8). Atrial fibrillation and flutter were the most common arrhythmia subtypes. Male sex, index age and pulmonary arterial hypertension were significant risk factors for arrhythmia in SSc. Incident arrhythmia was significantly associated with mortality (HR 2.2; 95% CI 1.6 to 3.0).

Conclusion

SSc is associated with higher incidence of cardiac arrhythmia compared with general population. Arrhythmia seems to be an early manifestation of SSc and is associated with higher mortality.
Seeds and sequences of element abundances in solar energetic particle events
Authors: Reames Donald V.
Published: August 2024

Solar energetic particles (SEPs) in the small “impulsive” events, primarily accelerated during magnetic reconnection in solar jets, have strong enhancements of the abundances of increasingly heavy elements. In contrast, the shock acceleration of ambient coronal plasma in most large “gradual” SEP events produces flat or decreasing abundances vs. element mass-to-charge ratios A/Q. However, heavy-ion enhancements in the largest gradual SEP events can occur in two ways: (1) strong streaming of protons away from the shock amplifies Alfvén waves that preferentially scatter and retard protons near the shock while increasingly heavy ions can leak out, and (2) strong shock waves reaccelerate SEPs fed from persistent impulsive SEP events streaming from some active regions, with their pre-enhanced heavy ions becoming dominant. Power-law fits of abundance enhancements versus A/Q can distinguish the latter events by the presence of both impulsive and coronal seed components and the best-fit charges Q define characteristic source temperatures. Ironically, ions with high observed charges, e.g., QFe ≈ 20, are yet another signature of impulsive seed ions that are routinely stripped after initial acceleration. Intense impulsively seeded events can occur in sequences fed from a single persistent active region as it rotates across the disk of the Sun. Three-week-long event sequences, each producing two or three very large events, occur early in the strong solar-cycle 23 (1997 – 2008). The weak solar cycle 24 produces only one impulsively seeded event sequence—perhaps a dearth of both impulsive seeds and sufficiently strong shocks. Solar cycle 25 has produced an unusual active period of short strong impulsive events. In contrast, there are other active regions where large events alternate SEPs with and without impulsively seeded sources. We also find that events with moderate Alfvén-wave trapping near the shock can release ions slowly or rapidly as a function of A/Q. This A/Q-dependent trapping acts almost as a magnetic spectrometer that separates elements in space and time.
Jet substructure
Authors: Apolinário Liliána , Chien Yang-Ting , Mendez Leticia Cunqueiro
Published: August 2024

Jet substructure observables hold the keys to identifying the inner working of the quark–gluon plasma through its imprints in jet modification patterns. Because of the multi-scale nature of jet evolution, the strategy has focused on developing jet reclustering-based and jet shape-based observables to specifically probe different stages of jet evolution, which provide multi-dimensional quantification of jet particle distribution phase spaces. The developments of jet substructure in the past few years allowed us to explore the correlations among jet observables. The richer information beyond single-observable modifications could give provides a crucial step beyond the energy loss paradigm. This review surveys the theory and phenomenology of modern jet substructure observables, which help constraining the energy scales of medium interactions and identifying heavy flavor quarks within jets. Also, the peculiar soft activities point to more refined studies of medium responses to jets.
A COMPUTATIONAL AND FRACTIONAL MATHEMATICAL MODEL FOR ASSESSING HEPATITIS B WITH OPTIMAL THERAPY
Authors: CARDOSO LISLAINE C. , TORO PAULO F. , CAMARGO RUBENS F. , SANTOS FERNANDO L. P.
Published: August 2024

This paper presents a mathematical study applied to Hepatitis B disease utilizing fractional calculus and numerical methods. We begin by discussing mathematical fundamentals, focusing on fractional calculus concepts and relevant numerical aspects for disease modeling. We then formulate the problem, describing a nonlinear fractional differential system that models hepatitis B virus (HBV) infection and its response to drug therapy. A detailed theoretical analysis explores system properties and biological implications. We provide a qualitative analysis of the model, discussing important dynamic behaviors such as stability and parameter sensitivity. Subsequently, numerical analysis is performed to validate the model and estimate unknown parameters from patient data. Our findings include significant insights into biological parameters and their impact on therapeutic response. We conclude that the proposed fractional-order model is effective, offering optimal therapeutic strategies for hepatitis B.
Experience: A Comparative Analysis of Multivariate Time-Series Generative Models: A Case Study on Human Activity Data
Authors: Alzahrani Naif , Cała Jacek , Missier Paolo
Published: August 2024

Human activity recognition (HAR) is an active research field that has seen great success in recent years due to advances in sensory data collection methods and activity recognition systems. Deep artificial intelligence (AI) models have contributed to the success of HAR systems lately, although still suffering from limitations such as data scarcity, the high costs of labelling data instances, and datasets’ imbalance and bias. The temporal nature of human activity data, represented as time series data, impose an additional challenge to using AI models in HAR, because most state-of-the-art models do not account for the time component of the data instances. These limitations have inspired the time-series research community to design generative models for sequential data, but very little work has been done to evaluate the quality of such models. In this work, we conduct a comparative quality analysis of three generative models for time-series data, using a case study in which we aim to generate sensory human activity data from a seed public dataset. Additionally, we adapt and clearly explain four evaluation methods of synthetic time-series data from the literature and apply them to assess the quality of the synthetic activity data we generate. We show experimentally that high-quality human activity data can be generated using deep generative models, and the synthetic data can thus be used in HAR systems to augment real activity data. We also demonstrate that the chosen evaluation methods effectively ensure that the generated data meets the essential quality benchmarks of realism, diversity, coherence, and utility. Our findings suggest that using deep generative models to produce synthetic human activity data can potentially address challenges related to data scarcity, biases, and expensive labeling. This holds promise for enhancing the efficiency and reliability of HAR systems.
Increasing Street Credibility: Cartography-Aware Forensic Analysis of GNSS Trace Validity
Authors: Hammer Andreas , Cerny Christian , Jung Christoph , Eichenmüller Christian , Freiling Felix
Published: August 2024

Geolocation data recorded by consumer electronics is usually considered very helpful in criminal investigations: Every few steps, every few seconds, the location of a suspect, victim, witness, or others can be pinpointed as it was automatically recorded in the background. Compared to the commonly used cell tower location data, device-local data from a
global navigation satellite system
(GNSS) has far higher precision (both spatial and temporal), but suffers from a lack of trust, because data provenance is under potential control of the user. In this article, we propose two approaches of validating and analyzing such data with high confidence. The first approach formulates and checks internal consistency criteria of GNSS data, while the second approach also takes external data sources about the surrounding environment in the form of OpenStreetMap data into account. In both approaches, we formalize the concept of a
data anomaly
and argue that an absence of anomalies implies more trustworthy data and thus higher evidential value. This way, the vast information contained in high-density location data may actually lead to more detailed insights instead of only increasing data noise in investigations.
Opportunities with Multi-Layer Weave Structures in Woven E-Textile Design
Authors: Pouta Emmi , Mikkonen Jussi Ville , Salovaara Antti
Published: August 2024

Most textiles in day-to-day use are products of weaving. The versatility of this manufacturing technique, which readily supports a multi-layered structure, inclusion of several yarn types, malleability and other valuable characteristics, has attracted attention from HCI researchers intrigued by its potential to expand the interaction capabilities of e-textiles. Research nonetheless has barely scratched the surface of the wealth of weaving techniques and woven structures available. Therefore, a design-research project anchored in practice investigated how touch-sensitive e-textiles’ capabilities might be enriched via advanced multi-layer weaving techniques. The research process, which drew inspiration from literature both on textile design and on woven e-textiles, produced 25 distinct e-textile samples. Results from evaluating the structural properties, electrical capabilities and overall utility of each point to numerous unexplored opportunities from woven multi-layer e-textiles. Even holding potential for entirely new forms of interaction, these represent promising starting points for in-depth investigation.
Uncertainties as Generative Resources in Research through Design: Three Dynamics for Moving in a Design Space
Authors: Epp Felix Anand , Rosén Anton Poikolainen , Salovaara Antti , Sanchez Camilo
Published: August 2024

In HCI and design research, it has recently been suggested that, instead of risks and threats, uncertainties can be generative resources. This aligns particularly well with practice-based design research and research through design (RtD), where uncertainties are pervasive and unavoidable due to the approach’s interest in open-ended problems, contexts under transformation and unknown futures. Building on the idea that uncertainties drive design activity, we describe the design process as framing acts where a designer-researcher moves along perceived uncertainties. We identify three dynamics for a generative mode of working with uncertainties that can make designers aware of uncertainties, circle in towards those that appear essential while seeking to avoid others and stay with those that offer new perspectives. We exemplify these dynamics by drawing from our experiences from three RtD projects and highlight this viewpoint’s value in providing new reflective tools for designer-researchers.
Shifting Ambiguity, Collapsing Indeterminacy: Designing with Data as Baradian Apparatus
Authors: Reed Courtney N. , Benito Adan L. , Caspe Franco , McPherson Andrew P.
Published: August 2024

This article examines how digital systems designers distil the messiness and ambiguity of the world into concrete data that can be processed by computing systems. Using Karen Barad's agential realism as a guide, we explore how data is fundamentally entangled with the tools and theories of its measurement. We examine data-enabled artefacts acting as Baradian apparatuses: they do not exist independently of the phenomenon they seek to measure but rather collect and co-produce observations from within their entangled state: the phenomenon and the apparatus co-constitute one another. Connecting Barad's quantum view of indeterminacy to the prevailing HCI discourse on the opportunities and challenges of ambiguity, we suggest that the very act of trying to stabilise a conceptual interpretation of data within an artefact has the paradoxical effect of amplifying and shifting ambiguity in interaction. We illustrate these ideas through three case studies from our own practices of designing digital musical instruments (DMIs). DMIs necessarily encode symbolic and music-theoretical knowledge as part of their internal operation, even as conceptual knowledge is not their intended outcome. In each case, we explore the nature of the apparatus, what phenomena it co-produces, and where the ambiguity lies to suggest approaches for design using these abstract theoretical frameworks.
Pain Management Strategies before Pan‐Retinal Photocoagulation for Diabetic Retinopathy: A Systematic Review
Authors: Johari Mohammadkarim , Moallem Mehdi , Amini Abdulrahim , Sanie-Jahromi Fatemeh
Published: August 2024

Purpose. This systematic review aims to consolidate key findings regarding the efficacy of pain relief medications administered prior to pan‐retinal photocoagulation (PRP) for diabetic retinopathy (DR). Methods. A comprehensive search of major databases from 1993 to 2023 was conducted. Clinical trials comparing pain relief drugs before PRP in patients diagnosed with DR requiring PRP treatment were eligible for inclusion. The assessment of pain scores involved the use of various scales, such as the visual analog scale (VAS), numerical rating scale (NRS), verbal rating scale (VRS), and other ordinal pain scales. In addition, laser parameters were taken into consideration during the analysis. Results. Twenty‐two clinical trials from initial 150 studies were included in the review. Nine studies evaluated the pain relief effects of nonsteroidal anti‐inflammatories NSAIDs (selective NSAID and nonselective NSAID), two studies compared the effects of opioids (conventional opioids and atypical opioids), and eleven studies investigated the effects of benzodiazepines, lidocaine, and other sedatives. Conclusion. This review synthesizes findings from multiple studies reporting pain as an adverse outcome of PRP in patients with advanced DR. Based on the evidence from reviewed clinical trials, the administration of lidocaine 2% via transconjunctival, retrobulbar, or peribulbar block along with specific NSAIDs, such as topical ketorolac administrated 24 hours before treatment or oral diclofenac potassium (50 mg) prior to PRP, demonstrated beneficial effects among patients with DR.
Table S7 from High-Dose Intravenous Vitamin C Combined with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase II Trial
Authors: Paller Channing J. , Zahurak Marianna L. , Mandl Adel , Metri Nicole A. , Lalji Aliya , Heath Elisabeth , Kelly William K. , Hoimes Christopher , Barata Pedro , Taksey Jason , Garrison Dominique A. , Patra Kartick , Milne Ginger L. , Anders Nicole M. , Nauroth Julie M. , Durham Jennifer N. , Marshall Catherine H. , Markowski Mark C. , Eisenberger Mario A. , Antonarakis Emmanuel S. , Carducci Michael A. , Denmeade Samuel R. , Levine Mark
Published: August 2024

Table S7 shows Serious Adverse Events (N = 11 patients), by Type and Grade. Attributions Assigned Docetaxel versus HDIVC or Placebo
“Sementes do mal”: essencialização e agência na sustentação do racismo em unidades socioeducativas do Rio de Janeiro
Authors: Vinuto Juliana
Published: August 2024

O objetivo deste artigo é analisar processos de essencialização de adolescentes que cumprem medida socioeducativa de internação no estado do Rio de Janeiro, considerando as disputas profissionais sobre a dimensão racial de tais processos de essencialização. Para tanto, diferentes materiais de pesquisas de campo realizadas desde 2015 foram retomados, o que permitiu discutir a regularidade de representações racializadas sobre adolescentes internados, mesmo quando tal dimensão racial não foi percebida ou intencional. Ao constatar a centralidade da expressão “sementes do mal”, comum em unidades socioeducativas fluminenses, será possível dialogar criticamente com o conceito de racismo estrutural de modo a ressaltar a dimensão de agência na produção e reprodução de desigualdades raciais na medida socioeducativa de  internação.
Complicações da linguagem sociológica
Authors: Bittencourt Matheus Boni
Published: August 2024

This is a review of the book Troubling sociological concepts: an interrogation, by Martyn Hammersley. The work presents an instigating reflection on some of the main concepts used by sociologists in research and teaching activities, which have controversial and divergent meanings, mixing scientific, ethical and political meanings. From a Weberian perspective, the work intends to encourage sociologists to make a cautious use of the concepts, attentive to their methodological validity.
Antifeminismo como identidade política: o caso da deputada Chris Tonietto
Authors: Miguel Luis Felipe , Fontenelle Alana
Published: August 2024

El artículo discute la relevancia de las cuestiones de género en la agitación política de la extrema derecha en Brasil, abordando la reacción virulenta contra los avances de los movimientos feminista y LGBT+. El “desorden de género” es un tema central en la agenda de una derecha radical que se ha unificado bajo el liderazgo de Jair Bolsonaro, junto con la corrupción, el punitivismo criminal, la posesión de armas, el negacionismo climático y otros. Para algunos de ellos, el género es la cuestión dominante, como en el caso de la congresista católica ultraconservadora Chris Tonietto (PL-RJ). El análisis de su cuenta de Instagram muestra el predominio de una agenda antifeminista, en particular la lucha contra el derecho al aborto. Tonietto no sólo reacciona cuando el tema aparece en la agenda pública, sino que también lo aborda activamente e invierte en contenidos destinados a formar activismo contra los derechos de las mujeres. Es un uso del mandato parlamentario con el objetivo, no exclusivo, pero sí importante, de instruir ideológicamente. Esta es una característica de parte de la nueva extrema derecha, que presenta a Antonio Gramsci como su archienemigo, pero que ha absorbido sus lecciones sobre la necesidad de conquistar la hegemonía –y cómo la disputa sobre los valores y las representaciones del mundo social es central. a este proceso.