bluuebunny/crossref_metadata_2025_split huggingface dataset:
An inner membrane complex protein IMC1g in
Plasmodium berghei
is involved in asexual stage schizogony and parasite transmission
Authors: Liu Yinjie , Cheng Shitong , He Gang , He Dawei , Wang Duo , Wang Sicong , Chen Lumeng , Zhu Liying , Feng Yonghui , Cui Liwang , Cao Yaming , Zhu Xiaotong 
Published: November 2024

ABSTRACT

The inner membrane complex (IMC), a double-membrane organelle underneath the plasma membrane in apicomplexan parasites, plays a significant role in motility and invasion and confers shape to the cell. We characterized the function of PbIMC1g, a component of the IMC1 family member in
Plasmodium berghei
. PbIMC1g is recruited to the IMC in late schizonts, activated gametocytes, and ookinetes. Pairwise yeast two-hybrid assays demonstrate that PbIMC1g interacts with IMC1c, a component of the PHIL1 complex, and the core sub-repeat motif “EKI(V)V(I)EVP” in PbIMC1g is essential for this interaction. Localization of PbIMC1g to the IMC was dependent on its IMCp domain, while its C-terminus and palmitoylation sites were required for the full efficiency of proper IMC targeting. PbIMC1g is required for asexual stage development, and its conditional knockdown resulted in a defect in schizogony. Additionally, PbIMC1g was also important for male gametogenesis and ookinete development. As an IMC component that assists in anchoring the glideosome to the subpellicular network, PbIMC1g was also involved in ookinete motility and mosquito midgut invasion. IMC1g from the human parasite
Plasmodium vivax
could functionally replace PbIMC1g in
P. berghei
, confirming the evolutionary conservation of IMC1g proteins in
Plasmodium
spp. Together, this work reveals an essential role of IMC1g in the parasite life cycle and suggests that IMC1 family members likely contribute to parasite gliding and invasion.

IMPORTANCE

The malaria parasite’s inner membrane complex is critical to maintain its structural integrity and motility. Here, we identified the function of the IMC1g protein, a member of the IMC1 family, in invasive and proliferative stages of
P. berghei
. We found that the IMCp domain of PbIMC1g is critical for proper IMC targeting, and PbIMC1g interacts with PbIMC1c. Conditional knockdown of PbIMC1g expression affects schizogony, gametogenesis, and ookinete conversion. PbIMC1g interacts with IMC1c to firmly anchor the glideosome to the subpellicular network. Additionally, we confirmed that IMC1g is functionally conserved in
Plasmodium
spp. These data reveal the function of IMC1g protein in anchoring the glideosome, providing further insight into the mechanism of the glideosome function.
Decoding the whole-genome sequence of multidrug-resistant
Escherichia coli
strain Hakim RU_BHWS isolated from wastewater in Bangladesh
Authors: Islam Md. Shamsul , Khan Muhib Ullah , Zahan Nusrat , Saklain K. M. Golam , Liu Miaomiao , Kitajima Masaaki , Haque Md. Hakimul 
Published: November 2024

ABSTRACT

This report presents the draft genome sequence of the multidrug-resistant
Escherichia coli
strain Hakim RU_BHWS isolated from wastewater. The genome assembly is 4.6 Mb, with 32.16× coverage and a GC content of 50.7%. It includes five CRISPR arrays, 16 prophages, 56 antibiotic resistance genes, and 35 virulence factor genes.
Amoeba plate test with
Acanthamoeba castellanii
as an innovative tool for
Nocardia
recovery from sputum samples: a proof-of-concept study
Authors: Espinasse Coralie , Descours Ghislaine , Ibranosyan Marine , Beraud Laetitia , Ginevra Christophe , Chastang Joelle , Dumitrescu Oana , Laurent Frédéric , Rodriguez Nava Verónica , Jarraud Sophie , Allam Camille 
Published: November 2024

ABSTRACT

Nocardia
recovery from pulmonary samples is challenging due to the lack of a specific medium and the abundance of overgrown respiratory flora. This study aimed to compare the amoeba plate test (APT), an amoebic coculture with
Acanthamoeba castellanii
, with the axenic culture to recover
Nocardia
from pulmonary samples.
Nocardia
serial dilutions (
n
= 15 strains from seven species, concentrations ranging: 10
7
–10
2
CFU/mL) in water and spiked overgrown sputa (
n
= 8) were simultaneously plated on agar with amoebic monolayer (APT) and without (control). Culture positivity rates, minimal growth concentrations, growth times, and abundance of flora overgrowth were compared for each condition. In water,
Nocardia
culture positivity rates were not significantly different between APT (86%, 30/35) and control (94%, 33/35;
P
= 0.246). In sputa, APT resulted in greater
Nocardia
growth (63%, 22/35 vs 37%, 13/35;
P
= 0.008). In addition, the elimination of interfering flora was more frequent using APT (34%, 12/35 vs 11%, 4/35;
P
= 0.01), and the overall abundance of flora was lower (median [interquartile range, IQR]: 1 [0–2] vs 3 [1-3];
P
< 0.0001). The most grown species using APT were
N. mexicana
and
N. otitidiscaviarum,
whereas
N. abscessus
and
N. nova
were the most fastidious to grow under both conditions. This study reports
Nocardia’
s ability to grow in amoebic coculture, with some growth kinetic differences depending on the species, presumably implying their intra-amoebic multiplication. Furthermore, in APT,
Nocardia
recovery from overgrown sputa was greater, and flora decontamination was more effective. The present findings are strong arguments to implement APT as a complementary technique for
Nocardia
isolation from heavily contaminated samples.

IMPORTANCE

The culture-proven diagnosis of Nocardiosis is challenging due to the difficulties in recovering
Nocardia
colonies from respiratory samples containing a complex polymicrobial flora. However, the isolation of
Nocardia
strains remains necessary to perform antibiotic susceptibility testing and adapt the antibiotic regimen of the patients. This study provides an innovative culture method based on a solid medium amoebic coculture, the amoeba plate test (APT), to cultivate
Nocardia
strains from clinical sputa samples.
Nocardia
grew across the APT amoebic monolayer. Moreover, the APT, which is already used in a reference center for the recovery of
Legionella
strains, exhibited good performances for
Nocardia
recovery and decontamination of interfering flora, thereby representing a promising second line tool to improve
Nocardia
culture.
AI-assisted diagnosis of vulvovaginal candidiasis using cascaded neural networks
Authors: Wang Zhongxiao , Wang Ruliang , Guo Haichun , Zhao Qiannan , Ren Huijun , Niu Jumin , Wang Ying , Wu Wei , Liang Bingbing , Yi Xin , Zhang Xiaolei , Xu Shiqi , Dong Xianling , Wang Liqun , Liao Qinping 
Published: November 2024

ABSTRACT

Vulvovaginal candidiasis (VVC) is a prevalent fungal ailment affecting women globally. Timely and accurate diagnosis is crucial. Traditional methods, relying on clinical evaluation and manual microscopic examination, have limitations. Artificial intelligence (AI) offers potential improvements in diagnostic accuracy and efficiency by objectively analyzing microscopic images of lower genital tract infections in women. A cascaded model was developed using 100,387 microscope images and 1,761 slides to diagnose VVC at slide level. The model’s diagnostic accuracy was compared with experts’. Five hundred thirteen slides were used to evaluate whether the experts’ diagnostic skills could be improved using the model as an AI-assisted tool. The consistency between experts’ interpretations of microscopic digital images and microscopic examination under eyepiece was assessed to determine whether the collected images adequately represented the slides. The model obtained AUC = 0.9447, 0.9711, and 0.9793 for slide-level diagnosing yeast hyphae, budding yeast, and yeast. Compared with the average performance of experts, the Youden indexes of our model’s best points were improved by 0.0069, 0.0772, 0.0579, and 0.0907 for yeast hyphae, budding yeast, yeast, and VVC. The average accuracy of the experts was improved by 5.98%, 5.20%, 4.82%, and 8.19% using our model as an AI-assisted tool. The consistency rates and Cohen’s kappa coefficients between experts’ interpretations of microscopic digital images and microscopic examination under eyepiece exceeded 93% and 0.83 for the three different morphologic states of yeast. Our model exhibits superior diagnostic accuracy for VVC compared to experts. Experts can significantly improve their own diagnostic accuracies by using our model as an AI-assisted tool. The microscope images collected from each slide effectively represent the slide.

IMPORTANCE
A cascaded deep neural network model was developed for slide-level diagnosis of vulvovaginal candidiasis (VVC), demonstrating superior diagnostic accuracy compared to experts. Experts significantly enhanced their diagnostic accuracies by utilizing our model as an AI-assisted tool. Therefore, this model holds potential for clinical application to aid in the diagnosis of VVC.
Metagenomic insights and biosynthetic potential of
Candidatus
Entotheonella symbiont associated with
Halichondria
marine sponges
Authors: Kim Hiyoung , Ahn Jiyeong , Kim Jaebum , Kang Hahk-Soo 
Published: November 2024

ABSTRACT

Korea, being surrounded by the sea, provides a rich habitat for marine sponges, which have been a prolific source of bioactive natural products. Although a diverse array of structurally novel natural products has been isolated from Korean marine sponges, their biosynthetic origins remain largely unknown. To explore the biosynthetic potential of Korean marine sponges, we conducted metagenomic analyses of sponges inhabiting the East Sea of Korea. This analysis revealed a symbiotic association of
Candidatus
Entotheonella bacteria with Halichondria sponges. Here, we report a new chemically rich Entotheonella variant, which we named
Ca
. Entotheonella halido. Remarkably, this symbiont makes up 69% of the microbial community in the sponge
Halichondira dokdoensis
. Genome-resolved metagenomics enabled us to obtain a high-quality
Ca
. E. halido genome, which represents the largest (12 Mb) and highest quality among previously reported
Entotheonella
genomes. We also identified the biosynthetic gene cluster (BGC) of the known sponge-derived Halicylindramides from the
Ca
. E. halido genome, enabling us to determine their biosynthetic origin. This new symbiotic association expands the host diversity and biosynthetic potential of metabolically talented bacterial genus
Ca
. Entotheonella symbionts.

IMPORTANCE

Our study reports the discovery of a new bacterial symbiont
Ca
. Entotheonella halido associated with the Korean marine sponge
Halichondria dokdoensis
. Using genome-resolved metagenomics, we recovered a high-quality
Ca
. E. halido MAG (Metagenome-Assembled Genome), which represents the largest and most complete
Ca
. Entotheonella MAG reported to date. Pangenome and BGC network analyses revealed a remarkably high BGC diversity within the
Ca
. Entotheonella pangenome, with almost no overlapping BGCs between different MAGs. The cryptic and genetically unique BGCs present in the
Ca
. Entotheonella pangenome represents a promising source of new bioactive natural products.
Assessing national medicines policies: a protocol for systematic review of access to medicine assessment metrics and indicators
Authors: Ojo Tolulope , Saxena Ekanki , Persaud Nav 
Published: November 2024

IntroductionEfforts to improve access to essential medicines globally include the implementation and assessment of national medicine policies. Although existing assessment tools may identify gaps, they do not link these to health system functions and policy priority areas in a way that facilitates decision-making. This systematic review aims to identify and map out existing indicators assessing essential medicines policies; assess their strengths and limitations and understand the parameters required to develop a new instrument for assessing access to medicines in a way that better supports decision makers in identifying and addressing the gaps in their national medicine policies.Methods and analysisThis systematic review is guided by the updated Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. Eligible studies will be identified across scholarly databases (MEDLINE, Embase and Scopus) and grey literature using relevant subject headings and text words. Title, abstract screening and full-text screening will be conducted by two independent reviewers. Indicators or assessment tools focused on the performance of national medicine policies with respect to improving access to essential medicines will be eligible. Data will be extracted using a pretested data abstraction form. Findings will be reported in the form of a descriptive narrative. This study will provide insights into the relevance of existing indicators and tools for assessing access to essential medicines policies. This review will also discuss the opportunities for the development of a new instrument for the assessment of national medicines policies in a way that better supports decision makers to improve access to essential medicines.Ethics and disseminationThis systematic review does not require ethics approval as it only aims to synthesise evidence from the literature. Findings will be disseminated to key health stakeholders including researchers and global and public health organisations and published in a peer-review journal. This protocol has been registered on PROSPERO (CRD42023493052).
Effect of remimazolam besylate versus propofol on haemodynamic profiles in patients undergoing thyroid surgery with recurrent laryngeal nerve monitoring: a protocol for a randomised controlled trial
Authors: Lu Dianyu , Zeng Qingmei , Zhang Anyu , Wei Wei , Huang Haiyan , Chen Weiquan , Li Jinfei , Yao Yonghua , Gu Yu 
Published: November 2024

IntroductionThyroid surgery with intraoperative nerve monitoring under total intravenous anaesthesia often requires deeper sedation due to limitations or lack of neuromuscular blocking agents, usually resulting in haemodynamic instability. Remimazolam, a newly developed sedative, is being studied for its effect on the haemodynamic profile of patients undergoing this procedure and compared with propofol.Methods and analysisThis will be a single-centre, single-blind, randomised, controlled trial in American Society of Anesthesiologists I-III patients between the ages of 18 and 65 who require recurrent laryngeal nerve monitoring for thyroid surgery. Patients will be randomised 1:1 to either remimazolam besylate or propofol, with 142 cases in each group according to a randomised, computer-generated cohort. The primary outcome is the occurrence of hypotension from induction of anaesthesia to full recovery. Secondary outcomes include the administration of vasoactive agents, the number of hypotension or hypertension episodes, the cumulative duration of hypotension or hypertension, the dose of intraoperative rescue sedation and analgesia, the time to extubation and awakening and the incidence of adverse events.Ethics and disseminationEthical approval for this study was obtained from the Medical Ethics Committee of the Affiliated Cancer Hospital and Institute of Guangzhou Medical University (2023–2024). The study protocol was modified according to the reviewers’ comments, and the revised version was approved by the Ethics Committee (2024 Research Ethics Amendment No. 3). On completion of the study, we will commit to ensuring that the results are made available to the public, regardless of the outcome. This will include either publication in an appropriate journal or oral presentation at academic conferences.Trial registration numberChiCTR2300076583.
Lesson in understanding parents’ perspective: perception of quality of care and COVID-19-related fears among users of paediatric health services over the COVID-19 pandemic in 11 facilities in Italy
Authors: Dalena Paolo , Zago Alessandro , Troisi Angela , Trobia Gian Luca , Lucarelli Annunziata , Bressan Silvia , Fasoli Silvia , Martelossi Stefano , Lubrano Riccardo , Parrino Roberta , Felici Enrico , Pilotto Chiara , Sforzi Idanna , Barbi Egidio , Lazzerini Marzia 
Published: November 2024

BackgroundThe COVID-19 pandemic had an important psychological impact on children and their families. This study aims to explore paediatric health services users’ perceptions of quality of care (QOC) and COVID-19-related fears, and their evolution over time in relation to COVID-19 pandemic.MethodsIn a multicentre cross-sectional study involving 11 public hospitals providing paediatric care across the Italian territory, we collected data from services users through a validated questionnaire. We analysed four indicators—(1) QOC perceived in relation to COVID-19; (2) overall QOC perceived; (3) fear of accessing health services due to COVID-19; (4) fear of contracting COVID-19 in hospital—and calculated Spearman’s correlation indexes (ρ) with the number of COVID-19 new cases over time. Subgroup analyses were conducted by macroregions and single facility.ResultsData from 956 services users were analysed. QOC indicators were stable over time at values close to the maximum (range 77–100 and median 100 for COVID-19 QOC, range 74–98 and median 80 for overall QOC), and no correlations were found with the COVID-19 new cases (ρ=−0.073 and −0.016, respectively). Fear of accessing care and fear of contracting the infection varied over time in between 0%–52% and 0%–53%, respectively, but did not correlate directly with number of COVID-19 new cases (ρ=0.101, 0.107 and 0.233, 0.046, respectively). At subgroup analyses, significantly higher frequencies of fear (p values <0.05) and lower QOC (p values <0.001) were reported in South Italy, and three facilities showed moderate correlation between these indicators.ConclusionsCOVID-19-related fears and perceived QOC may be mediated by more complex cultural and facility/regional-level factors, than simply by epidemic peaks. Subgroup analyses can help unpack major differences within the same country.
Cardiovascular effects of exercise training in pregnant people with a high body mass index: secondary results from a randomised controlled trial (ETIP)
Authors: Moholdt Trine , Garnæs Kirsti Krohn , Vik Idunn Pernille , Mørkved Siv , Salvesen Kjell Åsmund , Ingul Charlotte Björk 
Published: November 2024

ObjectivesWe aimed to determine the effectiveness of exercise training during pregnancy on peak oxygen uptake (V̇O2peak), cardiac function and flow-mediated dilatation (FMD) of the brachial artery throughout pregnancy and post partum in individuals with a prepregnancy body mass index (BMI) ≥28 kg/m2.Trial designParallel-group randomised controlled trial (RCT).MethodsThe exercise group in the Exercise Training in Pregnancy (ETIP) RCT was offered 3 weekly supervised exercise sessions comprising 35 min of moderate-intensity treadmill walking followed by 25 min of strength exercises. The intervention started in gestational weeks 12–18 and continued throughout pregnancy. We measured V̇O2peak and FMD at baseline, in gestational weeks 34–37 and 3 months post partum and offered echocardiography in gestational weeks 14, 20, and 32, and 6–8 weeks postpartum.ResultsOf the 91 participants included in ETIP, 87 participants (age: 31.3±4.2 years, BMI: 34.6±4.3 kg/m2) provided data on V̇O2peak, cardiac function and/or FMD. There was no statistically significant effect of exercise training on V̇O2peak in gestational weeks 34–37, with an estimated effect of 1.7 mL/min/kg (95% CI −0.4 to 3.7, p=0.112) or post partum (1.6 mL/min/kg, 95% CI −0.2 to 3.4, p=0.079), compared with the control group. There were no statistically significant between-group differences in either FMD or any of the echocardiographic outcomes. Only 50% of the participants in the exercise group fulfilled our prespecified adherence criteria.ConclusionOffering pregnant individuals with BMI ≥28 kg/m2, a supervised exercise intervention did not improve cardiorespiratory fitness, cardiac function or FMD.Trial registration numberNCT01243554.
Sintilimab plus decitabine for higher-risk treatment-naïve myelodysplastic syndromes: efficacy, safety, and biomarker analysis of a phase II, single-arm trial
Authors: Wang Jing , Li Siqi , Jiang Hao , Chang Ying-Jun , Zhao Xiaosu , Jia Jinsong , Zhu Xiaolu , Gong Lizhong , Liu Xiaohong , Yu Wenjing , Huang Xiaojun 
Published: November 2024

BackgroundImmunotherapy combined with azacitidine was feasible in higher-risk myelodysplastic syndromes (MDSs) with limited sample size of treatment-naïve patients, while the optimization of treatment strategies, including the optimal immune checkpoint inhibitor and hypomethylating agent and possible benefiting population, remained undefined. This study first evaluates the efficacy and safety of sintilimab, a PD-1 blockade, plus decitabine in treatment-naïve higher-risk MDS patients and investigates biomarkers for predicting treatment response.MethodsIn this phase II, single-arm trial (ChiCTR2100044393), treatment-naïve higher-risk MDS patients with an International Prognostic Scoring System-Revised score >3.5 received sintilimab (200 mg, days 1 and 22) and decitabine (20 mg/m2, day 1–5) over 6-week cycles. The primary endpoint was the overall response rate (ORR), including complete remission (CR), partial remission (PR) or marrow CR.ResultsA total of 54 eligible patients were enrolled and treated, with 25 (46.3%) having very high-risk MDS. Among 53 evaluable patients, the ORR was 77.4% (n=41), including 26.4% CR (n=14). The overall clinical improvement rate (CR, PR, marrow CR or hematological improvement) reached 81.1%. With a median follow-up of 20.0 months, the median event-free survival was 23 months with 12 progressing to acute myeloid leukemia. Median overall survival was not reached. Treatment was generally well tolerated, with hematologic toxicities being the most common adverse events. Biomarker analysis highlighted a negative correlation between T cell exhaustion markers, particularly TIM-3 and PD-1, with ORR.ConclusionsThe combination of sintilimab and decitabine shows promise efficacy for higher-risk MDS, with a favorable safety profile. The potential predictive value of T cell exhaustion biomarkers might help screen the possible benefiting population.Trial registration numberChiCTR210044393.