bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifunctional hydrogel electronics for closed-loop antiepileptic treatment
Authors: Qu Jin , Xie Kai , Chen Shu , He Xingdao , Wang Yuan , Chamberlin Matthew , Zhao Xi , Zhu Guangyu , Xu Chenjie , Shi Peng
Published: November 2024

Closed-loop strategies offer advanced therapeutic potential through intelligent disease management. Here, we develop a hydrogel-based, single-component, organic electronic device for closed-loop neurotherapy. Fabricated out of conductive hydrogels, the device consists of a flexible array of microneedle electrodes, each of which can be individually addressed to perform electrical recording and control chemical release with sophisticated spatiotemporal control, thus pioneering a smart antiseizure therapeutic system by combining electrical and pharmacological interventions. The recorded neural signal acts as the trigger for a voltage-driven drug release in detected pathological conditions predicted by real-time electrophysiology analysis. When implanted into epileptic animals, the device enables autonomous antiseizure management, where the dosing of antiepileptic drug is controlled in a time-sensitive, region-selective, and dose-adaptive manner, allowing the inhibition of seizure outbursts through the delivery of just-necessary drug dosages. The side effects are minimized with dosages three orders of magnitude lower than the usage in approaches simulating existing clinical treatments.
Sudden death of quantum advantage in correlation generations
Authors: Sun Weixiao , Wei Fuchuan , Shao Yuguo , Wei Zhaohui
Published: November 2024

Quantum noise is one of the most profound obstacles to implementing large-scale quantum algorithms and schemes. In particular, the dynamical process by which quantum noise, varying in strength from 0 to critical levels, affects and destroys quantum advantage has not been well understood. Meanwhile, correlation generation serves as a precious theoretical model for information processing tasks, where quantum advantage can be precisely quantified. In this study, we show that this model provides valuable insights into the understanding of this dynamical process. We prove that, as the strength of quantum noise continuously increases from 0, the quantum advantage diminishes gradually and eventually vanishes. Unexpectedly, in some cases, we observe the phenomenon of a sudden death of quantum advantage: When the noise strength exceeds a certain threshold, the quantum advantage abruptly disappears from a substantial level. This phenomenon, once again, reveals the tremendous impact of noise on quantum information processing tasks.
Chicken GSDME, a major pore-forming molecule responsible for RNA virus-induced pyroptosis in chicken
Authors: Chen Zhi , Chang He , Zhang Shujun , Gao Hui , Gao Li , Cao Hong , Li Xiaoqi , Wang Yongqiang , Zheng Shijun J.
Published: November 2024

Pyroptosis is an inflammatory type of programmed cell death that mainly depends on the formation of plasma membrane pores by Gasdermin D (GSDMD) in mammals. However, the genetic deficiency of GSDMD in chicken renders avian pyroptosis elusive. Here, we show that infection of DF-1 cells (a chicken cell line) with infectious bursal disease virus (IBDV) induced cell death associated with chicken GSDME (chGSDME) cleavage, and so did cells with other RNA virus (VSV, AIV, or NDV) infections, indicating a broad role of chGSDME in RNA virus-induced pyroptosis in chicken. Furthermore, infection of DF-1 cells by IBDV or treatment of cells with Poly(I:C) initiated MDA5-mediated signaling pathway, followed by the activation of chCaspase-3/7 cleaving chGSDME at a specific site
270
DAVD
273
. Moreover, knockdown or knockout of chGSDME expression in cells markedly reduced IBDV-induced pyroptosis and viral release. These results unravel the mechanisms of pyroptosis in chickens with RNA virus infection, providing important clues to uncover the role of GSDM proteins of different species in host response against pathogenic infection.

IMPORTANCE

Pyroptosis is an inflammatory type of programmed cell death that mainly depends on the function of GSDMD in mammals and plays a crucial role in the pathogenesis of viral infection, whereas the mechanism of pyroptosis in chicken remains elusive. Herein, we show that IBDV and other RNA virus induced pyroptosis through the chMDA5-CASP8/9-CASP3/7-chGSDME pathway. The finding advances our understanding of GSDM proteins of different species in host response against pathogenic infection.
Colibactin-induced damage in bacteria is cell contact independent
Authors: Lowry Emily , Mitchell Amir
Published: November 2024

The bacterial toxin colibactin, produced primarily by the B2 phylogroup of
Escherichia coli
, underlies some cases of colorectal cancers. Colibactin crosslinks DNA and induces genotoxic damage in both mammalian and bacterial cells. While the mechanisms facilitating colibactin delivery remain unclear, results from multiple studies supported a delivery model that necessitates cell-cell contact. We directly tested this requirement in bacterial cultures by monitoring the spatiotemporal dynamics of the DNA damage response using a fluorescent transcriptional reporter. We found that in mixed-cell populations, DNA damage saturated within 12 hours and was detectable even in reporter cells separated from colibactin producers by hundreds of microns. Experiments with distinctly separated producer and reporter colonies revealed that the intensity of DNA damage decays similarly with distance regardless of colony contact. Our work reveals that cell contact is inconsequential for colibactin delivery in bacteria and suggests that contact dependence needs to be reexamined in mammalian cells as well.

IMPORTANCE

Colibactin is a bacteria-produced toxin that binds and damages DNA. It has been widely studied in mammalian cells due to its potential role in tumorigenesis. However, fundamental questions about its impact in bacteria remain underexplored. We used
Escherichia coli
as a model system to study colibactin toxicity in neighboring bacteria and directly tested if cell-cell contact is required for toxicity, as has previously been proposed. We found that colibactin can induce DNA damage in bacteria hundreds of microns away, and the intensity of DNA damage presents similarly regardless of cell-cell contact. Our work further suggests that the requirement for cell-cell contact for colibactin-induced toxicity also needs to be reevaluated in mammalian cells.
Structural basis of a microbial trimethylamine transporter
Authors: Gao Chao , Ding Hai-Tao , Li Kang , Cao Hai-Yan , Wang Ning , Gu Zeng-Tian , Wang Qing , Sun Mei-Ling , Chen Xiu-Lan , Chen Yin , Zhang Yu-Zhong , Fu Hui-Hui , Li Chun-Yang
Published: November 2024

Trimethylamine (TMA), a simple trace biogenic amine resulting from the decomposition of proteins and other macromolecules, is ubiquitous in nature. It is found in the human gut as well as in various terrestrial and marine ecosystems. While the role of TMA in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans has only recently been explored, many microbes are well known for their ability to utilize TMA as a carbon, nitrogen, and energy source. Here, we report the first structure of a TMA transporter, TmaT, originally identified from a marine bacterium. TmaT is a member of the betaine-choline-carnitine transporter family, and we show that TmaT is an Na
+
/TMA symporter, which possessed high specificity and binding affinity toward TMA. Furthermore, the structures of TmaT and two TmaT-TMA complexes were solved by cryo-EM. TmaT forms a homotrimer structure in solution. Each TmaT monomer has 12 transmembrane helices, and the TMA transport channel is formed by a four-helix bundle. TMA can move between different aromatic boxes, which provides the structural basis of TmaT importing TMA. When TMA is bound in location I, residues Trp146, Trp151, Tyr154, and Trp326 form an aromatic box to accommodate TMA. Moreover, Met105 also plays an important role in the binding of TMA. When TMA is transferred to location II, it is bound in the aromatic box formed by Trp325, Trp326, and Trp329. Based on our results, we proposed the TMA transport mechanism by TmaT. This study provides novel insights into TMA transport across biological membranes.

IMPORTANCE

The volatile trimethylamine (TMA) plays an important role in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans and serves as a key nutrient source for a variety of ubiquitous marine microbes. While the TMA transporter TmaT has been identified from a marine bacterium, the structure of TmaT and the molecular mechanism involved in TMA transport remain unclear. In this study, we elucidated the high-resolution cryo-EM structures of TmaT and TmaT-TMA complexes and revealed the TMA binding and transport mechanisms by structural and biochemical analyses. The results advance our understanding of the TMA transport processes across biological membranes.
Klebsiella pneumoniae
induces dose-dependent shock, organ dysfunction, and coagulopathy in a nonhuman primate critical care model
Authors: Strich Jeffrey R. , Ramos-Benitez Marcos J. , Warner Seth , Kendall Heather , Stein Sydney , Platt Andrew P. , Ramelli Sabrina C. , Curran Shelly J. , Lach Izabella , Allen Kiana , Babyak Ashley , Perez-Valencia Luis J. , Minai Mahnaz , Sun Junfeng , Vannella Kevin M. , Alves Derron , Herbert Richard , Chertow Daniel S.
Published: November 2024

Nonhuman primate models that closely emulate the disease course, pathogenesis, and supportive care provided to human patients in the modern intensive care unit with bacterial sepsis are urgently needed to study pathogenesis and assess novel therapies. We therefore developed a non-human primate model of septic shock that includes supportive care akin to a modern intensive care unit. In this study, we characterized pathogen kinetics and evaluated the physiologic, immunologic, and pathologic responses in this model of septic shock induced by the clinically relevant pathogen
Klebsiella pneumoniae
across a three-log dose range. We observed dose-dependent bacteremia and circulating levels of
Klebsiella pneumoniae
DNA and endotoxin. Tachycardia and hypotension occurred in all animals and the study endpoint occurred in 8 of 12 animals that were euthanized. The infused bacterial dose was significantly associated with the severity of renal insufficiency and coagulopathy. Neutrophil activation evidenced by increased CD11b expression, decreased CD62L expression, and increased circulating levels of myeloperoxidase, lactoferrin, and neutrophil extracellular traps; monocyte activation evidenced by increased circulating levels of interleukin-6, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1; and endothelial activation evidenced by increased circulating levels of syndecan-1 and angiopoietin-II were all consistent with human sepsis. Our model provides an opportunity to study pathogenesis and investigate novel therapeutics for the treatment of bacterial sepsis in the setting of modern supportive care.

IMPORTANCE

There is currently a disconnect between the efficacy of sepsis therapies in pre-clinical animal models and human clinical trials. Therefore, developing nonhuman primate models that closely mimic human sepsis pathogenesis to study novel host-targeted therapeutics is a priority. In this study, we developed a model of septic shock with a clinically relevant bacteria (
Klebsiella pneumoniae
) that provides standard supportive care including mechanical ventilation, invasive hemodynamic monitoring, volume resuscitation, vasopressors, antibiotics, and steroids. In a dose-dependent manner, we observed that this model closely emulates the hemodynamic, end-organ dysfunction, and cellular and soluble responses associated with human sepsis. This validated model provides a unique opportunity to study the pathogenesis of acute septic shock and evaluate host-directed therapeutics in a large animal model that closely emulates the modern-day intensive care unit and supportive critical care.
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

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

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

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

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

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

Introduction

Efforts 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 analysis

This 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 dissemination

This 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

Introduction

Thyroid 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 analysis

This 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 dissemination

Ethical 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 number

ChiCTR2300076583.
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

Background

The 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.

Methods

In 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.

Results

Data 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.

Conclusions

COVID-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

Objectives

We 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 design

Parallel-group randomised controlled trial (RCT).

Methods

The 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.

Results

Of 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.

Conclusion

Offering pregnant individuals with BMI ≥28 kg/m2, a supervised exercise intervention did not improve cardiorespiratory fitness, cardiac function or FMD.

Trial registration number

NCT01243554.
Multimodal intervention based on physical exercise, mindfulness, behaviour change and education to improve pain and health in patients with chronic primary low back pain: a study protocol of the HEALTHYBACK randomised controlled trial
Authors: Tsiarleston Gavriella , López-Fernández María Dolores , Pavón-Muñoz Rodrigo , Aguilera-García Iván , López-Corchón María , Delgado-Fernández Manuel , Castellote-Caballero María Yolanda , Donoso Belén , Mesa-Ruiz Antonio Manuel , Pozuelo-Calvo Rocío , Ríos-Ortiz Ángela María , Álvarez-Corral Gemma , Marín-Jiménez Nuria , Martinez-Garcia Dario , Chirosa Ríos Ignacio Jesús , Segura-Jiménez Víctor
Published: November 2024

The HEALTHYBACK trial is based on a multimodal intervention to determine the effectiveness of a supervised physical exercise, mindfulness, behaviour change and pain neuroscience education programme on several health variables in individuals with chronic primary low back pain (CPLBP). The study will be a randomised controlled trial among 70 individuals diagnosed with CPLBP (aged 18–65 years). The intervention will be conducted in person within a hospital setting for 16 weeks and comprises a first phase (16 sessions supervised physical exercise (2 days/week, 45 min/session), mindfulness (1 day/week, 2.5 hours/session), behaviour change (daily/24 hours via a wrist-worn activity prompting device) and pain neuroscience education (1 day/biweekly, 2 hours/session)) and a second phase (16 sessions functional full-body muscle strengthening exercise, 3 days/week, 50 min/session). The primary outcomes will include perceived acute pain, pain pressure threshold, conditioned pain modulation, temporal summation of pain and disability due to pain. Secondary measures will include physical fitness, body composition, gait parameters, device-measured physical activity and sedentary behaviour, haematological profile, self-reported sedentary behaviour, quality of life, pain catastrophising, mental health, sleep duration and quality, and symptoms related to central sensitisation. The groups will undergo pretest (before the intervention), post-test (after each phase of the intervention) and retest (at a 6-week detraining period after the intervention) measurements. The results will determine the effectiveness of multidimensional interventions on several health parameters in individuals with CPLBP. They will provide knowledge for pain management and functioning in affected individuals, which might diminish the need for primary healthcare services. Trial registration number:NCT06114264.
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

Background

Immunotherapy 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.

Methods

In 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.

Results

A 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.

Conclusions

The 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 number

ChiCTR210044393.
Safety and efficacy of the Contour Neurovascular System for treating intracranial aneurysms: a systematic review and meta-analysis
Authors: Günkan Ahmet , Scarcia Luca , Ferreira Marcio Yuri , Vilardo Marina , Fabrini Paleare Luis Flavio , Bocanegra-Becerra Jhon E , Fouad Mohamed E M , Maia Henrique Garcia , Semione Gabriel , Alexandre Andrea Maria , Vilardo Leonardo , Clarençon Frédéric , Serulle Yafell , Jabbour Pascal
Published: November 2024

Background

The Contour Neurovascular System (CNS, Stryker, Kalamazoo, MI) has a unique design that allows it to address various aneurysm morphologies, including wide-necked, irregular, and shallow-shaped lesions. However, evidence of its safety and efficacy remains limited. This systematic review and meta-analysis synthesizes the current data on CNS performance.

Methods

A comprehensive search guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) standards was performed across PubMed, Embase, and Web of Science, including studies with ≥5 patients reporting on CNS use. Efficacy outcomes included immediate and last follow-up adequate aneurysm occlusion and technical success. Safety outcomes included good functional outcome (modified Rankin Scale (mRS) score of 0–2 at last follow-up), procedure-related morbidity (permanent neurological deficits), procedure-related mortality, intraoperative and postoperative complications. Pooled analyses with 95% confidence intervals (CI) were conducted, with heterogeneity assessed using I² statistics, and a random-effects model was applied.

Results

Nine studies, including 483 patients (58.8% female; mean age: 59.3±15.6 years) with 484 aneurysms, were analyzed. Of the 467 patients in whom rupture status was reported, 81.8% presented with unruptured aneurysms and 18.2% with ruptured aneurysms. Immediate adequate aneurysm occlusion rate was 53% (95% CI: 1% to 100%), with follow-up adequate occlusion at 93% (95% CI: 88% to 97%) and technical success at 98% (95% CI: 95% to 100%). Intraoperative and postoperative complication rates were 3% (95% CI: 0% to 7%) and 7% (95% CI: 3% to 12%), respectively. Procedure-related morbidity was 2% (95% CI: 0% to 3%), with no procedure-related mortality.

Conclusion

The CNS is a safe and effective novel intrasaccular device for treating intracranial aneurysms.
Evaluation and randomised controlled trial of home urinalysis testing in patients with SLE at elevated risk for developing lupus nephritis: a study protocol
Authors: Gold Heather T , El Shahawy Omar , Izmirly Peter M , Masson Mala , Cohen Brooke , Buyon Jill P
Published: November 2024

Introduction

Lupus nephritis (LN) is a frequent complication of SLE, occurring in up to 60% of adult patients and ultimately progressing from acute inflammation to chronicity with fibrosis and end-stage kidney failure in 10%–30% of patients. Racial/ethnic minority patients with lupus have worse long-term outcomes, including progression to end-stage renal disease and overall mortality. A major challenge in the management of patients with SLE is delayed identification of early kidney disease, which ultimately leads to a greater burden on both patients and the health system.

Methods and analysis

Using a mixed methods approach, this study will develop, adapt and evaluate a home urine sampling protocol with a text-messaging reminder and data capture system for patients at elevated risk of de novo LN or relapse. First, a feasibility pilot using a single-group trial design (n=18) will be implemented, with a feasibility assessment and qualitative, debriefing interviews with patients to further refine the intervention. The second phase is a comparative effectiveness trial of the intervention (n=160) with the primary outcome of biopsy eligibility, that is, the participant has a clinical indication for a kidney biopsy (urine protein–creatinine ratio≥0.5), whether or not the patient actually undergoes the biopsy procedure. The randomised trial includes an economic evaluation of the adapted home urinalysis protocol.

Discussion and dissemination

It is unknown whether weekly home-based urine sampling can identify proteinuria sooner than standard care; if found sooner, kidney problems could be diagnosed earlier, hopefully leading to earlier care for less-involved disease and subsequent reduced morbidity. The data collected in this trial will inform future feasibility and effectiveness of text-messaging-based home urine sampling interventions.

Trial registration number

The randomised trial will be registered with ClincialTrials.gov prior to enrolment start.
Canada-wide survey of school food programs
Authors: Blais Annette , Ahmed Mavra , L'Abbé Mary , Sellen Daniel , Malik Vasanti
Published: November 2024

Canada remains one of few Organisation for Economic Co-operation and Development (OECD) countries without a well-established nationally harmonized and funded school food program (SFP); however, the Canadian federal government recently announced the development and implementation of a national SFP that might supersede the uncoordinated patchwork of SFPs currently delivered across Canada. We designed and conducted novel survey research to systematically identify the characteristics of organization-led SFPs, building on previous research that focused on the characteristics of provincial and territorial government involvement in school food programming. An electronic survey was developed to include items deemed most relevant based on applicable literature and expert content validation, and distributed to organizations involved in the purchasing, planning, and/or preparation of school foods. Responses were categorized post hoc into the RE-AIM categories to assess SFP Reach, Effectiveness, Adoption, Implementation, and Maintenance. Analysis identified key SFP implementation characteristics (including funding source, payment model, and student eligibility), program components, SFP goals/mandates, and factors that determine what foods are served; and assessed correlations among key characteristics. Results from 67 SFPs across 10 provinces indicate considerable variability in SFP characteristics. SFP-delivering organizations reported a predominant goal of reducing student food insecurity, while nutrition and cost were cited as the main factors determining food served. Collectively, organizations were found to rely primarily on donations, while provincial funding accounted for only 30% of total funding. These findings reveal strengths and areas for improvement within Canada's current school food landscape and highlight important gaps that could be addressed with federal involvement.
Empirical prediction of horizontal movements induced by tunnelling in fine-grained soils
Authors: Wong Eugene K. L. , Franza Andrea , Viggiani Giulia M. B.
Published: November 2024

For tunnelling in fine-grained soils, available evidence indicates that the focal depth of displacement vectors along the ground surface decreases with the transverse distance from the tunnel centre-line. Based on field and centrifuge observations, this paper presents a new empirical method in which the focal depth is a function of the transverse offset and, possibly, the tunnel volume loss. The comparison with experimental data from centrifuge experiments and case histories confirms the reliability of the proposed method, in terms of both surface horizontal displacements and strains. In particular, the predicted horizontal displacement profiles, both in terms of maximum value and extent, are in better agreement with the available experimental evidence than those obtained using the empirical and analytical methods currently adopted in design. Finally, an operational way to obtain the complete horizontal displacement field at the surface, near-surface, and at depths down to the tunnel crown is suggested and the importance of carrying out field monitoring for surface and subsurface horizontal displacements is highlighted.
Topologically modified Einstein equation: a solution with singularities on $${\mathbb {S}}^3$$
Authors: Vigneron Quentin , Szabó Áron , Mourier Pierre
Published: November 2024

Vigneron (Found Phys 54:15, https://doi.org/10.1007/s10701-023-00749-z, 2024) recently proposed a modification of general relativity in which a non-dynamical term related to the spatial topology is introduced in the Einstein equation. The original motivation for this theory is to allow for the non-relativistic limit to exist in any physical topology. In the present paper, we derive a first inhomogeneous exact vacuum solution of this theory for a spherical topology, assuming staticity and spherical symmetry. The metric represents a black hole and a repulsive singularity at opposite poles of a 3-sphere. The solution is similar to the Schwarzschild metric, but the spacelike infinity is cut, and replaced by a repulsive singularity at finite distance, implying that the spacelike hypersurfaces have finite volume, and the total mass is zero. We discuss how this solution paves the way to massive, non-static solutions of this theory, more directly relevant for cosmology.
Insights into gravitinos abundance, cosmic strings and stochastic gravitational wave background
Authors: El Bourakadi K. , Otalora G. , Burton-Villalobos A. , Chakir H. , Ferricha-Alami M. , Bennai M.
Published: November 2024

In this paper, we investigate D-term inflation within the framework of supergravity, employing the minimal Kähler potential. Following previous studies that revealed that this model can overcome the $$\eta $$
η
-problem found in F-term models, we explore reheating dynamics and gravitino production, emphasizing the interplay between reheating temperature, spectral index, and gravitino abundance. Our analysis indicates that gravitino production is sensitive to the equation of state during reheating, affecting the reheating temperature and subsequent dark matter relic density. Furthermore, we analyze gravitational waves generated by cosmic strings, providing critical constraints on early Universe dynamics and cosmic string properties, the energy scales of both inflation and string formation influence the stochastic gravitational wave background (SGWB) generated by these cosmic strings.
Electromagnetic fields in topologically charged traversable wormholes
Authors: Kurbah Meshwa Garnet , Ahmed Faizuddin
Published: November 2024

In this research paper, we focus on analyzing the electromagnetic fields within the framework of a traversable wormhole that incorporates a cosmic string. We then extend our investigation to a traversable wormhole with a global monopole charge, addressing the same problem in this new context. To facilitate our study, we compute the electromagnetic field tensor and derive Maxwell’s vacuum field equations, which govern the behavior of the electric and magnetic fields. Using an analytical approach, we obtain solutions for the electromagnetic fields and compare them with the results from conventional Minkowski flat space. Our study demonstrates significant deviations in the electromagnetic fields, and thus, changes the behavior of electromagnetic waves in the presence of a cosmic string and a global monopole charges within this wormhole background.