bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formulation and evaluation of atovaquone-loaded macrophage-derived exosomes against
Toxoplasma gondii
:
in vitro
and
in vivo
assessment
Authors: Goudarzi Fatemeh , Jajarmi Vahid , Shojaee Saeedeh , Mohebali Mehdi , Keshavarz Hossein 
Published: November 2023

ABSTRACT

This study aimed to prepare and assess atovaquone (ATQ)-loaded exosomes (EXO-ATQ) against
Toxoplasma gondii
to improve their therapeutic activities on acute and chronic phases of murine toxoplasmosis. Exosomes were isolated from a mouse macrophage cell line (J774A.1). The isolated exosomes were loaded with ATQ (EXO-ATQ), applying the co-incubation method.
In vitro
efficacy of EXO-ATQ against
T. gondii
infection was assessed in Vero cell culture. An
in vivo
experiment was carried out in BALB/c mice infected with RH (acute strain) and Tehran (chronic strain) of
T. gondii,
followed by treatment with EXO-ATQ. Their survival time and parasite load were compared with that in the suspension of ATQ (S-ATQ) as a positive control group. The
in vitro
study showed that exosomes improved the efficacy of ATQ, and EXO-ATQ significantly reduced intracellular proliferation of
T. gondii
tachyzoites compared to S-ATQ (
P
≤  0.05). In acute experimental toxoplasmosis, the mice treated with EXO-ATQ showed a significant reduction in tachyzoites count of the peritoneal cavity and a longer survival time (
P
≤  0.05). Furthermore, EXO-ATQ administration significantly decreased the mean number (97.3% cyst reduction) and the average size of the brain cysts of chronically infected mice with
T. gondii
, Tehran strain (
P
≤  0.05). Besides, the decrease in cyst numbers was confirmed by the down-regulation of
BAG1
using a real-time PCR assay. Our results implied that exosomes have the potential to be used as an efficient drug delivery system, and the loading of ATQ into the exosomes ameliorates the effect of ATQ against
T. gondii
. This study suggests a new strategy for improving the effectiveness of ATQ against acute and chronic phases of
T. gondii
.

IMPORTANCE

This study is the first of its kind that suggests exosomes as a nano-carrier loaded with atovaquone (ATQ), which could be considered as a new strategy for improving the effectiveness of ATQ against acute and chronic phases of
Toxoplasma gondii
.
Role of DEAD-box RNA helicases in low-temperature adapted growth of Antarctic
Pseudomonas syringae
Lz4W
Authors: Hussain Ashaq , Ray Malay Kumar 
Published: November 2023

ABSTRACT

Pseudomonas syringae
possesses genes for all five major DEAD-box RNA helicases,
rhlE
,
srmB
,
csdA
,
dbpA
, and
rhlB
, that are found in γ-proteobacteria. Bioinformatic analysis of the RNA helicase genes provided detailed insights into their genomic organization, promoter characteristics, regulatory 3′ regions, and sequence similarity. Disruption of
rhlB
and
rhlE
genes did not have any effect on growth of the
P. syringae
mutants at optimum (22°C) or at low (4°C) temperatures. On the other hand, disruption of
srmB
and
dbpA
genes caused a slow-growing phenotype in the mutants at low temperature (4°C). In comparison to the above-mentioned helicases, deletion of
csdA
gene caused the mutant (Δ
csdA
) to be totally incapable of growing at 4°C while marginally affecting the growth (resulting in slow growth) at the optimum temperature (22°C). Functional complementation studies revealed that RNA helicases are functionally non-redundant, as the roles performed by different helicases are individual and specific.

IMPORTANCE

RNA metabolism is important as RNA acts as a link between genomic information and functional biomolecules, thereby playing a critical role in cellular response to environment. We investigated the role of DEAD-box RNA helicases in low-temperature adapted growth of
P. syringae
, as this group of enzymes play an essential role in modulation of RNA secondary structures. This is the first report on the assessment of all major DEAD-box RNA helicases in any Antarctic bacterium. Of the five RNA helicases, three (
srmB
,
csdA
, and
dbpA
) are important for the growth of the Antarctic
P. syringae
at low temperature. However, the requisite role of
dbpA
and the indispensable requirement of
csdA
for low-temperature adapted growth are a novel finding of this study. Growth analysis of combinatorial deletion strains was performed to understand the functional interaction among helicase genes. Similarly, genetic complementation of RNA helicase mutants was conducted for identification of gene redundancy in
P. syringae
.
Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial
Authors: Lee Kuan Ken , Doudesis Dimitrios , Ferry Amy V , Chapman Andrew R , Kimenai Dorien M , Fujisawa Takeshi , Bularga Anda , Lowry Matthew T H , Taggart Caelan , Schulberg Stacey , Wereski Ryan , Tuck Chris , Strachan Fiona E , Newby David E , Anand Atul , Shah Anoop S V , Mills Nicholas L 
Published: November 2023

Abstract

Objective
To evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome.

Design
Secondary observational analysis of a stepped wedge, cluster randomised controlled trial.

Setting
10 secondary and tertiary care centres in Scotland, UK.

Participants
48 282 consecutive patients with suspected acute coronary syndrome. Myocardial injury was defined as any high sensitivity assay result for cardiac troponin I >99th centile of 16 ng/L in women and 34 ng/L in men.

Intervention
Hospital sites were randomly allocated to either early (n=5 hospitals) or late (n=5 hospitals) implementation of a high sensitivity cardiac troponin I assay with sex specific diagnostic thresholds.

Main outcome measure
The main outcome was myocardial infarction or death at five years.

Results

10 360 patients had cardiac troponin concentrations greater than the 99th centile, of whom 1771 (17.1%) were reclassified by the high sensitivity assay. The five year incidence of subsequent myocardial infarction or death before and after implementation of the high sensitivity assay was 29.4% (5588/18 978)
v
25.9% (7591/29 304), respectively, in all patients (adjusted hazard ratio 0.97, 95% confidence interval 0.93 to 1.01), and 63.0% (456/720)
v
53.9% (567/1051), respectively, in those reclassified by the high sensitivity assay (0.82, 0.72 to 0.94). After implementation of the high sensitivity assay, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischaemic myocardial injury (0.83, 0.75 to 0.91) but not in those with type 1 or type 2 myocardial infarction (0.92, 0.83 to 1.01 and 0.98, 0.84 to 1.14).

Conclusions
Implementation of a high sensitivity cardiac troponin I assay in the assessment of patients with suspected acute coronary syndrome was associated with a reduced risk of subsequent myocardial infarction or death at five years in those reclassified by the high sensitivity assay. Improvements in outcome were greatest in patients with non-ischaemic myocardial injury, suggesting a broader benefit beyond the identification of myocardial infarction.

Trial registration

ClinicalTrials.gov
NCT01852123
.
Effectiveness of a government-led, multiarm intervention on early childhood development and caregiver mental health: a study protocol for a factorial cluster-randomised trial in rural China
Authors: Jiang Qi , Wang Boya , Qian Yiwei , Emmers Dorien , Li Shanshan , Pappas Lucy , Tsai Eleanor , Sun Letao , Singh Manpreet , Fernald Lia , Rozelle Scott 
Published: November 2023

IntroductionThe high incidences of both the developmental delay among young children and the mental health problems of their caregivers are major threats topublic healthin low-income and middle-income countries. Parental training interventions during early childhood have been shown to benefit early development, yet evidence on strategies to promote caregiver mental health remains limited. In addition, evidence on the optimal design of scalable interventions that integrate early child development and maternal mental health components is scarce.Methods and analysisWe design a single-blind, factorial, cluster-randomised controlled, superiority trial that will be delivered and supervised by local agents of the All China Women’s Federation (ACWF), the nationwide, government-sponsored social protection organisation that aims to safeguard the rights and interests of women and children. We randomise 125 villages in rural China into four arms: (1) a parenting stimulation arm; (2) a caregiver mental health arm; (3) a combined parenting stimulation and caregiver mental health arm and (4) a pure control arm. Caregivers and their children (aged 6–24 months at the time of baseline data collection) are selected and invited to participate in the 12-month-long study. The parenting stimulation intervention consists of weekly, one-on-one training sessions that follow a loose adaptation of the Reach Up and Learn curriculum. The caregiver mental health intervention is comprised of fortnightly group activities based on an adaptation of the Thinking Healthy curriculum from the WHO. Primary outcomes include measures of child development and caregiver mental health. Secondary outcomes include a comprehensive set of physical, psychological and behavioural outcomes. This protocol describes the design and evaluation plan for this programme.Ethics and disseminationThis study received approval from the Institutional Review Board of Stanford University (IRB Protocol #63680) and the Institutional Review Board of the Southwestern University of Finance and Economics in Chengdu, Sichuan, China. Informed oral consent will be obtained from all caregivers for their own and their child’s participation in the study. The full protocol will be publicly available in an open-access format. The study findings will be published in economics, medical and public health journals, as well as Chinese or English policy briefs.Trial registration numberAEA RCT Registry (AEARCTR-0010078) and ISRCTN registry (ISRCTN84864201).
Association of living condition using urbanisation level and neighbourhood deprivation with loneliness and social isolation during COVID-19 pandemic: a cross-sectional study of the nationwide data in Japan
Authors: Sasaki Natsu , Tabuchi Takahiro , Okubo Ryo , Nishi Daisuke 
Published: November 2023

ObjectivesThe aim of this study was to investigate the association of living condition (deprivation and urbanisation level) with loneliness and social isolation.Study designCross-sectional study.MethodsData were retrieved from the Japan COVID-19 and Society Internet Survey, a nationwide online cohort study, conducted from September to October 2021. Area Deprivation Index and Densely Inhabited District data were used as indicators of living condition. The Japanese version of the University of California, Los Angeles Loneliness Scale and Lubben Social Network Scale-6 were used to assess loneliness and social isolation, respectively. Analysis of covariance was performed to compare the difference in outcome variables by living conditions (four categories), adjusting for gender, age, educational attainment, income, marital status, people living with, work status and subjective health status.ResultsA total of 27 520 community dwelling people were included in this study. For loneliness, living condition did not show a significant difference in the adjusted model, while deprived area had a tendency to show high loneliness. For social isolation, there was a significant group difference in the adjusted model (p<0.001), and living in a higher urbanisation level and lower deprivation showed the highest score for social isolation.ConclusionOverall, the effects of the living condition on loneliness and social isolation were small. Further study is needed to explore more comprehensive environment factors affecting loneliness and social isolation.
Exploring the knowledge and practices on road safety measures among motorbikers in Dhaka, Bangladesh: a cross-sectional study
Authors: Das Sadhan Kumar , Tamannur Tahazid , Nesa Arifatun , Noman Abdullah Al , Dey Piue , Kundu Shuvojit Kumar , Sultana Hafiza , Riaz Baizid Khoorshid , Islam ANM Shamsul , Sharower Golam , Dhar Bablu Kumar , Rahman Mohammad Meshbahur 
Published: November 2023

IntroductionRoad traffic injuries (RTIs), particularly motorbike injuries, are one of the leading causes of death worldwide and have been a serious concern in low- and middle-income countries like Bangladesh. Therefore, this study aimed to assess the level of knowledge and practices on road safety measures among motorbikers in Dhaka, Bangladesh.MethodsThis cross-sectional study was conducted from January 2022 to December 2022 among 350 motorbikers of Dhaka city via a series of face-to-face interviews. Motorbikers who regularly ride a motorcycle were interviewed about their road safety knowledge and practices through a two-stage cluster sampling technique. Frequency distribution, independent sample t-test and one-way analysis of variance (ANOVA) were performed in data analysis.ResultsOut of the 350 motorbikers, only 54.6% had good knowledge and 16.9% had poor knowledge on the signs and safety regulations of roads. Moreover, only 50.6% of respondents followed good practices while 23.4% followed poor practices of road safety measures. One-way ANOVA analysis demonstrates that the average knowledge score was significantly (p<0.05) higher among higher-educated, unmarried and non-smokers. Additionally, higher education level, non-smoking status and being Muslim were significantly (p<0.05) associated with good road safety practices.ConclusionsThe overall good knowledge level and practices of road safety measures among the motorbikers was not satisfactory although the majority of them knew individual signs and regulations. Therefore, this study suggests that education and strict enforcement of traffic rules may increase their knowledge and practice behaviour regarding road safety which in turn would minimise traffic injuries and fatalities.
Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit?
Authors: Jia BaiXue , Zhang Longhui , Pan Yuesong , Tong Xu , Zhang Xuelei , Mo Dapeng , Ma Ning , Luo Gang , Song Ligang , Li Xiaoqing , Wang Bo , Nguyen Thanh N , Gao Feng , Miao Zhongrong 
Published: November 2023

Background
Angioplasty and/or stenting is a rescue therapy for mechanical thrombectomy (MT) in acute intracranial large vessel occlusion. This study was undertaken to determine whether rescue angioplasty and/or stenting improves the outcome after MT and to investigate whether outcomes differ by subgroup of rescue indication.

Methods
We performed propensity score matching (PSM) with data from a prospective multicenter registry of patients with acute large vessel occlusion receiving endovascular treatment. Patients were divided into the MT alone group and the MT with rescue therapy group. The primary outcome was functional independence (modified Rankin Scale score of 0–2) at 90 days. PSM was also performed in the failed MT (modified Thrombolysis In Cerebral Infarction (mTICI) 0–2a) and the residual severe stenosis (mTICI 2b–3) subgroups, respectively.

Results
326 patients of mean±SD age 62.7±12.0 years (90 women, 27.6%) were matched from 1274 patients. In the matched cohort, functional independence at 90 days was higher in the rescue therapy group than in the MT alone group (44.2% vs 29.5%; OR 1.90, 95% CI 1.18 to 3.06, P=0.008). In the failed MT subgroup with 66 matched pairs, more patients had functional independence in the rescue therapy group than in the MT alone group (39.0% vs 17.0%; OR 3.12, 95% CI 1.29 to 7.59, P=0.01). In the residual stenosis subgroup with 63 matched pairs, functional independence rates were similar in the rescue therapy and the MT alone groups (51.6% vs 55.7%; OR 0.85, 95% CI 0.42 to 1.72, P=0.65).

Conclusion
Rescue angioplasty and/or stenting could improve the clinical outcome in patients with acute large vessel occlusion with failed MT, while no benefit was seen in those with residual severe stenosis but substantial reperfusion.
First-principles study on the adsorption of divalent heavy metal ions by black phosphorus in water
Authors: Wang Ying , Wang Haining , Liu Guili , Wei Lin , Zhang Guoying 
Published: November 2023

With the rapid development of electronics, the application and research of two-dimensional materials have been at the forefront of the world’s scientific research. Black phosphorus (BP) has the advantages of large specific surface area, anisotropy, band tunability, high electrical conductivity and high theoretical specific capacity, which make it very promising for research in the fields of medicine, aerospace and electrochemistry. This paper calculates the electronic structure and adsorption properties of BP in water for different heavy metal ions of Pb[Formula: see text], Hg[Formula: see text] and Cd[Formula: see text], including adsorption energy, bandgap, electron density and Mulliken population analysis, based on the first-principles approach of density generalized theory. First principles are quantum mechanical calculations based on density functional theory (DFT), which is a dominant well-developed method in the field of materials simulations, with low errors and high efficiency, especially in systems containing metallic particles. The results showed that the Pb[Formula: see text] adsorption system in water was more stable than the Hg[Formula: see text] adsorption system and the Cd[Formula: see text] adsorption system. The bandgap values of 0.617, 0.785 and 0.715[Formula: see text]eV of BP after adsorption of Pb[Formula: see text], Hg[Formula: see text] and Cd[Formula: see text] in water are smaller compared to 0.891[Formula: see text]eV of intrinsic BP, and its properties change from direct bandgap semiconductor to indirect bandgap semiconductor. The higher the stability of a system for the adsorption of different heavy metal ions by BP, the higher the internal electron activity of the adsorption system and the amount of electron transfer. Meanwhile, it is concluded that the electrons mainly transfer from P to heavy metal ions in all the adsorption systems. The electron transfer of the BP-Pb[Formula: see text], Hg[Formula: see text], and Cd[Formula: see text] adsorption system occurs mainly in the p, s, and s/p orbitals, respectively. The above content investigated the electronic structure changes and internal electron transfer of heavy metal ions adsorbed by black phosphorus in water, expecting to provide a new reference basis for the detection of heavy metal ions in industrial wastewater using black phosphorus.
PACMNET, V1, CoNEXT3, December 2023 Editorial
Authors: Mellia Marco , Steenkiste Peter , Qiu Lili , Bonaventure Olivier 
Published: November 2023

The Proceedings of the ACM on Networking (PACMNET) series present the highest-quality research conducted in the areas of emerging computer networks and their applications. We encourage submissions that present new technologies, novel experimentation, creative use of networking technologies, and new insights made possible using analysis. The journal is strongly supported by the ACM Special Interest Group on Communications and Computer Networks (SIGCOMM) and involves top-level researchers in its Editorial Board.
This issue contains papers submitted for the June '23 deadline. 129 long papers and 19 short papers were submitted to this deadline. 24 of the long papers and 5 of the short papers have been accepted after a rigorous review process organized with 50 Associate Editors and a few external reviewers. After review, each paper was conditionally accepted (with shepherding), allowed a "oneshot- major" revision, or rejected. The review process was split into two rounds. All submissions received at least 3 reviews in the first round. The papers that advanced to the second round received at least two additional reviews. After an online discussion phase among the reviewers, papers were extensively discussed during an online Associate Editors' meeting where the final decisions were made. In case of major revision, the authors have been invited to address the reviewers' comments and prepare a thoroughly revised version of their contribution. Revised papers have been then thoroughly reviewed again before being either accepted or rejected. This issue collects papers that have been finally accepted for publication after going through the minor revision process.
The long papers published in this issue and in the two previous ones will be presented at the CoNEXT 2023 conference on December 5-8, in Paris, France together with the short papers that appear in the conference proceedings.
DDoS2Vec: Flow-Level Characterisation of Volumetric DDoS Attacks at Scale
Authors: Singh Samra Ravjot , Barcellos Marinho 
Published: November 2023

Volumetric Distributed Denial of Service (DDoS) attacks have been a severe threat to the Internet for more than two decades. Some success in mitigation has been achieved based on numerous defensive techniques created by the research community, implemented by the industry, and deployed by network operators. However, evolution is not a privilege of mitigations, and DDoS attackers have found better strategies and continue to cause harm. A key challenge in winning this race is understanding the various characteristics of DDoS attacks in network traffic at scale and in a realistic manner.
In this paper, we propose DDoS2Vec, a novel approach to characterise DDoS attacks in real-world Internet traffic using Natural Language Processing (NLP) techniques. DDoS2Vec is a domain-specific application of Latent Semantic Analysis that learns vector representations of potential DDoS attacks. We look into the link between natural language and computer network communication in a way that has not been previously studied. Our approach is evaluated on a large-scale dataset of flow samples collected from an Internet eXchange Point (IXP) in one year. We evaluate the performance of DDoS2Vec via multi-label classification in a Machine Learning (ML) scenario. DDoS2Vec characterises DDoS attacks more clearly than other baselines - including NLP-based approaches inspired by recent networks research and a basic non-NLP solution.
FlexCP: A Scalable Multipath TCP Proxy for Cellular Networks
Authors: Kim Duckwoo , Moon YoungGyoun , Hwang Jaehyun , Park KyoungSoo 
Published: November 2023

Research has shown that Multipath TCP (MPTCP) improves the quality of a TCP connection by exploiting multiple paths, but its adoption in the wide area network is still fledgling. While MPTCP-TCP proxying is often employed as a practical solution, the performance of a split-connection proxy is suboptimal – it wastes CPU cycles on content relaying between two connections while it does not efficiently leverage multiple CPU cores in packet processing.
We present FlexCP, a high-performance MPTCP-TCP proxy based on the following properties. First, FlexCP operates by translating the two protocols on a packet level. This approach not only avoids the overhead of flow reassembly and memory copying, but it greatly simplifies the implementation as the proxy stays away from reliable data transfer, socket buffer management, and per-hop congestion/flow control. Second, FlexCP maintains connection-to-core affinity for multiple subflows of the same MPTCP connection and its corresponding TCP connection by leveraging SmartNIC. This enables a lock-free implementation for packet processing, which significantly improves the performance. Our evaluation demonstrates that FlexCP achieves 281 Gbps of connection proxying on a single machine, outperforming existing proxies by up to 6.3× in terms of throughput while it incurs little extra latency over direct TCP/MPTCP connections.