bluuebunny/crossref_metadata_2025 huggingface dataset:
PEXEL is a proteolytic maturation site for both exported and non-exported
Plasmodium
proteins
Authors: Fierro Manuel A. , Muheljic Ajla , Sha Jihui , Wohlschlegel James , Beck Josh R.
Published: February 2024

Obligate intracellular malaria parasites dramatically remodel their erythrocyte host through effector protein export to create a niche for survival. Most exported proteins contain a pentameric

P
lasmodium

ex
port
el
ement (PEXEL)/host-targeting motif that is cleaved in the parasite ER by the aspartic protease Plasmepsin V (PMV). This processing event exposes a mature N terminus required for translocation into the host cell and is not known to occur in non-exported proteins. Here, we report that the non-exported parasitophorous vacuole protein UIS2 contains a
bona fide
PEXEL motif that is processed in the
P. falciparum
blood stage. While the N termini of exported proteins containing the PEXEL and immediately downstream ~10 residues are sufficient to mediate translocation into the RBC, the equivalent UIS2 N terminus does not promote the export of a reporter. Curiously, the UIS2 PEXEL contains an unusual aspartic acid at the fourth position, which constitutes the extreme N-terminal residue following PEXEL cleavage (P1′, RIL↓DE). Using a series of chimeric reporter fusions, we show that Asp at P1′ is permissive for PMV processing but abrogates export. Moreover, mutation of this single UIS2 residue to alanine enables export, reinforcing that the mature N terminus mediates export, not PEXEL processing
per se
. Prompted by this observation, we further show that PEXEL sequences in the N termini of other non-exported rhoptry proteins are also processed, suggesting that PMV may be a more general secretory maturase than previously appreciated, similar to orthologs in related apicomplexans. Our findings provide new insight into the unique N-terminal constraints that mark proteins for export.

IMPORTANCE

Host erythrocyte remodeling by malaria parasite-exported effector proteins is critical to parasite survival and disease pathogenesis. In the deadliest malaria parasite
Plasmodium falciparum
, most exported proteins undergo proteolytic maturation via recognition of the pentameric

P
lasmodium

ex
port
el
ement (PEXEL)/host-targeting motif by the aspartic protease Plasmepsin V, which exposes a mature N terminus that is conducive for export into the erythrocyte host cell. While PEXEL processing is considered a unique mark of exported proteins, we demonstrate that PEXEL motifs are present and processed in non-exported proteins. Importantly, we show that specific residues at the variable fourth position of the PEXEL motif inhibit export despite being permissive for processing, reinforcing that features of the mature N terminus, and not PEXEL cleavage, identify cargo for export. This opens the door to further inquiry into the nature and evolution of the PEXEL motif.
Refined understanding of the impact of the
Mycobacterium tuberculosis
complex diversity on the intrinsic susceptibility to pretomanid
Authors: Rupasinghe Praharshinie , Reenaers Rabab , Vereecken Jens , Mulders Wim , Cogneau Sari , Merker Matthias , Niemann Stefan , Vally Omar Shaheed , Rigouts Leen , Köser Claudio U. , Decroo Tom , de Jong Bouke C.
Published: February 2024

Previous work reported unprecedented differences in the intrinsic
in vitro
susceptibility of the
Mycobacterium tuberculosis
complex (MTBC) to pretomanid (Pa) using the Mycobacteria Growth Indicator Tube (MGIT) system. We tested 125 phylogenetically diverse strains from all known MTBC lineages (
1
–
9
) without known Pa resistance mutations and four strains with known resistance mutations as controls. This confirmed that MTBC, unlike most bacteria-antimicrobial combinations, displayed substantial differences in the intrinsic susceptibility relative to the technical variation of Pa MIC testing. This was also the case for the Middlebrook 7H11 (7H11) medium, demonstrating that these differences were not specific to MGIT. Notably, lineage 1 was confirmed to have intrinsically elevated MICs compared with lineages 2, 3, 4, and 7 (L2–4/7), underlining the urgent need for WHO to publish its decision of whether lineage 1 should be deemed treatable by BPaL(M), the now preferred all-oral regimen for treating rifampin-resistant tuberculosis. Lineages 5 and 6, which are most frequent in West Africa, responded differently to Pa, with lineage 5 being more similar to L2–4/7 and lineage 6 being more susceptible. More data are needed to determine whether 7H11 MICs are systematically lower than those in MGIT.

IMPORTANCE

This study confirmed that the
Mycobacterium tuberculosis
complex lineage 1, responsible for 28% of global tuberculosis cases, is less susceptible to pretomanid (Pa). It also refined the understanding of the intrinsic susceptibilities of lineages 5 and 6, most frequent in West Africa, and lineages 8 and 9. Regulators must review whether these
in vitro
differences affect the clinical efficacy of the WHO-recommended BPaL(M) regimen and set breakpoints for antimicrobial susceptibility testing accordingly. Notably, regulators should provide detailed justifications for their decisions to facilitate public scrutiny.
A 6-year retrospective study of clinical features, microbiology, and genomics of Shiga toxin-producing
Escherichia coli
in children who presented to a tertiary referral hospital in Costa Rica
Authors: Perez-Corrales Cristian , Peralta-Barquero Valeria , Duarte-Martinez Francisco , Oropeza-Barrios Gletty
Published: February 2024

Shiga-toxin-producing
Escherichia coli
(STEC) is associated with diarrhea and hemolytic uremic syndrome (HUS). STEC infections in Costa Rica are rarely reported in children. We gathered all the records of STEC infections in children documented at the National Children’s Hospital, a tertiary referral hospital, from 2015 to 2020. Clinical, microbiological, and genomic information were analyzed and summarized. A total of 3,768 diarrheal episodes were reviewed. Among them, 31 STEC were characterized (29 fecal, 1 urine, and 1 bloodstream infection). The prevalence of diarrheal disease due to STEC was estimated at 0.8% (
n
= 29/3,768), and HUS development was 6.4% (
n
= 2/31). The
stx1
gene was found in 77% (
n
= 24/31) of STEC strains.
In silico
genomic predictions revealed a predominant prevalence of serotype O118/O152:H2, accompanied by a cluster exhibiting allele differences ranging from 33 to 8, using a core-genome multilocus sequence typing (cgMLST) approach. This is the first study using a genomic approach for STEC infections in Costa Rica.

IMPORTANCE

This study provides a comprehensive description of clinical, microbiological, genomic, and demographic data from patients who attended the only pediatric hospital in Costa Rica with Shiga-toxin-producing
Escherichia coli
(STEC) infections. Despite the low prevalence of STEC infections, we found a predominant serotype O118/O152:H2, highlighting the pivotal role of genomics in understanding the epidemiology of public health threats such as STEC. Employing a genomic approach for this pathogen for the first time in Costa Rica, we identified a higher prevalence of STEC in children under 2 years old, especially those with gastrointestinal comorbidities, residing in densely populated regions. Limitations such as potential geographic bias and lack of strains due to direct molecular diagnostics are acknowledged, emphasizing the need for continued surveillance to uncover the true extent of circulating serotypes and potential outbreaks in Costa Rica.
Microbiome composition and function within the Kellet’s whelk perivitelline fluid
Authors: Daniels Benjamin N. , Nurge Jenna , De Smet Chanel , Sleeper Olivia , White Crow , Davidson Jean M. , Fidopiastis Pat
Published: February 2024

Microbiomes have gained significant attention in ecological research, owing to their diverse interactions and essential roles within different organismal ecosystems. Microorganisms, such as bacteria, archaea, and viruses, have profound impact on host health, influencing digestion, metabolism, immune function, tissue development, and behavior. This study investigates the microbiome diversity and function of Kellet’s whelk (
Kelletia kelletii
) perivitelline fluid (PVF), which sustains thousands of developing
K. kelletii
embryos within a polysaccharide and protein matrix. Our core microbiome analysis reveals a diverse range of bacteria, with the
Roseobacter
genus being the most abundant. Additionally, genes related to host-microbe interactions, symbiosis, and quorum sensing were detected, indicating a potential symbiotic relationship between the microbiome and Kellet’s whelk embryos. Furthermore, the microbiome exhibits gene expression related to antibiotic biosynthesis, suggesting a defensive role against pathogenic bacteria and potential discovery of novel antibiotics. Overall, this study sheds light on the microbiome’s role in Kellet’s whelk development, emphasizing the significance of host-microbe interactions in vulnerable life history stages. To our knowledge, ours is the first study to use 16S sequencing coupled with RNA sequencing (RNA-seq) to profile the microbiome of an invertebrate PVF.

IMPORTANCE

This study provides novel insight to an encapsulated system with strong evidence of symbiosis between the microbial inhabitants and developing host embryos. The Kellet’s whelk perivitelline fluid (PVF) contains microbial organisms of interest that may be providing symbiotic functions and potential antimicrobial properties during this vulnerable life history stage. This study, the first to utilize a comprehensive approach to investigating Kellet’s whelk PVF microbiome, couples 16S rRNA gene long-read sequencing with RNA-seq. This research contributes to and expands our knowledge on the roles of beneficial host-associated microbes.
Personal strategies to reduce the effects of landscape fire smoke on asthma-related outcomes: a protocol for systematic review and meta-analysis
Authors: Beyene Tesfalidet , Gibson Peter G , Murphy VE , Jensen Megan E , McDonald Vanessa M
Published: February 2024

Introduction

Landscape fire smoke (LFS) contains several hazardous air pollutants that are known to be detrimental to human health. People with asthma are more vulnerable to the health impact of LFS than general populations. The aim of this review is to investigate the effectiveness of personal strategies to reduce the effect of LFS on asthma-related outcomes.

Methods and analysis

We will electronically search databases such as Medline, Embase, CINAHL and Cochrane Clinical Trials Register to identify eligible articles for the review. Screening of search results and data extraction from included studies will be completed by two independent reviewers. The risk of bias (RoB 2) will be assessed using the Risk of Bias Assessment Tool for Non-Randomised Studies for observational studies, the Cochrane Collaboration tool for assessing the RoB 2 for randomised controlled trials (RCTs) and the Risk Of Bias In Nonrandomized Studies of Interventions tool for non-RCTs. A random-effect meta-analysis will be performed to determine the pooled summary of findings of the included studies. If meta-analysis is not possible, we will conduct a narrative synthesis. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Ethics and dissemination

This study will synthesise the available evidence obtained from published studies and as such, no ethical approval is required. The review will be disseminated through peer-reviewed publications and conference presentations.

PROSPERO registration number

CRD42022341120.
How the commercial virtual care industry gathers, uses and values patient data: a Canadian qualitative study
Authors: Spithoff Sheryl , McPhail Brenda , Vesely Leslie , Rowe Robyn K , Mogic Lana , Grundy Quinn
Published: February 2024

Objectives

To understand and report on the direct-to-consumer virtual care industry in Canada, focusing on how companies collect, use and value patient data.

Design

Qualitative study using situational analysis methodology.

Setting

Canadian for-profit virtual care industry.

Participants

18 individuals employed by or affiliated with the Canadian virtual care industry.

Methods

Semistructured interviews were conducted between October 2021 and January 2022 and publicly available documents on websites of commercial virtual care platforms were retrieved. Analysis was informed by situational analysis, a constructivist grounded theory methodology, with a continuous and iterative process of data collection and analysis; theoretical sampling and creation of theoretical concepts to explain findings.

Results

Participants described how companies in the virtual care industry highly valued patient data. Companies used data collected as patients accessed virtual care platforms and registered for services to generate revenue, often by marketing other products and services. In some cases, virtual care companies were funded by pharmaceutical companies to analyse data collected when patients interacted with a healthcare provider and adjust care pathways with the goal of increasing uptake of a drug or vaccine. Participants described these business practices as expected and appropriate, but some were concerned about patient privacy, industry influence over care and risks to marginalised communities. They described how patients may have agreed to these uses of their data because of high levels of trust in the Canadian health system, problematic consent processes and a lack of other options for care.

Conclusions

Patients, healthcare providers and policy-makers should be aware that the direct-to-consumer virtual care industry in Canada highly values patient data and appears to view data as a revenue stream. The industry’s data handling practices of this sensitive information, in the context of providing a health service, have implications for patient privacy, autonomy and quality of care.
Investigating healthcare workforce recruitment and retention: a mixed-methods study protocol
Authors: Alkan Erkan , Cushen-Brewster Noreen , Anyanwu Philip
Published: February 2024

Introduction

Although the sustainability of the health workforce has been identified as essential to achieving health and wider development objectives, challenges with securing and retaining the healthcare workforce persist. In the UK, there are notable shortages across a wide range of National Health Service (NHS) staff groups, with a high staff turnover indicating retention issues in the healthcare workforce. In addition, gaps exist in understanding the root cause of individual organisation’s workforce deficiencies and how their practice environment factors interact to impact workforce recruitment and retention.

Methods and analysis

An exploratory mixed-methods approach will be conducted to investigate the impact of organisational practice environment factors on healthcare workforce recruitment and retention in two Integrated Care Systems (ICS) in the East of England. We will conduct an online survey of newly qualified and established nurses and allied health professionals using a questionnaire adapted from two validated instruments. Our calculation suggests a sample size of 373 participants, we will aim to surpass this in our recruitment to strengthen the statistical analyses. Multilevel linear regression models will be fitted to evaluate the association between organisational practice environmental factors and staff recruitment and retention. The qualitative interviews will explore the experiences and perspectives of staff and senior leaders to explain the survey results and any significant associations therein. Also, the interviews will explore how to strengthen the partnership between higher education institutions, Health Education England, health and care service providers, NHS nursing and allied health professional staff to enhance recruiting and retaining staff. An exploratory inductive coding and analysis will follow Braun and Clarke’s recommendations to generate key themes from transcribed interview data.

Ethics and dissemination

Ethical approval has been obtained through the University of Suffolk Research Ethics Committee (approval number: RETH(S)22/051). Findings from our work will be disseminated through publications in peer-reviewed journals; presentations at stakeholders’ events, professional and academic conferences; and short reports for stakeholders, including participating ICSs.
Adequacy of cancer-related pain management using the Pain Management Index among patients with cancer in the Northwest oncology centres of Ethiopia: an institutional-based cross-sectional study
Authors: Mihiretie Endalamaw Aschale , Siyum Tewodros Solomon , Tamene Fasil Bayafers
Published: February 2024

Objective

The aim of this study was to assess the adequacy of cancer-related pain (CRP) management and associated factors among patients with cancer in the Northwest oncology centres of Ethiopia.

Design and setting

An institutional-based multicentre cross-sectional study was conducted among patients with cancer in the Northwest oncology centres of Ethiopia from May to July 2022.

Participants

All oncology patients at selected hospitals who fulfilled the inclusion criteria during the data collection period were the study population.

Main outcome measures

The main outcome of this study was the adequacy of CRP management, which was measured by the Pain Management Index (PMI). A systematic random sampling technique was used to select representatives from each study area. Data entry and analysis were done using EpiData V.4.6.1 and SPSS V.26, respectively. Binary logistic regression was conducted to determine independent predictors of the adequacy of CRP management. A p value of <0.05 was considered statistically significant.

Results

From a total of 422 included respondents, about 67.5% of the participants had adequate CRP management (95% CI 62.8 to 72). Good performance status (adjusted OR (AOR)=0.44; 95% CI 0.24 to 0.80), presence of comorbidity (AOR=3.28; 95% CI 1.68 to 6.38) and pain history (AOR=0.33; 95% CI 0.01 to 0.11) were significantly associated with the adequacy of cancer pain management.

Conclusion

Using PMI status in the Northwest oncology centre of Ethiopia, more than two-thirds of patients with CRP obtained adequate pain management. The adequacy of CRP management was found to be influenced by factors like comorbidity, past pain history and Eastern cooperative oncology group performance status.
Assessment of COVID-19 vaccine uptake and associated factors among healthcare workers in selected health facilities of the Somali Region, Eastern Ethiopia: a cross-sectional study conducted in 2021
Authors: Wassihun Yosef , Berhe Trhas Tadesse , Melesse Addisalem , Wolde Maereg , Sharma Rachana , Mon Hnin Su , Simireta Tesfaye , Addisu Hailemariam
Published: February 2024

Background

The global COVID-19 pandemic poses substantial health challenges. Vaccination is key in preventing COVID-19, particularly among healthcare workers (HCWs), essential in curbing the pandemic. Despite global data on HCWs’ vaccine uptake, information about vaccination among HCWs in the Somali Region, Ethiopia, is scarce.

Objective

This study aimed to assess COVID-19 uptake and determinant factors for HCWs in the Somali Region, Eastern Ethiopia, 2021.

Methods

A facility-based cross-sectional study was conducted from 20 October 2021 to 30 October 2021, involving 440 systematically selected participants. Data were collected through self-administered questionnaires, cleaned, coded and entered into Epi Info software (V.3.5.1; CDC). Subsequently, the data were exported to Stata software (V14.1) for analysis. Descriptive statistics were used to report frequency, percentage, mean and SD. Multiple logistic regression analysis was performed to predict the relationship between independent and dependent variables. In the final model, statistical significance was determined with a 95% CI and a p<0.05.

Result

A total of 427 HCWs were involved in this study. About 192 (45%) of the participants had a history of test for COVID-19 and 64 (15%) were tested positive for COVID-19 infection. Three hundred and three (76%) at 95% CI (70.3% to 80.6%) of HCWs got at least one dose of the COVID-19 vaccine. Other professions such as paramedics, environmental health and pharmacist were less likely to get COVID-19 vaccine than nurses (adjusted OR, AOR 0.2; 95% CI (0.06 to 0.53)). Participants who were concerned about the availability of the COVID-19 vaccine were less likely to receive it than individuals who were not concerned (AOR 0.01; 95% CI (0.002 to 0.052)).

Conclusion

The vaccination uptake among HCWs in the region was relatively low, with the type of profession and concerns about vaccine availability being significant factors affecting the uptake.
Can ‘life writing’ be therapeutic in response to trauma? An exploratory research project in Medical Humanities in South Africa
Authors: Garisch Dawn , Giddy Janet , Griffin Giles , Reid Steve
Published: February 2024

The therapeutic benefit of expressive writing has been well researched in the Global North but there is no literature from the Global South. Potentially healing interventions need to be investigated in different contexts, particularly where there is a need to build social cohesion. South Africa has a violent past and is a highly stressed society. An exploration of self-reports by a diverse group of South Africans on the effects of life writing on their health and well-being was conducted using qualitative methods. Twenty members of a writing collective, the Life Righting Collective (LRC:www.liferighting.co.za), were purposively sampled and interviewed by medical students as part of a Medical Humanities special study module. Five major interconnected themes emerged. The LRC as a specific intervention was central to the benefits described. The findings of this study indicated that life writing is a useful non-medical, cost-efficient method to improve resilience to trauma, as well as improving the psychological well-being of the participants. In addition, participants reported positive experiences regarding personal development, overall wellness and mental health, and that life writing can engender a sense of community. Resource-constrained countries in the Global South, like South Africa, where there have been historical and ongoing multiple traumas, need interventions for healing and wellness that are low cost and can be replicated.
Paravertebral and erector spinae plane blocks decrease length of stay compared with local infiltration analgesia in autologous breast reconstruction
Authors: Ayyala Haripriya S , Assel Melissa , Aloise Joseph , Serafin Joanna , Tan Kay See , Mehta Meghana , Puttanniah Vinay , McCormick Patrick , Malhotra Vivek , Vickers Andrew , Matros Evan , Lin Emily
Published: February 2024

Background

Autologous breast reconstruction is associated with significant pain impeding early recovery. Our objective was to evaluate the impact of replacing surgeon-administered local infiltration with preoperative paravertebral (PVB) and erector spinae plane (ESP) blocks for latissimus dorsi myocutaneous flap reconstruction.

Methods

Patients who underwent mastectomy with latissimus flap reconstruction from 2018 to 2022 were included in three groups: local infiltration, PVB, and ESP blocks. Block effect on postoperative length of stay (LOS) and the association between block status and pain, opioid consumption, time to first analgesic, and postoperative antiemetic administration were assessed.

Results

122 patients met the inclusion criteria for this retrospective cohort study: no block (n=72), PVB (n=26), and ESP (n=24). On adjusted analysis, those who received a PVB block had a 20-hour shorter postoperative stay (95% CI 11 to 30; p<0.001); those who received ESP had a 24-hour (95% CI 15 to 34; p<0.001) shorter postoperative stay compared with the no block group, respectively. Using either block was associated with a reduction in intraoperative opioids (23 morphine milligram equivalents (MME)), 95% CI 14 to 31, p<0.001; ESP versus no block: 23 MME, 95% CI 14 to 32, p<0.001).

Conclusions

Replacing surgical infiltration with PVB and ESP blocks for autologous breast reconstruction reduces LOS. The comparable reduction in LOS suggests that ESP may be a viable alternative to PVB in patients undergoing latissimus flap breast reconstruction following mastectomy. Further research should investigate whether ESP or PVB have better patient outcomes in complex breast reconstruction.
Longitudinal associations between body mass index and changes in disease activity and radiographic progression in rheumatoid arthritis patients treated with infliximab
Authors: Burkard Theresa , Vallejo-Yagüe Enriqueta , Lauper Kim , Finckh Axel , Hügle Thomas , Burden Andrea M
Published: February 2024

Objectives

Treatment response is worse in obese patients with rheumatoid arthritis (RA), including patients on weight-adjusted therapies like infliximab. We aimed to assess the association between body mass index (BMI) and changes in RA disease activity and radiographic progression over time.

Methods

We included infliximab users with an RA diagnosis in the Swiss Clinical Quality Management in Rheumatic Diseases registry (1997–2020). Two cohorts were defined: (1) starting from their first BMI measurement or disease activity score (DAS28-esr), and (2) from their first BMI measurement or radiographic assessment (Rau score). We evaluated the coefficient and 95% CI of BMI with changes in mean DAS28-esr (cohort 1) and mean Rau scores (a structural joint damage score, cohort 2) using generalised estimation equations, overall and stratified by BMI categories.

Results

Cohort 1 comprised 412 patients (74% women, mean age 53 years, mean BMI 25). We observed no change in mean DAS28-esr with increasing BMI overall (adjusted coefficient: 0.00, 95% CI −0.02 to 0.02), or in BMI categories. Cohort 2 comprised 187 patients highly alike to those in cohort 1. We observed a significant decrease of 1.05 in mean Rau scores for every increase in BMI unit (adjusted coefficient: −1.05, 95% CI −1.92 to −0.19). Results remained statistically non-significant across BMI categories.

Conclusions

Our longitudinal investigation suggests that BMI increase may not lead to changes in DAS28-esr in patients receiving infliximab, despite the weight-adapted dose. Yet, there may be a decrease in erosions with increasing weight non-limited to obese patients.
Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial
Authors: Chen Tianzhu , Chen Tianyan , Zhang Yong , Wu Kang , Zou Yihuai
Published: February 2024

Background

Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity.

Methods

IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation.

Results

46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=−0.716, p=0.000) fitting the linear regression model (R
2
=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event.

Conclusions

The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.
Using k-means assistant event selection strategy to study anomalous quartic gauge couplings at muon colliders
Authors: Zhang Shuai , Yang Ji-Chong , Guo Yu-Chen
Published: February 2024

The search for new physics beyond the Standard Model is one of the central problems of current high energy physics interest. As the luminosities of current and near-future colliders continue to increase, the search for new physics has increased the requirements for processing large amounts of data. Meanwhile, quantum computing which is rapidly evolving, has great potential to become a powerful tool to help search for new physics signals. Since the k-means algorithm is known to be able to be accelerated with the help of quantum computing, we investigate and propose an event selection strategy based on k-means algorithm to search for new physics signals. Taking the case of tri-photon processes at the muon colliders as an example, the event selection strategy is shown to be effective in helping to search for the signals of dimension-8 operators contributing to anomalous quartic gauge couplings. Compared with traditional event selection strategy, the expected constraints are generally tighter.
Multicomponent scalar dark matter with an extended Gauge sector
Authors: Coleppa Baradhwaj , Loho Kousik , Sarkar Agnivo
Published: February 2024

We consider an extension of the Standard Model of particle physics with an additional SU(2) gauge sector along with an additional scalar bidoublet and a non-linear sigma field. The neutral components of the bidoublet serve as dark matter candidates by virtue of the bidoublet being odd under a $$Z_2$$

Z
2

symmetry. Generic beyond Standard Model constraints like vacuum stability, invisible decay of Higgs, Higgs alignment limit and collider constraints on heavy gauge bosons restrict the parameter space of this model. In this multicomponent dark matter scenario, we investigate the interplay between the annihilation and co-annihilation channels originating from the new gauge sector as those contribute to the relic abundance. We also inspect the direct detection constraints on scattering cross-sections of the dark matter particles with the detector nucleons and present our observations.
TLPGNN: A Lightweight Two-level Parallelism Paradigm for Graph Neural Network Computation on Single and Multiple GPUs
Authors: Fu Qiang , Ji Yuede , Rolinger Thomas , Huang H. Howie
Published: February 2024

Graph Neural Networks (GNNs) are an emerging class of deep learning models specifically designed for graph-structured data. They have been effectively employed in a variety of real-world applications, including recommendation systems, drug development, and analysis of social networks. The GNN computation includes regular neural network operations and general graph convolution operations, which take most of the total computation time. Though several recent works have been proposed to accelerate the computation for GNNs, they face the limitations of heavy pre-processing, low efficiency atomic operations, and unnecessary kernel launches. In this article, we designTLPGNN, a lightweight two-level parallelism paradigm for GNN computation. First, we conduct a systematic analysis of the hardware resource usage of GNN workloads to understand the characteristics of GNN workloads deeply. With the insightful observations, we then divide the GNN computation into two levels, i.e.,vertex parallelismfor the first level andfeature parallelismfor the second. Next, we employ a novel hybrid dynamic workload assignment to address the imbalanced workload distribution. Furthermore, we fuse the kernels to reduce the number of kernel launches and cache the frequently accessed data into registers to avoid unnecessary memory traffic. To scaleTLPGNNto multi-GPU environments, we propose an edge-aware row-wise 1-D partition method to ensure a balanced workload distribution across different GPU devices. Experimental results on various benchmark datasets demonstrate the superiority of our approach, achieving substantial performance improvement over state-of-the-art GNN computation systems, including Deep Graph Library (DGL), GNNAdvisor, and FeatGraph, with speedups of 6.1×, 7.7×, and 3.0×, respectively, on average. Evaluations of multiple-GPUTLPGNNalso demonstrate that our solution achieves both linear scalability and a well-balanced workload distribution.
SLAP: Segmented Reuse-Time-Label Based Admission Policy for Content Delivery Network Caching
Authors: Liu Ke , Wu Kan , Wang Hua , Zhou Ke , Wang Peng , Zhang Ji , Li Cong
Published: February 2024

‘‘Learned” admission policies have shown promise in improving Content Delivery Network (CDN) cache performance and lowering operational costs. Unfortunately, existing learned policies are optimized with a few fixed cache sizes while in reality, cache sizes often vary over time in an unpredictable manner. As a result, existing solutions cannot provide consistent benefits in production settings.

We present
SLAP
, a learned CDN cache admission approach based on segmented object reuse time prediction.
SLAP
predicts an object’s reuse time range using the Long-Short-Term-Memory model and admits objects that will be reused (before eviction) given the current cache size.
SLAP
decouples model training from cache size, allowing it to adapt to arbitrary sizes. The key to our solution is a novel segmented labeling scheme that makes
SLAP
without requiring precise prediction on object reuse time. To further make
SLAP
a practical and efficient solution, we propose aggressive reusing of computation and training on sampled traces to optimize model training, and a specialized predictor architecture that overlaps prediction computation with miss object fetching to optimize model inference. Our experiments using production CDN traces show that SLAP achieves significantly lower write traffic (38%-59%), longer SSDs lifetime (104%-178%), a consistently higher hit rate (3.2%-11.7%), and requires no effort to adapt to changing cache sizes, outperforming existing policies.
Experimental Investigation of a 64 Ah Lithium-Ion Pouch Cell
Authors: Hamed Hamid , Choobar Behnam Ghalami , Hamtaei Sarallah , D’Haen Jan , Vermang Bart , Safari Mohammadhosein
Published: February 2024

This study presents a meticulous investigation and characterization of a 64 Ah commercial lithium-ion pouch cell. Notably, an exhaustive analysis of the cell’s open-circuit voltage and kinetics attributes is conducted, with particular emphasis on the temperature-dependent dynamics. Subsequently, a teardown experiment is performed, offering an incisive insight into the macro-geometrical properties underpinning the cell’s architecture. Further details about the microstructural features and formulation inherent to the cathode and anode are revealed after image processing of the electrodes’ cross sections. The details of cell balancing and cycling window of the electrodes in the pouch cell are determined and discussed based on the open-circuit-voltage measurements of the individual electrodes and a simple optimization algorithm. The methodologies presented in this work are insightful on the characterization and model parametrization of the high-capacity commercial lithium-ion cells.
Determination of the Ion Concentrations in VRFB by Non-Invasive Optical Techniques Due to Chemical Reactions, Complexes, and Side Reactions
Authors: Krowne Clifford M.
Published: February 2024

The Vanadium redox flow battery has been intensively examined since the 1970s, with researchers looking at its electrochemical time varying electrolyte concentration time variation (both tank and cells, for negative and positive half cells), its thermal time variation, and fluid flow behavior. Chemistry behavior of the electrolyte ions have also been intensively examined too. Our focus in this paper is to examine the disturbance and effect of other chemical reactions and constituents to those typically found in the positive electrode electrolyte, while handling the less problematic negative electrode. Appropriate formulas are developed which allow assessment of the size of the effect, and their evaluation indicates something on the order of up to 14%. Therefore, for unambiguous non-invasive optical measurements, knowledge of the disturbance effect, and taking it into account will allow proper concentration determination. This treatment includes a comprehensive examination of identified side reactions which occur due to crossover ions between the electrodes.
Optimization of the Electrochemical Nature of Ni/Co MOF Assisted by Zn Metal Centres for Better Electrode Performance in Hybrid Devices
Authors: Roman Muhammad , Zahid Uswa , Arif Shafaq , Zeba I. , Sanderson Joseph , Khan Arif , Gillani S. S. A.
Published: February 2024

Owing to the exceptional porous coordination chemistry and expanded redox culture of mixed metal organic framework (MMOF) materials are now presenting a hot matter for their potential usage in battery-supercapacitor electrodes. Here, we synthesized Ni/Co-MOF and its based Zn
x
-(Ni/Co)y-MOF nanoparticles containing different transition metals ratio; x: y = 0.25:0.75, 0.50:0.50, and 0.75:0.25 by hydrothermal process and named as ZMOF1, ZMOF2 and ZMOF3. Their electrochemical profile was carried out by CV, GCD and EIS characterization in three electrode setup. Among the MOFs nanoparticles, partially Zn enriched ZMOF1 shows prominent specific capacity of 177.23 and 181.12 C g−1 in 1.0 and 3.0 M KOH electrolyte solution at current density of 0.3 A g−1 along with good rate capability performance. Meanwhile, it retains brilliant specific capacity ∼ 86% of its original value compared to other displayed by ZMOF2 and ZMOF3 (80% and 69%) after charging-discharging for 3000 cycles at j = 4.0 A g−1. Moreover, modified power law was utilized to estimate the battery-type charge storage worth of ZMOF1 from CV cycle (at 5 mV s−1) in 1.0 and 3.0 M electrolytes medium thereby found the contribution 91.58% and 94.32%, respectively. These features of ZMOF1 attributed to particle diverse morphology, enriched redox sites and admiring electrical conductivity.
Translation of a Diabetes Remission Service into Australian Primary Care: Findings from the Evaluation of DiRECT‐Australia
Authors: Chimoriya Ritesh , Mitlehner Kimberly , Khoo Chee L. , Osuagwu Uchechukwu Levi , Thomson Russell , Si Lei , Lean Michael , Simmons David , Piya Milan K.
Published: February 2024

Background. The Diabetes Remission Clinical Trial (DiRECT) study demonstrated that an intensive and structured weight management program in UK primary care resulted in high rates of diabetes remission in adults with recent onset type 2 diabetes mellitus (T2DM). This study was aimed at evaluating the translation of the DiRECT intervention into an Australian primary care setting. Methods. All patients enrolled in the DiRECT‐Australia Type 2 Diabetes Remission Service in a region of Sydney (Macarthur region, South Western Sydney, Australia) were included. Eligible participants were aged 20–70 years, noninsulin treated, with T2DM of ≤6 years’ duration, and body mass index (BMI) ≥ 27 kg/m2. Total diet replacement of 825‐853 kcal/day using meal replacements was implemented for 12 weeks, followed by an ongoing structured program until 52 weeks, with regular follow‐up with a general practitioner, dietitian, and/or practice nurse. Results. Of 39 recruited participants, 32 (82.1%) and 27 (69.2%) completed 12 weeks and 52 weeks of the structured program, respectively. Decrease in weight by ‐12.0 kg (95% CI: ‐9.6, ‐14.4; p < 0.001) and ‐9.1 kg (95% CI: ‐5.2, ‐12.9; p < 0.001) and decrease in glycated haemoglobin (HbA1c) by ‐1.1% (95% CI: ‐0.6, ‐1.6; p < 0.001) and ‐0.6% (95% CI: ‐0.1, ‐1.1; p = 0.013) were observed at 12 and 52 weeks, respectively. At the end of 12 and 52 weeks, 93.8% (30/32) and 55.6% (15/27) of those with follow‐up data met the criteria for diabetes remission, respectively. Quality of life and wellbeing scores increased over the course of 12 weeks, remaining significantly higher at 52 weeks. Participants reported they would be willing to pay A$92.50 (95% CI: A$75.80, A$109.30) per fortnight for the low‐calorie meal replacement shakes. Conclusions. These findings support the feasibility of a structured diabetes remission service in an Australian primary care setting to achieve improvements in glycaemia, weight, and quality of life and wellbeing, and suggest a substantial willingness to pay for diet replacement products among participants.
Molecular Detection and Quantification of Ovine Papillomavirus DNA in Equine Sarcoid
Authors: De Falco Francesca , Cutarelli Anna , Pellicanò Roberta , Brandt Sabine , Roperto Sante
Published: February 2024

Equine sarcoids are caused by infection with bovine papillomavirus (BPV) types 1, 2, and possibly 13. However, a number of sarcoids lack BPV DNA, and new potential etiological agents for sarcoid diseases need to be considered. High‐performance digital droplet polymerase chain reaction (ddPCR) was used for the quantitative detection of ovine papillomavirus (OaPV) types 1–4 DNA from 63 sarcoid DNA samples collected in Austria. All samples were comparatively evaluated for OaPV DNA loads by qPCR. Conventional PCR and amplicon sequencing were used to validate the data. Of the 63 sarcoid DNA isolates, ddPCR was able to detect 22 samples harboring OaPV DNA (34.92%), whereas only five of the OaPV‐positive samples were revealed by qPCR (22.72%). The differences in detection by ddPCR and qPCR were statistically significant (p < 0.05). The detected OaPV types were OaPV1, 3, and 4. Both methods failed to detect OaPV2 DNA, which could be due to the limited number of examined samples. Importantly, ddPCR detected multiple types of OaPV DNA in seven cases, whereas the qPCR failed to detect multiple infections. This study is the first to provide evidence of the presence of OaPV types 1, 3, and 4 DNA in a subset of equine sarcoids. The comparative detection approach underscores the superior sensitivity of ddPCR compared to that of qPCR.
Antiplatelet and Antithrombotic Activities of Lespedeza cuneata via Pharmacological Inhibition of Integrin αIIbβ3, MAPK, and PI3K/AKT Pathways and FeCl3-Induced Murine Thrombosis
Authors: Akram Abdul Wahab , Saba Evelyn , Rhee Man Hee
Published: February 2024

Cardiovascular diseases (CVDs) have been the major cause of mortality all around the globe. Lespedeza cuneata abbreviated as L. cuneata with the authority name of Dumont de Courset (G. Don) is a perennial flowering plant commonly grown in Asian countries such as Korea, Japan, China, and Taiwan. We aimed to investigate the L. cuneata extract’s antiplatelet and antithrombotic properties as GC-MS analysis indicated that the extract contained short-chain fatty acids, which have been reported to possess beneficial cardiovascular effects. L. cuneata was extracted using water, 50% EtOH, 70% EtOH, and 100% EtOH. For in vitro antiplatelet analysis, washed platelets were prepared and incubated with L. cuneata with 200 μg/mL of 50% EtOH in the presence of 1 mM of CaCl2 for 1 minute followed by agonist (collagen 2.5 μg/mL or ADP 10 μM or thrombin 0.1 U/mL) stimulation for 5 minutes over light transmission aggregometer. Scanning electron microscopy was performed to assess platelet shape change. ATP release and intracellular calcium mobilization were quantified to assess the granular content. Fibrinogen-binding assay and clot retraction assay assessed integrin αIIbβ3-mediated inside-out and outside-in signaling. Protein phosphorylation expression was investigated by western blot analysis. Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400 mg/kg and aspirin 100 mg/kg for 7 days, and tail bleeding and FeCl3-induced murine thrombus model were performed. In vitro platelet aggregation and platelet shape change were dose-dependently suppressed by L. cuneata. Calcium mobilization, dense granules secretion, integrin αIIbβ3-mediated inside-out and outside-in signaling, and protein phosphorylation of MAPK and PI3K/Akt pathways were significantly inhibited. In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects.
The Wound Healing of Autologous Regenerative Factor on Recurrent Benign Airway Stenosis: A Canine Experimental and Pilot Study
Authors: Chen Xiaobo , Wang Wenhao , Ye Yongshun , Yang Yixi , Chen Difei , He Ruiting , Xiao Zhulin , Liu Jingwei , Xu Tingting , Cai Yongna , Feng Haiqi , Zhong Changgao , Xiao Weiqun , Gu Yingying , Lu Liya , Xiong Hailin , Zhang Zhiyong , Li Shiyue
Published: February 2024

Introduction: Benign airway stenosis (BAS) is a severe pathologic condition. Complex stenosis has a high recurrence rate and requires repeated bronchoscopic interventions for achieving optimal control, leading to recurrent BAS (RBAS) due to intraluminal granulation. Methods: This study explored the potential of autologous regenerative factor (ARF) for treating RBAS using a post-intubation tracheal stenosis canine model. Bronchoscopic follow-ups were conducted, and RNA-seq analysis of airway tissue was performed. A clinical study was also initiated involving 17 patients with recurrent airway stenosis. Results: In the animal model, ARF demonstrated significant effectiveness in preventing further collapse of the injured airway, maintaining airway patency and promoting tissue regeneration. RNA-seq results showed differential gene expression, signifying alterations in cellular components and signaling pathways. The clinical study found that ARF treatment was well-tolerated by patients with no severe adverse events requiring hospitalization. ARF treatment yielded a high response rate, especially for post-intubation tracheal stenosis and idiopathic tracheal stenosis patients. Conclusion: The study concludes that ARF presents a promising, effective, and less-invasive method for treating RBAS. ARF has shown potential in prolonging the intermittent period and reducing treatment failure in patients with recurrent tracheal stenosis by facilitating tracheal mucosal wound repair and ameliorating tracheal fibrosis. This novel approach could significantly impact future clinical applications.