bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of LuxS on virulence and pathogenicity in
Klebsiella pneumoniae
exhibiting varied mucoid phenotypes
Authors: Tang Miran , Zhao Deyi , Zhang Ying , Qian Changrui , Chen Huale , Chen Lijiang , Ye Jianzhong , Zhou Tieli
Published: February 2024

How the LuxS/AI-2 quorum sensing (QS) system influences the pathogenicity of
K. pneumoniae
is complicated by the heterogeneity of the bacterial mucoid phenotypes. This study aims to explore the LuxS-mediated regulation of the pathogenicity of
K. pneumoniae
with diverse mucoid phenotypes, including hypermucoid, regular-mucoid, and nonmucoid. The wild-type,
luxS
knockout, and complemented strains of three
K. pneumoniae
clinical isolates with distinct mucoid phenotypes were constructed. The results revealed the downregulation of virulence genes of regular-mucoid, and nonmucoid but not hypermucoid strains. The deletion of
luxS
reduced the pathogenicity of the regular-mucoid, and nonmucoid strains in mice; while in hypermucoid strain,
luxS
knockout reduced virulence in late growth but enhanced virulence in the early growth phase. Furthermore, the absence of
luxS
led the regular-mucoid and nonmucoid strains to be more sensitive to the host cell defense, and less biofilm-productive than the wild-type at both the low and high-density growth state. Nevertheless,
luxS
knockout enhanced the resistances to adhesion and phagocytosis by macrophage as well as serum-killing, of hypermucoid
K. pneumoniae
at its early low-density growth state, while it was opposite to those in its late high-density growth phase. Collectively, our results suggested that LuxS plays a crucial role in the pathogenicity of
K. pneumoniae
, and it is highly relevant to the mucoid phenotypes and growth phases of the strains. LuxS probably depresses the capsule in the early low-density phase and promotes the capsule, biofilm, and pathogenicity during the late high-density phase, but inhibits lipopolysaccharide throughout the growth phase, in
K. pneumoniae
.

IMPORTANCE

Characterizing the regulation of physiological functions by the LuxS/AI-2 quorum sensing (QS) system in
Klebsiella pneumoniae
strains will improve our understanding of this important pathogen. The genetic heterogeneity of
K. pneumoniae
isolates complicates our understanding of its pathogenicity, and the association of LuxS with bacterial pathogenicity has remained poorly addressed in
K. pneumoniae
. Our results demonstrated strain and growth phase-dependent variation in the contributions of LuxS to the virulence and pathogenicity of
K. pneumoniae
. Our findings provide new insights into the important contribution of the LuxS/AI-2 QS system to the networks that regulate the pathogenicity of
K. pneumoniae
. Our study will facilitate our understanding of the regulatory mechanisms of LuxS/AI-2 QS on the pathogenicity of
K. pneumoniae
under the background of their genetic heterogeneity and help develop new strategies for diminished bacterial virulence within the clinical
K. pneumoniae
population.
Coding-complete genome sequences of two bovine viral diarrhea virus 1a isolates from Uruguay
Authors: Maya L. , Panzera Y. , Pérez R. , Marandino A. , Colina R.
Published: February 2024

Bovine viral diarrhea virus (BVDV) is an economically relevant pathogen affecting cattle production and reproduction worldwide. We report the coding-complete sequences of two BVDV-1a subtype isolates, circulating in Uruguay.
Complete genome sequence of a species of the genus
Agarivorans
from the Sea of Japan
Authors: Kawase Yuka , Yoshida Masa-aki
Published: February 2024

A strain of
Agarivorans
sp., named OAG1, predicted to be capable of degrading agar, was isolated from the Sea of Japan. Its 4.7 Mbp genome with 4,224 predicted protein-coding genes offers insight into the varied genes responsible for agar degradation, as observed in the comparative genomic study of
Agarivorans
species.
Genomic insights into antibiotic resistance genes in
Leuconostoc citreum
strains isolated from artisanal buffalo milk curd in Bangladesh through whole-genome sequencing
Authors: Habiba Mst. Umme , Hoque M. Nazmul , Ahmed Shabbir , Islam Md. Tofazzal , Deb Gautam Kumar , Rahman Md. Morshedur
Published: February 2024

We sequenced the genome of
Leuconostoc citreum
strains BSMRAU-M1L6 and BSMRAU-M1L13 isolated from artisanal buffalo milk curd in Bangladesh. The draft genomes of BSMRAU-M1L6 and BSMRAU-M1L13 are 1,869,891 and 1,890,611 bp, respectively, with 50.0× coverage (both) and 65 and 75 contigs, respectively.
Axial dystonia as a manifestation of stiff-person syndrome in a paediatric patient
Authors: Shukla Vanita , Singh Virendra Rajesh Sarabjit , Edwards Anna-Marie , Fernandes Maritza
Published: February 2024

Stiff-person syndrome (SPS) is a rare neurological condition that frequently affects adults, with the neurologist diagnosing only one or two cases during his or her career. Reports of paediatric SPS are exceedingly rare, with less than 20 cases described in the literature.

The patient presented was initially diagnosed with a functional movement disorder then a genetic dystonia, with a poor response to treatment trials and negative genetic testing. Consideration of Wilson’s disease was refuted with non-supportive investigations and assessments.

We aim to present the long road to diagnosing our first paediatric patient with SPS, who presented in middle childhood.
Neurodiversity and disability: what is at stake?
Authors: Jones Eleanor K , Orchard Vivienne
Published: February 2024

Neurodiversity has come hugely to the fore in recent years in a variety of contexts, and is now subject to academic debate, activist discussion, and increasingly embedded in a range of institutional and corporate settings in the Global North, from workplaces to early years education, from psychotherapy to mainstream political discourses. The term has gained traction in Medical Humanities, as well as debate within bioethics, philosophy of psychology, and of law. Institutionally, it is now relied on in therapeutic practice, autism service provision, as well as in higher education, in particular. In this conceptual article we examine what is at stake in these usages and the implications in need of scrutiny. We resituate neurodiversity in relation to questions of disability by examining the deployment of neurology as the basis for identity, rights and benefits. The emergence of the term and the understandings to which it gives rise, we argue, leave out urgent questions of what is at stake for disabled people in a political climate of increasing harshness and ableism.
Aetiological molecular identification of sexually transmitted infections that cause urethral discharge syndrome and genital ulcer disease in Brazilian men: a nationwide study
Authors: Bazzo Maria Luiza , Machado Hanalydia de Melo , Martins Jessica Motta , Schörner Marcos André , Buss Ketlyn , Barazzetti Fernando Hartmann , Gaspar Pamela Cristina , Bigolin Alisson , Benzaken Adele , de Carvalho Simone Veloso Faria , Andrade Lidiane da Fonseca , Ferreira William Antunes , Figueiroa François , Fontana Rafael Mialski , da Silva Miralba Freire de Carvalho Ribeiro , Silva Roberto José Carvalho , Aires Junior Luiz Fernando , Neves Lis Aparecida de Souza , Miranda Angelica Espinosa , Network Brazilian-GASP
Published: February 2024

Background

Little is known about the aetiology of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil due to limited access to laboratory tests and treatment based mainly on the syndromic approach.

Objectives

To update Brazilian treatment guidelines according to the current scenario, the first nationwide aetiological study for UDS and GUD was performed.

Methods

Male participants with urethral discharge (UD) and/or genital ulcer (GU) reports were enrolled. Sample collection was performed by 12 sentinel sites located in the five Brazilian regions. Between 2018 and 2020, 1141 UD and 208 GU samples were collected in a Universal Transport Medium-RT (Copan). A multiplex quantitative PCR kit (Seegene) was used to detect UD:Chlamydia trachomatis(CT),Mycoplasma genitalium(MG),M. hominis(MH),Neisseria gonorrhoeae(NG),Trichomonas vaginalis(TV),Ureaplasma parvum(UP),U. urealyticum(UU) and another kit to detect GU: cytomegalovirus (CMV),Haemophilus ducreyi(HD), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), lymphogranuloma venereum (LGV),Treponema pallidum(TP) and varicella-zoster virus (VZV).

Results

In UD samples, the frequency of pathogen detection was NG: 78.38%, CT: 25.6%, MG: 8.3%, UU: 10.4%, UP: 3.5%, MH: 3.5% and TV: 0.9%. Coinfection was assessed in 30.9% of samples, with 14.3% of NG/CT coinfection. The most frequent pathogen identified in GU was HSV2, present in 40.8% of the samples, followed by TP at 24.8%, LGV and CMV at 1%, and HSV1 at 0.4%. Coinfection of TP/HSV2 was detected in 4.4% of samples. VZV and HD were not detected. In 27.7% of the GU samples, no pathogen was detected.

Conclusion

This study provided the acquisition of unprecedented data on the aetiology of UDS and GUD in Brazil, demonstrated the presence of a variety of pathogens in both sample types and reaffirmed the aetiologies known to be most prevalent globally.
The impact of 48 h high carbohydrate diets with high and low FODMAP content on gastrointestinal status and symptoms in response to endurance exercise, and subsequent endurance performance
Authors: Scrivin Rachel , Slater Gary , Mika Alice , Rauch Christopher , Young Pascale , Martinez Isabel , Costa Ricardo J.S.
Published: February 2024

This study investigated the effects of a high carbohydrate diet, with varied fermentable oligo-, di-, and mono-saccharide and polyol (FODMAP) content, before endurance exercise on gastrointestinal integrity, motility, and symptoms; and subsequent exercise performance. Twelve endurance athletes were provided with a 48 h high carbohydrate (mean ± SD: 12.1 ± 1.8 g kg day−1) diet on two separate occasions, composed of high (54.8 ± 10.5 g day−1) and low FODMAP (3.0 ± 0.2 g day−1) content. Thereafter, participants completed a 2 h steady-state running exercise at 60% of [Formula: see text] (22.9 ± 1.2 °C, 46.4 ± 7.9% RH), followed by a 1 h distance performance test. Pre-exercise and every 20 min during steady-state exercise, 100 mL maltodextrin (10%  w/ v) solution was consumed. A 150 mL lactulose (20 g) solution was consumed 30 min into the distance performance test to determine orocecal transit time (OCTT) during exercise. Blood was collected pre- and post exercise to determine gastrointestinal integrity biomarkers (i.e., I-FABP, sCD14, and CRP). Breath hydrogen (H2) and gastrointestinal symptoms (GIS) were determined pre-exercise, every 15 min, during and throughout recovery. No differences in gastrointestinal integrity biomarkers, OCTT, or distance completed were observed between trials. Pre-exercise total-GIS (1.3 ± 2.9 vs. 4.3 ± 4.4), gut discomfort (9.9 ± 8.1 vs. 15.8 ± 9.0), and upper-GIS (2.8 ± 2.6 vs. 5.7 ± 4.8) during exercise were less severe on high carbohydrate low FODMAP (HC-LFOD) versus high carbohydrate high FODMAP (HC-HFOD) ( p < 0.05). Gut discomfort (3.4 ± 4.4 vs. 0.2 ± 0.6) and total-GIS (4.9 ± 6.8 vs. 0.2 ± 0.6) were higher during recovery on HC-LFOD versus HC-HFOD ( p < 0.05). The FODMAP content of a 48 h high carbohydrate diet does not impact gastrointestinal integrity or motility in response to endurance exercise. However, a high FODMAP content exacerbates GIS before and during exercise, but this does not impact performance outcomes.
MSEConv: A Unified Warping Framework for Video Frame Interpolation
Authors: Ding Xiangling , Huang Pu , Zhang Dengyong , Liang Wei , Li Feng , Yang Gaobo , Liao Xin , Li Yue
Published: February 2024

Within the context of video frame interpolation, complex motion modeling is the task of capturing, in a video sequence, where the moving objects are located in the interpolated frame, and how to maintain the temporal consistency of motion. Existing video frame interpolation methods typically assign either a fixed size of the motion kernel or a refined optical flow to model complex motions. However, they have the limitation of data redundancy and inaccuracy representation of motion. This paper introduces a unified warping framework, named multi-scale expandable deformable convolution (MSEConv), for simultaneously performing complex motion modeling and frame interpolation. In the proposed framework, a deep fully convolutional neural network with global attention is proposed to estimate multiple small-scale kernel weights with different expansion degrees and adaptive weight allocation for each pixel synthesis. Moreover, most of the kernel-based interpolation methods can be treated as the special case of the proposed MSEConv, thus, MSEConv can be easily transferred to other kernel-based frame interpolation methods for performance improvement. To further improve the robustness of motion occlusions, an operation of mask occlusion is introduced. As a consequence, our proposed MSEConv shows strong performance on par or even better than the state-of-the-art kernel-based frame interpolation works on public datasets. Our source code and visual comparable results are available at https://github.com/Pumpkin123709/MSEConv.
MRAAC: A Multi-stage Risk-aware Adaptive Authentication and Access Control Framework for Android
Authors: Chen Jiayi , Hengartner Urs , Khan Hassan
Published: February 2024

Adaptive authentication enables smartphones and enterprise apps to decide when and how to authenticate users based on contextual and behavioral factors. In practice, a system may employ multiple policies to adapt its authentication mechanisms and access controls to various scenarios. However, existing approaches suffer from contradictory or insecure adaptations, which may enable attackers to bypass the authentication system. Besides, most existing approaches are inflexible and do not provide desirable access controls. We design and build a multi-stage risk-aware adaptive authentication and access control framework (MRAAC), which provides the following novel contributions:
Multi-stage:
MRAAC organizes adaptation policies in multiple stages to handle different risk types and progressively adapts authentication mechanisms based on context, resource sensitivity, and user authenticity.
Appropriate access control:
MRAAC provides libraries to enable sensitive apps to manage the availability of their in-app resources based on MRAAC’s risk awareness.
Extensible:
While existing proposals are tailored to cater to a single use case, MRAAC supports a variety of use cases with custom risk models. We exemplify these advantages of MRAAC by deploying it for three use cases: an enhanced version of Android Smart Lock, guest-aware continuous authentication, and corporate app for BYOD. We conduct experiments to quantify the CPU, memory, latency, and battery performance of MRAAC. Our evaluation shows that MRAAC enables various stakeholders (device manufacturers, enterprise and secure app developers) to provide complex adaptive authentication workflows on COTS Android with low processing and battery overhead.
UETOPSIS: A Data-Driven Intelligence Approach to Security Decisions for Edge Computing in Smart Cities
Authors: Xiao Lijun , Han Dezhi , Li Kuan-Ching , Khan Muhammad Khurram
Published: February 2024

Despite considerable technological advances for smart cities, they still face problems such as instability of cloud server connection, insecurity during data transmission, and slight deficiencies in TCP/IP network architecture. To address such issues, we propose a data-driven intelligence approach to security decisions under Named Data Networking (NDN) architecture for edge computing, taking into consideration factors that impact device entry in smart cities, such as device performance, load, Bluetooth signal strength, and scan frequency. Despite existing techniques for Order Preference by Similarity to Ideal Solution (TOPSIS)-based on entropy weights methods are improved and applied, there exist unstable decision results. Due to this, we propose a technique for Order Preference by Similarity to Ideal Solution (TOPSIS)-based on utility function and entropy weights, named UETOPSIS, where the corresponding utility function is applied according to the influence of each attribute on the decision, ensuring the stability of the ranking of decision results. We rely on an entropy-based weights mechanism to select a suitable master controller for the design of the multi-control protocol in the smart city system, and utilize a utility function to calculate the attribute values and then combine the normalized attribute values of utility numbers, starting by analyzing the main work of the controllers. Lastly, a prototype is developed for performance evaluation purposes. Experimental evaluation and analysis show that the proposed work has better authenticity and reliability than existing works and can reduce the workload of edge computing devices when forwarding data, with stability 24.7% higher than TOPSIS, significantly improving the performance and stability of system fault tolerance and reliability in smart cities, as the second-ranked controller can efficiently take over the work when a central controller fails or damaged.
SOH Estimation for Lithium-Ion Batteries Based on Health Indicators Extraction and MKRVR
Authors: Zhang Mei , Zhang Jian , Le Lv
Published: February 2024

Aiming at the problems of difficult feature extraction and low State of Health (SOH) prediction accuracy of lithium-ion batteries, this paper proposes a SOH estimation approach that involves extracting Health Indicators (HIs) and utilizing mixed kernel function relevance vector regression (MKRVR). In order to accurately and efficiently extract battery HIs, the paper first examines the limitations of extracting HIs based on Incremental Capacity (IC) curves and puts forward an alternative method of HIs extraction based on voltage-capacity (V-C) curves. Following correlation analysis of the HIs, the paper establishes the MKRVR model that combines a range of kernel functions to estimate SOH. To determine the hyper-parameters and weight coefficients of the MKRVR model, the paper integrates Differential Evolution (DE) and Levy flight into the Gray Wolf Optimizer (GWO) to enhance the population diversity and random search ability of GWO. Finally, the paper conducts experimental validation utilizing three distinct battery datasets. The results indicate that the proposed approach outperforms Support Vector Regression (SVR) and Relevance Vector Regression (RVR), with evaluation index values of MAE, MSE, and RMSE all below 1%. Moreover, the coefficients of determination exceed 0.95, which demonstrates the superiority of this approach over other methods.
Ionic Diffusion in Slurry Electrolytes for Redox Flow Batteries
Authors: Tam Vincent , Wainright Jesse
Published: February 2024

Slurry electrodes have been proposed as a method to decouple the storage and power capacities of hybrid redox flow batteries by allowing the reduced metal to adhere to a flowing dispersion of electrically conductive particles rather than accumulate in the flow cell. In this work, the ionic mass transport through these slurry electrolytes is investigated via voltammetry at a rotating disc electrode and in a parallel channel flow cell. A modified Levich equation,

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is developed to describe limiting currents to a rotating disc electrode when using a particle filled electrolyte. Mass transfer is demonstrated to be enhanced by greater particle loading so long as there are sufficient particles such that their respective flow velocity boundary layers interact. In the flow cell, faradaic current in a carbon black slurry electrolyte was observed to decrease over time. This suggests that the carbon particles adhere and accumulate on the stationary electrode, impeding mass transport by imposing diffusion path tortuosity. This accumulation is undesirable in hybrid redox flow batteries as it encourages metal deposition in the cell, limiting the scalability of the technology.
Distinct developmental reprogramming footprint of macrophages during acute kidney injury across species
Authors: Mrug Michal , Mrug Elias , Rosenblum Frida , Chen Jiandong , Cui Xiangqin , Agarwal Anupam , Zarjou Abolfazl
Published: February 2024

Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species.
Incidence, Phenotypes, and Genotypes of Neonatal Diabetes: A 16-Year Experience. The Rare Genetic Etiologies of Neonatal Diabetes Are Common in Sudan
Authors: Hassan Samar S. , Musa Salwa A. , De Franco Elisa , Donis Frew Russel , Babiker Omer O. , Mohamadsalih Ghassan F. , Ibrahim Areej A. , Abu Samra Samar , Abdullah Mohamed A.
Published: February 2024

Neonatal diabetes (ND) is a rare subtype of diabetes occurring in the first 6 months of life. High incidence has been reported among populations with high rates of consanguineous marriage. However, there is paucity of reported data from sub-Saharan African countries. We report the incidence, genotype, and phenotype of ND in a large cohort from Sudan and compare these findings to regional and international data. All infants with onset of diabetes in the first 6 months of life, attending one of the only two tertiary pediatric diabetes centers in Sudan, Gaafar Ibn Auf Pediatric Tertiary Hospital and Sudan Childhood Diabetes Center, during the period of January 2006 to December 2022 were included. Medical records were reviewed for demographic and clinical information. Genetic testing was performed for 48 patients by the Exeter Genomics laboratory in the UK and for one patient by the University of Cambridge, Metabolic Research Laboratories, UK. The estimated incidence was 4.8 per 100,000 live births. Forty-nine ND patients from 45 unrelated families were identified, and a genetic diagnosis was confirmed in 37 patients (75.5%) from 33 unrelated families. Consanguinity was reported in 34 families (75.6%). The commonest genetic cause for permanent neonatal diabetes was EIF2AK3 recessive variants causing Wolcott–Rallison syndrome (18.92%). Pathogenic variants in two recently identified genes, ZNF808 and NARS2, were found in three patients each (8.11%). Activating variants in KCNJ11 and ABCC8 were identified in four (10.81%) and two (5.41%) patients, respectively. Apart from hyperglycemia, the commonest clinical presentations included dehydration, failure to thrive, and diabetic ketoacidosis. ND in Sudan has a different pattern of etiologies compared to Western and Asian populations yet similar to some Arab countries with EIF2AK3 mutations being the commonest cause. Pathogenic variants in recently identified genes reflect the impact of genome sequencing on increasing the rate of genetic diagnosis.
The Effect of Clopidogrel and Ticagrelor on Human Adipose Mesenchymal Stem Cell Osteogenic Differentiation Potential: In Vitro Comparative Study
Authors: Mohamed Sally S. , Zaki Hala F. , Raafat Shereen N.
Published: February 2024

Ticagrelor (TICA) and clopidogrel (CLP) are extensively used antiplatelet drugs that act by antagonizing the P2Y12 receptors that are found on platelets in addition to bone cells. Aim. The purpose of this study was to investigate the effect of clopidogrel and ticagrelor on stem cells osteogenic differentiation in vitro. Methods. Human adipose-derived mesenchymal stem cells (hAd-MSCs) were divided into (1) control group, (2) osteogenic group (osteo group), (3) clopidogrel group (CLP group), and (4) ticagrelor group (TICA group). The osteogenic differentiation potential was determined by mineralization nodule formation using Alizarin Red S staining, measuring ALP enzyme activity by alkaline phosphatase assay. Quantitative determination for osteogenic markers included osteocalcin (OC); runt-related transcription factor 2 (RUNX2) performed using western blot; osteoprotegerin (OPG) using enzyme-linked immunosorbent assay (ELISA) and inflammatory markers; and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) measured using real-time polymerase chain reaction quantitative (RT-PCR) and ELISA. Results. In comparison to all study groups, the TICA group showed significant increase in the mineralized extracellular matrix, ALP enzyme activity, and bone markers expression as RUNX2 (P<0.0001), OC, and OPG (P<0.05). The expression of IL-6 and TNF-α was determined by RT-qPCR and ELISA techniques. TICA and CLP significantly decreased both markers compared to the control group. The TICA group showed statistically significant lower levels of both markers (P<0.0001) than the CLP and control groups via the ELISA technique. Conclusion. TICA may possess a positive effect on hAd-MSCs osteogenic differentiation compared to CLP.
Different Levels of Autophagy Activity in Mesenchymal Stem Cells Are Involved in the Progression of Idiopathic Pulmonary Fibrosis
Authors: Tao Hongxia , Lv Qin , Zhang Jing , Chen Lijuan , Yang Yang , Sun Wei
Published: February 2024

Idiopathic pulmonary fibrosis (IPF) is an age‐related lung interstitial disease that occurs predominantly in people over 65 years of age and for which there is a lack of effective therapeutic agents. It has demonstrated that mesenchymal stem cells (MSCs) including alveolar epithelial cells (AECs) can perform repair functions. However, MSCs lose their repair functions due to their distinctive aging characteristics, eventually leading to the progression of IPF. Recent breakthroughs have revealed that the degree of autophagic activity influences the renewal and aging of MSCs and determines the prognosis of IPF. Autophagy is a lysosome‐dependent pathway that mediates the degradation and recycling of intracellular material and is an efficient way to renew the nonnuclear (cytoplasmic) part of eukaryotic cells, which is essential for maintaining cellular homeostasis and is a potential target for regulating MSCs function. Therefore, this review focuses on the changes in autophagic activity of MSCs, clarifies the relationship between autophagy and health status of MSCs and the effect of autophagic activity on MSCs senescence and IPF, providing a theoretical basis for promoting the clinical application of MSCs.
New Viscometers for Measuring the Viscosity of Liquids
Authors: Shamuratov Jamshidbek , Mustafayev Oybek , Kadirov Islom
Published: February 2024

This article’s goal is to present a viscometer that makes use of a novel viscometry measurement technique. The post will also suggest brand‐new vibration viscometers. The development of new viscometers has allowed for the continuous and instantaneous measurement of liquid viscosity. The viscosity can be precisely measured automatically using these viscometers, which are made for industrial application. These viscosity measurement tools can currently be applied to a number of different tasks, including the research of recently developed oil products, the choice of the best flow characteristics for different transfer situations, and the advancement and refinement of fuel preparation techniques.
A Single‐Center Experience in Low Ejection Fraction Coronary Artery Bypass Surgery
Authors: Malhotra Amber , Islam Md Anamul , Tavilla Giuseppe , Reddy Ramachandra , d’Amato Thomas , Gupta Sameer , Baldawi Mustafa
Published: February 2024

Background. Coronary artery bypass graft (CABG) in patients with an ejection fraction (EF) ≤ 35% predisposes them to higher complications and mortality risks. Given the usually compromised status of other end organs in low EF patients, ONCAB, involving cardiopulmonary bypass (CPB) and aortic cross‐clamping, might intuitively pose more complications than OPCAB. Objective. To explore short‐ and long‐term outcomes between ONCAB and OPCAB procedures in patients with EF ≤ 35%. Methods. A retrospective and observational analysis was conducted in 196 patients with EF ≤ 35% who underwent ONCAB (n = 58) or OPCAB (n = 138) procedures at a single center between January 2015 and May 2023. Baseline characteristics were well matched using the stabilized inverse probability treatment weighted matching technique. Results. After matching, ONCAB and OPCAB had comparable 30‐day mortality and 30‐day cardiac mortality. OPCAB exhibited significantly shorter length of hospital and ICU stays, with a trend towards more discharges to home. Rates of composite complication and its individual components such as acute kidney injury, reoperation bleeding, stroke, pneumonia, GI disease, and atrial fibrillation were similar between the two groups. Rates of sepsis, liver dysfunction, and blood transfusion were significantly lower in the OPCAB group. As assessed by EF and LVDD, neither procedure showed superiority in improving cardiac function. Median follow‐up time was 4.9 (interquartile range: 2.1–7.2) years. After matching, long‐term overall survival (1, 3, 7 years) and cardiac mortality rates were comparable between OPCAB and ONCAB. Cumulative rates of cardiac arrest, heart failure, myocardial infarction (MI), atrial fibrillation (Afib), renal disease, and readmission (overall and cardiac) at 7 years were similar. Conclusion. This study demonstrates comparable short‐term and long‐term outcomes between ONCAB and OPCAB in patients with reduced EF, with OPCAB favoring faster recovery. OPCAB appears as a safer and equally effective option for low EF CABG patients. Larger samples and longer follow‐ups are needed for conclusive clinical evidence.
Supplementary Figure S1 from A Large-Scale Meta-Analysis Reveals Positive Feedback between Macrophages and T Cells That Sensitizes Tumors to Immunotherapy
Authors: Yang Jing , Liu Qi , Shyr Yu
Published: February 2024

Associations of TMB with overall survival and progression free survival across multiple data sets. A and B. The association between TMB and overall survival and progression free survival in the discovery cohort. C. The association between TMB and progression free survival in the validation datasets.
Data from Deep Learning–Based 3D Single-Cell Imaging Analysis Pipeline Enables Quantification of Cell–Cell Interaction Dynamics in the Tumor Microenvironment
Authors: Liu Bodong , Zhu Yanting , Yang Zhenye , Yan Helen H.N. , Leung Suet Yi , Shi Jue
Published: February 2024

Abstract
The three-dimensional (3D) tumor microenvironment (TME) comprises multiple interacting cell types that critically impact tumor pathology and therapeutic response. Efficient 3D imaging assays and analysis tools could facilitate profiling and quantifying distinctive cell–cell interaction dynamics in the TMEs of a wide spectrum of human cancers. Here, we developed a 3D live-cell imaging assay using confocal microscopy of patient-derived tumor organoids and a software tool, SiQ-3D (single-cell image quantifier for 3D), that optimizes deep learning (DL)–based 3D image segmentation, single-cell phenotype classification, and tracking to automatically acquire multidimensional dynamic data for different interacting cell types in the TME. An organoid model of tumor cells interacting with natural killer cells was used to demonstrate the effectiveness of the 3D imaging assay to reveal immuno-oncology dynamics as well as the accuracy and efficiency of SiQ-3D to extract quantitative data from large 3D image datasets. SiQ-3D is Python-based, publicly available, and customizable to analyze data from both in vitro and in vivo 3D imaging. The DL-based 3D imaging analysis pipeline can be employed to study not only tumor interaction dynamics with diverse cell types in the TME but also various cell–cell interactions involved in other tissue/organ physiology and pathology.
Significance:
A 3D single-cell imaging pipeline that quantifies cancer cell interaction dynamics with other TME cell types using primary patient-derived samples can elucidate how cell–cell interactions impact tumor behavior and treatment responses.
Multiomic-Based Molecular Landscape of FaDu Xenograft Tumors in Mice after a Combinatorial Treatment with Radiation and an HSP90 Inhibitor Identifies Adaptation-Induced Targets of Resistance and Therapeutic Intervention
Authors: Bylicky Michelle A. , Shankavaram Uma , Aryankalayil Molykutty J. , Chopra Sunita , Naz Sarwat , Sowers Anastasia L. , Choudhuri Rajani , Calvert Valerie , Petricoin Emanuel F. , Eke Iris , Mitchell James B. , Coleman C. Norman
Published: February 2024

Treatments involving radiation and chemotherapy alone or in combination have improved patient survival and quality of life. However, cancers frequently evade these therapies due to adaptation and tumor evolution. Given the complexity of predicting response based solely on the initial genetic profile of a patient, a predetermined treatment course may miss critical adaptation that can cause resistance or induce new targets for drug and immunotherapy. To address the timescale for these evasive mechanisms, using a mouse xenograft tumor model, we investigated the rapidity of gene expression (mRNA), molecular pathway, and phosphoproteome changes after radiation, an HSP90 inhibitor, or combination. Animals received radiation, drug, or combination treatment for 1 or 2 weeks and were then euthanized along with a time-matched untreated group for comparison. Changes in gene expression occur as early as 1 week after treatment initiation. Apoptosis and cell death pathways were activated in irradiated tumor samples. For the HSP90 inhibitor and combination treatment at weeks 1 and 2 compared with Control Day 1, gene-expression changes induced inhibition of pathways including invasion of cells, vasculogenesis, and viral infection among others. The combination group included both drug-alone and radiation-alone changes. Our data demonstrate the rapidity of gene expression and functional pathway changes in the evolving tumor as it responds to treatment. Discovering these phenotypic adaptations may help elucidate the challenges in using sustained treatment regimens and could also define evolving targets for therapeutic efficacy.
Close Collaboration with Parents Affects the Length of Stay and Growth in Preterm Infants: A Register-Based Study in Finland
Authors: Itoshima Ryo , Helenius Kjell , Ahlqvist-Björkroth Sari , Vahlberg Tero , Lehtonen Liisa
Published: February 2024

Introduction: This study aimed to evaluate how Close Collaboration with Parents (CC), a neonatal intensive care unit (NICU)-wide educational model for healthcare staff to improve their family-centred care practices, affects the length of stay (LOS), growth, and later hospital visits and rehospitalizations of preterm infants. Methods: This register-based study included all preterm infants born below 35 weeks of gestation in Finland from 2006 to 2020. Eligible infants were classified into the Full Close Collaboration (Full-CC) group (n = 2,104) if the NICUs of both the delivery and discharge hospitals had implemented the intervention; into the Partial-CC group (n = 515) if only one of the NICUs had implemented the intervention; and into the control group (n = 11,621) if neither had implemented the intervention. Results: The adjusted LOS, the primary outcome, was 1.8 days or 6% shorter in the Full-CC group than in the control group (geometric mean ratio 0.94, 95% confidence interval [95% CI] 0.89–1.00). Growth was better in the Full-CC group compared to the control group: adjusted group difference 11.7 g/week (95% CI, 1.4–22.0) for weight, 1.3 mm/week (95% CI, 0.6–2.0) for length. The Full-CC group infants had lower odds of having any unscheduled outpatient visits compared to the control group (adjusted odds ratio 0.81; 95% CI, 0.67–0.98). No significant differences were found in any other comparisons. Discussion/Conclusion: The unit-wide intervention improving family-centred care practices in NICUs may lead to more efficient use of hospital resources by shortening the LOS, improving growth, and decreasing hospital visits of preterm infants.
Cost-Effectiveness of an Individualised Management Program after Stroke: A Trial-Based Economic Evaluation
Authors: Orman Zhomart , Olaiya Muideen T. , Thrift Amanda G. , Cadilhac Dominique A. , Phan Thanh , Nelson Mark R. , Ung David , Srikanth Velandai K. , Bladin Christopher F. , Gerraty Richard P. , Phillipos Joseph , Kim Joosup
Published: February 2024

Introduction: Evidence on the cost-effectiveness of comprehensive post-stroke programs is limited. We assessed the cost-effectiveness of an individualised management program (IMP) for stroke or transient ischaemic attack (TIA). Methods: A cost-utility analysis alongside a randomised controlled trial with a 24-month follow-up, from both societal and health system perspectives, was conducted. Adults with stroke/TIA discharged from hospitals were randomised by primary care practice to receive either usual care (UC) or an IMP in addition to UC (intervention). An IMP included stroke-specific nurse-led education and a specialist review of care plans at baseline, 3 months, and 12 months, and telephone reviews by nurses at 6 months and 18 months. Costs were expressed in 2021 Australian dollars (AUD). Costs and quality-adjusted life years (QALYs) beyond 12 months were discounted by 5%. The probability of cost-effectiveness of the intervention was determined by quantifying 10,000 bootstrapped iterations of incremental costs and QALYs below the threshold of AUD 50,000/QALY. Results: Among the 502 participants (65% male, median age 69 years), 251 (50%) were in the intervention group. From a health system perspective, the incremental cost per QALY gained was AUD 53,175 in the intervention compared to the UC group, and the intervention was cost-effective in 46.7% of iterations. From a societal perspective, the intervention was dominant in 52.7% of iterations, with mean per-person costs of AUD 49,045 and 1.352 QALYs compared to mean per-person costs of AUD 51,394 and 1.324 QALYs in the UC group. The probability of the cost-effectiveness of the intervention, from a societal perspective, was 60.5%. Conclusions: Care for people with stroke/TIA using an IMP was cost-effective from a societal perspective over 24 months. Economic evaluations of prevention programs need sufficient time horizons and consideration of costs beyond direct healthcare utilisation to demonstrate their value to society.
Standard Cannulation versus Fistulotomy for Biliary Access in Endoscopic Retrograde Cholangiopancreatography: Should We Expect the Same Success when Treating Choledocholithiasis?
Authors: Moreira Marta , Tarrio Isabel , Andrade Alda João , Araújo Tarcísio , Fernandes João Sousa Silva , Canena Jorge , Lopes Luís
Published: February 2024

Introduction: To access the common bile duct in endoscopic retrograde cholangiopancreatography (ERCP), needle-knife fistulotomy (NKF) can be associated with a shorter sphincterotomy compared to standard cannulation. We aimed to compare the success and safety of NKF versus standard cannulation in the treatment of choledocholithiasis. Methods: A cohort of 379 naïve patients with choledocholithiasis who underwent ERCP between 2005 and 2022 was retrospectively analyzed. The patients were divided into two groups: group A (179 consecutive patients) underwent NKF, while group B (180 patients) received standard biliary access and were matched for stone characteristics and ERCP year. Results: Stone removal success rate for group A was significantly lower than that for group B in the initial ERCP (82.0% vs. 92.1%, p = 0.003). In group A, success rates for stone removal were 90.2%, 80%, and 29.4% for stone sizes <10 mm, 10 mm–15 mm, and >15 mm, respectively (p < 0.001). In contrast, group B showed success rates of 99.2%, 81.5%, and 71.4% for the same stone size categories (p < 0.001). Pancreatitis occurred in 3.7% of group A and 5.8% of group B patients (p = 0.340). Regression analysis revealed that NKF cannulation, stone size (>10 mm), and having 4 or more stones were associated with lower stone removal success compared to standard cannulation in the initial ERCP (OR 0.34, p = 0.015; stone size 10–15 mm: OR 0.20, p < 0.001; stone size >15 mm: OR 0.05, p < 0.001; 4 or more stones: OR 0.4, p = 0.040). Conclusions: The removal of common bile duct stones after NKF access, although safe and effective, is less successful than after a standard cannulation, especially at the baseline ERCP.
Pretreatment of Hybrid Ceramics Using Alumina (Al2O3) Nanoparticles, Hydrofluoric Acid, and Holmium: YAG Laser for Optimizing Surface Roughness, Shear Bond Strength, and Topography
Authors: Albakri Ahmed S.
Published: February 2024

Evaluation of different conditioning regimes i.e., hydrofluoric acid (HFA), sandblasting (SB), selfetching ceramic primer (SECP), and Holmium: YAG (Ho: YAG) laser on the surface roughness (Ra) and shear bond strength (SBS) of hybrid ceramics. One hundred and ten hybrid ceramic discs
were fabricated using the CAD-CAM technique. The discs were randomly allocated into five groups. Group 1: No Conditioning (Control), Group 2: HFA etching, Group 3: SB, Group 4: SECP and Group 5: Ho: YAG laser. The quantitative measurement of the roughness (Ra) (n = 10) from each group
was conducted using a profilometer. The dual cure resin cement was bonded on the remaining fifty samples. Shear bond strength (SBS) and failure analysis were performed using a universal testing machine (UTM) and stereomicroscope. One-way analysis of variance (ANOVA) with post hoc Tukey tests
was used to assess and compare the mean values of Ra and SBS among study groups. Specimens pretreated with SB displayed the maximum Ra value and bond scores. The control specimens exhibited minimum Ra and SBS. Intergroup comparison analysis indicated that HFA and Ho: YAG laser-treated groups
displayed comparable outcomes of Ra and bond integrity. Sandblasting using alumina particles proved to be the most favorable pretreatment modality for hybrid ceramic surface pretreatment for attaining optimum surface roughness and shear bond strength.
Case Study on Instrumenting and Monitoring Geosynthetic-Reinforced Pile-Supported Mechanically Stabilized Earth Wall Built over Soft Soil
Authors: Izadifar MohammadAli , Abu-Farsakh Murad Y. , Chen Shengli
Published: February 2024

This paper presents a case study on instrumenting, monitoring, and finite element modeling (FEM) of geosynthetic-reinforced pile-supported (GRPS) mechanically stabilized earth (MSE) walls. The GRPS-MSE wall was monitored using various instruments such as piezometers, earth pressure cells, shape-acceleration arrays (SAAs), and strain gauges. The performance criteria included efficacy, stress concentration ratio (SCR), differential settlement, and reinforcement tension. Collected data, such as excess pore-water pressures, contact pressures on pile and soft soil, differential settlements, and lateral displacement of MSE wall, were analyzed thoroughly. A 3D FEM was also developed to simulate the GRPS MSE wall, and the results are in good agreement with field data. The results demonstrated significant load transfer from soil to piles as a result of soil arching, yielding 30–32 SCR. The field efficacy was measured at 37.69 %, while the FEM efficacy was estimated as 42.4. Strains in geogrids within the geosynthetic-reinforced load transfer platform (GLTP) system were under 1%, less than the 5% maximum recommended by FHWA. The maximum differential settlement measured between pile cap and soft soil from SAAs is 7.1 mm, while it is estimated to be 8.3 mm from FEM. The MSE wall exhibited low lateral displacement (<25 mm), indicating enhanced stability because of GLTP. The comparison between five analytical GLTP design methods showed that the CUR226 methods gave the closest results to field measurements and FEM results. This study offers crucial insights into leveraging GLTP and MSE walls in highway construction.
Who Cares for Older Adults? A Cross-National Study of Care Sources for Older Adults With Functional Limitations and Associated Determinants
Authors: Kong Dexia , Lu Peiyi , Wu Bei , Davitt Joan K. , Shelley Mack
Published: February 2024

The study compared care source typologies for older adults in China and the United States. Data from the 2014 U.S. Health and Retirement Study and the 2013 China Health and Retirement Longitudinal Study were used. The respondents included community-dwelling older adults aged 65 years or older with at least one limitation in activities of daily living (ADLs) or instrumental ADLs (IADLs) ( N China = 2476, N US = 2898). Respondents reported whether they received assistance from spouse, child/grandchild, relatives, others, and formal helpers. Latent class analysis and multinomial logistic regression were applied. Four classes were identified in China and the U.S, separately. In both countries, ADLs and IADLs were strong determinants of care source typologies. Care sources were more diverse and included formal assistance among older Americans. Older Chinese relied largely on their spouses and children/grandchildren for support. Policy efforts are needed to expand formal long-term services and supports, particularly in China.
Anti-rabies humoral immune response in cats after concurrent vs separate vaccination against rabies and feline leukaemia virus using canarypox-vectored vaccines
Authors: Weidinger Anna-Karina , Bergmann Michèle , König Matthias , Zablotski Yury , Hartmann Katrin
Published: February 2024

Objectives

Some expert groups recommend that cats should be vaccinated with non-adjuvanted feline leukaemia virus (FeLV) and rabies vector vaccines, which, in the European Union, are currently not licensed for concurrent use and have to be administered at least 14 days apart (different from the USA) and thus at separate visits, which is associated with more stress for cats and owners. The aim of this study was to assess the anti-rabies antibody response in cats after vaccination against rabies and FeLV at concurrent vs separate (4 weeks apart) visits using two canarypox-vectored vaccines (Purevax Rabies and Purevax FeLV; Boehringer Ingelheim) and to evaluate the occurrence of vaccine-associated adverse events (VAAEs).

Methods

Healthy FeLV antigen-negative client-owned kittens (n = 106) were prospectively included in this randomised study. All kittens received primary vaccinations against rabies (week 0) and FeLV (weeks 4 and 8). After 1 year, the study group (n = 52) received booster vaccinations against rabies and FeLV concurrently at the same visit (weeks 50–52). The control group (n = 54) received booster vaccinations against rabies (weeks 50–52) and FeLV (weeks 54–56) separately. Anti-rabies virus antibodies (anti-RAV Ab) were determined by fluorescent antibody virus neutralisation assay at weeks 4, 50–52 and 54–56, and compared between both groups using a Mann–Whitney U-test.

Results

Four weeks after the first rabies vaccination, 87/106 (82.1%) kittens had a titre ⩾0.5 IU/ml and 19/106 (17.9%) had a titre <0.5 IU/ml. Four weeks after the 1-year rabies booster, all cats had adequate anti-RAV Ab according to the World Organisation for Animal Health (⩾0.5 IU/ml), and the titres of the study group (median = 14.30 IU/ml) and the control group (median = 21.39 IU/ml) did not differ significantly ( P = 0.141). VAAEs were observed in 7/106 (6.6%) cats.

Conclusions and relevance

Concurrent administration of Purevax FeLV and Purevax Rabies vector vaccines at the 1-year booster does not interfere with the development of anti-RAV Ab or cause more adverse effects and thus represents a better option than separate vaccination visits for cats and owners.