bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in cadmium tolerance of closely related
Listeria monocytogenes
isolates originating from dairy processing environments
Authors: Domen Andrea , Porter Jenna , Johnson Jared , Molyneux James , McIntyre Lorraine , Kovacevic Jovana , Waite-Cusic Joy 
Published: November 2024

ABSTRACT

Increased tolerance to cadmium in
Listeria monocytogenes
has been suggested to contribute to their persistence in natural and food production environments. This study investigated the phenotypic cadmium response of
L. monocytogenes
strains with efflux pump
cadAC
(variants 1–4) and related strains with
cadA1C1
. Growth of
cadAC
variant strains (
n
= 5) in 0 µM–120 µM cadmium salts (CdCl
2
, CdSO
4
) in Mueller-Hinton broth (MHB) was evaluated. Additionally, 88
L
.
monocytogenes
strains from dairy processing facilities were exposed to 43.8 µM CdCl
2
in MHB, and their lag phase duration (LPD) was measured. Strains with
cadA1
through
cadA3
showed similar growth trends in the presence of cadmium, while the
cadA4
variant (Scott A) had the highest CdCl
2
minimum inhibitory concentration (175 µM). Growth varied between the two salts, with CdSO
4
significantly increasing LPD (
P
< 0.05) compared to CdCl
2
. In 43.8 µM CdCl
2
,
cadA1
strains displayed LPDs ranging from 0.99 ± 0.14 h to 6.44 ± 0.08 h, with no clear genomic differences explaining this variability. Strains without
cadA
did not grow at 43.8 µM CdCl
2
but exhibited low tolerance (10.9 µM CdCl
2
), potentially due to non-specific soft metal ATPases (626 aa; 737 aa) and soft metal resistance proteins encoded by
czc
genes (289 aa; 291 aa; 303 aa) within their chromosomes. These findings enhance our understanding of
L. monocytogenes
cadmium tolerance and underscore the need for further research to explore the genetic and physiological factors underlying these trends.

IMPORTANCE

Mobile genetic elements in
Listeria monocytogenes
contribute to its survival in natural and food processing environments. This study focused on how different genetic variants of the efflux pump gene
cadAC
and group of closely related
cadA1C1
strains respond to cadmium exposure. When exposed to two cadmium salts, cadmium chloride and cadmium sulfate, we observed varying growth patterns, with a significantly longer lag phase in cadmium sulfate compared to cadmium chloride. Strains with
cadA1
to
cadA3
had similar growth trends, whereas a strain with the
cadA4
variant had the highest minimum inhibitory concentration value. Among 88 strains from dairy processing facilities, significant phenotypic differences were observed despite core genome similarities, indicating other underlying genetic and physiological factors contribute to cadmium tolerance. Since cadmium tolerance studies in
L. monocytogenes
are limited, with rare phenotypic comparisons between closely related strains, our study makes an important observation and contribution to understanding of
L. monocytogenes
tolerance to cadmium by providing phenotypic comparisons between numerous strains within the same clonal group (<16 single nucleotide polymorphisms).
Features of the eGFP Gene Expression in Transplastomic Tobacco Plants
Authors: Sidorchuk Yu. V. , Belavin P. A. , Zagorskaya A. A. , Marenkova T. V. , Kuznetsov V. V. , Khairulina E. S. , Deineko E. V. 
Published: November 2024

Abstract
Transplastomic tobacco plants expressing a reporter gene egfp and selectable marker gene aadA as part of a bicistronic operon were obtained using the bioballistics method. Features of egfp gene expression were studied in two groups of transplastomic plants: seed progeny obtained from self-pollination and plants obtained as a result of two successive regeneration cycles from the leaves of the original transformants. A comparative fluorimetric analysis of the recombinant protein accumulation in groups of transplastomic plants and nuclear transformants was carried out. It was found that the amount of recombinant eGFP protein accumulated in the leaves of transplastomic plants was unexpectedly low and did not exceed the level established for nuclear transformants. Real-time PCR results showed that the low level of recombinant eGFP accumulation was not associated with low levels of transgene expression or the presence of nontransgenic copies of the plastid genome in chloroplasts. This is most likely due to limitations imposed at the level of translation of recombinant proteins in chloroplasts.
Facilitators and barriers to survivorship support access: a qualitative study of rectal cancer survivors’ experiences in Texas
Authors: You Xinyue , Chen Qi , Fichera Alessandro , Ivatury Joga 
Published: November 2024

ObjectiveThis qualitative study aimed to analyse rectal cancer survivors’ lived experiences to identify facilitators and barriers to support access.DesignWe conducted one-on-one semi-structured interviews and employed thematic analysis to identify key themes and insights.Setting/participantsParticipants included eight rectal cancer survivors and three caregivers recruited at Texas Colorectal Collaborative sites.ResultsResults showed that adequate hospital resources, high health literacy and close connections with clinicians and peers who share similar experiences facilitate survivors’ access to social support. Conversely, ineffective healthcare team communication, financial challenges and low self-motivation hindered access.ConclusionSurvivorship experiences were shaped by varying degrees of social support access, influenced by internal and external factors. We aim to establish a cross-institutional survivorship support network to address these factors, ensuring equitable access to support services and enhancing survivorship experiences.
Cost-effectiveness of robotic surgery compared to conventional laparoscopy for the management of early-stage cervical cancer: a model-based economic evaluation in China
Authors: Chen Chunlan , Zhang Min , Tang Junying , Pu Kexue 
Published: November 2024

ObjectivesThe aim of this study is to assess cost-effectiveness of robotic radical hysterectomy (RRH) vs laparoscopic radical hysterectomy (LRH) in early-stage cervical cancer (ECC).DesignModel-based cost-effectiveness analysis.SettingBased on long-term survival data, a three-state Markov model was constructed using TreeAge Pro 2022 to simulate the possible recurrence of ECC. Data on clinical efficacy and costs were derived from published literature and local databases.ParticipantsA hypothetical cohort of 1000 individuals diagnosed with early-stage cervical cancer (FIGO 2009 stages<IIB) who underwent RRH or LRH management.Outcome measuresThe study endpoints were quality-adjusted life years (QALYs), total costs (in Chinese renminbi (RMB) adjusted to 2023-year values using the Consumer Price Index) and incremental cost-effectiveness ratio (ICER). A willingness-to-pay threshold of 268 074 RMB per QALY was used to assess cost-effectiveness.ResultsRobotic group gained more 4.84 QALYs than the laparoscopic group, but total costs for robotic strategy are substantially higher, with the incremental costs of 1 031 108 RMB. The ICER of robotic strategy is 213 054 RMB per QALY. Outcomes were robust in most one-way sensitivity and probabilistic sensitivity analyses.ConclusionsRobotic strategy is on the efficient frontier but incurs substantial initial cost. Our findings indicated that this strategy is a cost-effective treatment option for ECC patients if assessed over a time horizon of patients’ lifetime. This study underscores the need for long-term clinical trials in early-stage cervical cancer patients with follow-up data that capture financial and quality-of-life end points.
Low effective coverage of HIV testing and counselling services during antenatal care in Ethiopia: evidence from the demographic and health survey and service provision assessment
Authors: Alemu Melaku Birhanu , Norman Richard , Dantas Jaya , Getachew Theodros , Tadele Ashenif , Tegegne Teketo Kassaw , Pereira Gavin , Tessema Gizachew A 
Published: November 2024

IntroductionPrevention of mother-to-child transmission contributes to avert nearly 4000 new HIV infections in 2022. HIV testing and counselling (HTC) during antenatal care (ANC) is an effective strategy to reduce the vertical transmission of HIV. While the utilisation of HTC services in Ethiopia has been explored, there is limited evidence exploring the effective coverage of HTC during ANC. We aimed to assess the quality-adjusted (effective) coverage of HTC during ANC in Ethiopia.MethodsWe linked the 2016 Ethiopian Demographic Health Survey and the 2021–2022 Ethiopian Service Provision Assessment (ESPA) surveys to determine the crude coverage and assess the quality of HTC provision. The ESPA service quality framework, which has structural and process-related components, was used. We used a weighted additive approach of 61 indicators (38 structural and 23 process) to estimate the quality of care score. Administrative boundary linkage was used to link the two datasets. The effective coverage was calculated as the product of crude coverage and the quality of care score.ResultsDuring ANC contacts/visits, 17.2% (95% CI 16.0 to 18.4) of women received HTC. The effective coverage of HTC during ANC was 10.8 (95% CI 9.8 to 11.8), with substantial disparities among administrative regions, ranging from 1.6% (95% CI 1.3, 2.0) in the Somali region to 55.5% (95% CI 53.5 to 57.5) in Addis Ababa. The overall service quality was 45.2% (95% CI 42.8 to 47.1). Health facilities in Harari (31.4% (95% CI 19.0 to 43.8)), Somali (34.1% (95% CI 26.8 to 41.6)) and Dire Dawa (34.9% (95% CI 24.71 to 45.0)) demonstrated low-quality service provision. Health posts (5.8%, SD=8.4), health facilities located in rural areas (30.6%, SD=27.3) and public health facilities (44.2%, SD=29.4) had low-quality HTC provision.ConclusionNearly 9 in 10 women did not receive quality HTC during ANC provision. The crude coverage, quality of services provision and effective coverage significantly vary across administrative regions. Afar and Somali regions lagged behind the Addis Ababa and Amhara administrative regions. To effectively mitigate mother-to-child transmission of HIV, policymakers need to prioritise enhancing the quality of care in HTC during ANC and expanding service delivery.
Myocardial Performance Index to assess cardiac function in autoimmune connective tissue disease: a systematic review and meta-analysis
Authors: Hidayat Rudy , Nasution Sally Aman , Parlindungan Faisal , Dalimunthe Naomi Niari , Alvianto Steven , Widjanarko Nicolas Daniel , Kultsum Ummi , Efendi Cristopher , Gotama Yovita 
Published: November 2024

ObjectivesThis study aimed to evaluate cardiac function using Myocardial Performance Index (MPI) in autoimmune connective tissue disease (ACTD) patients without cardiovascular abnormalities.MethodsA systematic search of databases including Medline, Google Scholar, ProQuest, Scopus and Cochrane Library was conducted to identify relevant studies on ACTD and MPI from 1995 to 2023. ACTD included in the search were rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), Sjögren syndrome (SjD), polymyositis and dermatomyositis. Quality assessment was performed using the Newcastle-Ottawa Scale, followed by meta-analysis computation of mean differences (MDs) of MPI using Review Manager V.5.4.ResultsA total of 22 studies for qualitative and 19 for quantitative synthesis were included. We found six studies on RA, eight studies on SSc, five studies on SLE, two studies on SjD and one on mixed connective tissue disorder. Conventional echocardiography and tissue Doppler imaging (TDI) were used to assess the MPI. Both conventional MPI and tissue Doppler MPI values were elevated compared with healthy control (MD=0.11, 95% CI 0.08 to 0.14, p value<0.00001 and MD=0.06, 95% CI 0.03 to 0.10, p value=0.00001, respectively).ConclusionsWe found elevated MPI values in patients with ACTD compared with healthy controls. MPI assessment has the potential for early detection and management of cardiac dysfunction in patients with ACTD, but further studies are required to corroborate these findings.PROSPERO registration numberCRD42023490643.
Impact of autoantibody status on stratifying the risk of organ involvement and mortality in SSc: experience from a multicentre French cohort of 1605 patients
Authors: Didier Kevin , Sobanski Vincent , Robbins Ailsa , Truchetet Marie-Elise , Barnetche Thomas , Contin-Bordes Cécile , Hot Arnaud , Fort Romain , Guilpain Philippe , Maria Alexandre , Agard Christian , Pennaforte Jean-Loup , Viguier Manuelle , Martin Thierry , Jolly Damien , Barbe Coralie , Giusti Delphine , Launay David , Servettaz Amélie 
Published: November 2024

IntroductionSystemic sclerosis (SSc) is a rare autoimmune disease currently classified into two subgroups based on skin extension. The aim of this study was to determine in a large cohort whether the determination of autoantibody (AAb) profile among a full antinuclear AAbs panel including nine specificities had a higher impact than skin phenotype on stratifying the risk of organ involvement and mortality in SSc.MethodsData for patients with SSc followed in seven French university hospitals were retrospectively analysed in terms of skin phenotype, AAbs (anti-topoisomerase I (ATA), anticentromere (ACA), anti-RNA polymerase III (anti-RNAPIII), anti-U1RNP, anti-U3RNP, anti-Pm/Scl, anti-Ku, anti-Th/To, anti-NOR90), organ involvement and mortality. Multivariate analyses were performed to identify independent factors associated with organ involvement and mortality.ResultsWe included 1605 patients with SSc (367 with diffuse cutaneous SSc). On multivariate analysis, ATAs were associated with interstitial lung disease and mortality (OR=3.27 (95% CI 2.42 to 4.42); HR=1.9 (95% CI 1.01 to 3.58)), anti-RNAPIII with scleroderma renal crisis and mortality (OR=7.05 (95% CI 2.98 to 16.72); HR=2.35 (95% CI 1.12 to 4.93)), anti-U1RNP with arthritis (OR=3.79 (95% CI 2.16 to 6.67)), anti-Pm/Scl and anti-Ku with myositis (OR=7.09 (95% CI 3.87 to 12.98) and 7.99 (95% CI 2.41 to 26.46)). The skin phenotype was not associated with survival or organ involvement on multivariate analysis without stepwise selection.ConclusionThis study unravels, by contrast with skin phenotype, a strong association between AAbs specificities, organ involvement and outcome in SSc and suggests that patients’ classification based on only skin extension is not sufficient for defining prognosis and phenotype.
ESATED: Leveraging Extra-weak Supervision with Auxiliary Task for Enhanced Non-intrusiveness in Energy Disaggregation
Authors: Xia Peng , Zhou Hao , Yang Tianjian , Zhou Wangqiu , Liu Zhi , Wang Xiaoyan , Li Xiang-Yang 
Published: November 2024

Non-intrusive load monitoring (NILM) is crucial to smart grid, which enables applications such as energy conservation and human activity recognition. As a typical task of NILM, energy disaggregation is to decompose total power consumption into appliance-level ones. Despite the remarkable achievements of deep-learning-based methods, their training phase still requires intrusively collected appliance-level power data as strong labels, which are directly used for supervising predictions.
In this paper, we present ESATED, a novel energy disaggregation system which instead utilizes non-intrusively collected binary on-off states of appliances as labels, thus enhancing non-intrusiveness throughout the life cycle. However, our labels are inherently weak labels due to the weak correlation between labels (binary states) and predictions (real-valued power), thus making our model struggle in terms of feasible supervision and acceptable performance. To tackle this challenge, we first explore the feasibility of binary-state-based weak supervision, and then integrate it into an auxiliary learning system, where an auxiliary subtask (i.e., state classification) is introduced to further enhance the performance of the primary task (i.e., energy disaggregation). We conduct extensive experiments on two real-world public datasets, and also implement the prototype system in a practical scenario. Corresponding results reveal that even using weak labels, ESATED could achieve performance and transferability second only to the state-of-the-art model. This result demonstrates the effectiveness of the proposed approach to extract information and train the model from extra weak labels.
Perceived Physical Activity Levels and Objective Measures: A Mixed‐Methods Study of Residents Aged 65 and Above in Assisted Living Homes in Australia
Authors: Alowaydhah Samaher , Weerasekara Ishanka , Walmsley Sarah , Keir Sally , Marquez Jodie 
Published: November 2024

Background and Purpose: Communities face a mounting social, economic and health burden as the global population of older adults continues to grow. Regular physical activity is consistently reported as an effective means of maintaining health and independence in older adults, yet engagement in activity remains low. This study assesses the activity levels of adults aged over 65 years residing in Australian assisted living homes, and extended to examine their perception of their activity and explore possible factors that hinder or promote their engagement in physical activity.Methods: Thirty‐five older adults were recruited to this mixed‐methods study from four separate assisted living homes. Objective activity data from five consecutive days of accelerometer wear were collected in combination with data from standardised and demographic questionnaires, and semistructured interviews. Qualitative data from interview transcripts were thematically analysed using NVivo software to develop themes relating to physical activity levels of older adults. Quantitative data from accelerometers and questionnaires were descriptively analysed, and associations between variables were examined using STATA software.Results and Discussion: Findings indicated that females were more active than males, and those who were younger and those with lower body mass index (BMI) displayed higher activity levels. Additionally, residents in assisted living facility (number 4) and those who did not need ambulatory assistance are more active. Conversely, those utilising support services and those with more comorbidities demonstrated lower activity levels. Marital status and cognitive function did not show any association with activity levels of older adults. During the interviews, many older adults acknowledged the importance of physical activity, and some believed they were active. However, objective results contradicted this perception.Conclusion: This study provides valuable insight into the demographic and health factors contributing to higher levels of activity, and the perceptions of activity among older adults vulnerable to health conditions associated with inactivity.
Mapping of the T-cell Landscape of Biliary Tract Cancer Unravels Anatomic Subtype-Specific Heterogeneity
Authors: Nie Jianhua , Zhang Shuyuan , Guo Ying , Liu Caiqi , Shi Jiaqi , Wu Haotian , Na Ruisi , Liang Yingjian , Yu Shan , Quan Fei , Liu Kun , Li Mingwei , Zhou Meng , Zhao Ying , Li Xuehan , Luo Shengnan , Zhang Qian , Wang Guangyu , Zhang Yanqiao , Yao Yuanfei , Xiao Yun , Tai Sheng , Zheng Tongsen 
Published: November 2024

Abstract
Biliary tract cancer (BTC), encompassing diseases such as intrahepatic (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer, is not only increasing but also poses a significant and urgent health threat due to its high malignancy. Genomic differences point to the possibility that these subtypes represent distinct diseases. Elucidation of the specific distribution of T-cell subsets, critical to cancer immunity, across these diseases could provide better insights into the unique biology of BTC subtypes and help identify potential precision medicine strategies. To address this, we conducted single-cell RNA sequencing and T-cell receptor sequencing on CD3+ T cells from 36 samples from 16 patients with BTC across all subtypes and analyzed 355 pathologic slides to examine the spatial distribution of T cells and tertiary lymphoid structures. Compared with ICC and gallbladder cancer, ECC possessed a unique immune profile characterized by T-cell exhaustion, elevated CXCL13 expression in CD4+ T helper–like and CD8+CXCL13+ exhausted T cells, more mature tertiary lymphoid structures, and fewer desert immunophenotypes. Conversely, ICC displayed an inflamed immunophenotype with an enrichment of IFN-related pathways and high expression of LGALS1 in activated regulatory T cells, associated with immunosuppression. Inhibition of LGALS1 reduced tumor growth and regulatory T-cell prevalence in ICC mouse models. Overall, this study unveils T-cell diversity across BTC subtypes at the single-cell and spatial level that could open paths for tailored immunotherapies.
Significance: Single-cell and spatial analyses detailed the T-cell characteristics specific to anatomic subtypes of biliary tract cancer, identifying unique immunologic features that could potentially be harnessed to improve patient outcomes.
Andexanet Alfa–Associated Heparin Resistance in Cardiac Surgery: Mechanism and In Vitro Perspectives
Authors: Chabata Charlene V. , Yu Haixiang , Ke Lei , Frederiksen James W. , Patel Prakash A. , Sullenger Bruce A. , Thalji Nabil K. 
Published: November 2024

BACKGROUND:
Andexanet alfa (andexanet) is the only Food and Drug Administration–approved antidote for direct FXa (factor Xa) inhibitors but has been reported to cause resistance to unfractionated heparin (UFH). This has delayed anticoagulation for procedures requiring cardiopulmonary bypass. The mechanism, andexanet and UFH dose dependence, and thrombotic risk of andexanet-associated heparin resistance are unknown.

METHODS:
The effect of andexanet in vitro was determined using activated clotting times and thromboelastography. Ex vivo cardiopulmonary bypass circuits were used to determine whether andexanet impaired anticoagulation for extracorporeal circulation. Kinetics of AT (antithrombin) inhibition of FXa and thrombin were measured in the presence of andexanet. Equilibrium modeling and thrombin generation assay validation were used to predict the role of andexanet, AT, and UFH concentrations in andexanet-associated heparin resistance.

RESULTS:
Andexanet prevented UFH-mediated prolongation of activated clotting times and thromboelastography times. At lower concentrations of andexanet, heparin resistance could be overcome with suprapharmacologic doses of UFH, but not at higher andexanet concentrations. Andexanet rendered standard doses of UFH inadequate to prevent circuit thrombosis, and suprapharmacologic UFH doses were only partially able to overcome this. Scanning electron microscopy demonstrated coagulation activation in circuits. Andexanet prevented UFH enhancement of AT-mediated inhibition of FXa and thrombin. Equilibrium modeling and thrombin generation assay validation demonstrated that andexanet creates a triphasic equilibrium with UFH and AT: initial UFH unresponsiveness, normal UFH responsiveness when andexanet is depleted, and finally AT depletion. Sufficient cardiopulmonary bypass heparinization can only occur at low therapeutic andexanet doses and normal AT levels. Higher andexanet doses or AT deficiency may require high UFH doses and potentially AT supplementation.

CONCLUSIONS:
Andexanet causes heparin resistance due to redistribution of UFH-bound AT. If andexanet cannot be avoided before heparinization and direct thrombin inhibitors are undesirable, our in vitro study suggests excess UFH should be considered as a potential strategy before AT supplementation.