bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent epigenetic signals propel a senescence-associated secretory phenotype and trained innate immunity in CD34+ hematopoietic stem cells from diabetic patients
Authors: Vinci Maria Cristina , Costantino Sarah , Damiano Giulia , Rurali Erica , Rinaldi Raffaella , Vigorelli Vera , Sforza Annalisa , Carulli Ermes , Pirola Sergio , Mastroiacovo Giorgio , Raucci Angela , El-Osta Assam , Paneni Francesco , Pompilio Giulio 
Published: March 2024

Abstract
Background
Diabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed to investigate in humans whether epigenetic signals involved in immune cell activation and inflammation are initiated in hematopoietic stem/progenitor cells (HSPCs) and transferred to differentiated progeny.

Methods and results
High glucose (HG)-exposure of cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by cell proliferation lowering, ROS production, telomere shortening, up-regulation of p21 and p27genes, upregulation of NFkB-p65 transcription factor and increased secretion of the inflammatory cytokines TNFα and IL6. Chromatin immunoprecipitation assay (ChIP) of p65 promoter revealed that H3K4me1 histone mark accumulation and methyltransferase SetD7 recruitment, along with the reduction of repressive H3K9me3 histone modification, were involved in NFkB-p65 upregulation of HG-HSPCs, as confirmed by increased RNA polymerase II engagement at gene level. The differentiation of HG-HSPCs into myeloid cells generated highly responsive monocytes, mainly composed of intermediate subsets (CD14hiCD16+), that like the cells from which they derive, were characterized by SASP features and similar epigenetic patterns at the p65 promoter. The clinical relevance of our findings was confirmed in sternal BM-derived HSPCs of T2DM patients. In line with our in vitro model, T2DM HSPCs were characterized by SASP profile and SETD7 upregulation. Additionally, they generated, after myeloid differentiation, senescent monocytes mainly composed of proinflammatory intermediates (CD14hiCD16+) characterized by H3K4me1 accumulation at NFkB-p65 promoter.

Conclusions
Hyperglycemia induces marked chromatin modifications in HSPCs, which, once transmitted to the cell progeny, contributes to persistent and pathogenic changes in immune cell function and composition.
Genomic insights into the evolution and mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae co-harboring blaKPC and blaNDM: implications for public health threat mitigation
Authors: Wang Qian , Liu Yue , Chen Ran , Zhang Meng , Si Zaifeng , Wang Yueling , Jin Yan , Bai Yuanyuan , Song Zhen , Lu Xinglun , Hao Mingju , Hao Yingying 
Published: March 2024

Abstract
Background
Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) co-producing blaKPC and blaNDM poses a serious threat to public health. This study aimed to investigate the mechanisms underlying the resistance and virulence of CR-hvKP isolates collected from a Chinese hospital, with a focus on blaKPC and blaNDM dual-positive hvKP strains.

Methods
Five CR-hvKP strains were isolated from a teaching hospital in China. Antimicrobial susceptibility and plasmid stability testing, plasmid conjugation, pulsed-field gel electrophoresis, and whole-genome sequencing (WGS) were performed to examine the mechanisms of resistance and virulence. The virulence of CR-hvKP was evaluated through serum-killing assay and Galleria mellonella lethality experiments. Phylogenetic analysis based on 16 highly homologous carbapenem-resistant K. pneumoniae (CRKP) producing KPC-2 isolates from the same hospital was conducted to elucidate the potential evolutionary pathway of CRKP co-producing NDM and KPC.

Results
WGS revealed that five isolates individually carried three unique plasmids: an IncFIB/IncHI1B-type virulence plasmid, IncFII/IncR-type plasmid harboring KPC-2 and IncC-type plasmid harboring NDM-1. The conjugation test results indicated that the transference of KPC-2 harboring IncFII/IncR-type plasmid was unsuccessful on their own, but could be transferred by forming a hybrid plasmid with the IncC plasmid harboring NDM. Further genetic analysis confirmed that the pJNKPN26-KPC plasmid was entirely integrated into the IncC-type plasmid via the copy-in route, which was mediated by TnAs1 and IS26.

Conclusion
KPC-NDM-CR-hvKP likely evolved from a KPC-2-CRKP ancestor and later acquired a highly transferable blaNDM-1 plasmid. ST11-KL64 CRKP exhibited enhanced plasticity. The identification of KPC-2-NDM-1-CR-hvKP highlights the urgent need for effective preventive strategies against aggravated accumulation of resistance genes.
Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC
Authors: Yang Huizhen , Mu Weiwei , Yuan Shijun , Yang Han , Chang Lili , Sang Xiao , Gao Tong , Liang Shuang , Liu Xiaoqing , Fu Shunli , Zhang Zipeng , Liu Yongjun , Zhang Na 
Published: March 2024

AbstractImmune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to “cold” tumors’ immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.
Graphical Abstract
Establishing conditions for the generation and maintenance of estrogen receptor-positive organoid models of breast cancer
Authors: Oliphant Michael U J , Akshinthala Dipikaa , Muthuswamy Senthil K. 
Published: March 2024

AbstractPatient-derived organoid models of estrogen receptor-positive (ER+) breast cancer would provide a much-needed tool to understand drug resistance and disease progression better. However, the establishment and long-term maintenance of ER expression, function, and response in vitro remains a significant challenge. Here, we report the development of an ER+ breast tumor organoid medium (BTOM-ER) that conserves ER expression, estrogen responsiveness, and dependence, as well as sensitivity to endocrine therapy of ER+ patient-derived xenograft organoids (PDXO). Our findings demonstrate the utility of subtype-specific culture conditions that better mimic the characteristics of the breast epithelial biology and microenvironment, providing a powerful platform for investigating therapy response and disease progression of ER+ breast cancer.
Evaluation of feline heartworm disease based on gross necropsy, serology, pulmonary histopathology, and radiographic evidence in adult shelter cats in northeastern Alabama
Authors: Nelson C. Thomas , Johnson Calvin M. 
Published: March 2024

Abstract
Background
: Veterinary knowledge regarding feline heartworm has been increasing significantly over the past two decades. Necropsy surveys of shelter cats have shown feline adult heartworm infection prevalence to be 5–20% of the rate in unprotected dogs; however, other studies have shown feline heartworm antibody prevalence up to 33%, reflecting higher exposure rates and potential immature adult infections. Thus, the true prevalence of feline heartworm infection is likely underestimated due to the limitations of current diagnostic techniques, inadequate testing protocols, and the high likelihood of cats exhibiting transient clinical signs or dying without confirmation of infection. Diagnosing Feline Heartworm Disease (FHWD), also referred to as Heartworm Associated Respiratory Disease (HARD), is one of the conundrums of veterinary medicine. The purpose of this study was to evaluate and characterize the occurrence of Heartworm Associated Respiratory Disease [HARD] in shelter cats, naturally-infected with D.immitis.

Methods
Fifty shelter cats slated for euthanasia between December 2009 and June 2010 were investigated by gross necropsy, radiography, serology, and lung histopathology using techniques that have been established in experimental models of cat heartworm infection. The relationship between pulmonary vascular disease and serological markers for heartworm was also examined using correlations and statistical modeling. Serology included standard heartworm antigen test and a commonly used heartworm antibody test. Also included were heat-treated heartworm antigen test and two additional heartworm antibody tests previously evaluated on experimentally-infected cats.

Results
None of the cats were heartworm antibody (HW Ab) positive on a commonly used HW Ab test used by many reference laboratories even though 20% of the study cats were heartworm antigen (HW Ag) positive on heat-treated samples. Two additional HW Ab test were positive on 26% and 22% of the study cats. The combination of heat-treated HW Ag, HW Ab tests, and histopathology indicated 34% of the study cats had HARD.

Conclusions
Utilizing both, the above tests, and thoracic radiographs, enhanced the ability to predict vascular disease, possibly caused by infection with immature and adult heartworms and supported the premise that cats develop heartworm disease at the same rate as dogs.

Graphical Abstract
Optimizing malaria vector control in the Greater Mekong Subregion: a systematic review and mathematical modelling study to identify desirable intervention characteristics
Authors: Wang Yuqian , Chitnis Nakul , Fairbanks Emma L. 
Published: March 2024

Abstract
Background
In the Greater Mekong Subregion (GMS), new vector-control tools are needed to target mosquitoes that bite outside during the daytime and night-time to advance malaria elimination.

Methods
We conducted systematic literature searches to generate a bionomic dataset of the main malaria vectors in the GMS, including human blood index (HBI), parity proportion, sac proportion (proportion with uncontracted ovary sacs, indicating the amount of time until they returned to host seeking after oviposition) and the resting period duration. We then performed global sensitivity analyses to assess the influence of bionomics and intervention characteristics on vectorial capacity.

Results
Our review showed that Anopheles minimus, An. sinensis, An. maculatus and An. sundaicus display opportunistic blood-feeding behaviour, while An. dirus is more anthropophilic. Multivariate regression analysis indicated that environmental, climatic and sampling factors influence the proportion of parous mosquitoes, and resting duration varies seasonally. Sensitivity analysis highlighted HBI and parity proportion as the most influential bionomic parameters, followed by resting duration. Killing before feeding is always a desirable characteristic across all settings in the GMS. Disarming is also a desirable characteristic in settings with a low HBI. Repelling is only an effective strategy in settings with a low HBI and low parity proportion. Killing after feeding is only a desirable characteristic if the HBI and parity proportions in the setting are high.

Conclusions
Although in general adopting tools that kill before feeding would have the largest community-level effect on reducing outdoor transmission, other modes of action can be effective. Current tools in development which target outdoor biting mosquitoes should be implemented in different settings dependent on their characteristics.

Graphical Abstract
Determinants of COVID-19 vaccine uptake: evidence from a vulnerable global South setting
Authors: Amoah John Oti , Abraham Susanna Aba , Adongo Charles Atanga , Sekimpi Deogratias Kaheeru , Adukpo David Cudjoe , Obiri-Yeboah Dorcas , Doku David Teye 
Published: March 2024

Abstract
Objective
Studies are paying increasing attention to complex social determinants in explaining the variation in the rates COVID-19 vaccine uptake. This study examines the influence of various individual, contextual, and vaccine-related factors on COVID-19 vaccine uptake behaviour in a resource-scarce and vulnerable setting using a quantitative research approach. Using a multi-staged cluster sampling approach, 408 individuals from 204 households in Cape Coast, Ghana’s tourism hub, were surveyed. Probit and logistic regression models were estimated to test the vaccine-related factors.

Results
A significant difference is observed between wait time and vaccination status (χ2 = 21.17; p = 0.000). Moreover, age and religion, as controlled variables, equally played significant roles in influencing the adoption of the vaccine. Other factors encompass the perceived risk of contracting COVID-19, the perceived benefits of the vaccine in relation to its side effects, and the level of trust individuals have in the concern of vaccine producers for their health. These findings call for targeted campaigns by the Ministry of Health, health facilities and other institutions promoting the COVID-19 vaccine. These actors should emphasize the benefits of vaccination, prioritize trust-building initiatives, and provide clear guidance on vaccination schedules, and manage waiting time.
From voice to ink (Vink): development and assessment of an automated, free-of-charge transcription tool
Authors: Tolle Hannah , Castro Maria del Mar , Wachinger Jonas , Putri Agrin Zauyani , Kempf Dominic , Denkinger Claudia M. , McMahon Shannon A. 
Published: March 2024

Abstract
Background
Verbatim transcription of qualitative audio data is a cornerstone of analytic quality and rigor, yet the time and energy required for such transcription can drain resources, delay analysis, and hinder the timely dissemination of qualitative insights. In recent years, software programs have presented a promising mechanism to accelerate transcription, but the broad application of such programs has been constrained due to expensive licensing or “per-minute” fees, data protection concerns, and limited availability of such programs in many languages. In this article, we outline our process of adapting a free, open-source, speech-to-text algorithm (Whisper by OpenAI) into a usable and accessible tool for qualitative transcription. Our program, which we have dubbed “Vink” for voice to ink, is available under a permissive open-source license (and thus free of cost).

Results
We conducted a proof-of-principle assessment of Vink’s performance in transcribing authentic interview audio data in 14 languages. A majority of pilot-testers evaluated the software performance positively and indicated that they were likely to use the tool in their future research. Our usability assessment indicates that Vink is easy-to-use, and we performed further refinements based on pilot-tester feedback to increase user-friendliness.

Conclusion
With Vink, we hope to contribute to facilitating rigorous qualitative research processes globally by reducing time and costs associated with transcription and by expanding free-of-cost transcription software availability to more languages. With Vink running on standalone computers, data privacy issues arising within many other solutions do not apply.
The multifaceted therapeutic value of targeting steroid receptor coactivator-1 in tumorigenesis
Authors: Chen Qiang , Guo Peng , Hong Yilin , Mo Pingli , Yu Chundong 
Published: March 2024

AbstractSteroid receptor coactivator-1 (SRC-1, also known as NCOA1) frequently functions as a transcriptional coactivator by directly binding to transcription factors and recruiting to the target gene promoters to promote gene transcription by increasing chromatin accessibility and promoting the formation of transcriptional complexes. In recent decades, various biological and pathological functions of SRC-1 have been reported, especially in the context of tumorigenesis. SRC-1 is a facilitator of the progression of multiple cancers, including breast cancer, prostate cancer, gastrointestinal cancer, neurological cancer, and female genital system cancer. The emerging multiorgan oncogenic role of SRC-1 is still being studied and may not be limited to only steroid hormone-producing tissues. Growing evidence suggests that SRC-1 promotes target gene expression by directly binding to transcription factors, which may constitute a novel coactivation pattern independent of AR or ER. In addition, the antitumour effect of pharmacological inhibition of SRC-1 with agents including various small molecules or naturally active compounds has been reported, but their practical application in clinical cancer therapy is very limited. For this review, we gathered typical evidence on the oncogenic role of SRC-1, highlighted its major collaborators and regulatory genes, and mapped the potential mechanisms by which SRC-1 promotes primary tumour progression.
Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study
Authors: Malherbe Jolan , Godard Pierre , Lacherade Jean-Claude , Coirier Valentin , Argaud Laurent , Hyvernat Hervé , Schneider Francis , Charpentier Julien , Wallet Florent , Pocquet Juliette , Plantefeve Gaëtan , Quenot Jean-Pierre , Bay Pierre , Delbove Agathe , Georges Hugues , Urbina Tomas , Schnell David , Le Moal Charlène , Stanowski Matthieu , Muris Corentin , Jonas Maud , Sauneuf Bertrand , Lesieur Olivier , Lhermitte Amaury , Calvet Laure , Gueguen Ines , du Cheyron Damien 
Published: March 2024

AbstractBackgroundDue to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019.ResultsOne-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001).ConclusionOverall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.
A precise mathematical approach for analyzing the performance of MIMO space–time block code systems over Weibull fading channels
Authors: Bessate Abdelmajid , Miftah Youssef , Ben-Azza Hussain , El Bouanani Faissal 
Published: March 2024

AbstractMultiple-input–multiple-output (MIMO) systems have effectively addressed today’s high demand for 5G communications and beyond. Further, MIMO-assisted space–time block codes (STBCs) have been shown to enhance the system’s performance and provide a complete variety of coherent flat-fading channels. Additionally, the closed-form expression of the probability density function of the summation of correlated Weibull random variables remains unknown. In this work, we investigate the performance analysis of MIMO-STBC-enabled systems subject to the Weibull fading channel. New tight approximate expressions for numerous system performance metrics, e.g., outage probability, average capacity under various rate adaption methods, and average symbol/bit error rate, have been obtained. The Monte Carlo simulation method has corroborated all the presented results.