bluuebunny/crossref_metadata_2025 huggingface dataset:
A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation
Authors: Domínguez-Horta Maria del Carmen , Serrano-Díaz Anabel , Hernández-Cedeño Mabel , Martínez-Donato Gillian , Guillén-Nieto Gerardo
Published: April 2023

Cytokines are secretion proteins that mediate and regulate immunity and inflammation. They are crucial in the progress of acute inflammatory diseases and autoimmunity. In fact, the inhibition of proinflammatory cytokines has been widely tested in the treatment of rheumatoid arthritis (RA). Some of these inhibitors have been used in the treatment of COVID-19 patients to improve survival rates. However, controlling the extent of inflammation with cytokine inhibitors is still a challenge because these molecules are redundant and pleiotropic. Here we review a novel therapeutic approach based on the use of the HSP60–derived Altered Peptide Ligand (APL) designed for RA and repositioned for the treatment of COVID-19 patients with hyperinflammation. HSP60 is a molecular chaperone found in all cells. It is involved in a wide diversity of cellular events including protein folding and trafficking. HSP60 concentration increases during cellular stress, for example inflammation. This protein has a dual role in immunity. Some HSP60-derived soluble epitopes induce inflammation, while others are immunoregulatory. Our HSP60-derived APL decreases the concentration of cytokines and induces the increase of FOXP3+ regulatory T cells (Treg) in various experimental systems. Furthermore, it decreases several cytokines and soluble mediators that are raised in RA, as well as decreases the excessive inflammatory response induced by SARS-CoV-2. This approach can be extended to other inflammatory diseases.
The resurgence of the Adora2b receptor as an immunotherapeutic target in pancreatic cancer
Authors: Strickland Lincoln N. , Faraoni Erika Y. , Ruan Wei , Yuan Xiaoyi , Eltzschig Holger K. , Bailey-Lundberg Jennifer M.
Published: April 2023

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of the 4 receptors, Adora2b has the lowest affinity for adenosine and thus, has important consequences when stimulated by adenosine binding in the hypoxic TME. We and others have shown that Adora2b is present in normal pancreas tissue, and in injured or diseased pancreatic tissue, Adora2b levels are significantly elevated. The Adora2b receptor is present on many immune cells, including macrophages, dendritic cells, natural killer cells, natural killer T cells, γδ T cells, B cells, T cells, CD4+ T cells, and CD8+ T cells. In these immune cell types, adenosine signaling through Adora2b can reduce the adaptive anti-tumor response, augmenting immune suppression, or may contribute to transformation and changes in fibrosis, perineural invasion, or the vasculature by binding the Adora2b receptor on neoplastic epithelial cells, cancer-associated fibroblasts, blood vessels, lymphatic vessels, and nerves. In this review, we discuss the mechanistic consequences of Adora2b activation on cell types in the tumor microenvironment. As the cell-autonomous role of adenosine signaling through Adora2b has not been comprehensively studied in pancreatic cancer cells, we will also discuss published data from other malignancies to infer emerging therapeutic considerations for targeting the Adora2b adenosine receptor to reduce the proliferative, invasive, and metastatic potential of PDAC cells.
T follicular helper cells and T follicular regulatory cells in autoimmune diseases
Authors: Qi Jingjing , Liu Chang , Bai Ziran , Li Xia , Yao Genhong
Published: April 2023

T follicular helper (Tfh) cells are heterogeneous and mainly characterized by expressing surface markers CXCR5, ICOS, and PD-1; cytokine IL-21; and transcription factor Bcl6. They are crucial for B-cell differentiation into long-lived plasma cells and high-affinity antibody production. T follicular regulatory (Tfr) cells were described to express markers of conventional T regulatory (Treg) cells and Tfh cells and were able to suppress Tfh-cell and B-cell responses. Evidence has revealed that the dysregulation of Tfh and Tfr cells is positively associated with the pathogenic processes of autoimmune diseases. Herein, we briefly introduce the phenotype, differentiation, and function of Tfh and Tfr cells, and review their potential roles in autoimmune diseases. In addition, we discuss perspectives to develop novel therapies targeting Tfh/Tfr balance.
A century of human interventions on sediment flux variations in the Danube-Black Sea transition zone
Authors: Constantinescu Adriana Maria , Tyler Andrew N. , Stanica Adrian , Spyrakos Evangelos , Hunter Peter D. , Catianis Irina , Panin Nicolae
Published: April 2023

Many deltas around the world have recorded a decreasing sediment input, mostly due to retention in dams constructed on the river or in the river basin. The Danube River has recorded a significant decrease of its sediment supply to the Danube Delta and the NW Black Sea. This study uses 210Pb and 137Cs dating, to investigate the effects of the decreasing sediment flux in lakes, lagoons, delta front and prodelta area. Both the effects of the Iron Gate I and II dams and other local factors are discussed. These results define the period of 1960-1990 as the ‘major anthropic interventions period’ in the Danube Delta. Results show a decrease in siliciclastic flux, especially in lakes, the Sahalin lagoon and the prodelta area and a general increase in the Musura lagoon and the delta front area. Sand content is also shown to decrease in most areas and is replaced by silt. The changes in sediment accumulation rates depend mostly on the hydrological connectivity of the area and the local hydrotechnical works. Overall, the local anthropic interventions in the delta affect sediment flux in the subaerial delta and the delta front, while the prodelta is affected by the overall decrease caused by interventions in the river basin. This study can contribute to improving management strategies in the area and to a better understanding of future research needs in the Danube Delta-Black Sea system.
The use and sustainable development of marine animal drugs by the Kinh people in Beibu Gulf
Authors: Luo Binsheng , Nong You , Zhang Ting , Zhang Shuai , Hu Renchuan
Published: April 2023

The Kinh people of China have historically migrated from Tushan and other areas of Vietnam since the 16th century. They are now settled in Fangchenggang City in the Beibu Gulf region of Guangxi, China. The local Kinh people have lived by fishing and have a rich fishing culture. Accordingly, the Kinh people of China have a long history of using traditional marine animal drugs for their daily medicinal needs. However, with the advent of modern medicine, there is a risk of losing the valuable traditional knowledge of marine animal drugs. Thus, this study aimed to document the types of marine animal drugs and related traditional knowledge of the Kinh people and explore the sustainability of their access to marine animal drugs. Ethnobiological methods, including snowball sampling and semi-structured interviews are used to collect information about the animal drugs used locally during the study. Through field investigations in the “Three Islands of Kinh,” we collected ethnozoological data on 61 marine animal drugs belonging to 52 families across six animal phyla. Chordata and Mollusca are the most represented phyla, while Arthropoda, Echinodermata, Sipuncula, and Cnidaria are less represented. According to the analysis, animal meat is the most frequent medicinal part; the Kinh prefer decoction or making soup, and internal administration is the most frequent use mode. Our statistical analysis revealed that nourishing was the most common purpose for the recorded marine animal drugs in the study area. Our study found that 6 documented species are listed as threatened on the IUCN Red List but receive little targeted protection. The article provides recommendations for protecting traditional knowledge, promoting sustainable development of marine resources, and conserving endangered species.
Treatment of condylomata acuminata caused by low-risk human papillomavirus with chloroquine phosphate gel
Authors: Li Xiangling , Guan Zhisheng , Liu Qi , Yang Wei , Huang Jie , Yuan Manli , Yu Junlong
Published: April 2023

Objective

To observe the stability and therapeutic effect of chloroquine phosphate gel on human condylomata acuminata (CA) caused by low-risk human papillomavirus (HPV).

Methods

The appearance, viscosity, pH, chloroquine concentration, deethylchloroquine concentration and content uniformity of chloroquine phosphate gel were examined for 24 months, the gel met the quality standards throughout the 24-month observation. A nude mouse model harboring CA xenografts was used to observe the therapeutic effect of this gel on CAin vivo.

Results

After 14 days of gel administration, compared with the control group, the treatment group had significantly smaller warts and significantly reduced DNA copy numbers of HPV6 and HPV11 in the wart tissues. Immunohistochemistry analysis of p53 protein expression in the wart tissues of the treatment group was significantly increased.

Conclusion

Chloroquine phosphate gel was stable and effective against CA, possibly through the promotion of p53 protein expression to induce apoptosis, leading to the involution of warts.
Characterization of microbiomic and geochemical compositions across the photosynthetic fringe
Authors: Weeks Katelyn , Trembath-Reichert Elizabeth , Boyer Grayson , Fecteau Kristopher , Howells Alta , De Martini Francesca , Gile Gillian H. , Shock Everett L.
Published: April 2023

Hot spring outflow channels provide geochemical gradients that are reflected in microbial community compositions. In many hot spring outflows, there is a distinct visual demarcation as the community transitions from predominantly chemotrophs to having visible pigments from phototrophs. It has been hypothesized that this transition to phototrophy, known as the photosynthetic fringe, is a result of the pH, temperature, and/or sulfide concentration gradients in the hot spring outflows. Here, we explicitly evaluated the predictive capability of geochemistry in determining the location of the photosynthetic fringe in hot spring outflows. A total of 46 samples were taken from 12 hot spring outflows in Yellowstone National Park that spanned pH values from 1.9 to 9.0 and temperatures from 28.9 to 92.2°C. Sampling locations were selected to be equidistant in geochemical space above and below the photosynthetic fringe based on linear discriminant analysis. Although pH, temperature, and total sulfide concentrations have all previously been cited as determining factors for microbial community composition, total sulfide did not correlate with microbial community composition with statistical significance in non-metric multidimensional scaling. In contrast, pH, temperature, ammonia, dissolved organic carbon, dissolved inorganic carbon, and dissolved oxygen did correlate with the microbial community composition with statistical significance. Additionally, there was observed statistical significance between beta diversity and the relative position to the photosynthetic fringe with sites above the photosynthetic fringe being significantly different from those at or below the photosynthetic fringe according to canonical correspondence analysis. However, in combination, the geochemical parameters considered in this study only accounted for 35% of the variation in microbial community composition determined by redundancy analysis. In co-occurrence network analyses, each clique correlated with either pH and/or temperature, whereas sulfide concentrations only correlated with individual nodes. These results indicate that there is a complex interplay between geochemical variables and the position of the photosynthetic fringe that cannot be fully explained by statistical correlations with the individual geochemical variables included in this study.
Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI)
Authors: Ip Kevan L. , Thomas Monique A. , Behar Kevin L. , de Graaf Robin A. , De Feyter Henk M.
Published: April 2023

Introduction

There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to-brain image contrast.

Methods

RG2 cells were incubated with choline and the level of intracellular choline and its metabolites measured in cell extracts using high resolution 1H NMR. In rats with orthotopically implanted RG2 tumors deuterium metabolic imaging (DMI) was applied in vivo during, as well as 1 day after, intravenous infusion of 2H9-choline. In parallel experiments, RG2-bearing rats were infused with [1,1′,2,2′-2H4]-choline and tissue metabolite extracts analyzed with high resolution 2H NMR to identify molecule-specific 2H-labeling in choline and its metabolites.

Results

In vitro experiments indicated high uptake and fast phosphorylation of exogenous choline in RG2 cells. In vivo DMI studies revealed a high signal from the 2H-labeled pool of choline + metabolites (total choline, 2H-tCho) in the tumor lesion but not in normal brain. Quantitative DMI-based metabolic maps of 2H-tCho showed high tumor-to-brain image contrast in maps acquired both during, and 24 h after deuterated choline infusion. High resolution 2H NMR revealed that DMI data acquired during 2H-choline infusion consists of free choline and phosphocholine, while the data acquired 24 h later represent phosphocholine and glycerophosphocholine.

Discussion

Uptake and metabolism of exogenous choline was high in RG2 tumors compared to normal brain, resulting in high tumor-to-brain image contrast on DMI-based metabolic maps. By varying the timing of DMI data acquisition relative to the start of the deuterated choline infusion, the metabolic maps can be weighted toward detection of choline uptake or choline metabolism. These proof-of-principle experiments highlight the potential of using deuterated choline combined with DMI to metabolically characterize brain tumors.
Radiomic and clinical nomogram for cognitive impairment prediction in Wilson’s disease
Authors: Tian Liwei , Dong Ting , Hu Sheng , Zhao Chenling , Yu Guofang , Hu Huibing , Yang Wenming
Published: April 2023

Objective

To investigate potential biomarkers for the early detection of cognitive impairment in patients with Wilson’s disease (WD), we developed a computer-assisted radiomics model to distinguish between WD and WD cognitive impairment.

Methods

Overall, 136 T1-weighted MR images were retrieved from the First Affiliated Hospital of Anhui University of Chinese Medicine, including 77 from patients with WD and 59 from patients with WD cognitive impairment. The images were divided into training and test groups at a ratio of 70:30. The radiomic features of each T1-weighted image were extracted using 3D Slicer software. R software was used to establish clinical and radiomic models based on clinical characteristics and radiomic features, respectively. The receiver operating characteristic profiles of the three models were evaluated to assess their diagnostic accuracy and reliability in distinguishing between WD and WD cognitive impairment. We combined relevant neuropsychological test scores of prospective memory to construct an integrated predictive model and visual nomogram to effectively assess the risk of cognitive decline in patients with WD.

Results

The area under the curve values for distinguishing WD and WD cognitive impairment for the clinical, radiomic, and integrated models were 0.863, 0.922, and 0.935 respectively, indicative of excellent performance. The nomogram based on the integrated model successfully differentiated between WD and WD cognitive impairment.

Conclusion

The nomogram developed in the current study may assist clinicians in the early identification of cognitive impairment in patients with WD. Early intervention following such identification may help improve long-term prognosis and quality of life of these patients.
Personality traits and pattern of beliefs of near-death(-like) experiencers
Authors: Bicego Aminata , Cassol Héléna , Simon Jessica , Fritz Pauline , Abagnale Simona , Vanhaudenhuyse Audrey , Laureys Steven , Martial Charlotte
Published: April 2023

Introduction

Little is known about the potential personality and psychological predictors of near-death experiences (NDEs), and fewer yet those of near-death-like experiences (NDEs-like; similar phenomenology reported after a non-life-threatening context). This study investigated whether personality traits (Openness, Extraversion, Pleasantness, Conscientiousness, and Neuroticism), dissociative experiences, Fantasy proneness, disposition toward auditory hallucinations, absorption trait, and endorsement of paranormal and spiritual beliefs could be associated with the recall of NDEs(-like).

Methods

To this aim, we invited four groups of people to retrospectively fill in questionnaires assessing the following factors: NDE experiencers (n = 63), NDE(-like) experiencers (n = 31), controls with a life-threatening situation but no NDE(-like) (n = 43), and controls without a life-threatening situation or an NDE(-like) (n = 44). We carried out univariate analyses for each factor and then performed a multiple regression analysis and a discriminant analysis.

Results

The multivariate logistic regression analysis revealed that the endorsement of spiritual beliefs was associated with the recall of NDEs-like while Openness and Fantasy proneness were associated with the recall of NDEs. The discriminant analysis showed that these variables produce 35% of correct classification.

Discussion

Albeit retrospective, these results pave the way for future research on psychological predictors of NDEs(-like) by highlighting the influence of Spirituality, Openness, and Fantasy proneness on these phenomena.
Viability of AMURA biomarkers from single-shell diffusion MRI in clinical studies
Authors: Martín-Martín Carmen , Planchuelo-Gómez Álvaro , Guerrero Ángel L. , García-Azorín David , Tristán-Vega Antonio , de Luis-García Rodrigo , Aja-Fernández Santiago
Published: April 2023

Diffusion Tensor Imaging (DTI) is the most employed method to assess white matter properties using quantitative parameters derived from diffusion MRI, but it presents known limitations that restrict the evaluation of complex structures. The objective of this study was to validate the reliability and robustness of complementary diffusion measures extracted with a novel approach, Apparent Measures Using Reduced Acquisitions (AMURA), with a typical diffusion MRI acquisition from a clinical context in comparison with DTI with application to clinical studies. Fifty healthy controls, 51 episodic migraine and 56 chronic migraine patients underwent single-shell diffusion MRI. Four DTI-based and eight AMURA-based parameters were compared between groups with tract-based spatial statistics to establish reference results. On the other hand, following a region-based analysis, the measures were assessed for multiple subsamples with diverse reduced sample sizes and their stability was evaluated with the coefficient of quartile variation. To assess the discrimination power of the diffusion measures, we repeated the statistical comparisons with a region-based analysis employing reduced sample sizes with diverse subsets, decreasing 10 subjects per group for consecutive reductions, and using 5,001 different random subsamples. For each sample size, the stability of the diffusion descriptors was evaluated with the coefficient of quartile variation. AMURA measures showed a greater number of statistically significant differences in the reference comparisons between episodic migraine patients and controls compared to DTI. In contrast, a higher number of differences was found with DTI parameters compared to AMURA in the comparisons between both migraine groups. Regarding the assessments reducing the sample size, the AMURA parameters showed a more stable behavior than DTI, showing a lower decrease for each reduced sample size or a higher number of regions with significant differences. However, most AMURA parameters showed lower stability in relation to higher coefficient of quartile variation values than the DTI descriptors, although two AMURA measures showed similar values to DTI. For the synthetic signals, there were AMURA measures with similar quantification to DTI, while other showed similar behavior. These findings suggest that AMURA presents favorable characteristics to identify differences of specific microstructural properties between clinical groups in regions with complex fiber architecture and lower dependency on the sample size or assessing technique than DTI.
The association between oxidative balance score and periodontitis in adults: a population-based study
Authors: Qu Haitao
Published: April 2023

Introduction

The pathogenesis between oxidative stress and periodontitis was correlated. The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. However, the association between OBS and periodontitis has not been reported previously.

Methods

Sixteen dietary factors and four lifestyle factors were selected to score the OBS. Multivariate logistic regression and sensitivity analysis were used to investigate the relationship between OBS and periodontitis based on data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations.

Results

This study included 3,706 participants. There was a negative linear association between OBS and periodontitis in all participants [0.89 (0.80, 0.97)], and after converting OBS to a quartile variable, participants with OBS in the highest quartile had a 29% lower risk of periodontitis than those with OBS in the lowest quartile [0.71 (0.42, 0.98)]. This negative association differed with respect to age and diabetes.

Conclusion

There is a negative association between OBS and periodontitis in US adults. Our results suggest that OBS may be used as a biomarker for measuring periodontitis.
Incremental value of radiomics with machine learning to the existing prognostic models for predicting outcome in renal cell carcinoma
Authors: Xing Jiajun , Liu Yiyang , Wang Zhongyuan , Xu Aiming , Su Shifeng , Shen Sipeng , Wang Zengjun
Published: April 2023

Purpose

To systematically evaluate the potential of radiomics coupled with machine-learning algorithms to improve the predictive power for overall survival (OS) of renal cell carcinoma (RCC).

Methods

A total of 689 RCC patients (281 in the training cohort, 225 in the validation cohort 1 and 183 in the validation cohort 2) who underwent preoperative contrast-enhanced CT and surgical treatment were recruited from three independent databases and one institution. 851 radiomics features were screened using machine-learning algorithm, including Random Forest and Lasso-COX Regression, to establish radiomics signature. The clinical and radiomics nomogram were built by multivariate COX regression. The models were further assessed by Time-dependent receiver operator characteristic, concordance index, calibration curve, clinical impact curve and decision curve analysis.

Result

The radiomics signature comprised 11 prognosis-related features and was significantly correlated with OS in the training and two validation cohorts (Hazard Ratios: 2.718 (2.246,3.291)). Based on radiomics signature, WHOISUP, SSIGN, TNM Stage and clinical score, the radiomics nomogram has been developed. Compared with the existing prognostic models, the AUCs of 5 years OS prediction of the radiomics nomogram were superior to the TNM, WHOISUP and SSIGN model in the training cohort (0.841 vs 0.734, 0.707, 0.644) and validation cohort2 (0.917 vs 0.707, 0.773, 0.771). Stratification analysis suggested that the sensitivity of some drugs and pathways in cancer were observed different for RCC patients with high-and low-radiomics scores.

Conclusion

This study showed the application of contrast-enhanced CT-based radiomics in RCC patients, creating novel radiomics nomogram that could be used to predict OS. Radiomics provided incremental prognostic value to the existing models and significantly improved the predictive power. The radiomics nomogram might be helpful for clinicians to evaluate the benefit of surgery or adjuvant therapy and make individualized therapeutic regimens for patients with renal cell carcinoma.
Why is advance care planning underused in oncology settings? A systematic overview of reviews to identify the benefits, barriers, enablers, and interventions to improve uptake
Authors: Guccione Lisa , Fullerton Sonia , Gough Karla , Hyatt Amelia , Tew Michelle , Aranda Sanchia , Francis Jill
Published: April 2023

Background

Advance care planning (ACP) centres on supporting people to define and discuss their individual goals and preferences for future medical care, and to record and review these as appropriate. Despite recommendations from guidelines, rates of documentation for people with cancer are considerably low.

Aim

To systematically clarify and consolidate the evidence base of ACP in cancer care by exploring how it is defined; identifying benefits, and known barriers and enablers across patient, clinical and healthcare services levels; as well as interventions that improve advance care planning and are their effectiveness.

Methods

A systematic overview of reviews was conducted and was prospectively registered on PROSPERO. PubMed, Medline, PsycInfo, CINAHL, and EMBASE were searched for review related to ACP in cancer. Content analysis and narrative synthesis were used for data analysis. The Theoretical Domains Framework (TDF) was used to code barriers and enablers of ACP as well as the implied barriers targeted by each of the interventions.

Results

Eighteen reviews met the inclusion criteria. Definitions were inconsistent across reviews that defined ACP (n=16). Proposed benefits identified in 15/18 reviews were rarely empirically supported. Interventions reported in seven reviews tended to target the patient, even though more barriers were associated with healthcare providers (n=40 versus n=60, respectively).

Conclusion

To improve ACP uptake in oncology settings; the definition should include key categories that clarify the utility and benefits. Interventions need to target healthcare providers and empirically identified barriers to be most effective in improving uptake.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42021288825.
Histogram analysis of multi-model high-resolution diffusion-weighted MRI in breast cancer: correlations with molecular prognostic factors and subtypes
Authors: Qin Yanjin , Wu Feng , Hu Qilan , He Litong , Huo Min , Tang Caili , Yi Jingru , Zhang Huiting , Yin Ting , Ai Tao
Published: April 2023

Objective

To investigate the correlations between quantitative diffusion parameters and prognostic factors and molecular subtypes of breast cancer, based on a single fast high-resolution diffusion-weighted imaging (DWI) sequence with mono-exponential (Mono), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) models.

Materials and Methods

A total of 143 patients with histopathologically verified breast cancer were included in this retrospective study. The multi-model DWI-derived parameters were quantitatively measured, including Mono-ADC, IVIM-D, IVIM-D*, IVIM-f, DKI-Dapp, and DKI-Kapp. In addition, the morphologic characteristics of the lesions (shape, margin, and internal signal characteristics) were visually assessed on DWI images. Next, Kolmogorov–Smirnov test, Mann-Whitney U test, Spearman’s rank correlation, logistic regression, receiver operating characteristic (ROC) curve, and Chi-squared test were utilized for statistical evaluations.

Results

The histogram metrics of Mono-ADC, IVIM-D, DKI-Dapp, and DKI-Kapp were significantly different between estrogen receptor (ER)-positive vs. ER-negative groups, progesterone receptor (PR)-positive vs. PR-negative groups, Luminal vs. non-Luminal subtypes, and human epidermal receptor factor-2 (HER2)-positive vs. non-HER2-positive subtypes. The histogram metrics of Mono-ADC, DKI-Dapp, and DKI-Kapp were also significantly different between triple-negative (TN) vs. non-TN subtypes. The ROC analysis revealed that the area under the curve considerably improved when the three diffusion models were combined compared with every single model, except for distinguishing lymph node metastasis (LNM) status. For the morphologic characteristics of the tumor, the margin showed substantial differences between ER-positive and ER-negative groups.

Conclusions

Quantitative multi-model analysis of DWI showed improved diagnostic performance for determining the prognostic factors and molecular subtypes of breast lesions. The morphologic characteristics obtained from high-resolution DWI can be identifying ER statuses of breast cancer.
HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer
Authors: Olivera-Salguero Rubén , Seguí Elia , Cejalvo Juan Miguel , Oliveira Mafalda , Tolosa Pablo , Vidal Maria , Malumbres Marcos , Gavilá Joaquín , Saura Cristina , Pernas Sonia , López Rafael , Margelí Mireia , Balmaña Judith , Muñoz Montserrat , Blancas Isabel , Boni Valentina , Ciruelos Eva , Galve Elena , Perelló Antonia , Sánchez-Bayona Rodrigo , de la Cruz Susana , de la Hoya Miguel , Galván Patricia , Sanfeliu Esther , Gonzalez-Farre Blanca , Sirenko Valeria , Blanch-Torras Aura , Canes Jordi , Masanas Helena , Olmos Rosa , Forns Margarita , Prat Aleix , Casas Ana , Pascual Tomás
Published: April 2023

Background

Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients’ outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems.

Trial design

After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient’s medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment.

Clinical trial registration

www.soltihope.com, identifier NCT04497285.
Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles
Authors: Khalili Dilan , Kunc Martin , Herbrich Sarah , Müller Anna M. , Theopold Ulrich
Published: April 2023

Introduction

Chitinase-like proteins (CLPs) are associated with tissue-remodeling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, CLP’s role in tumors is far from clear.

Methods

Here, we utilize Drosophila melanogaster and molecular genetics to investigate the function of CLPs (imaginal disc growth factors; Idgf’s) in RasV12 dysplastic salivary glands.

Results and discussion

We find one of the Idgf’s members, Idgf3, is transcriptionally induced in a JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged endosomal vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization. The process is mediated via the downstream component, aSpectrin, which localizes to the EnVs. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.
A scoping review of psychiatric conditions associated with chronic pain in the homeless and marginally housed population
Authors: Rintoul Kathryn , Song Esther , McLellan-Carich Rachel , Schjelderup Elizabeth N. R. , Barr Alasdair M.
Published: April 2023

The present review sought to examine and summarise the unique experience of concurrent pain and psychiatric conditions, that is often neglected, within the population of homeless individuals. Furthermore, the review examined factors that work to aggravate pain and those that have been shown to improve pain management. Electronic databases (MEDLINE, EMBASE, psycINFO, and Web of Science) and the grey literature (Google Scholar) were searched. Two reviewers independently screened and assessed all literature. The PHO MetaQAT was used to appraise quality of all studies included. Fifty-seven studies were included in this scoping review, with most of the research being based in the United States of America. Several interacting factors were found to exacerbate reported pain, as well as severely affect other crucial aspects of life that correlate directly with health, within the homeless population. Notable factors included drug use as a coping mechanism for pain, as well as opioid use preceding pain; financial issues; transportation problems; stigma; and various psychiatric disorders, such as post-traumatic stress disorder, depression, and anxiety. Important pain management strategies included cannabis use, Accelerated Resolution Therapy for treating trauma, and acupuncture. The homeless population experiences multiple barriers which work to further impact their experience with pain and psychiatric conditions. Psychiatric conditions impact pain experience and can work to intensify already adverse health circumstances of homeless individuals.
Pharmacokinetics and bioequivalence study of esomeprazole magnesium enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions
Authors: Chu Nannan , Ding Ying , Que Linling , Huang Kai , Chen Yuanxing , Qin Wei , Qian Zhenzhong , Shi Yunfei , Xu Zhen , He Qing
Published: April 2023

Objective: The main purpose of this study was to evaluate the pharmacokinetics, bioequivalence, and safety properties between a new generic and a brand reference formulation of esomeprazole enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions.

Methods: The fasting study was an open-label, randomized, two-period crossover study conducted in 32 healthy Chinese volunteers, and the fed study was a four-period crossover study conducted in 40 healthy Chinese volunteers. Blood samples were collected at the specified time points and determined to obtain the plasma concentrations of esomeprazole. The primary pharmacokinetic parameters were calculated using the non-compartment method. Bioequivalence was analyzed by the geometric mean ratios (GMRs) of the two formulations and the corresponding 90% confidence intervals (CIs). The safety of the two formulations was assessed.

Results: The fasting and fed study showed that the pharmacokinetics of the two formulations was similar. Under the fasting condition, the 90% CIs of GMRs of the test-to-reference formulation were 87.92%–104.36% for Cmax, 87.82%–101.45% for AUC0-t, and 87.99%–101.54% for AUC0-∞; under the fed condition, the 90% CIs of GMRs of the test-to-reference formulation were 80.53%–94.95% for Cmax, 87.46%–97.26% for AUC0-t, and 87.46%–97.16% for AUC0-∞. The 90% CIs of GMRs fall within the bioequivalence range of 80.00%–125.00%. The two formulations had good safety and were well-tolerated, and no serious adverse events occurred.

Conclusion: According to relevant regulatory standards, esomeprazole enteric-coated generic and reference products exhibited bioequivalence and good safety in healthy Chinese subjects.

Clinical Trials Registration:http://www.chinadrugtrials.org.cn/index.html, identifier CTR20171347 and CTR20171484
Joint engagement and early language abilities in young children with Down syndrome
Authors: Mattie Laura J. , Fanta Daniela
Published: April 2023

Introduction

Early social strengths likely serve as a foundation for language acquisition for young children with Down syndrome (DS). One way to characterize early social skills is to examine a child’s engagement with a caregiver around an object of interest. The current study examines joint engagement in young children with DS and its relation to language abilities at two-time points in early development.

Methods

Participants were 16 young children with DS and their mothers. At two time points, mother–child free plays were completed and coded for joint engagement. Language abilities were measured at both time points using the Vineland Adaptive Behavior Scales 3rd edition and the number of words understood and produced on the MacArthur-Bates Communication Development Inventory.

Results

Young children with DS spent more time in supported joint engagement than coordinated joint engagement at both time points. Using a weighted joint engagement variable, children with DS who had higher weighted joint engagement had lower expressive language raw scores on the Vineland when controlling for age at Time 1. At Time 2, children with DS who had higher weighted joint engagement had higher expressive and receptive language raw scores on the Vineland when controlling for age. Predictively, children with DS who had a higher weighted joint engagement at Time 1 had a lower number of words produced at Time 2 when controlling for age at Time 1.

Discussion

Our results suggest that young children with DS may compensate for their difficulties with language by using joint engagement. These results highlight the importance of teaching parents to be responsive during interactions with their child to move them into both supported and coordinated engagement, which in turn may foster language development.
Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review
Authors: Pollack Beth , von Saltza Emelia , McCorkell Lisa , Santos Lucia , Hultman Ashley , Cohen Alison K. , Soares Letícia
Published: April 2023

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID. These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause. We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.
Designing implementation strategies to improve identification, cascade testing, and management of families with familial hypercholesterolemia: An intervention mapping approach
Authors: Jones Laney K. , Calvo Evan M. , Campbell-Salome Gemme , Walters Nicole L. , Brangan Andrew , Rodriguez Gabriela , Ahmed Catherine D. , Morgan Kelly M. , Gidding Samuel S. , Williams Marc S. , Brownson Ross C. , Seaton Terry L. , Goldberg Anne C. , McGowan Mary P. , Rahm Alanna K. , Sturm Amy C.
Published: April 2023

Introduction

Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care.

Methods

Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific literature was searched using key words including “barriers” or “facilitators” and “familial hypercholesterolemia” from inception to December 1, 2021. The parallel mixed method study recruited individuals and families with FH to participate in either dyadic interviews (N = 11 dyads/22 individuals) or online surveys (N = 98 respondents). Data generated from the scoping review, dyadic interviews, and online surveys were used in the 6-step intervention mapping process. Steps 1–3 included a needs assessment, development of program outcomes and creation of evidence-based implementation strategies. Steps 4–6 included program development, implementation, and evaluation of implementation strategies.

Results

In steps 1–3, a needs assessment found barriers to FH care included underdiagnosis of the condition which led to suboptimal management due to a myriad of determinants including knowledge gaps, negative attitudes, and risk misperceptions by individuals with FH and clinicians. Literature review highlighted barriers to FH care at the health system level, notably the relative lack of genetic testing resources and infrastructure needed to support FH diagnosis and treatment. Examples of strategies to overcome identified barriers included development of multidisciplinary care teams and educational programs. In steps 4–6, an NHLBI-funded study, the Collaborative Approach to Reach Everyone with FH (CARE-FH), deployed strategies that focused on improving identification of FH in primary care settings. The CARE-FH study is used as an example to describe program development, implementation, and evaluation techniques of implementation strategies.

Conclusion

The development and deployment of evidence-based implementation strategies that address barriers to FH care are important next steps to improve identification, cascade testing, and management.
Endothelial cell provenance: an unclear role in transplant medicine
Authors: Pace Autumn , Steiner Marie E. , Vercellotti Gregory M. , Somani Arif
Published: April 2023

An understanding of the interplay between both donor endothelial progenitors and the recipient endothelium (in the case of hematopoietic cell transplant) and recipient endothelial provenance upon the established donor endothelium (in the case of solid organ transplant) is unknown. It is postulated that this interplay and consequences of purported dual endothelial populations may be a component of the post-transplant disease process and contribute to complications of engraftment or rejection. To address this potential confounding and often overlooked arena of vascular biology, a directed brief overview primarily focused on literature presented over the last decade is presented herein.