Miracle-dz/UniFAR-FTUs huggingface dataset:
Repurposing Ferumoxytol as a Breast Cancer-Associated Macrophage Tracer with Five-Dimensional Quantitative [Fe]MRI of SPION Dynamics

Simple Summary With the incorporation of immune-modulating therapies into the standard management of triple-negative breast cancer, there is increased interest in the non-invasive imaging of the tumor immune microenvironment. Ferumoxytol is FDA-approved as an iron replacement therapy for iron-deficiency anemia and is also a superparamagnetic iron oxide nanoparticle (SPION) resulting in negative enhancement on T2-weighted MR imaging. It has previously been established that ferumoxytol is taken up by macrophages. In the current study, we used ferumoxytol-contrasted MRI to quantitatively image the iron concentration, and, by extension, the tumor-associated macrophage infiltration within the tumor microenvironment of a highly inflammatory model of triple-negative breast cancer. Abstract Tumor-associated macrophages (TAMs) in breast cancer regulate inflammation, immunosuppression, angiogenesis, and metastasis. However, TAM imaging remains a clinical challenge. Ferumoxytol has long been an FDA-approved superparamagnetic iron oxide nanoparticle (SPION) preparation used as an intravenous (IV) treatment for iron-deficiency anemia. Given its high transverse relaxivity, ferumoxytol produces a negative image contrast upon cellular uptake in T2-weighted magnetic resonance imaging (MRI) studies. Here we evaluated ferumoxytol as a contrast agent to image/quantify TAMs in an aggressive mouse model of breast cancer: We developed [Fe]MRI to measure the 5-dimensional function c(x,y,z,t), where c is the concentration of nanoparticle iron and {x,y,z,t} is the 4-dimensional set of tumor space-time coordinates. Ferumoxytol SPIONs are readily phagocytosed (~104/cell) by the F4/80+CD11b+ TAMs within breast tumors. Quantitative [Fe]MRIs served to determine both the spatial and the temporal distribution of the SPION iron, and hence to measure [Fe] = c(x,y,z,t), a surrogate for TAM density. In single-dose pharmacokinetic studies, after an IV dose of 5 mg/Kg iron, [Fe]MRI measurements showed that c(x,y,z,t) within breast tumors peaked around [Fe] = 70 μM at 42 h post-administration, and decayed below the [Fe]MRI detection limit (~2 μM) by day 7. There was no SPION uptake in control organs (muscle and adipose tissue). Optical microscopy of tissue sections confirmed that F4/80+CD11b+ TAMs infiltrated the tumors and accumulated SPION iron. Our methodology and findings have translational applications for breast cancer patients.
The Impact of Income Inequality on Subjective Environmental Pollution: Individual Evidence from China

Numerous studies have investigated the relationship between income inequality and objective environmental pollution, but few focus on the nexus between income inequality and subjective environmental pollution (SEP). Using micro data from the Chinese General Society Survey (CGSS) in 2013 and official statistical data at the provincial level, this paper tests the impact of individual-level income inequality on subjective environmental pollution in China. The results show that individual-level income inequality has an inverted U-shape relationship with subjective environmental pollution, which indicates that increasing the income inequality at the individual level will first rise and then reduce their perceived subjective environmental pollution after reaching the peak. For about 84% of respondents, their subjective environmental pollution decreases with the increase of individual-level income inequality. Furthermore, the heterogeneity analyses show that the income inequality of urban residents and of the locals have an inverted U-shape effect on SEP, and the SEP of females and of individuals with positive environmental attitude are more sensitive to the effect of income inequality. Additionally, we find that subjective well-being plays a mediating role in the relation between income inequality and SEP. Individual income inequality decreases their self-reported well-being, and an increase in well-being has a negative effect on their subjectively perceived environmental quality. We also find non-television media exposures, such as newspaper, magazine, broadcasting, Internet, and mobile custom messages, will amplify the effect of individual-level income inequality on subjective environmental pollution.
The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer

Simple Summary Next-generation sequencing (NGS) has revolutionized care for patients with advanced and metastatic non-small cell lung cancer through the identification of specific oncogenic driver mutations and pairing with matched targeted therapies. The application of NGS technologies also has the potential to improve outcomes in patients with earlier-stage disease who undergo surgery as their first line of treatment. We review clinically relevant topics in this patient cohort, for whom NGS technologies have spearheaded our understanding of tumor heterogeneity, the underlying genomic features associated with lung adenocarcinoma histologic subtypes, the prediction of recurrence after surgery, the identification of minimal residual disease by circulating tumor DNA, the discernment of intrapulmonary metastases versus synchronous or metachronous disease, and the identification of patients with early-stage non-small cell lung cancer who are likely to benefit from induction or adjuvant therapies. Abstract During the last two decades, next-generation sequencing (NGS) has played a key role in enhancing non-small cell lung cancer treatment paradigms through the application of “targeted therapy” in advanced and metastatic disease. The use of specific tyrosine kinase inhibitors in patients with oncogenic driver alterations, such as EGFR, ALK, ROS1, BRAF V600E, MET, and NTRK mutations, among others, has changed treatment approaches and improved outcomes in patients with late-stage disease. Although NGS technology has mostly been used in the setting of systemic therapy to identify targets, response to therapy, and mechanisms of resistance, it has multiple potential applications for patients with earlier-stage disease, as well. In this review, we discuss the emerging role of NGS technologies to better understand tumor biology in patients with non-small cell lung cancer who are undergoing surgery with curative intent. In this patient cohort, we examine tumor heterogeneity, the underlying tumor genomics associated with lung adenocarcinoma subtypes, the prediction of recurrence after complete surgical resection, the use of plasma circulating tumor DNA for detection of early cancers and monitoring for minimal residual disease, the differentiation of separate primaries from intrapulmonary metastases, and the use of NGS to guide induction and adjuvant therapies.
Antibiotic administration exacerbates acute graft vs. host disease-induced bone marrow and spleen damage in lymphopenic mice

Background Hematopoietic stem cell transplantation is a potential cure for certain life-threatening malignant and nonmalignant diseases. However, experimental and clinical studies have demonstrated that pre-transplant myeloablative conditioning damages the gut leading to translocation of intestinal bacteria and the development of acute graft vs. host disease (aGVHD). The overall objective of this study was to determine whether administration of broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD in lymphopenic mice that were not subjected to toxic, pre-transplant conditioning. Results We found that treatment of NK cell-depleted recombination activating gene-1-deficient (-NK/RAG) recipients with an Abx cocktail containing vancomycin and neomycin for 7 days prior to and 4 weeks following adoptive transfer of allogeneic CD4+ T cells, exacerbated the development of aGVHD-induced BM failure and spleen damage when compared to untreated–NK/RAG recipients engrafted with syngeneic or allogeneic T cells. Abx-treated mice exhibited severe anemia and monocytopenia as well as marked reductions in BM- and spleen-residing immune cells. Blinded histopathological analysis confirmed that Abx-treated mice engrafted with allogeneic T cells suffered significantly more damage to the BM and spleen than did untreated mice engrafted with allogeneic T cells. Abx-induced exacerbation of BM and spleen damage correlated with a dramatic reduction in fecal bacterial diversity, marked loss of anaerobic bacteria and remarkable expansion of potentially pathogenic bacteria. Conclusions We conclude that continuous Abx treatment may aggravate aGVHD-induced tissue damage by reducing short chain fatty acid-producing anaerobes (e.g. Clostridium, Blautia) and/or by promoting the expansion of pathobionts (e.g. Akkermansia) and opportunistic pathogens (Cronobacter).
Protocol Paper: Conducting Life History Interviews to Explore the Journeys of People with Disability from Syrian and Iraqi Refugee Backgrounds Settling in Australia

This paper outlines a research protocol to be undertaken with people with disability from Syrian and Iraqi refugee backgrounds settling in Australia. Since 2012, the numbers of people with disability arriving from these countries has increased with limited understanding about the impact of their refugee journeys on their settlement. The aim of this small-scale exploratory study is to learn about the journeys made by people with disability from Syrian and Iraqi refugee backgrounds from their countries of origin, through transit countries, to Australia in order to understand the impact of these journeys on inclusion and participation in Australian society. This participatory action research study employs a bilingual co-researcher with disability from a Syrian background to conduct life history interviews with up to five participants. Participants will recount their journeys with a focus on the impact of their disability on this experience. The study design is informed by BenEzer and Zetter’s 2014 seminal paper on the importance of the refugee journey to settlement. This study has the potential to foreground the voices and experiences of people with disability from refugee backgrounds who are often absent, silenced or excluded in research and, in so doing, hopefully impact Australian refugee policy.
Self-Learning Methodology in Simulated Environments (MAES©) as a Learning Tool in Perioperative Nursing. An Evidence-Based Practice Model for Acquiring Clinical Safety Competencies

Background: The self-learning Methodology in Simulated Environments (Spanish acronym: MAES©, (Murcia, Spain) is a type of self-directed and collaborative training in health sciences. The objective of the present study was to compare the level of competence of postgraduate surgical nursing students in the clinical safety of surgical patients, after training with the MAES© methodology versus traditional theoretical–practical workshops, at different points in time (post-intervention, after three months, six months post-intervention, and at the end of the clinical training period, specifically nine months post-intervention). Methods: We conducted a prospective study with an experimental group of surgical nursing postgraduate students who participated in MAES© high-fidelity simulation sessions, and a control group of postgraduate nursing students who attended traditional theoretical–practical sessions at two universities in Catalonia (Spain). The levels of competence were compared between the two groups and at different time points of the study. Results: The score was higher and statistically significantly different in the experimental group for all the competencies, with a large effect size at every measurement point previously mentioned. Conclusions: The postgraduate nurses were the most competent in the clinical safety of surgical patients when they trained with the MAES© methodology than when they learned through traditional theoretical–practical workshops. The learning of surgical safety competencies was more stable and superior in the experimental group who trained with MAES©, as compared to the control group.
TUMOSPEC: A Nation-Wide Study of Hereditary Breast and Ovarian Cancer Families with a Predicted Pathogenic Variant Identified through Multigene Panel Testing

Simple Summary TUMOSPEC was designed for estimating the risk of cancer for carriers of a predicted pathogenic variant (PPV) in a gene usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and are tested for the familial PPV. Genetic, clinical, family and epidemiological data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. This showed that the study logistics are well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) is smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene. Abstract Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and genotyped for the familial PPV. Clinical, family and epidemiological data are collected, and all data including sequencing data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. When invited by the coordinating centre, 65.3% of the relatives of index cases (5.7 relatives per family, on average) accepted the invitation to participate. The study logistics were well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) was smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene.
The Association between IgG and Disease Severity Parameters in CF Patients

Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = −0.527, p < 0.001 and r = −0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.
Change in Shoulder Function in the Early Recovery Phase after Breast Cancer Surgery: A Prospective Observational Study

Breast cancer surgery significantly affects the shoulder’s range of motion (ROM) and strength. However, the extent of shoulder impairment, as well as patterns of recovery immediately after surgery, is not fully understood. Therefore, we aimed to investigate shoulder ROM and strength during the early recovery phase after surgery. Thirty-two breast cancer patients were observed five times: the day before surgery, discharge day (postoperative day 1 (POD1) or (POD2)), first outpatient visit (POD7–10), second outpatient visit (POD14–20), and third outpatient visit (POD21–30). We assessed shoulder passive ROM and strength for both affected and unaffected arms at each observation. ROM decreased in both affected and unaffected sides post-surgery. ROM on the affected side did not recover to the pre-surgery level until the third outpatient visit (POD24). In contrast, the ROM on the unaffected side recovered to the pre-surgery level by the first outpatient visit (POD10). The shoulder strength of both arms declined and did not recover to pre-surgery levels. Shoulder strength in the affected arm significantly decreased immediately after surgery (52.9% of the pre-surgery levels) and did not recover until the third outpatient visit (62.5% of the pre-surgery levels), whereas that in the unaffected arm decreased gradually (83.1 ± 2.3 at POD 1 and 78.9 ± 2.9 at POD 24). Descriptively, patterns of recovery in ROM may vary according to types of surgery while patterns of recovery in shoulder strength did not: shoulder strength significantly decreased and did not recover notably regardless of types of surgery. Both shoulder ROM and strength reduced during the early recovery phase after breast cancer surgery regardless of types of surgery, although the degree of reduction was greater in shoulder strength than ROM. Our findings suggest that rehabilitation exercises should be implemented in both upper limbs.
Unexpected Outcomes of Renal Function after Radical Nephrectomy: Histology Relevance along with Clinical Aspects

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common events after radical nephrectomy (RN). In this study we aimed to predict AKI and CKD after RN relying on specific histological aspects. We collected data from a cohort of 144 patients who underwent radical nephrectomy. A histopathological review of the healthy part of the removed kidney was performed using an established chronicity score (CS). Logistic regression analyses were performed to predict AKI after RN, while linear regression analysis was adopted for estimated glomerular filtration rate (eGFR) variation at 1 year. The outcomes of the study were to determine variables correlated with AKI onset, and with eGFR decay at 1 year. The proportion of AKI was 64%. Logistic analyses showed that baseline eGFR independently predicted AKI (odds ratio 1.04, 95%CI 1.02:1.06). Moreover, AKI (Beta −16, 95%CI −21:−11), baseline eGFR (Beta −0.42, 95%CI −0.52:−0.33), and the presence of arterial narrowing (Beta 10, 95%CI 4:15) were independently associated with eGFR decline. Our findings showed that AKI onset and eGFR decline were more likely to occur with higher baseline eGFR and lower CS, highlighting that RN in normal renal function patients represents a more traumatic event than its CKD counterpart.
Evidence and Applicability of Stress Cardiovascular Magnetic Resonance in Detecting Coronary Artery Disease: State of the Art

Cardiovascular magnetic resonance is increasingly used in clinical practice, as it has emerged over the years as an invaluable imaging technique for diagnosis and prognosis, with clear-cut applications in managing patients with both ischemic and non-ischemic heart disease. In this review, we focus on the evidence and clinical application of stress CMR in coronary artery disease from diagnosis to prognosis.
Perioperative score for octogenarian patients eligible for rectal cancer surgery

Colorectal cancer incidence increases with age; therefore, rectal cancer treatment in elderly patients is increasingly common. Surgery is a common rectal cancer treatment, and the risks involve complicated surgical decisions. There are currently few surgical outcome data for rectal cancer in elderly patients. The aim of this study is to identify new perioperative risk factors that could be associated with higher 30‐ and 180‐day mortality in elderly patients in good clinical condition considering traditional perioperative risk scores and to develop a risk score.
Broadband Unidirectional Forward Scattering with High Refractive Index Nanostructures: Application in Solar Cells

High refractive index dielectric (HRID) nanoparticles are a clear alternative to metals in nanophotonic applications due to their low losses and directional scattering properties. It has been demonstrated that HRID dimers are more efficient scattering units than single nanoparticles in redirecting the incident radiation towards the forward direction. This effect was recently reported and is known as the “near zero-backward” scattering condition, attained when nanoparticles forming dimers strongly interact with each other. Here, we analyzed the electromagnetic response of HRID isolated nanoparticles and aggregates when deposited on monolayer and graded-index multilayer dielectric substrates. In particular, we studied the fraction of radiation that is scattered towards a substrate with known optical properties when the nanoparticles are located on its surface. We demonstrated that HRID dimers can increase the radiation emitted towards the substrate compared to that of isolated nanoparticles. However, this effect was only present for low values of the substrate refractive index. With the aim of observing the same effect for silicon substrates, we show that it is necessary to use a multilayer antireflection coating. We conclude that dimers of HRID nanoparticles on a graded-index multilayer substrate can increase the radiation scattered into a silicon photovoltaic wafer. The results in this work can be applied to the design of novel solar cells.
The Active Mechanism of Nucleosome Depletion by Poly(dA:dT) Tracts In Vivo

Poly(dA:dT) tracts cause nucleosome depletion in many species, e.g., at promoters and replication origins. Their intrinsic biophysical sequence properties make them stiff and unfavorable for nucleosome assembly, as probed by in vitro nucleosome reconstitution. The mere correlation between nucleosome depletion over poly(dA:dT) tracts in in vitro reconstituted and in in vivo chromatin inspired an intrinsic nucleosome exclusion mechanism in vivo that is based only on DNA and histone properties. However, we compile here published and new evidence that this correlation does not reflect mechanistic causation. (1) Nucleosome depletion over poly(dA:dT) in vivo is not universal, e.g., very weak in S. pombe. (2) The energy penalty for incorporating poly(dA:dT) tracts into nucleosomes is modest (<10%) relative to ATP hydrolysis energy abundantly invested by chromatin remodelers. (3) Nucleosome depletion over poly(dA:dT) is much stronger in vivo than in vitro if monitored without MNase and (4) actively maintained in vivo. (5) S. cerevisiae promoters evolved a strand-biased poly(dA) versus poly(dT) distribution. (6) Nucleosome depletion over poly(dA) is directional in vivo. (7) The ATP dependent chromatin remodeler RSC preferentially and directionally displaces nucleosomes towards 5′ of poly(dA). Especially distribution strand bias and displacement directionality would not be expected for an intrinsic mechanism. Together, this argues for an in vivo mechanism where active and species-specific read out of intrinsic sequence properties, e.g., by remodelers, shapes nucleosome organization.