Miracle-dz/UniFAR-FTUs huggingface dataset:
FUCCI Real-Time Cell-Cycle Imaging as a Guide for Designing Improved Cancer Therapy: A Review of Innovative Strategies to Target Quiescent Chemo-Resistant Cancer Cells

Simple Summary Chemotherapy of solid tumors has made very slow progress over many decades. A major problem has been that solid tumors very often contain non-dividing cells due to lack of oxygen deep in the tumor and these non-dividing cells resist most currently-used chemotherapy which usually only targets dividing cells. The present review demonstrates how a unique imaging system, FUCCI, which color codes cells depending on whether they are in a dividing or non-dividing phase, is being used to design very novel therapy that targets non-dividing cancer cells which can greatly improve the efficacy of cancer chemotherapy. Abstract Progress in chemotherapy of solid cancer has been tragically slow due, in large part, to the chemoresistance of quiescent cancer cells in tumors. The fluorescence ubiquitination cell-cycle indicator (FUCCI) was developed in 2008 by Miyawaki et al., which color-codes the phases of the cell cycle in real-time. FUCCI utilizes genes linked to different color fluorescent reporters that are only expressed in specific phases of the cell cycle and can, thereby, image the phases of the cell cycle in real-time. Intravital real-time FUCCI imaging within tumors has demonstrated that an established tumor comprises a majority of quiescent cancer cells and a minor population of cycling cancer cells located at the tumor surface or in proximity to tumor blood vessels. In contrast to most cycling cancer cells, quiescent cancer cells are resistant to cytotoxic chemotherapy, most of which target cells in S/G2/M phases. The quiescent cancer cells can re-enter the cell cycle after surviving treatment, which suggests the reason why most cytotoxic chemotherapy is often ineffective for solid cancers. Thus, quiescent cancer cells are a major impediment to effective cancer therapy. FUCCI imaging can be used to effectively target quiescent cancer cells within tumors. For example, we review how FUCCI imaging can help to identify cell-cycle-specific therapeutics that comprise decoy of quiescent cancer cells from G1 phase to cycling phases, trapping the cancer cells in S/G2 phase where cancer cells are mostly sensitive to cytotoxic chemotherapy and eradicating the cancer cells with cytotoxic chemotherapy most active against S/G2 phase cells. FUCCI can readily image cell-cycle dynamics at the single cell level in real-time in vitro and in vivo. Therefore, visualizing cell cycle dynamics within tumors with FUCCI can provide a guide for many strategies to improve cell-cycle targeting therapy for solid cancers.
Ductal Carcinoma In Situ Underestimation of Microcalcifications Only by Stereotactic Vacuum-Assisted Breast Biopsy: A New Predictor of Specimens without Microcalcifications

The mammographic appearance of ductal carcinoma in situ (DCIS) is mostly observed as microcalcifications. Although stereotactic vacuum-assisted breast biopsy (VABB) is a reliable alternative to surgical biopsy for suspicious microcalcifications, underestimation of VABB-proven DCIS is inevitable in clinical practice. We therefore retrospectively analyzed the variables in the prediction of DCIS underestimation manifesting as microcalcifications only proved by stereotactic VABB. In 1147 consecutive VABB on microcalcification-only lesions from 2010 to 2016, patients diagnosed with DCIS were selected to evaluate the underestimation rate. The analyzed variables included clinical characteristics, mammographic features, VABB procedure, and biomarkers. Univariate and multivariate analyses were used, and a p value < 0.05 was considered statistically significant. Of the 131 VABB-proven DCIS, 108 cases were diagnosed with DCIS and 23 were upgraded to invasive ductal carcinoma (IDC) after subsequent surgery. The small extent of microcalcification, grouped microcalcifications distribution, nearly complete microcalcification removal, and non-calcified specimens without DCIS were low for DCIS underestimation. Among them, the results of non-calcified specimens with or without DICS were the only statistically significant variables by multivariate logistic regression. These results indicate that the histology of non-calcified specimens was highly predictive of DCIS underestimation. Specimens without DCIS had a low upgrade rate to IDC.
Diversity within the master regulatory p53 transcriptional network: Impact of sequence, binding motifs and mutations

Jennifer J. Jordan Diversity within the master regulatory p53 transcriptional network: impact of sequence, binding motifs and mutations (Under the direction of Michael A. Resnick, PhD) In response to cellular stress and DNA damage, the master regulatory gene p53 directly controls the differential expression of target genes within its extensive transcriptional network through promoter response elements (REs) to elicit many biological responses, including cell cycle arrest and apoptosis. Tetrameric p53 binds the consensus sequence RRRCWWGYYY (n= 0-13) RRRCWWGYYY, where R=purine, W=A/T and Y=pyrimidine. Phenotypic diversity within the p53 transcriptional network occurs as a result of a variety of factors including cell type, post-translational modifications, stress-inducing stimuli, and mutations in p53 that alter transactivation function through changes in the strength of gene activation or spectra of genes regulated. We have developed an isogenomic diploid yeast-based reporter system to evaluate the contribution of target binding sequence, organization and level of p53 on transactivation at target REs by wild-type and mutant p53. The chromosomal position for all of the human derived REs was identical and the number of p53 molecules/cell could be varied over a hundred-fold using an integrated rheostatable GAL1::p53 promoter that is sensitive to level of galactose in the medium. We confirm transactivation by WT p53 differs between REs where small differences in sequence can
Proliferative and chondrogenic potential of mesenchymal stromal cells from pluripotent and bone marrow cells.

INTRODUCTION Mesenchymal stromal cells (MSCs) can be derived from a wide range of fetal and adult sources including pluripotent stem cells (PSCs). The properties of PSC-derived MSCs need to be fully characterized, in order to evaluate the feasibility of their use in clinical applications. PSC-MSC proliferation and differentiation potential in comparison with bone marrow (BM)-MSCs is still under investigation. The objective of this study was to determine the proliferative and chondrogenic capabilities of both human induced pluripotent stem cell (hiPSC-) and embryonic stem cell (hESC-) derived MSCs, by comparing them with BM-MSCs. METHODS MSCs were derived from two hiPSC lines (hiPSC-MSCs), the well characterized Hues9 hESC line (hESC-MSCs) and BM from two healthy donors (BM-MSCs). Proliferation potential was investigated using appropriate culture conditions, with serial passaging, until cells entered into senescence. Differentiation potential to cartilage was examined after in vitro chondrogenic culture conditions. RESULTS BM-MSCs revealed a fold expansion of 1.18x105 and 2.3x105 while the two hiPSC-MSC lines and hESC-MSC showed 5.88x1010, 3.49x108 and 2.88x108, respectively. Under chondrogenic conditions, all MSC lines showed a degree of chondrogenesis. However, when we examined the formed chondrocyte micromasses by histological analysis of the cartilage morphology and immunohistochemistry for the chondrocyte specific markers Sox9 and Collagen II, we observed that PSC-derived MSC lines had formed pink rather than hyaline cartilage, in contrast to BM-MSCs. CONCLUSION In conclusion, MSCs derived from both hESCs and hiPSCs had superior proliferative capacity compared to BM-MSCs, but they were inefficient in their ability to form hyaline cartilage.
Men’s gendered experiences of rehabilitation and recovery following traumatic brain injury: A reflexive thematic analysis

ABSTRACT Research shows that gender influences men’s health-related beliefs and behaviours – including those within the context of traumatic brain injury (TBI) – making it a factor that should be considered when designing and implementing interventions for this population. To incorporate an understanding of such gendered influences in future educational materials for men with TBI, as well as their caregivers and clinicians, this qualitative study was informed by social constructionism, and aimed to explore how gender is related to men’s post-TBI perceptions and behaviours in rehabilitation and recovery. Semi-structured interviews were conducted with 22 men with mild and moderate-severe TBI at the acute (≤ 3 months post-TBI) and chronic (> 3 months post-TBI) phases of injury. A reflexive thematic analysis approach was applied to interview data, guided by the concept of hegemonic masculinity as described by Connell, R.W. (2005. Masculinities [2nd ed.]. Polity). Three key themes were identified: (1) “I’m a man, I’m a rock”: Undermining treatment, (2) “I’m going to face that challenge”: Facilitation of recovery, and (3) “I don’t feel as useful as a guy as I was before”: Perceptions on return to work. These findings may be translated into gender-informed therapy strategies and materials.
Barriers to accessing primary healthcare services for people with disabilities in low and middle-income countries, a Meta-synthesis of qualitative studies

Abstract Background: Access to healthcare contributes to the attainment of health and is a fundamental human right. People with disabilities are believed to experience widespread poor access to healthcare services, due to inaccessible environments and discriminatory belief systems and attitudes. Qualitative data on these barriers has not previously been systematically reviewed. A meta-synthesis was undertaken of qualitative studies exploring the barriers to primary healthcare services experienced by people with disabilities in low- and middle-income countries. Methods Six electronic databases were searched for relevant studies from 2000 to 2019. Forty-one eligible studies were identified. Results Findings suggest that the people with disabilities’ choice to seek healthcare services or not, as well as the quality of intervention provided by primary healthcare providers, are influenced by three types of barriers: cultural beliefs or attitudinal barriers, informational barriers, and practical or logistical barriers. Conclusion In order to achieve full health coverage at acceptable quality for people with disabilities, it is necessary not only to consider the different barriers, but also their combined effect on people with disabilities and their households. It is only then that more nuanced and effective interventions to improve access to primary healthcare, systematically addressing barriers, can be designed and implemented. IMPLICATIONS FOR REHABILITATION People with disabilities in both high income and low- and middle-income country settings are more likely to experience poorer general health than people without disabilities. Barriers to accessing primary healthcare services for people with disabilities result from a complex and dynamic interacting system between attitudinal and belief system barriers, informational barriers, and practical and logistical barriers. Given primary healthcare is often the initial point of contact for referral to specialty care and rehabilitation services, it is crucial for people with disabilities to access primary healthcare services in order to get appropriate referrals for such services, specifically rehabilitation as appropriate. To achieve full health coverage at acceptable quality for people with disabilities, starting with primary healthcare, it is necessary for healthcare stakeholders, including rehabilitation professionals, to consider the combined and cumulative effects of the various barriers to healthcare on people with disabilities and their families and develop an understanding of how healthcare decisions are made by people with disabilities at the personal and the household level.
Application of 3D-print silica bolus for nasal NK/T-cell lymphoma radiation therapy

Abstract The aim of the study was to evaluate the clinical feasibility of a 3D-print silica bolus for nasal NK/T-cell lymphoma radiation therapy. Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were designed using an anthropomorphic head phantom with a 3D-print silica bolus and other kinds of bolus used clinically, and the surface dose was measured by a metal oxide semiconductor field-effect transistor (MOSFET) dosimeter. Four nasal NK/T patients with or without 3D-print silica bolus were treated and the nose surface dose was measured using a MOSFET dosimeter during the first treatment. Plans for the anthropomorphic head phantom with 3D-print bolus have more uniform dose and higher conformity of the planning target volume (PTV) compared to other boluses; the homogeneity index (HI) and conformity index (CI) of the VMAT plan were 0.0589 and 0.7022, respectively, and the HI and CI of the IMRT plan were 0.0550 and 0.7324, respectively. The MOSFET measurement results showed that the surface dose of the phantom with 3D-print bolus was >180 cGy, and that of patients with 3D-print bolus was higher than patients without bolus. The air gap volume between the 3D-print bolus and the surface of patients was <0.3 cc. The 3D-print silica bolus fitted well on the patient’s skin, effectively reducing air gaps between bolus and patient surface. Meanwhile, the 3D-print silica bolus provided patients with higher individuation, and improved the conformity and uniformity of the PTV compared to other kinds of boluses.
Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH (p = 0.001) and occipital DWMH (p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH (p = 0.003), as well as occipital DWMH (p = 0.001) and temporal DWMH (p = 0.002) loads. FRS-CVD was associated with frontal PWMHs (p = 0.003) and frontal DWMHs (p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.
Genetic Diversity and Population Structure of Maize Inbred Lines with Varying Levels of Resistance to Striga hermonthica Using Agronomic Trait-Based and SNP Markers

Striga hermonthica is a serious biotic stress limiting maize production in sub-Saharan Africa. The limited information on the patterns of genetic diversity among maize inbred lines derived from source germplasm with mixed genetic backgrounds limits the development of inbred lines, hybrids, and synthetics with durable resistance to S. hermonthica. This study was conducted to assess the level of genetic diversity in a panel of 150 diverse maize inbred lines using agronomic and molecular data and also to infer the population structure among the inbred lines. Ten Striga-resistance-related traits were used for the phenotypic characterization, and 16,735 high-quality single-nucleotide polymorphisms (SNPs), identified by genotyping-by-sequencing (GBS), were used for molecular diversity. The phenotypic and molecular hierarchical cluster analyses grouped the inbred lines into five clusters, respectively. However, the grouping patterns between the phenotypic and molecular hierarchical cluster analyses were inconsistent due to non-overlapping information between the phenotypic and molecular data. The correlation between the phenotypic and molecular diversity matrices was very low (0.001), which is in agreement with the inconsistencies observed between the clusters formed by the phenotypic and molecular diversity analyses. The joint phenotypic and genotypic diversity matrices grouped the inbred lines into three groups based on their reaction patterns to S. hermonthica, and this was able to exploit a broad estimate of the actual diversity among the inbred lines. The joint analysis shows an invaluable insight for measuring genetic diversity in the evaluated materials. The result indicates that wide genetic variability exists among the inbred lines and that the joint diversity analysis can be utilized to reliably assign the inbred lines into heterotic groups and also to enhance the level of resistance to Striga in new maize varieties.
Structure and foaming properties of viscous exopolysaccharides from a wild grape-associated basidiomycetous yeast Papiliotrema flavescens formerly known as Cryptococcus flavescens.

Exopolysaccharide produced by a yeast Papiliotrema flavescens isolated from wine grape berries of Champagne vineyard, was investigated for both chemical and functional characterization. SEC-MALLS and colorimetric assay analyses showed that EPS is high MW heteropolymer (2.37×106 g/mol) majorily consisted of mannose, glucose, xylose and glucuronic acid as monosaccharide constituents, with two substituents (sulphate and phosphate groups), and a minor protein moiety. Structural enchainment of these carbohydrates based on methylation, GC-MS and NMR analyses revealed a linear main backbone built up of α-(1→3)-D-mannopyranosyl residues on which are branched side chains consisted of single β-D-glucopyranosyluronic acid residue and β-(1→2)-xylopyranoses (2-5 residues). Suggestion of some xylopyranose side chains containing a mannose residue at nonreducing terminal end was also proposed. This is first report on exopolysaccharides from the grape Papiliotrema flavescens yeast with such structural characteristics. Furthermore, investigations for valuating the application performance of these EPS in relation with their structural features were carried out in 8% alcohol experiment solutions. Very exceptional viscosifying and foaming properties were reported by comparison with commercial biopolymers as Arabic, gellan and xanthan gums. The intrinsic properties of the natural biopolymer from this wild grape-associated Papiliotrema flavescens yeast make it potential candidate for use in various fields of biotechnology applications.
French Translation and Validation of the Synkinesis Assessment Questionnaire

ABSTRACT: Synkinesis is a distressing sequela of peripheral facial palsy (PFP). This study aimed to translate and validate the Synkinesis Assessment Questionnaire (SAQ), a reliable patient-reported outcome evaluation tool for synkinesis, in French. The SAQ was translated following a standard forward–backward translation procedure. After a cognitive debriefing with 10 PFP patients, the SAQ-F was assessed amongst 50 patients for internal consistency, known-group validity, construct validity, criterion validity, and test–retest reliability. Results demonstrated that the SAQ-F was valid, reliable, and had a unidimensional structure. The SAQ-F should be accompanied by clinician-based scales, to provide valuable additional information on the severity of synkinesis.
The temperature induced current transport characteristics in the orthoferrite YbFeO3− δ thin film/p-type Si structure

The perovskite ytterbium ferrite is a new ferroelectric semiconductor material. We presented the temperature induced current–voltage (I–V) characteristics of the Al/YbFeO3−δ /p-Si/Al hetero-junction. The orthoferrite YbFeO3−δ thin films were deposited on a single crystal p-type Si substrate by a radio frequency magnetron sputtering system. The potential barrier height (BH) and ideality factor n of the heterojunction were obtained by thermionic emission current method based on the recommendations in the literature. The fact that the calculated slopes of I–V curves become temperature independent implying that the field emission current mechanism takes place across the device, which has been explained by the presence of the spatial inhomogeneity of BHs or potential fluctuations. Moreover, a tunneling transmission coefficient value of 26.67 was obtained for the ferroelectric YbFeO3−δ layer at the Al/p-Si interface.
Vertical transmission: A vector-independent transmission pathway of Babesia microti in the natural reservoir host Peromyscus leucopus.

BACKGROUND Babesia microti, a malaria-like pathogen, is increasing in mammal and human populations in endemic areas and is unlikely to be the sole result of horizontal pathogen transmission. METHODS Peromyscus leucopus mice, natural reservoir hosts, were infected via Ixodes scapularis nymphs. Infected parental females (n = 6) produced F1 offspring (n = 36) that were screened for B. microti using quantitative PCR. Xenodiagnostic larvae were fed on infected offspring to determine horizontal transmission and pathogen viability. Fifty engorged larvae were screened; the rest were allowed to molt and then screened to determine transstadial transmission. Infected F1 generation offspring were placed in breeding groups, producing 34 F2 offspring and screened for B. microti infection. Chronic infection was monitored in parental females since time of initial vector infection. RESULTS Vertical transmission of B. microti was 74% efficient in offspring born in the first 6 mo. Horizontal transmission occurred in larvae (61% prevalence) and molted nymphs (58% prevalence); these nymphs were able to infect susceptible hosts. F2 generation offspring infection prevalence was 38%. Chronic infection persisted for 1 yr in some adults. CONCLUSIONS These results demonstrate that vertical transmission is an important non-vector mediated pathway of B. microti transmission in the natural reservoir host.
The effect of chloroquine on the TRPC1, TRPC6, and CaSR in the pulmonary artery smooth muscle cells in hypoxia‐induced experimental pulmonary artery hypertension

Pulmonary arterial hypertension (PAH) is a life‐threatening disease characterized by a constant high pulmonary artery pressure and the remodeling of the vessel. Chloroquine (CLQ) has been observed to inhibit calcium influx. The aim of this study is to investigate the effect of CLQ on transient receptor cationic proteins (TRPC1 and TRPC6) and extracellular calcium‐sensitive receptor (CaSR) in a hypoxic PAH model. In this study, 8‐ to 12‐week‐old 32 male Wistar albino rats, weighing 200 to 300 g, were used. The rats were studied in four groups, including normoxy control, n = 8; normoxy CLQ (50 mg/kg/28 d), n = 8; hypoxia (HX; 10% oxygen/28 d) control, n = 8; and HX (10% oxygen/28 d) + CLQ (50 mg/kg), N = 8. Pulmonary arterial medial wall thickness, pulmonary arteriole wall, TRPC1, TRPC6, and CaSR expressions were evaluated by immunohistochemistry, polymerase chain reaction, and enzyme‐linked immunosorbent assay methods. At the end of the experiment, a statistically significant increase in the medial wall thickness was observed in the hypoxic group as compared with the control group. However, in the HX + CLQ group, there was a statistically significant decrease in the vessel medial wall as compared with the HX group. In the TRPC1‐, TRPC6‐, and CaSR‐immunopositive cell numbers, messenger RNA expressions and biochemical results showed an increase in the HX group, whereas they were decreased in the HX + CLQ group. The inhibitory effect of CLQ on calcium receptors in arterioles was observed in PAH.