Miracle-dz/UniFAR-FTUs huggingface dataset:
Iodine-stained fragmented thromboembolism

Aim Iodine-stained fragmented thromboembolism (ISFT) is a rare phenomenon encountered in the immediate aftermath of mechanical thrombectomy or rarely as a complication of post–carotid stenting. The aim was to describe the imaging appearance and discuss its pathophysiology. Method This is a retrospective review of patients who underwent mechanical thrombectomy for acute stroke at a single institution over the period of one year. All patients underwent the standard acute stroke imaging protocol (CT head, CT angiogram (CTA) and CT brain perfusion) and when clinically appropriate followed by catheter angiogram and mechanical thrombectomy. ISFT was defined as an arterial luminal filling defect with Hounsfield density equal to or greater than iodine seen on the biplanar CT or conventional CT. The presence and location of ISFT were documented. Standard CT angiogram (CTA) or magnetic resonance angiogram (MRA) was performed 24–48 hours after the neurointerventional procedure to assess for recanalization, volume of infarction and the fate of the ISFT. Results ISFTs were identified in eight (five males and three females, age range 18–80 years) out of 49 patients in the following locations: distal M1 (n = 1), M2 (n = 4), M3 (n = 1), A1 (n = 1), distal A2 (n = 1). ISFT and vessel recanalization occurred in five patients on follow-up. ISFT and vessel occlusion persisted in two patients. Conclusion ISFT is likely the result of mechanical disruption of a thromboembolus, and porosity of the thromboembolus fragment may transiently retain iodinated contrast. Recognition of this entity may be important to aid detection of residual thromboembolism and avoid misinterpretation as calcified thromboembolism.
Sensitivity and Specificity of the Modified Epworth Sleepiness Scale in Children With Craniopharyngioma.

STUDY OBJECTIVES Children with craniopharyngioma are at risk for excessive daytime sleepiness (EDS). Multiple Sleep Latency Testing (MSLT) is the gold standard for objective evaluation of EDS; however, it is time and resource intensive. We compared the reliability, sensitivity, and specificity of the modified Epworth Sleepiness Scale (M-ESS) and MSLT in monitoring EDS in children with craniopharyngioma. METHODS Seventy patients (ages 6 to 20 years) with craniopharyngioma completed the M-ESS and were evaluated by polysomnography and MSLT. Evaluations were made after surgery, if performed, and before proton therapy. RESULTS MSLT revealed that 66 participants (81.8%) had EDS, as defined by a mean sleep latency (MSL) < 10 minutes, with only 28.8% reporting EDS on the M-ESS by using a cutoff score of 10. The M-ESS demonstrated adequate internal consistency and specificity (91.7%) but poor sensitivity (33.3%) with the established cutoff score of 10. A cutoff score of 6 improved the sensitivity to 64.8% but decreased the specificity to 66.7%. CONCLUSIONS Patients with craniopharyngioma are at high risk for EDS, as documented objectively on the MSLT, but they frequently do not recognize or accurately report their sleepiness. Future sleep studies should investigate whether specific items or alternative self- and parent-reported measures of sleepiness may have greater clinical utility in monitoring sleepiness in this population.
Potential Tools for Eradicating HIV Reservoirs in the Brain: Development of Trojan Horse Prodrugs for the Inhibition of P-Glycoprotein with Anti-HIV-1 Activity

Combination antiretroviral therapy is the mainstay of HIV treatment, lowering plasma viral levels below detection. However, eradication of HIV is a major challenge due to cellular and anatomical viral reservoirs that are often protected from treatment by efflux transporters, such as P-glycoprotein (P-gp) at the blood–brain barrier (BBB). Herein we described a Trojan horse approach to therapeutic evasion of P-gp based on a reversibly linked combination of HIV reverse transcriptase and protease inhibitors. Potent inhibition of P-gp efflux in cells, including human brain endothelial cells, was observed with the linked heterodimeric compounds. In vitro regeneration of active monomeric drugs was observed in a reducing environment with these dimeric prodrugs, with the superior leaving group promoting more facile release from the tether. These release trends were mirrored in the efficacy of the in cyto anti-HIV-1 activity of the Trojan horse heterodimers.
Weight Gain Associated with Integrase Stand Transfer Inhibitor Use in Women.

BACKGROUND Integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for HIV management. Although studies have suggested associations between INSTIs and weight gain, women living with HIV (WLHIV) are underrepresented. We evaluated the effect of switching or adding INSTIs among WLHIV. METHODS Women enrolled in the Women's Interagency HIV Study (WIHS) from 2006-2017 who switched to or added an INSTI to ART (SWAD) were compared to women on non-INSTI ART (STAY). Body weight, body mass index (BMI), percentage body fat (PBF), and waist, hip, arm, and thigh circumferences, were measured 6-12 months before and 6-18 months after INSTI switch/add in SWAD with comparable time points in STAY. Linear regression models compared change over time by SWAD/STAY group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen. RESULTS 1118 women (234 SWAD and 884 STAY) were followed for a mean 2.0 ([+/- 0.1 standard deviation (SD)] years; mean age 48.8 [+/- 8.8] years, and 61% were Black. On average, compared to the STAY group, the SWAD group experienced mean greater increases of 2.1 kg in body weight, 0.8 kg/m² in BMI, 1.4% in PBF, and 2.0, 1.9, 0.6, and 1.0 cm in waist, hip, arm, and thigh circumference, respectively (all p <0.05). No differences in magnitude of these changes were observed by INSTI type. CONCLUSION In WLHIV, a switch to INSTI was associated with significant increases in body weight, body circumferences, and fat percentages compared to non-INSTI ART. The metabolic and other health effects of these changes deserve further investigation.
Genetically Engineered Mouse Models of Gliomas: Technological Developments for Translational Discoveries

The most common brain tumours, gliomas, have significant morbidity. Detailed biological and genetic understanding of these tumours is needed in order to devise effective, rational therapies. In an era generating unprecedented quantities of genomic sequencing data from human cancers, complementary methods of deciphering the underlying functional cancer genes and mechanisms are becoming even more important. Genetically engineered mouse models of gliomas have provided a platform for investigating the molecular underpinning of this complex disease, and new tools for such models are emerging that are enabling us to answer the most important questions in the field. Here, I discuss improvements to genome engineering technologies that have led to more faithful mouse models resembling human gliomas, including new cre/LoxP transgenic lines that allow more accurate cell targeting of genetic recombination, Sleeping Beauty and piggyBac transposons for the integration of transgenes and genetic screens, and CRISPR-cas9 for generating genetic knockout and functional screens. Applications of these technologies are providing novel insights into the functional genetic drivers of gliomagenesis, how these genes cooperate with one another, and the potential cells-of-origin of gliomas, knowledge of which is critical to the development of targeted treatments for patients in the clinic.
Conjugation of Carbon Dots with β-Galactosidase Enzyme: Surface Chemistry and Use in Biosensing

Nanoparticles have been conjugated to biological systems for numerous applications such as self-assembly, sensing, imaging, and therapy. Development of more reliable and robust biosensors that exhibit high response rate, increased detection limit, and enhanced useful lifetime is in high demand. We have developed a sensing platform by the conjugation of β-galactosidase, a crucial enzyme, with lab-synthesized gel-like carbon dots (CDs) which have high luminescence, photostability, and easy surface functionalization. We found that the conjugated enzyme exhibited higher stability towards temperature and pH changes in comparison to the native enzyme. This enriched property of the enzyme was distinctly used to develop a stable, reliable, robust biosensor. The detection limit of the biosensor was found to be 2.9 × 10−4 M, whereas its sensitivity was 0.81 µA·mmol−1·cm−2. Further, we used the Langmuir monolayer technique to understand the surface properties of the conjugated enzyme. It was found that the conjugate was highly stable at the air/subphase interface which additionally reinforces the suitability of the use of the conjugated enzyme for the biosensing applications.
Reversible Mechanical Regulation and Splicing Ability of Alginate-Based Gel Based on Photo-Responsiveness of Molecular-Level Conformation

In this study, benefiting from the sensitive molecular conformation transversion in azobenzene, a new strategy for fabricating alginate gels with the abilities of splicing and photo-responsive mechanical adjustment is reported. Firstly, a 4,4’-azobis(benzoylhydrazide) (Azo-hydrazide) linker was used to crosslink alginate physically via the electrostatic interaction between hydrazide groups and carboxyl groups. It was then shaped and transferred in situ to a chemically crosslinked gel via 450 nm light irradiation. Under the irradiation, the molecular conformation change of azobenzene in the linker was able to form covalent bonds at the crosslinking points of the gels. Furthermore, the reversible conformation transformation of azobenzene was able to induce the increase and decrease of the storage modulus under irradiation with 365 nm light and 450 nm light, respectively, while also providing gel-like mechanical properties, depending upon the irradiation time and given wavelength. Meanwhile, the results also indicated that active groups could contribute to the splicing ability of the gel and construct a hollow cavity structure. It is believed that this work could provide a versatile strategy for preparing photo-responsive gels with reversibly tunable mechanical properties.
Choking in Children: What to Do and How to Prevent.

Choking happens when a child's airway is blocked by a foreign substance that impairs oxygenation and ventilation. It is one of the most frightening scenarios a parent can imagine. It happens suddenly and can have the direst of consequences. Small objects, such as food and candy, are the usual offenders. Child-related risk factors are largely developmental due to physical and cognitive immaturity. This article describes the magnitude of the problem, delineates some of the risks, and outlines prevention. [Pediatr Ann. 2019;48(9):e338-e340. ].
Temozolomide and Other Alkylating Agents in Glioblastoma Therapy

The alkylating agent temozolomide (TMZ) together with maximal safe bulk resection and focal radiotherapy comprises the standard treatment for glioblastoma (GB), a particularly aggressive and lethal primary brain tumor. GB affects 3.2 in 100,000 people who have an average survival time of around 14 months after presentation. Several key aspects make GB a difficult to treat disease, primarily including the high resistance of tumor cells to cell death-inducing substances or radiation and the combination of the highly invasive nature of the malignancy, i.e., treatment must affect the whole brain, and the protection from drugs of the tumor bulk—or at least of the invading cells—by the blood brain barrier (BBB). TMZ crosses the BBB, but—unlike classic chemotherapeutics—does not induce DNA damage or misalignment of segregating chromosomes directly. It has been described as a DNA alkylating agent, which leads to base mismatches that initiate futile DNA repair cycles; eventually, DNA strand breaks, which in turn induces cell death. However, while much is assumed about the function of TMZ and its mode of action, primary data are actually scarce and often contradictory. To improve GB treatment further, we need to fully understand what TMZ does to the tumor cells and their microenvironment. This is of particular importance, as novel therapeutic approaches are almost always clinically assessed in the presence of standard treatment, i.e., in the presence of TMZ. Therefore, potential pharmacological interactions between TMZ and novel drugs might occur with unforeseeable consequences.
Hybrid Sequencing of Full-Length cDNA Transcripts of the Medicinal Plant Scutellaria baicalensis

Scutellaria baicalensis is a well-known medicinal plant that produces biologically active flavonoids, such as baicalin, baicalein, and wogonin. Pharmacological studies have shown that these compounds have anti-inflammatory, anti-bacterial, and anti-cancer activities. Therefore, it is of great significance to investigate the genetic information of S. baicalensis, particularly the genes related to the biosynthetic pathways of these compounds. Here, we constructed the full-length transcriptome of S. baicalensis using a hybrid sequencing strategy and acquired 338,136 full-length sequences, accounting for 93.3% of the total reads. After the removal of redundancy and correction with Illumina short reads, 75,785 nonredundant transcripts were generated, among which approximately 98% were annotated with significant hits in the protein databases, and 11,135 sequences were classified as lncRNAs. Differentially expressed gene (DEG) analysis showed that most of the genes related to flavonoid biosynthesis were highly expressed in the roots, consistent with previous reports that the flavonoids were mainly synthesized and accumulated in the roots of S. baicalensis. By constructing unique transcription models, a total of 44,071 alternative splicing (AS) events were identified, with intron retention (IR) accounting for the highest proportion (44.5%). A total of 94 AS events were present in five key genes related to flavonoid biosynthesis, suggesting that AS may play important roles in the regulation of flavonoid biosynthesis in S. baicalensis. This study provided a large number of highly accurate full-length transcripts, which represents a valuable genetic resource for further research of the molecular biology of S. baicalensis, such as the development, breeding, and biosynthesis of active ingredients.
Comprehensive autophagy evaluation in cardiac disease models

Abstract Autophagy is a highly conserved recycling mechanism essential for maintaining cellular homeostasis. The pathophysiological role of autophagy has been explored since its discovery 50 years ago, but interest in autophagy has grown exponentially over the last years. Many researchers around the globe have found that autophagy is a critical pathway involved in the pathogenesis of cardiac diseases. Several groups have created novel and powerful tools for gaining deeper insights into the role of autophagy in the aetiology and development of pathologies affecting the heart. Here, we discuss how established and emerging methods to study autophagy can be used to unravel the precise function of this central recycling mechanism in the cardiac system.
The Complex Relationships between Sex and the Brain

In the past decennia, our understanding of the sexual differentiation of the mammalian brain has dramatically changed. The simple model according to which testosterone masculinizes the brain of males away from a default female form, was replaced with a complex scenario, according to which sex effects on the brain of both females and males are exerted by genetic, hormonal, and environmental factors. These factors act via multiple partly independent mechanisms that may vary according to internal and external factors. These observations led to the “mosaic” hypothesis—the expectation of high variability in the degree of “maleness”/“femaleness” of different features within a single brain. Here, we briefly review animal data that form the basis of current understanding of sexual differentiation; present, in this context, the results of co-analyses of human brain measures obtained by magnetic resonance imaging or postmortem; discuss criticisms and controversies of the mosaic hypothesis and implications for research; and conclude that co-analysis of several (preferably, many) features and going back from the group level to that of the individual would advance our understanding of the relations between sex and the brain in health and disease.
The influence of treatment in alpine and moderate maritime climate on the composition of the skin microbiome in patients with difficult to treat atopic dermatitis

The skin microbiome, characterized by an overgrowth of Staphylococcus aureus, plays an important role in the pathogenesis of atopic dermatitis (AD). Multidisciplinary treatment in alpine climate is known for its positive effect on disease severity in children with AD and can result in a different immune response compared with moderate maritime climate. However, the effect on the composition of the skin microbiome in AD is unknown.
Robust gene expression control in human cells with a novel universal TetR aptamer splicing module

Abstract Fine-tuning of gene expression is desirable for a wide range of applications in synthetic biology. In this context, RNA regulatory devices provide a powerful and highly functional tool. We developed a versatile, robust and reversible device to control gene expression by splicing regulation in human cells using an aptamer that is recognized by the Tet repressor TetR. Upon insertion in proximity to the 5′ splice site, intron retention can be controlled via the binding of TetR to the aptamer. Although we were able to demonstrate regulation for different introns, the genomic context had a major impact on regulation. In consequence, we advanced the aptamer to develop a splice device. Our novel device contains the aptamer integrated into a context of exonic and intronic sequences that create and maintain an environment allowing a reliable and robust splicing event. The exon-born, additional amino acids will then be cleaved off by a self-cleaving peptide. This design allows portability of the splicing device, which we confirmed by demonstrating its functionality in different gene contexts. Intriguingly, our splicing device shows a high dynamic range and low basal activity, i.e. desirable features that often prove a major challenge when implementing synthetic biology in mammalian cell lines.
Serious life events and post-traumatic stress disorder in the Norwegian population

Background It has been suggested that countries with more resources and better healthcare have populations with a higher risk of post-traumatic stress disorder (PTSD). Norway is a high-income country with good public healthcare. Aims To examine lifetime trauma exposure and the point prevalence of PTSD in the general Norwegian population. Method A survey was administered to a national probability sample of 5500 adults (aged ≥18 years). Of 4961 eligible individuals, 1792 responded (36%). Responders and non-responders did not differ significantly in age, gender or urban versus rural residence. Trauma exposure was measured using the Life Events Checklist for the DSM-5. PTSD was measured with the PTSD Checklist for the DSM-5. We used the DSM-5 diagnostic guidelines to categorise participants as fulfilling the PTSD symptom criteria or not. Results At least one serious lifetime event was reported by 85% of men and 86% of women. The most common event categories were transportation accident and life-threatening illness or injury. The point prevalence of PTSD was 3.8% for men and 8.5% for women. The most common events causing PTSD were sexual and physical assaults, life-threatening illness or injury, and sudden violent deaths. Risk of PTSD increased proportionally with the number of event categories experienced. Conclusions High estimates of serious life events and correspondingly high rates of PTSD in the Norwegian population support the paradox that countries with more resources and better healthcare have higher risk of PTSD. Possible explanations are high expectations for a risk-free life and high attention to potential harmful mental health effects of serious life events. Declaration of interest None.
Arabinoxylan rice bran (MGN-3/Biobran) enhances radiotherapy in animals bearing Ehrlich ascites carcinoma†

ABSTRACT This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.
Virulence properties of three new Photobacterium species affecting cultured fish

Several virulence factors of three new Photobacterium species: Photobacterium toruni, Photobacterium malacitanum and Photobacterium andalusiense associated with diseases of cultured redbanded seabream (Pagrus auriga) were studied. The exoenzymatic activities, adherence and cytotoxic capabilities, and iron‐uptake mechanisms were determined both in bacterial extracellular products (ECP) and whole bacterial cells. The histopathology damages provoked on redbanded seabream by the ECP was also studied.
REPLATINUM Phase III randomized study: RRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer.

RRx-001 is a cysteine-directed anticancer alkylating agent with activity in a Phase II study in platinum refractory small cell lung cancer. Here, we describe the design of REPLATINUM, an open-label, Phase III trial. One hundred and twenty patients with previously platinum-treated small cell lung cancer in third line will be randomized 1:1 to receive RRx-001 followed by four cycles of a platinum doublet, and then alternating cycles of RRx-001 and single agent platinum until progression versus four cycles of a platinum doublet. At radiologic progression on the platinum doublet, patients may cross over to the RRx-001 arm. Primary objective: to demonstrate superior progression-free survival in the RRx-001 population. Secondary objectives: to demonstrate superiority for overall survival and objective response rate. Clinical Trial registration: NCT03699956.