Miracle-dz/UniFAR-FTUs huggingface dataset:
Semen exosomes: intrinsic inhibitors of HIV-1 infection

Exosomes are membranous extracellular nanovesicles of endocytic origin. Exosomes are known to carry host and pathogen-derived genomic, proteomic, lipidomic cargos and other extraneous molecules. Exosomes are secreted by diverse cell types into the extracellular milieu and are subsequently internalized by recipient neighboring or distal cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. Exosomes facilitate intercellular communication, modulate cellular phenotype, and regulate microbial pathogenesis. We have previously shown that semen exosomes (SE) inhibit HIV-1 replication in various cell types. Here, we describe detailed protocols for characterizing SE. This protocol can be adapted or modified and used for evaluation of other extracellular vesicles of interest. Introduction Exosomes are membranous nanovesicles originating as a result of inward budding of endosomal membranes within the late endosomal compartment of a multitude of cell types [174]. Exosomes are released by many cell types [175] into the extracellular milieu and are found in biological fluids including blood [176], urine [177], saliva [28], and breast milk [63, 104]. Human semen contains a heterogenous population of nanovesicles [62, 63] produced by tissues of the male genital tract including prostate secretory acinar cells [178] and epididymal epithelial cells [179] as well as cells of the vasa deferentia, testes, and the vesicular glands [144, 180]. The variability in the cells that secret exosomes is reflected in the composition and function of
Lactobacillus strains vary in their ability to interact with human endometrial stromal cells

The placental membranes that surround the fetus during pregnancy were suggested to contain a low abundance microbiota. Specifically, abundance of Lactobacillus, a probiotic and dominant member of the microbiome of the lower reproductive tract, has been shown to correlate with healthy, term pregnancies. We therefore sought to assess the interactions between four different Lactobacillus strains with immortalized decidualized endometrial cells (dT-HESCs), which were used as a model to represent the outermost layer of the placental membranes. Notably, we demonstrated that all four Lactobacillus strains could associate with dT-HESCs in vitro. L. crispatus was significantly more successful (p < 0.00005), with 10.6% of bacteria attaching to the host cells compared to an average of 0.8% for the remaining three strains. The four strains also varied in their ability to form biofilms. Dependent on media type, L. reuteri 6475 formed the strongest biofilms in vitro. To examine the impact on immune responses, levels of total and phosphorylated protein p38, a member of the Mitogen Activated Protein Kinase (MAPK) pathway, were examined following Lactobacillus association with dT-HESCs. Total levels of p38 were reduced to an average of 44% that of the cells without Lactobacillus (p < 0.05). While a trend towards a reduction in phosphorylated p38 was observed, this difference was not significant (p > 0.05). In addition, association with Lactobacillus did not result in increased host cell death. Collectively, these data suggest that varying types of Lactobacillus can attach to the outermost cells of the placental membranes and that these interactions do not contribute to inflammatory responses or host cell death. To our knowledge this is the first in vitro study to support the ability of Lactobacillus to interact with placental cells, which is important when considering its use as a potential probiotic within the reproductive tract.
Research Progress on Exploiting and Utilizing of Mulberry Leaves in the Field of Health Care

There are various effective ingredients in mulberry leaves. They are mineral constituents, vitamins, food fibers, amino acids, plant sterols, flavones, and so on. Mulberry leaves have such pharmacological effects as lowering blood glucose, lowering blood pressure, lowering cholesterol, resisting decrepitude, keeping digestive and excretory system healthy, preventing and resisting cancer, improving the immune ability,etc. Because of the existence of GABA and DNJ, mulberry leaves are the ideal materials for health care foods such as mulberry-tea, mulberry leaf juice, mulberry leaf noodle and mulberry leaf powder. The exploitation and utilizaion of mulberry leaves in the field of health care are reported in this paper. 
Active cholesterol 20 years on

This review considers the following hypotheses, some well‐supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter‐organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins—receptors, channels and transporters—at least in vitro.
Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Smart Drug Delivery Systems in the Treatment of Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common and malignant type of brain tumor. In fact, tumor recurrence usually appears a few months after surgical resection and chemotherapy, mainly due to many factors that make GBM treatment a real challenge, such as tumor location, heterogeneity, presence of the blood-brain barrier (BBB), and others. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) represent the most promising carriers for therapeutics delivery into the central nervous system (CNS) owing to their inherent ability to cross the BBB. In this review, we present the main challenges in GBM treatment, a description of SLNs and NLCs and their valuable role as drug carriers in GBM treatment, and finally, a detailed description of all modification strategies that aim to change composition of SLNs and NLCs to enhance treatment outcomes. This includes modification of SLNs and NLCs to improve crossing the BBB, reduced GBM cell resistance, target GBM cells selectively minimizing side effects, and modification strategies to enhance SLNs and NLCs nose-to-brain delivery. Finally, future perspectives on their use are also be discussed, to provide insight about all strategies with SLNs and NLCs formulation that could result in drug delivery systems for GBM treatment with highly effective theraputic and minimum undesirable effects.
Vacuum sealing drainage with instillation in the treatment of necrotising soft-tissue infection: a retrospective analysis.

OBJECTIVE Necrotising soft-tissue infection is a rare but life-threatening infectious disease with high morbidity and mortality. It is typically caused by toxin-producing bacteria and characterised clinically by a very rapid progression of the disease with significant local tissue destruction. In this study, we intend to explore effective wound management to control the invasive infection and to decrease the high mortality. METHOD This retrospective analysis explored the wound management and mortality in patients with necrotising soft-tissue infection. Extensive debridement, vacuum sealing drainage (VSD) with normal saline instillation combined with broad-spectrum or sensitive antibiotics, and supportive therapies were used. RESULTS All 17 patients included in the analysis survived. The microbiology of 11 patients was found to be polymicrobial. Of the patients, 14 were discharged with completely healed wounds and three were transferred to a local hospital after the systemic and invasive wound infection was controlled. CONCLUSION Our experiences revealed the outstanding effect of VSD with instillation in removing the debris of necrotising tissue on the wound bed, in the continual and complete drainage of wound exudates, and in prompting wound healing.
An interview with Claudio Stern.

Claudio Stern was born in Montevideo, Uruguay where he received his school education. He moved to the United Kingdom at age 18. This interview briefly explores his trajectory from Uruguay, through universities in the UK (Sussex, UCL, Cambridge and Oxford) and USA (Columbia) and how he was influenced by various mentors and experiences.
Core‐binding factor acute myeloid leukemia with inv(16): Older age and high white blood cell count are risk factors for treatment failure

Dear Editors: The core-binding factor (CBF) and acute myeloid leukemias (AML) are considered a distinct subgroup of AML due to similar molecular pathogenesis and clinical features.1 The two forms of CBFAML have rearrangements t(8;21)(q22;q22.1) [t(8;21)] and inv(16) (p13.1q22) or t(16;16)(p13.1;q22) [inv(16)] which result in the fusion genes RUNX1/RUNXT1 and CBFB/MYH11, respectively. Although survival of CBF-AML is superior than other subtypes of AML, relapse occurs in approximately 30%-40% of patients.1-4 Finding risk factors for treatment failure (eg, relapse or death) may be useful to manage patients individually. However, the relative rarity of CBF-AML (approximately 15%-20% of AML cases) and its relatively good prognosis has confounded these efforts.2,3 Moreover, recent studies clearly indicate each CBF-AML is a distinct disease regarding patient and disease characteristics,2-5 and should be evaluated separately. We previously published a scoring system (I-CBFit) for treatment failure for t(8;21),6 now here we present our analysis for inv(16). Eleven US and Europe centers collected data on 550 patients with CBF-AML; 290 patients had inv(16). Inclusion criteria were as follows: (a) AML patients with inv(16), t(16;16), or CBFB/MYH11 by fluorescence in situ hybridization confirmed by the reporting institutions; (b) cases diagnosed between July 1996 and January 2017, (c) diagnostic or at least postinduction bone marrow sample was available for review in the participating institution's pathology department. Data were uniformly collected using a predesigned data spreadsheet. The data forms included the following: patient characteristics (age, sex, and race); disease characteristics [date of diagnosis, white blood cell count (WBC) at diagnosis (×109/L), cytogenetics, KIT D816V mutational status, primary or secondary AML]; hematopoietic cell transplantation (HCT) (autologous HCT or allogeneic HCT (alloHCT), donor type, remission status at HCT); and events (relapse, death, or alive at last contact). Deidentified patient data were transferred to the University of Minnesota where the main database was created and managed. This study was approved by the Institutional Review Board: Human Subjects Committee at the University of Minnesota. Secondary AML was assigned if a patient had a history of chemotherapy/radiation therapy for a malignancy and/or had a history of preleukemic neoplastic bone marrow disease. The presence of 46 chromosomes in one clone or each clone was defined TA B L E 1 Characteristics of patients with inv(16) achieving CR
A randomized clinical trial of the effects of saphenous and perforating veins radiofrequency ablation on venous ulcer healing (VUERT trial)

Objectives To investigate whether radiofrequency endovenous ablation (RFA) of saphenous and perforating veins increases venous leg ulcer (VLU) healing rates and prevents ulcer recurrence. Method This prospective, open-label, randomized, controlled, single-center trial recruited 56 patients with VLU divided into: compression alone (CR, N = 29) and RFA plus compression (RF, N = 27). Primary endpoints were ulcer recurrence rate at 12 months; and ulcer healing rates at 6, 12, and 24 weeks. Secondary endpoints were ulcer healing velocity; and Venous Clinical Severity Score (VCSS). Results Recurrence was lower in the RF group (p < .001), as well as mean VCSS after treatment (p = .001). There were no significant between-group differences in healing rates. Healing velocity was faster in the RF group (p = 0.049). In the RF group, 2 participants had type 1 endovenous heat-induced thrombosis (EHIT). Conclusions RFA plus compression is an excellent treatment for VLU because of its safety, effectiveness, and impact on ulcer recurrence reduction and clinical outcome. Registration: Clinicaltrials.gov, NCT03293836, clinicaltrials.gov.
Exploration of Surgeon Motivations in Management of Abdominal Wall Hernias

Key Points Question How can implementation frameworks such as the Theoretical Domains Framework be used to identify domains associated with the adoption of best practices in surgery? Findings This qualitative study used abdominal wall hernia as a case study and found that the surgeon knowledge, beliefs about the consequences, social or professional role and identity, environmental context and resources, and social influences domains were associated with decision-making. Meaning These findings suggest that implementation frameworks offer a method for better understanding which factors motivate behavior change among surgeons.
Abdominal aorta calcification predicts cardiovascular but not non-cardiovascular outcome in patients receiving peritoneal dialysis

Abstract Abdominal aorta calcification (AAC) is associated with worse clinical outcomes in dialysis patients. However, the long-term prognostic values of AAC to cardiovascular (CV) and non-CV mortality in patients starting peritoneal dialysis (PD) remain unknown. This study is aimed to the analyze the predictive power of AAC to CV and non-CV mortality in PD patients. We prospectively enrolled 123 patients undergoing PD. All patients received quantitative analysis of AAC via abdominal computer tomography at enrollment. The AAC ratio was measured by the area of the whole aorta affected by aortic calcification above the iliac bifurcation. The CV mortality and non-CV mortality during the follow-up period were investigated using the Cox proportional hazard model and time-dependent receiver operating characteristic (ROC) analysis. After median 6.8 (interquartile range, 3.6–9.2) years of follow-up, there were 18 CV mortality, 24 non-CV mortality and 42 total mortality. The age and AAC ratio were significantly higher in CV mortality group compared with others without CV mortality. In time-dependent ROC analysis, AAC had excellent predictive power of CV mortality (AUC:0.787) but not non-CV mortality (AUC:0.537). The best cutoff value of AAC ratio to predict CV mortality was 39%. In addition, AAC was not associated with non-CV mortality but remained to be a significantly predictor of CV mortality after adjusted with clinical covariates in different Cox proportional hazard models. AAC has excellent prognostic value of CV mortality but is unable to predict non-CV morality in patients undergoing PD.
Distance-dependent regulation of NMDAR nanoscale organization along hippocampal neuron dendrites

Significance Glutamatergic synapses onto pyramidal neurons are diverse in shape, size, and NMDAR-dependent long-term plasticity according to their dendritic location, i.e., proximal or distal to the soma. Deciphering the fine organization of NMDAR subtypes along the dendritic arbor of hippocampal neurons is key to understand the functional diversity of these various synapses. We unveil that the nanoscale organization of NMDAR changes as a function of distance from the soma in a subunit-specific and CaMKII interaction-dependent manner at proximal dendritic segments. Hippocampal pyramidal neurons are characterized by a unique arborization subdivided in segregated dendritic domains receiving distinct excitatory synaptic inputs with specific properties and plasticity rules that shape their respective contributions to synaptic integration and action potential firing. Although the basal regulation and plastic range of proximal and distal synapses are known to be different, the composition and nanoscale organization of key synaptic proteins at these inputs remains largely elusive. Here we used superresolution imaging and single nanoparticle tracking in rat hippocampal neurons to unveil the nanoscale topography of native GluN2A- and GluN2B-NMDA receptors (NMDARs)—which play key roles in the use-dependent adaptation of glutamatergic synapses—along the dendritic arbor. We report significant changes in the nanoscale organization of GluN2B-NMDARs between proximal and distal dendritic segments, whereas the topography of GluN2A-NMDARs remains similar along the dendritic tree. Remarkably, the nanoscale organization of GluN2B-NMDARs at proximal segments depends on their interaction with calcium/calmodulin-dependent protein kinase II (CaMKII), which is not the case at distal segments. Collectively, our data reveal that the nanoscale organization of NMDARs changes along dendritic segments in a subtype-specific manner and is shaped by the interplay with CaMKII at proximal dendritic segments, shedding light on our understanding of the functional diversity of hippocampal glutamatergic synapses.
Escape of tumor cells from the NK cell cytotoxic activity

In recent years, NK cells, initially identified as potent cytotoxic effector cells, have revealed an unexpected complexity, both at phenotypic and functional levels. The discovery of different NK cell subsets, characterized by distinct gene expression and phenotypes, was combined with the characterization of the diverse functions NK cells can exert, not only as circulating cells, but also as cells localized or recruited in lymphoid organs and in multiple tissues. Besides the elimination of tumor and virus‐infected cells, these functions include the production of cytokines and chemokines, the regulation of innate and adaptive immune cells, the influence on tissue homeostasis. In addition, NK cells display a remarkable functional plasticity, being able to adapt to the environment and to develop a kind of memory. Nevertheless, the powerful cytotoxic activity of NK cells remains one of their most relevant properties, particularly in the antitumor response. In this review, the process of tumor cell recognition and killing mediated by NK cells, starting from the generation of cytolytic granules and recognition of target cell, to the establishment of the NK cell immunological synapse, the release of cytotoxic molecules, and consequent tumor cell death is described. Next, the review focuses on the heterogeneous mechanisms, either intrinsic to tumors or induced by the tumor microenvironment, by which cancer cells can escape the NK cell‐mediated attack.
Exploring empathy in genetic counseling students and new genetic counselors

Although empathy is widely recognized as an important trait for healthcare professionals, little research has examined empathy attributes in genetic counselors. Decreases in empathy levels have been recognized in other healthcare professionals over the span of their professional education program. This research sought to characterize empathy levels in first‐ and second‐year genetic counseling students and recent (2017) graduates, and to determine whether there are differences in empathy levels displayed by genetic counseling students at different points in their training. Additionally, this research examined whether experiences prior to graduate school, including specific aspects of advocacy experience, correlated with differences in self‐reported empathy levels among genetic counseling students and new genetic counselors. An online survey was administered to first‐ and second‐year genetic counseling students and practicing genetic counselors to determine whether there were differences in empathy levels between these groups, and to analyze for associations between pre‐graduate school advocacy work and levels of empathy as measured by the Interpersonal Reactivity Index (IRI). We identified significant differences in self‐reported empathy levels in several of the subscales of the IRI between first‐year students and second‐year students, and between first‐year students and recent graduates. Furthermore, we identified significantly lower scores on the personal distress subscale of the IRI in participants who engaged in advocacy work for longer than 12 months when compared to participants who engaged in advocacy work for between 6 and 12 months. Other advocacy and educational characteristics were also examined for correlations with IRI scores, and no significant associations were identified between these additional factors and self‐reported empathy scores. Practice implications and recommendations for future research are discussed.
‘We are very individual’: anticipated effects on stroke survivors of using their person-generated health data

Background Person-generated health data (PGHD) are produced by people when they use health information technologies. People who use PGHD may experience changes in their health and care process, such as engagement with their own healthcare, and their sense of social support and connectedness. Research into evaluating those reported effects has not kept up; thus, a method for measuring PGHD outcomes was previously designed and applied to the exemplar case of Kinect-based stroke rehabilitation systems. A key step of the method ensures that the patient’s voice is included. Allowing stroke survivors to participate in the development and evaluation of health services and treatment can inform healthcare providers on decisions about stroke care, and thereby improve health outcomes. Objective This paper presents the perspectives of stroke survivors and clinicians on the anticipated effects of stroke survivors’ use of PGHD from a poststroke simulated rehabilitation technology. Methods This study gathered the perspectives of stroke survivors and clinicians through three focus groups and three interviews, recruited for convenience. Participants were also asked questions intended to encourage them to comment on the initial items of the patient-reported outcome measure-PGHD. Deductive thematic analysis was performed. Results This paper has further demonstrated that outcomes of using PGHD can be measured. For instance, stroke survivors described that using PGHD could result in positive, negative and nil effects on their health behaviours. Survivors and clinicians had varying perspectives in three of the six themes presented, and emphasise the importance of allowing stroke survivors to participate in the evaluation of digital health services.