Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that primarily affects children and young adults. To identify and quantify MMc, we developed a panel of quantitative PCR assays targeting nontransmitted, nonshared maternal-specific HLA alleles. MMc was assayed in peripheral blood from 172 individuals, 94 with T1D, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in T1D patients than unaffected siblings and healthy subjects. Medians and ranges, respectively, were 0.09 (0–530), 0 (0–153), and 0 (0–7.9). Differences between groups were evident irrespective of HLA genotypes. However, for patients with the T1D-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally transmitted (14%). In other studies, we looked for female islet β cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and β cell insulin staining. Female islet β cells (presumed maternal) formed 0.39–0.96% of the total, whereas female hematopoietic cells were very rare. Thus, T1D patients have higher levels of MMc in their circulation than unaffected siblings and healthy individuals, and MMc contributes to islet β cells in a mother's progeny.
In-service nonintrusive measurement of noise and active speech level in telephone-type networks

The paper presents an in-service, nonintrusive technique for the measurement of noise level and active speech level in telecommunication systems. It is based on the segmentation of the signal observed during a telephone call into active speech and noise intervals and on an improved method for level estimation via the determination of the noise-level probability density function. Experimental results show the high accuracy of the method also under poor signal-to-noise ratio conditions and its robustness with respect to other real-life impairments found in telecommunication lines.
Cell-Free Circulating DNA Integrity Based on Peripheral Blood as a Biomarker for Diagnosis of Cancer: A Systematic Review

Background: Cell-free DNA integrity (cfDI) has been identified as a potential diagnostic biomarker for different types of cancer, suggesting the importance of liquid biopsy. Methods: This systematic review aims to assess the diagnostic performance of cfDI in cancer. After an extensive search of literature published through February 28, 2017, 25 articles that included 40 studies were identified. The descriptions of all the studies were analyzed. The sensitivity, specificity, positive and negative likelihood ratios, diagnostic ORs, weighted symmetric summary receiver operating characteristic curve, and the area under the curve (AUC) of cfDI in these studies were calculated. Results: Aberrant results of cfDI were observed. Some studies observed an increased cfDI in cancer patients, while some studies confirmed a decreased cfDI compared with healthy or benign controls. Conclusions: This review suggests that cfDI is controversial as a blood-based biomarker of cancers, although the sensitivity and AUC were relatively high. Impact: cfDI shows heterogeneity between different studies; more perspective studies are needed to further assess its diagnostic performance, especially with other markers in combination. Cancer Epidemiol Biomarkers Prev; 26(11); 1595–602. ©2017 AACR.
Modeling the Mechanics of Cell Division: Influence of Spontaneous Membrane Curvature, Surface Tension, and Osmotic Pressure

Many cell division processes have been conserved throughout evolution and are being revealed by studies on model organisms such as bacteria, yeasts, and protozoa. Cellular membrane constriction is one of these processes, observed almost universally during cell division. It happens similarly in all organisms through a mechanical pathway synchronized with the sequence of cytokinetic events in the cell interior. Arguably, such a mechanical process is mastered by the coordinated action of a constriction machinery fueled by biochemical energy in conjunction with the passive mechanics of the cellular membrane. Independently of the details of the constriction engine, the membrane component responds against deformation by minimizing the elastic energy at every constriction state following a pathway still unknown. In this paper, we address a theoretical study of the mechanics of membrane constriction in a simplified model that describes a homogeneous membrane vesicle in the regime where mechanical work due to osmotic pressure, surface tension, and bending energy are comparable. We develop a general method to find approximate analytical expressions for the main descriptors of a symmetrically constricted vesicle. Analytical solutions are obtained by combining a perturbative expansion for small deformations with a variational approach that was previously demonstrated valid at the reference state of an initially spherical vesicle at isotonic conditions. The analytic approximate results are compared with the exact solution obtained from numerical computations, getting a good agreement for all the computed quantities (energy, area, volume, constriction force). We analyze the effects of the spontaneous curvature, the surface tension and the osmotic pressure in these quantities, focusing especially on the constriction force. The more favorable conditions for vesicle constriction are determined, obtaining that smaller constriction forces are required for positive spontaneous curvatures, low or negative membrane tension and hypertonic media. Conditions for spontaneous constriction at a given constriction force are also determined. The implications of these results for biological cell division are discussed. This work contributes to a better quantitative understanding of the mechanical pathway of cellular division, and could assist the design of artificial divisomes in vesicle-based self-actuated microsystems obtained from synthetic biology approaches.
The Informal Caregivers' Perception of Wandering

Although the term wandering is routinely used by clinicians, researchers, and informal caregivers (ICs), the meaning of this term varies depending on the source of the definition and the context in which it is used. The purpose of this study was to examine the terms ICs used to describe different scenarios that have been identified in literature as “wandering,” determine their perception of risk, and compare their definitions of wandering with the perspectives of researchers. Structured interviews were conducted with 128 ICs of older adults with dementia. Informal Caregivers rarely used the term wandering to label different scenarios that had been previously identified in the literature as wandering. Responses to a survey of 17 wandering experts did not reflect agreement on a definition for wandering. These findings suggest that a broad set of terms should be used to describe this potentially dangerous behavior when health care providers communicate with ICs.
The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia

Abstract Objective: Special AT-rich sequence binding protein 1 (SATB1) play potential roles in invasion and metastasis of tumor cells, and involves in human placental and fetal development. The objective of this study is to explore the role of SATB1 in migration and invasion of trophoblast and the potential mechanism. Methods: Human placental tissues from first trimester, second trimester, term, and preeclampsia (PE) pregnancies were used to detect the expression and subcellular location of SATB1 and β-catenin. The human trophoblast cell line HTR8/SVneo, which was treated with hypoxia/re-oxygenation (H/R), lithium chloride (LiCl) or SATB1-siRNA to investigate the role of SATB1 and β-catenin signaling in human trophoblast function. Results: We observed that SATB1 specifically localized within trophoblast cells of placenta tissues. Gradually reduced expression of SATB1 was observed during gestation, and lower expression were detected in placenta of PE compared with normal pregnancy. Moreover, the expression of SATB1 was decreased in H/R-treated HTR8/Svneo cells and villous explants. The Wnt/β-catenin signaling pathway interacted with SATB1 expression and H/R treatment resulted in Wnt pathway inhibition in trophoblast, while lithium chloride (LiCl) treatment enhanced H/R-exposed HTR8/SVneo migration and invasion. Knockdown of SATB1 significantly reduced the level of β-catenin and the migratory and invasive abilities of trophoblast. Conclusions: Our data suggested that oxidative stress reduced SATB1 leading to inhibition of Wnt/β-catenin, and participate in the subdued migration and invasion of trophoblast, which indicated a potential pathological mechanism of PE.
Muscarinic Receptors in the Cochlear Nucleus and Auditory Nerve of the Guinea Pig

Abstract: The specific‐binding properties of l‐[3H]quinuclidinyl benzilate, a muscarinic acetylcholine‐receptor antagonist, were investigated in synaptic and other membrane preparations of the guinea pig cochlear nucleus and auditory nerve. Binding parameters for all experiments were consistent with a single binding site with a Hill coefficient of 1.0. The binding of the ligand was specific and of high affinity, with values of KD in the range of 30–80 pM. Bmax was 0.352 ± 0.023 pmol/mg protein for the dorsal cochlear nucleus and 0.215 ± 0.011 pmol/mg protein for the ventral cochlear nucleus. The dorsal cochlear nucleus/ventral cochlear nucleus ratio for density of muscarinic receptors (1.6/1.0) was maintained across two different buffer systems, which varied with respect to the inclusion of proteolysis inhibitors. The results for auditory nerve indicated a level of binding much below that of the cochlear nucleus, with Bmax= 0.052 ± 0.011 pmol/mg protein. The results of specific‐binding experiments for l‐[3H]quinuclidinyl benzilate support a role for acetylcholine as a neurotransmitter in the cochlear nucleus. The greater density of muscarinic receptors in the dorsal cochlear nucleus may indicate greater cholinergic activity in the dorsal relative to the ventral cochlear nucleus.
Pattern of long‐term sensorimotor recovery following intrastriatal and ‐accumbens DA micrografts in a rat model of Parkinson's disease

The functional restorative capacity of fetal dopaminergic (DA) transplants is governed by a number of critical parameters including graft location, survival of DA neurons, and transplantation technique. In addition, there is an ongoing controversy whether “too much” or “too little” survival of DA neurons is responsible for the incomplete functional recovery observed in some transplanted Parkinson's disease (PD) patients. Here we investigated two implantation sites, the nucleus accumbens (NAc) and the caudate‐putamen unit (CPU), and two different graft distributions within the CPU, i.e., two 0.75 μL deposits (CPU‐2) versus six 0.25 μL deposits (CPU‐6) in a rat model of PD. Grafts were derived from E14 rat ventral mesencephalon and the long‐term functional outcome was evaluated with a wide range of complex‐sensorimotor behavioral tests. The data show that forelimb stepping, balancing behavior, and skilled forelimb reaching behavior was more restored in CPU‐6‐grafted animals as compared to CPU‐2 animals, although the number surviving dopaminergic neurons and dopamine release were similar in the two groups. Furthermore, a correlation analysis revealed a number of inverse relationships between the rate of DA neuron survival and sensorimotor performances, e.g., for skilled forelimb use. DA grafts placed into the NAc induced a partial recovery in drug‐induced rotation tests but failed to restore any of the other sensorimotor behaviors tested. Taken together, these data have important implications both for a better understanding of the complex functional graft–host interactions as well as for the further optimization of clinical neural transplantation strategies in neurodegenerative diseases. J. Comp. Neurol. 515:41–55, 2009. © 2009 Wiley‐Liss, Inc.
Expression of c‐FLIP in pulmonary metastases in osteosarcoma patients and human xenografts

We have previously shown that Fas expression inversely correlates with the metastatic potential of osteosarcoma (OS) to the lung. FasL is constitutively expressed in the lung microenvironment and eliminates Fas+ OS cells leaving Fas− cells to form metastases. Absence of FasL in the lung epithelium or blocking the Fas‐signaling pathway interfered with this clearance mechanism allowing Fas+ cells to remain and form lung metastases. We also demonstrated that while the majority of patient OS lung metastases were Fas−, 10–20% of the lesions contained Fas+ cells, suggesting that these cells were not sensitive to FasL‐induced apoptosis. The expression of c‐FLIP, an inhibitor of the Fas pathway, has been associated with tumor development, progression, and resistance to chemotherapy. We therefore evaluated the expression of c‐FLIP in OS patient tumor specimens and human xenograft lung metastases.
1001 model organisms to study cilia and flagella

Most mammalian cell types have the potential to assemble at least one cilium. Immotile cilia participate in numerous sensing processes, while motile cilia are involved in cell motility and movement of extracellular fluid. The functional importance of cilia and flagella is highlighted by the growing list of diseases due to cilia defects. These ciliopathies are marked by an amazing diversity of clinical manifestations and an often complex genetic aetiology. To understand these pathologies, a precise comprehension of the biology of cilia and flagella is required. These organelles are remarkably well conserved throughout eukaryotic evolution. In this review, we describe the strengths of various model organisms to decipher diverse aspects of cilia and flagella biology: molecular composition, mode of assembly, sensing and motility mechanisms and functions. Pioneering studies carried out in the green alga Chlamydomonas established the link between cilia and several genetic diseases. Moreover, multicellular organisms such as mouse, zebrafish, Xenopus, Caenorhabditis elegans or Drosophila, and protists such as Paramecium, Tetrahymena and Trypanosoma or Leishmania each bring specific advantages to the study of cilium biology. For example, the function of genes involved in primary ciliary dyskinesia (due to defects in ciliary motility) can be efficiently assessed in trypanosomes.
The Pharmacologic Basis for Clinical Differences among GLP-1 Receptor Agonists and DPP-4 Inhibitors

Abstract The incretin system plays an important role in glucose homeostasis, largely through the actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Unlike GIP, the actions of GLP-1 are preserved in patients with type 2 diabetes mellitus, which has led to the development of injectable GLP-1 receptor (GLP-1R) agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1R agonists—which can be dosed to pharmacologic levels—act directly upon the GLP-1R. In contrast, DPP-4 inhibitors work indirectly by inhibiting the enzymatic inactivation of native GLP-1, resulting in a modest increase in endogenous GLP-1 levels. GLP-1R agonists generally lower the fasting and postprandial glucose levels more than DPP-4 inhibitors, resulting in a greater mean reduction in glycated hemoglobin level with GLP-1R agonists (0.4%–1.7%) compared with DPP-4 inhibitors (0.4%–1.0%). GLP-1R agonists also promote satiety and reduce total caloric intake, generally resulting in a mean weight loss of 1 to 4 kg over several months in most patients, whereas DPP-4 inhbitors are weight-neutral overall. GLP-1R agonists and DPP-4 inhibitors are generally safe and well tolerated. The glucose-dependent manner of stimulation of insulin release and inhibition of glucagon secretion by both GLP-1R agonists and DPP-4 inhibitors contribute to the low incidence of hypoglycemia. Although transient nausea occurs in 26% to 28% of patients treated with GLP-1R agonists but not DPP-4 inhibitors, this can be reduced by using a dose-escalation strategy. Other adverse events (AEs) associated with GLP-1R agonists include diarrhea, headache, and dizziness. The main AEs associated with DPP-4 inhibitors include upper respiratory tract infection, nasopharyngitis, and headache. Overall, compared with other therapies for type 2 diabetes mellitus with similar efficacy, incretin-based agents have low risk of hypoglycemia and weight gain. However, GLP-1R agonists demonstrate greater comparative efficacy and weight benefit than DPP-4 inhibitors.
A clinical, echocardiographic and genetic characterization of a Danish kindred with familial amyloid transthyretin methionine 111 linked cardiomyopathy.

AIMS To identify carriers and non-carriers of the mutant transthyretin methionine 111 linked familial amyloid disease, to detect early signs of the restrictive cardiomyopathy and other clinical manifestations characteristic of this inheritable disease. METHODS AND RESULTS Out of 125 living family members 99 were available for clinical, echocardiographic and genetic examination. Twenty-five family members were heterozygous carriers of the mutant transthyretin methionine 111 genotype, while 74 were non-carriers. Among the 25 carriers, none had overt clinical signs of heart disease. Eight carriers, all above the age of 35, showed echocardiographic abnormalities suggestive of developing or manifest restrictive cardiomyopathy. Three had biopsy-verified transthyretin-related amyloid cardiomyopathy. None of the 15 carriers in the younger age group exhibited aberrant echocardiographic patterns. Nine carriers had carpal tunnel syndrome as opposed to none of the non-carriers. CONCLUSION For early detection of familial amyloid cardiomyopathy, echocardiography is the investigation of choice. The first sign is diastolic dysfunction detected as an abnormal relaxation pattern. The appearance of echocardiographic aberrations solely in the older age group suggests that the cardiomyopathy is a late onset disease. Carpal tunnel syndrome appears to be the earliest presenting clinical symptom. A curative treatment seems to be an early liver transplantation.
Left‐Sided microsatellite unstable colorectal cancers show less frequent methylation of hMLH1 and CpG island methylator phenotype than right‐sided ones

We compared the methylation status of several loci between right‐sided and left‐sided colorectal cancers (CRCs). To the best of our knowledge, this is the first to report that left‐sided CRCs show significantly less frequent methylation at several loci and CpG island methylator phenotype (CIMP) than right‐sided ones.
Self-care of school-age children with diabetes: an integrative review.

AIM This paper is a report of an integrative review of findings from empirical studies on self-care in school-age children with type 1 diabetes. The purpose is to generate insight into opportunities to develop empowering patient education. BACKGROUND Managing diabetes is demanding and requires parental involvement in care. Good self-care forms the basis for diabetes management and self-care patterns are established at school age, but how and to what extent school-age children increase their self-care capabilities is unclear. DATA SOURCES A search for studies from 1998 to 2010 focusing on self-care in school-age children with diabetes was conducted through electronic databases. REVIEW METHODS Using integrative methods, quantitative and qualitative papers surveyed were analysed separately, but the themes that arose were combined at the end of the analysis. FINDINGS Self-care is formed in a learning process involving the objectives of normality, being able to cope and independence. The content of self-care is a combination of knowledge and skills. Children have the technical skill, but they need their parents to participate in the care and share responsibility for it. The factors related to self-care comprised the characteristics of the child; the nature of the illness and care; and support from the parents, school environment, peers and healthcare team. CONCLUSION A balance between diabetes care requirements and a child's maturity should be found. Nurses must adopt an empowering manner of education and recognize and assess a child's readiness to learn diabetes care and bear responsibility for it. Nurses must also help parents and other adults to gradually shift the responsibility to the children.
The LONFLIT4-VENORUTON Study A Randomized Trial Prophylaxis of Flight-Edema in Normal Subjects

This study evaluated the protective effects of Venoruton on the development of flight edema in normal subjects travelling in economy in long-haul flights (8-9 hours). Edema is a relevant aspect of long-haul flights affecting both venous patients and normal subjects. Edema and flight microangiopathy were studied in a group of 164 subjects randomized (after informed consent) into two groups to evaluate prophylaxis in 8 to 9-hour flights. The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. Edema was evaluated with a composite edema score based on the edema tester, on the measurements of ankle circumference, volume measurements, subjective swelling, and on a discomfort score. Items 1, 4, and 5 are based on an analogue scale line (I to 10) directly defined by the subjects before and after the flights. Of the included subjects, 151 completed the study. Dropouts were due to poor compliance, travelling, or connection problems. Age and gender distribution were comparable in the two groups as were risk factor distributions. The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.7 (SD 1.7) in the control group, while in the Venoruton group the score was on average 3 (SD 1.1) (p < 0.05). In the control group 77% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group, edema was clearly present only in 8% of subjects (associated with discomfort rated between 3 and 6 on the analogue scale line) and it was mild, not associated with symptoms. Therefore the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and non-parametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for subjects under prophylaxis with Venoruton.