Miracle-dz/UniFAR-FTUs huggingface dataset:
PTHrP Produced by Myeloma Plasma Cells Regulates Their Survival and Pro‐Osteoclast Activity For Bone Disease Progression

To promote their survival and progression in the skeleton, osteotropic malignancies of breast, lung, and prostate produce parathyroid hormone–related protein (PTHrP), which induces hypercalcemia. PTHrP serum elevations have also been described in multiple myeloma (MM), although their role is not well defined. When we investigated MM cells from patients and cell lines, we found that PTHrP and its receptor (PTH‐R1) are highly expressed, and that PTHrP is secreted both as a full‐length molecule and as small subunits. Among these subunits, the mid‐region, including the nuclear localization sequence (NLS), exerted a proliferative effect because it was accumulated in nuclei of MM cells surviving in starvation conditions. This was confirmed by increased transcription of several genes enrolled in proliferation and apoptosis control. PTHrP was also found to stimulate PTH‐R1 in MM cells. PTH‐R1's selective activation by the full‐length PTHrP molecule or the NH2‐terminal fragment resulted in a significant increase of intracellular Ca2+ influx, cyclic adenosine monophosphate (cAMP) content, and expression of receptor activator of NF‐κB ligand (RANKL) and monocyte chemoattractant protein‐1 (MCP‐1). Our data definitely clarify the role of PTHrP in MM. The PTHrP peptide is functionally secreted by malignant plasma cells and contributes to MM tumor biology and progression, both by intracrine maintenance of cell proliferation in stress conditions and by autocrine or paracrine stimulation of PTH‐R1, which in turn reinforces the production of osteoclastogenic factors. © 2014 American Society for Bone and Mineral Research.
Wnt Signaling Regulates Pulp Volume and Dentin Thickness

Odontoblasts, cementoblasts, ameloblasts, and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wntless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin (OCN), which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN‐Cre;Wlsfl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt‐mediated misregulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits dentin sialoprotein (DSP); this inhibition must be relieved for odontoblasts to differentiate. In OCN‐Cre;Wlsfl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2‐mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex. © 2014 American Society for Bone and Mineral Research.
Spinal fusion using tissue engineered bone. A prospective, randomized clinical pilot trial

Spinal fusion is performed using bone harvested from the ilium. However, graft harvest is associated with frequent complications and pain. If a tissue engineered bone (TEB) was available, spinal fusion could be performed without damaging normal tissues. In 8 patients, 10-20 mL of marrow fluid was collected from the iliac crest to fabricate. After primary culture in the standard medium, marrow mesenchymal cells were combined with porous tricalcium phosphate block and were cultured in osteogenic medium containing dexamethasone, b-glycerophosphate, vitamin C phosphate, and estriol. After 3 weeks of subculture, spinal fusion was performed using TEB. Nine patients who had undergone spinal fusion using iliac autografts served as the controls (AG group). In all patients, significant improvement in JOA score was seen in both TEB and AG groups. The radiographic fusion rate was 87.5% (7/8) in TEB group and 77.8% (2/9) in AG group at 6 months after surgery. The mean operating time in TEB group was shorter than in the AG group. Compared with the AG group, the patients receiving TEB graft had significantly less total blood loss. In the AG group, all of the patients complained of graft site pain for 2 to 4 weeks after the operation. Two patients (22.2%) still had graft site pain at 6 months postoperatively. Bone regeneration therapy using the TEB graft introduced in this report makes it possible to perform spinal fusion as is done using autogenous bone grafts, but with the minimally invasive procedure of bone marrow aspiration.
Deformable Registration of Supine and Prone Colons for Computed Tomographic Colonography

Computed tomographic colonography is a minimally invasive technique for detecting colorectal polyps and colon cancer. Most computed tomographic colonography protocols acquire both prone and supine images to improve the visualization of the lumen wall, reduce false-positives, and improve sensitivity. Comparisons between the prone and supine images can be improved by registration between the scans. In this paper, we propose registering colon lumens, segmented from prone and supine images, using feature matching of the colon centerline and nonrigid registration of the lumen shapes represented as distance functions. Experimental registration results (n = 21 subjects) show a correspondence accuracy of 13.77 ± 6.20 mm for a range of polyp sizes. The overlap in the registered lumen segmentations show an average Jaccard similarity coefficient of 0.915 ± 0.07.
'Learning to live with OCD is a little mantra I often repeat': understanding the lived experience of obsessive-compulsive disorder (OCD) in the contemporary therapeutic context.

OBJECTIVES While there has been an abundance of quantitative studies that examine the clinical features and treatment modalities of obsessive-compulsive disorder (OCD), only a few qualitative research studies examining the experience of OCD have been documented. Our objectives were to explore and understand psychosocial aspects of OCD and to provide qualitative accounts of the condition and its treatment rather than concentrating on its psychopathology. We also wanted to locate the role cognitive behavioural therapy (CBT) played in the condition for our participants. DESIGN Data for the study came from a series of nine semi-structured interviews carried out with individuals who self-identified as having OCD. Participants were recruited through two leading UK-based OCD charities. METHODS We used interpretative phenomenological analysis (IPA) to analyse the accounts and participants gave feedback as to the validity of the themes in early stages of analysis. RESULTS We report two superordinate themes--Having OCD (with subordinate themes 'wanting to be normal and fit it', 'failing at life' and 'loving and hating OCD') and The Impact of Therapy (with subordinate themes of 'wanting therapy', 'finding the roots' and 'a better self'). CONCLUSIONS Having OCD as a condition meant that individuals experienced a sense of overwhelming personal failure matched against age appropriate life cycle goals. This crisis of the self was bolstered by public and self-stigma about the condition. While clinical diagnosis and therapeutic interventions were significant, participants reported dialectical tensions experienced with OCD, pointing to the complexity of psychological functioning in the condition.
Comparison of Computed Tomography Angiography With Digital Subtraction Angiography in the Assessment of Clipped Intracranial Aneurysms

Purpose: To examine whether computed tomography angiography (CTA) is comparable to digital subtraction angiography (DSA) in assessing clipped intracranial aneurysms. Materials and Methods: Retrospective collection of clipped aneurysms that had both CTA and DSA within 2 months of one another. Computed tomography angiograms were independently reviewed by 2 blinded neuroradiologists; rereviewed by one at least 4 months later. Each was classified as complete obliteration, neck remnant, or residual aneurysm. Parent vessel was classified as patent or occluded. Digital subtraction angiograms were reviewed in a similar manner by a third blinded neuroradiologist. Results: Forty-eight patients with 53 clipped aneurysms were collected. On DSA, 35 were completely obliterated, 10 neck remnants, and 8 residual aneurysms. The ability of CTA to detect residual aneurysms versus complete obliterations or neck remnants was excellent (mean sensitivity, 88%; specificity, 100%; positive predictive value [PPV], 100%; negative predictive value [NPV], 98%). The ability of CTA to detect neck remnants versus complete obliterations was poor (mean sensitivity, 20%; specificity, 99%; PPV, 83%; NPV, 81%). The CTAs were good at detecting parent vessel occlusion (mean sensitivity, 88%; specificity, 97%; PPV, 75%; NPV, 99%). Interrater and intrarater agreement was good to excellent for aneurysm and parent vessel assessment, with &kgr; values ranging from 0.6 to 1.0. Conclusions: Computed tomography angiography has high sensitivity and specificity for residual aneurysm detection and parent vessel occlusion. It is not accurate in neck remnant detection, although these were small and of uncertain clinical significance. This suggests that CTA is useful for follow-up of clipped aneurysms. However, given the potential to miss neck remnants or small residual aneurysms, it is recommended to perform initial DSA and CTA to select cases in which CTA follow-up is appropriate.
Short‐term low‐dose triple therapy for the eradication of Helicobacter pylori

Background: Helicobacter pylori infection causes antral gastritis and is strongly associated with duodenal ulcer relapse. Eradication of H. pylori infection may be difficult to achieve due to antimicrobial resistance, side effects and poor patient compliance. Objective: To evaluate the efficacy, tolerability and patient compliance of short-term triple therapy with clarithromycin, omeprazole and tinidazole. Methods: Triple therapy, comprising clarithromycin 250 mg twice daily, omeprazole 20 mg once daily and tinidazole 500 mg twice daily, was administered to 65 patients with H. pylori gastritis for 1 week. H. pylori infection before and after treatment was determined by histology, the urease test and the 13C-urea breath test. Upper gastrointestinal endoscopy, during which four antral biopsy specimens were taken, and the 13C-urea breath test were performed in all patients before treatment and at 1 and 6 months after treatment. Drug tolerance was evaluated by patient interviews and compliance by counting returned pills at the end of treatment. Results: Sixty-three patients with H. pylori infection were studied. One month after treatment, on intent-to-treat analysis, H. pylori infection had been eradicated in 62 out of 65 patients (95.4%), confirmed by a negative urease test, 13C-urea breath test and histological examination of antral biopsy specimens. All patients were free of infection 6 months after treatment ended. All but one patient completed treatment and took more than 90% of the prescribed medication. There were no side effects except for one case of mild nausea (not severe enough to stop treatment) and one case of urticaria, following which treatment was withdrawn. Conclusions: Short-term, low-dose triple therapy with clarithromycin, omeprazole and tinidazole is highly effective for the eradication of H. pylori infection. The lack of side effects and good compliance are important for successful eradication.
The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I2 = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.
Is gross motor delay secondary to bilateral vestibular hypofunction in Jervell and Lange-Nielsen syndrome?

Abstract Jervell and Lange-Nielsen syndrome is a rare autosomal recessive condition characterized by bilateral profound sensorineural hearing loss, and prolonged QT interval that may result in ventricular tachycardia leading to syncope, cardiac arrest or sudden death. Treatment of the arrhythmias is often life-saving as this condition has a high mortality if untreated. We describe 3 cases of Jervell and Lange-Nielsen syndrome, who presented with profound sensorineural hearing loss and delayed gross motor milestones and have evidence of bilateral vestibular hypofunction on vestibular testing. We suggest that vestibular hypofunction is associated with this syndrome and evaluation of vestibular function may increase the diagnostic yield in the asymptomatic stage of this rare, but severe form of long QT syndrome. Clinicians should consider Jervell Lange-Nielsen in the differential diagnosis of ‘non-syndromic’ profound sensorineural hearing loss presenting with vestibular failure, along with Usher syndrome type 1, and morphological malformations of the vestibular apparatus. However, more studies are needed to confirm these findings.
Women’s post‐release experiences in the U.S: Recidivism and re‐entry

A survey of 166 women exiting prison in a large mid‐western U.S. state examined the extent to which demographics, family history and relationships, institutional experiences, offence history, and physical and emotional needs were associated with re‐arrest one year after release. Analyses revealed that three independent variables and two interactional effects accounted for 40% of the variability in re‐arrest: employment in the year prior to incarceration, history of psychiatric hospitalization, participation in prison industries programs, and the interaction of prior psychiatric hospitalization with in‐prison substance abuse programming and with employment history. Interviews with 55 women over five points in time revealed important interpersonal and environmental elements for 20 women six months out who had not been arrested. Implications for program and policy development are discussed.
Methylation of Bone SOST, Its mRNA, and Serum Sclerostin Levels Correlate Strongly With Fracture Risk in Postmenopausal Women

Inhibition of sclerostin, a glycoprotein secreted by osteocytes, offers a new therapeutic paradigm for treatment of osteoporosis (OP) through its critical role as Wnt/catenin signaling regulator. This study describes the epigenetic regulation of SOST expression in bone biopsies of postmenopausal women. We correlated serum sclerostin to bone mineral density (BMD), fractures, and bone remodeling parameters, and related these findings to epigenetic and genetic disease mechanisms. Serum sclerostin and bone remodeling biomarkers were measured in two postmenopausal groups: healthy (BMD T‐score > –1) and established OP (BMD T‐score < –2.5, with at least one low‐energy fracture). Bone specimens were used to analyze SOST mRNAs, single nucleotide polymorphisms (SNPs), and DNA methylation changes. The SOST gene promoter region showed increased CpG methylation in OP patients (n = 4) compared to age and body mass index (BMI) balanced controls (n = 4) (80.5% versus 63.2%, p = 0.0001) with replication in independent cohorts (n = 27 and n = 36, respectively). Serum sclerostin and bone SOST mRNA expression correlated positively with age‐adjusted and BMI‐adjusted total hip BMD (r = 0.47 and r = 0.43, respectively; both p < 0.0005), and inversely to serum bone turnover markers. Five SNPs, one of which replicates in an independent population‐based genomewide association study (GWAS), showed association with serum sclerostin or SOST mRNA levels under an additive model (p = 0.0016 to 0.0079). Genetic and epigenetic changes in SOST influence its bone mRNA expression and serum sclerostin levels in postmenopausal women. The observations suggest that increased SOST promoter methylation seen in OP is a compensatory counteracting mechanism, which lowers serum sclerostin concentrations and reduces inhibition of Wnt signaling in an attempt to promote bone formation. © 2014 American Society for Bone and Mineral Research.
Urokinase Receptor Mediates Osteoclastogenesis via M‐CSF Release From Osteoblasts and the c‐Fms/PI3K/Akt/NF‐κB Pathway in Osteoclasts

Bone remodeling is a dynamic process based on a fine‐tuned balance between formation and degradation of bone. Osteoblasts (OBLs) are responsible for bone formation and bone resorption is mediated by osteoclasts (OCLs). The mechanisms regulating the OBL‐OCL balance are critical in health and disease; however, they are still far from being understood. We reported recently that the multifunctional urokinase receptor (uPAR) mediates osteogenic differentiation of mesenchymal stem cells (MSCs) to OBLs and vascular calcification in atherosclerosis. Here, we address the question of whether uPAR may also be engaged in regulation of osteoclastogenesis. We show that uPAR mediates this process in a dual fashion. Thus, uPAR affected OBL‐OCL interplay. We observed that osteoclastogenesis was significantly impaired in co‐culture of monocyte‐derived OCLs and in OBLs derived from MSCs lacking uPAR. We show that expression and release, from OBLs, of macrophage colony‐stimulating factor (M‐CSF), which is indispensable for OCL differentiation, was inhibited by uPAR loss. We further found that uPAR, on the other hand, controlled formation, differentiation, and functional properties of macrophage‐derived OCLs. Expression of osteoclastogenic markers, such as tartrate‐resistant acid phosphatase (TRAP) and cathepsin K, was impaired in OCLs derived from uPAR‐deficient macrophages. The requirement of uPAR for osteoclastogenesis was further confirmed by immunocytochemistry and in bone resorption assay. We provide evidence that the underlying signaling mechanisms involve uPAR association with the M‐CSF binding receptor c‐Fms followed by c‐Fms phosphorylation and activation of the PI3K/Akt/NF‐κB pathway in OCLs. We further show that uPAR uses this pathway to regulate a balance between OCL differentiation, apoptosis, and cell proliferation. Our study identified uPAR as an important and multifaceted regulator of OBL‐OCL molecular interplay that may serve as an attractive target in bone disease and ectopic calcification. © 2014 American Society for Bone and Mineral Research.
Recognising Autism Spectrum Disorders in Primary Care: Perspectives of Speech and Language Therapists

Understanding the process of recognising autism spectrum disorders (ASD) in children is important, both for achieving timely identification of children's difficulties and for ensuring positive experiences for families. Professionals working in primary care services are suitably positioned to identify children requiring referral for diagnostic assessment of ASD through their early contact with children and their families. Speech and language therapists (SLTs) in particular are well situated to recognise ASD, as concerns regarding communication development are frequently raised by parents of children who later go on to receive an ASD diagnosis. This small-scale qualitative study aimed to explore primary care SLTs' experiences of recognising potential ASD in children. Five SLTs working in primary care services in the Republic of Ireland participated in semi-structured interviews. Thematic analysis of the data revealed that participants were concerned with two key events: firstly, accurately recognising potential ASD in children; and secondly, discussing the possibility of ASD with parents. The SLTs' experiences of these events were found to be influenced by both individual and wider organisational factors. The findings are discussed in the context of the current literature on ASD identification and implications for practice are considered.
Bone Volume Fraction and Fabric Anisotropy Are Better Determinants of Trabecular Bone Stiffness Than Other Morphological Variables

As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphology‐elasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro–computed tomography (μCT) reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae, and iliac crest were analyzed. Their morphology was assessed via 25 variables and their stiffness tensor ( CFE ) was computed from six independent load cases using micro finite element (μFE) analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology‐elasticity relationships. The statistically admissible morphological variables were included in a multiple linear regression model of the dependent variable CFE . The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of CFE (r2adj = 0.889), especially in combination with fabric anisotropy (r2adj = 0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (r2adj = 0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric anisotropy further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric anisotropy are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and postelastic properties. © 2015 American Society for Bone and Mineral Research.