Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone sialoprotein deficiency impairs osteoclastogenesis and mineral resorption in vitro

Bone sialoprotein (BSP) and osteopontin (OPN) belong to the small integrin‐binding ligand N‐linked glycoprotein (SIBLING) family, whose members interact with bone cells and bone mineral. Previously, we showed that BSP knockout (BSP−/−) mice have a higher bone mass than wild type (BSP+/+) littermates, with very low bone‐formation activity and reduced osteoclast surfaces and numbers. Here we report that approximately twofold fewer tartrate‐resistant acid phosphatase (TRACP)–positive cells and approximately fourfold fewer osteoclasts form in BSP−/− compared with BSP+/+ spleen cell cultures. BSP−/− preosteoclast cultures display impaired proliferation and enhanced apoptosis. Addition of RGD‐containing proteins restores osteoclast number in BSP−/− cultures to BSP+/+ levels. The expression of osteoclast‐associated genes is markedly altered in BSP−/− osteoclasts, with reduced expression of cell adhesion and migration genes (αV integrin chain and OPN) and increased expression of resorptive enzymes (TRACP and cathepsin K). The migration of preosteoclasts and mature osteoclasts is impaired in the absence of BSP, but resorption pit assays on dentine slices show no significant difference in pit numbers between BSP+/+ and BSP−/− osteoclasts. However, resorption of mineral‐coated slides by BSP−/− osteoclasts is markedly impaired but is fully restored by coating the mineral substrate with hrBSP and partly restored by hrOPN coating. In conclusion, lack of BSP affects both osteoclast formation and activity, which is in accordance with in vivo findings. Our results also suggest at least some functional redundancy between BSP and OPN that remains to be clarified. © 2010 American Society for Bone and Mineral Research.
White matter microstructural changes in psychogenic erectile dysfunction patients

Brain dysfunction in erectile dysfunction (ED) has been identified by multiple neuroimaging studies. A recent MRI study indicated grey matter alterations in ED patients. This study aims to investigate the microstructural changes of cerebral white matter (WM) in psychological ED patients and their possible correlations with clinical variables. Twenty‐seven psychological ED patients and 27 healthy subjects (HS) were included and underwent a magnetic resonance (MR) diffusion tensor imaging (DTI) scan. The tract‐based spatial statistics were employed to identify the WM structure alterations in psychological ED patients. The multiple DTI‐derived indices′ [fractional anisotropy (FA), axial diffusivity (AD) and mean diffusivity (MD)] correlations with the symptoms and their durations, respectively, were analysed. The IIEF‐5, quality of erection questionnaire (QEQ) and the self‐esteem and relationship (SEAR) questionnaire were used to assess the symptoms of psychological ED patients. Compared with HS, the psychological ED patients showed increased FA values, reduced MD values and reduced AD values in multiple WM tracts including the corpus callosum (genu, body and splenium), corticospinal tract, internal capsule, corona radiata, external capsule and superior longitudinal fasciculus (p < 0.05, threshold‐free cluster enhancement corrected). Both of the IIEF scores and QEQ scores of ED patients showed a significantly negative correlation with the average FA values, and positive correlation with average AD values and MD values in the splenium of the corpus callosum (p < 0.05). The results provided preliminary evidence of WM microstructural changes in patients with psychological ED. The morphological alterations in the splenium of the corpus callosum were related to the symptom severity.
Adenoid cystic carcinoma of buccal mucosa with extensive hyalinization: A unique case report

Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary glands, 50% of which affect the minor salivary glands. ACC is known for its prolonged clinical course, multiple recurrence rates, and delayed onset of distant metastasis. The tumor usually shows one of the three histopathological variants which are cribriform, tubular, or solid pattern. Here we present a case of ACC affecting rightbuccal mucosa which histopathologically showed cribriform pattern with abundant hyalinization. Surgical excision was the only treatment done without any additional modalities and patient is free of disease since 10 years.
Nf1 Haploinsufficiency Alters Myeloid Lineage Commitment and Function, Leading to Deranged Skeletal Homeostasis

Although nullizygous loss of NF1 leads to myeloid malignancies, haploinsufficient loss of NF1 (Nf1) has been shown to contribute to osteopenia and osteoporosis which occurs in approximately 50% of neurofibromatosis type 1 (NF1) patients. Bone marrow mononuclear cells of haploinsufficient NF1 patients and Nf1+/– mice exhibit increased osteoclastogenesis and accelerated bone turnover; however, the culprit hematopoietic lineages responsible for perpetuating these osteolytic manifestations have yet to be elucidated. Here we demonstrate that conditional inactivation of a single Nf1 allele within the myeloid progenitor cell population (Nf1‐LysM) is necessary and sufficient to promote multiple osteoclast gains‐in‐function, resulting in enhanced osteoclastogenesis and accelerated osteoclast bone lytic activity in response to proresorptive challenge in vivo. Surprisingly, mice conditionally Nf1 heterozygous in mature, terminally differentiated osteoclasts (Nf1‐Ctsk) do not exhibit any of these skeletal phenotypes, indicating a critical requirement for Nf1 haploinsufficiency at a more primitive/progenitor stage of myeloid development in perpetuating osteolytic activity. We further identified p21Ras‐dependent hyperphosphorylation of Pu.1 within the nucleus of Nf1 haploinsufficient myelomonocytic osteoclast precursors, providing a novel therapeutic target for the potential treatment of NF1 associated osteolytic manifestations. © 2015 American Society for Bone and Mineral Research
Establishing Biomechanical Mechanisms in Mouse Models: Practical Guidelines for Systematically Evaluating Phenotypic Changes in the Diaphyses of Long Bones

Mice are widely used in studies of skeletal biology, and assessment of their bones by mechanical testing is a critical step when evaluating the functional effects of an experimental perturbation. For example, a gene knockout may target a pathway important in bone formation and result in a “low bone mass” phenotype. But how well does the skeleton bear functional loads; eg, how much do bones deform during loading and how resistant are bones to fracture? By systematic evaluation of bone morphological, densitometric, and mechanical properties, investigators can establish the “biomechanical mechanisms” whereby an experimental perturbation alters whole‐bone mechanical function. The goal of this review is to clarify these biomechanical mechanisms and to make recommendations for systematically evaluating phenotypic changes in mouse bones, with a focus on long‐bone diaphyses and cortical bone. Further, minimum reportable standards for testing conditions and outcome variables are suggested that will improve the comparison of data across studies. Basic biomechanical principles are reviewed, followed by a description of the cross‐sectional morphological properties that best inform the net cellular effects of a given experimental perturbation and are most relevant to biomechanical function. Although morphology is critical, whole‐bone mechanical properties can only be determined accurately by a mechanical test. The functional importance of stiffness, maximum load, postyield displacement, and work‐to‐fracture are reviewed. Because bone and body size are often strongly related, strategies to adjust whole‐bone properties for body mass are detailed. Finally, a comprehensive framework is presented using real data, and several examples from the literature are reviewed to illustrate how to synthesize morphological, tissue‐level, and whole‐bone mechanical properties of mouse long bones. © 2015 American Society for Bone and Mineral Research
In-Hospital Nonvariceal Upper Gastrointestinal Bleeding following Cardiac Surgery: Patient Characteristics, Endoscopic Lesions and Prognosis

Background. Nonvariceal upper gastrointestinal bleeding (NVUGIB) can occur following cardiac surgery, with sparse contemporary data on patient characteristics and predictors of outcome in this setting. Aim. To describe the clinical and endoscopic characteristics of patients with NVUGIB following cardiac surgery and characterize predictors of outcome. Methods. Retrospective review of 131 consecutive patients with NVUGIB following cardiac surgery from 2002 to 2005. Demographic characteristics, therapeutic management, and predictors of outcomes were determined. Results. 69.5% were male, mean age: 68.8 ± 10.2 yrs, mean Parsonnet score: 24.6 ± 14.2. Commonest symptoms included melena (59.4%) or coffee ground emesis (25.8%). In-hospital medications included ASA (88.5%), heparin (95.4%, low molecular weight 6.9%), coumadin (48.1%), clopidogrel (22.9%), and NSAIDS (42%). Initial hemodynamic instability was noted in 47.1%. Associated laboratory results included hematocrit 26 ± 6, platelets 243 ± 133 109/L, INR 1.7 ± 1.6, and PTT 53.3 ± 35.6 s. Endoscopic evaluation (122 patients) yielded ulcers (85.5%) with high-risk lesions in 45.5%. Ulcers were located principally in the stomach (22.5%) or duodenum (45.9%). Many patients had more than one lesion, including esophagitis (28.7%) or erosions (26.8%). 48.8% received endoscopic therapy. Mean lengths of intensive care unit and overall stays were 10.4 ± 18.4 and 39.4 ± 46.9 days, respectively. Overall mortality was 19.1%. Only mechanical ventilation under 48 hours predicted mortality (O.R = 0.11; 95% CI = 0.04−0.34). Conclusions. This contemporary cohort of consecutive patients with NVUGIB following cardiac surgery bled most often from ulcers or esophagitis; many had multiple lesions. ICU and total hospital stays as well as mortality were significant. Mechanical ventilation for under 48 hours was associated with improved survival.
Androgen receptor polymorphisms and testicular cancer risk

Testicular cancer (TC) is currently the most common malignant solid tumour in Caucasian males aged 15–39 years. Epidemiological evidence suggests that its onset may be due to an imbalance in the action of steroidal sex hormones and their receptors. A faulty androgen receptor signalling pathway can, in fact, cause various male reproductive disorders. The androgen receptor (AR) gene has two polymorphic segments consisting of CAG and GGC repeats. The length of CAG repeats has been shown to affect the regulation of AR activity. In our study, we used fragment analysis to evaluate the AR gene repeats of 302 TC patients and 322 controls, to establish if there is any association between repeat number and TC. This study of the largest Italian caseload investigated to date highlighted three particularly significant aspects. First, a CAG repeat number of ≥25 may be considered a risk factor for the onset of TC, given its greater frequency in patients in comparison with controls. This difference became significant for the non‐seminoma group. Second, men with CAG repeats below 21 or above 24 were found to have a, respectively, 50 and 76% higher risk of TC than those with CAG 21–24, suggesting that these too can be considered a risk factor for TC. Finally, stage II patients were more likely to have a CAG repeat number <21 or >24 than stage I patients.
Topical alpha-interferon in recurrent conjunctival papilloma.

Purpose To report the effect of topical alpha-interferon (alpha-IF) in two cases of recurrent conjunctival papillomas. Methods One patient with a conjunctival papilloma and one patient with a limbus-based papilloma were treated with excision and cryotherapy. Recurrences included one in situ carcinoma. Retreatment included systemic and topical alpha-IF. Results In Case 1, the papillomas regressed with systemic alpha-IF followed by topical application of alpha-IF (2.8 x 106 U) for 1 year against recurrence. In Case 2, the papillomas disappeared with topical alpha-IF over 1 year. No recurrences were seen during follow-up (84 and 91 months, respectively). The possible side effect of topical alpha-IF was superficial keratitis. Retrospective polymerase chain reaction tests for HPV were positive and showed type 6 in Case 1 and type 33 in Case 2. Conclusion Topical alpha-IF can be used as adjuvant therapy in recurrent conjunctival papillomas.
Eruption of a Solar Filament Consisting of Two Threads

The trigger and driving mechanism for the eruption of a filament consisting of two dark threads was studied with unprecedented high cadence and resolution of He II 304 angstrom observations made by the Atmospheric Imagining Assembly (AIA) on board the Solar Dynamics Observatory (SDO) and the observations made by the Solar Magnetic Activity Research Telescope and the Extreme Ultraviolet Imager (EUVI) telescope on board the Solar Terrestrial Relations Observatory Ahead (STEREO-A). The filament was located at the periphery of the active region NOAA 11228 and erupted on 2011 June 6. At the onset of the eruption, a turbulent filament thread was found to be heated and to elongate in stride over a second one. After it rose slowly, most interestingly, the elongating thread was driven to contact and interact with the second one, and it then erupted with its southern leg being wrapped by a newly formed thread produced by the magnetic reconnection between fields carried by the two threads. Combining the observations from STEREO-A/EUVI and SDO/AIA 304 angstrom images, the three-dimensional shape of the axis of the filament was obtained and it was found that only the southern leg of the eruptive filament underwent rotation. We suggest that the eruption was triggered by the reconnection of the turbulent filament thread and the surrounding magnetic field, and that it was mainly driven by the kink instability of the southern leg of the eruptive filament that possessed a more twisted field introduced by the reconnection-produced thread.
Comparing Primary Tumors and Metastatic Nodes in Head and Neck Cancer Using Intravoxel Incoherent Motion Imaging: A Preliminary Experience

Objective This study aimed to use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and to evaluate IVIM efficacy in predicting outcome. Methods Sixteen patients with head and neck cancer underwent IVIM diffusion-weighted imaging on a 1.5-T magnetic resonance imaging scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival and overall survival were estimated using the Kaplan-Meier method. Results In comparison with metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (P < 0.0009) and lower diffusion coefficient (D) (P < 0.0002). Patients with lower SD for D had prolonged progression-free survival and overall survival (P < 0.05). Conclusions Pretreatment IVIM measures were feasible in investigating the physiologic differences between the 2 tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care.
Cataract backlog and output of cataract surgery in Plateau State, Nigeria.

Background : To assess the output of cataract surgeries in Plateau state in terms of cataract surgical rate, and number of cataract surgeries per surgeon. Methodology : All cataract surgical centres in the state were visited. The operation register for the period of one year (1st April 2002 to 31st March 2003) were reviewed and the number of eyes operated for age-related cataract were determined. The number and position of all surgeons were compiled. All surgical eye camps during the study period were noted and the number of cataract operations performed and position of surgeons involved were compiled. Information on Plateau state population was obtained. Cataract surgical rate and the cataract surgeries per surgeon in the state were assessed. Result : The cataract surgical rate (CSR) for Plateau state for the period was 540 operations/million/year. The main providers of cataract surgical services were the tertiary center, Jos University Teaching Hospital (JUTH) 404 eyes (26.9%), Church of Christ In Nigeria (COCIN) Hospital Mangu 336eyes (22.4%), and Evangelical Churches of West Africa (ECWA) Hospital 294 eyes (19.6%). A total of 660 e yes (43.9%) were operated in the 3 missionary hospitals. 164(11%) cataract surgeries were performed during eye camps. There were a total of 15 surgeons in the state. Our study revealed that the ophthalmic surgeon based in Plateau state performs an average of 104 cataract operations per year Conclusion : Cataract surgeries performed in the state annually (1502) is less than the incidence of cataract blindness in the state which is estimated at 2708. The present C SR is not enough to reduce the cataract backlog in the state. There is need to improve cataract services delivery in the state to reduce this backlog.
Milk Fat Globule‐Epidermal Growth Factor 8 (MFG‐E8) Is a Novel Anti‐inflammatory Factor in Rheumatoid Arthritis in Mice and Humans

Milk fat globule‐epidermal growth factor 8 (MFG‐E8) is an anti‐inflammatory glycoprotein that mediates the clearance of apoptotic cells and is implicated in the pathogenesis of autoimmune and inflammatory diseases. Because MFG‐E8 also controls bone metabolism, we investigated its role in rheumatoid arthritis (RA), focusing on inflammation and joint destruction. The regulation of MFG‐E8 by inflammation was assessed in vitro using osteoblasts, in arthritic mice and in patients with RA. K/BxN serum transfer arthritis (STA) was applied to MFG‐E8 knock‐out mice to assess its role in the pathogenesis of arthritis. Stimulation of osteoblasts with lipopolysaccharide (LPS) and tumor necrosis factor (TNF)‐α downregulated the expression of MFG‐E8 by 30% to 35%. MFG‐E8‐deficient osteoblasts responded to LPS with a stronger production of pro‐inflammatory cytokines. In vivo, MFG‐E8 mRNA levels were 52% lower in the paws of collagen‐induced arthritic (CIA) mice and 24% to 42% lower in the serum of arthritic mice using two different arthritis models (CIA and STA). Similarly, patients with RA (n = 93) had lower serum concentrations of MFG‐E8 (–17%) compared with healthy controls (n = 140). In a subgroup of patients who had a moderate to high disease activity (n = 21), serum concentrations of MFG‐E8 rose after complete or partial remission had been achieved (+67%). Finally, MFG‐E8‐deficient mice subjected to STA exhibited a stronger disease burden, an increased number of neutrophils in the joints, and a more extensive local and systemic bone loss. This was accompanied by an increased activation of osteoclasts and a suppression of osteoblast function in MFG‐E8‐deficient mice. Thus, MFG‐E8 is a protective factor in the pathogenesis of RA and subsequent bone loss. Whether MFG‐E8 qualifies as a novel biomarker or therapeutic target for the treatment of RA is worth addressing in further studies. © 2015 American Society for Bone and Mineral Research.
Three-Phase Parathyroid 4-Dimensional Computed Tomography Initial Experience: Inexperienced Readers Have High Accuracy and High Interobserver Agreement

Objective Multiphase multidetector contrast-enhanced parathyroid CT (4-dimensional computed tomography [4D-CT]) is an emerging tool for evaluating patients with primary hyperparathyroidism. Our goal was to describe the initial performance of 2 inexperienced readers in interpretation of 4D-CT. Methods Twenty-three subjects who received 4D-CT and successful surgical exploration were studied (14 initial and 9 repeat explorations; 15 single-gland disease and 8 multigland disease) A staff neuroradiologist prospectively interpreted all studies, and a neuroradiology fellow retrospectively interpreted all studies; their results were compared with the surgical findings for each side of the neck separately. Results The prospective readings were 78% accurate overall, 97% accurate in the subset of single-gland disease cases, and 89% accurate in re-exploration cases. There was 91% concordance in interpretation between observers, with &kgr; of 0.83. Conclusions Initial results after implementation of 4D-CT show high accuracy of interpretation for inexperienced observers, comparable to published data, and high interobserver agreement.
The prevalence of child sexual abuse among secondary school pupils in Gweru, Zimbabwe

Abstract Child sexual abuse is a social and public health concern locally and worldwide because it is associated with numerous and serious short-and long-term devastating consequences. This study investigated the prevalence of child sexual abuse among day secondary school pupils in Gweru, Zimbabwe. The sample comprised 268 secondary pupils (50% female; mean age=15.42, standard deviation=1.376). Data were collected by administering the Child Abuse Screening Tool Children's Version (ICAST-C). The study found an overall prevalence rate of 56.3%, with no significant gender differences. Both non-contact and contact forms of sexual abuse were prevalent. Both adults and peers were reported as perpetrators. Perpetrators were reported to be familiar people, which is consistent with the observation that the home was reported as the major place where abuse was perpetrated. Compared to western studies, this study showed higher rates for the various forms of child sexual abuse.
Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D‐Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

Studies using vitamin D‐binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single‐nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography–tandem mass spectrometry (LC‐MS/MS) did not differ by race, whereas a widely used monoclonal enzyme‐linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC‐MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort (CRIC). Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and showed that the polyclonal ELISA is not subject to this bias. Whereas ≤9% of the variability in DBP concentrations quantified using either LC‐MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA‐based measures was explained by genotype. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC‐MS/MS‐based results for Gc1f homozygotes (median difference –67%; interquartile range [IQR] –71%, –64%), 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC‐MS/MS, irrespective of genotype, with a median percent difference of +50% (IQR +33%, +65%). Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC‐MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype. © 2016 American Society for Bone and Mineral Research.