Miracle-dz/UniFAR-FTUs huggingface dataset:
Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3‐month treatment with PTH in rats

We previously reported that following mechanical ablation of the marrow from the midshaft of rat femurs, there is a rapid and abundant but transient growth of bone, and this growth is enhanced and maintained over a 3‐week period by the bone anabolic hormone parathyroid hormone (PTH). Here, we asked whether further treatment with PTH or bisphosphonates can extend the half‐life of the new bone formed in lieu of marrow. We subjected the left femur of rats to mechanical marrow ablation and treated the animals 5 days a week with PTH for 3 weeks (or with vehicle as a control) to replace the marrow by bone. Some rats were euthanized and used as positive controls or treated with vehicle, PTH, or the bisphosphonate alendronate for a further 9 weeks. We subjected both femurs from each rat to soft X‐ray, peripheral quantitative computed tomography (pQCT), micro‐computed tomography (µCT), dynamic histomorphometry analysis, and biomechanical testing. We also determined the concentrations of serum osteocalcin to confirm the efficacy of PTH. Treatment with PTH for 3 months dramatically enhanced endosteal and periosteal bone formation, leading to a 30% increase in cortical thickness. In contrast, alendronate protected the bone that had formed in the femoral marrow cavity after marrow ablation and 3 weeks of treatment with PTH but failed to promote endosteal bone growth or to improve the biomechanical properties of ablated femurs. We further asked whether calcium‐phosphate cements could potentiate the formation of bone after marrow ablation. Marrow cavities from ablated femurs were filled with one of two calcium‐phosphate cements, and rats were treated with PTH or PBS for 84 days. Both cements helped to protect the new bone formed after ablation. To some extent, they promoted the formation of bone after ablation, even in the absence of any anabolic hormone. Our data therefore expand the role of PTH in bone engineering and open new avenues of investigation to the field of regenerative medicine and tissue engineering. Local bone marrow aspiration in conjunction with an anabolic agent, a bisphosphonate, or a calcium‐phosphate cement might provide a new platform for rapid preferential site‐directed bone growth in areas of high bone loss. © 2010 American Society for Bone and Mineral Research
Sperm DNA integrity testing: big halo is a good predictor of embryo quality and pregnancy after conventional IVF

Sperm DNA integrity is a sperm functional parameter of male fertility evaluation. Two parameters of sperm DNA integrity were observed: DNA damage expressed as DNA fragmentation index (DFI) and percentage of the DNA undamaged spermatozoa expressed as big halo. Halosperm test was used for sperm DNA integrity determination. The aim of this study was to evaluate which DNA integrity parameter is better as an embryo quality and pregnancy prognostic parameter after the conventional IVF. We evaluated two embryo groups (positive and negative group) according to the 3rd day cumulative embryo score. Big halo and DFI, as we expected, showed good correlation (r = −0.69; p < 0.001). Receiver operating characteristic (ROC) analyses show that DFI and big halo are significant (p < 0.001) as prognostic parameters of embryo quality. ROC curves comparison of DFI and big halo revealed the AUC value for big halo to be significantly higher (DFI AUC = 0.71 vs. big halo AUC = 0.83; p = 0.025) than for DFI. Big halo was found to be the only independent predictor of embryo quality. Sperm DNA integrity both parameters are good prognostic parameters of embryo quality after the conventional IVF where big halo seems to be better. ROC analyses show DFI and big halo as significant prognostic parameters for achieved pregnancy (AUC ± SE for DFI was 0.67 ± 0.06 and 0.75 ± 0.06 for big halo). To our knowledge, this is the first study demonstrating the correlation between sperm DNA undamaged rate expressed as big halo parameter and semen characteristics as well as the influence on fertilization rate, embryo quality and pregnancy in conventional IVF.
FGF23 Regulates Bone Mineralization in a 1,25(OH)2D3 and Klotho‐Independent Manner

Fibroblast growth factor‐23 (Fgf23) is a bone‐derived hormone, suppressing phosphate reabsorption and vitamin D hormone (1,25(OH)2D3) production in the kidney. It has long been an enigma why lack of Fgf23 or of Klotho, the coreceptor for Fgf23, leads to severe impairment in bone mineralization despite the presence of hypercalcemia and hyperphosphatemia. Using Fgf23‐/‐ or Klotho‐/‐ mice together with compound mutant mice lacking both Fgf23 or Klotho and a functioning vitamin D receptor, we show that in Klotho‐/‐ mice the mineralization defect is solely driven by 1,25(OH)2D3‐induced upregulation of the mineralization‐inhibiting molecules osteopontin and pyrophosphate in bone. In Fgf23‐/‐ mice, the mineralization defect has two components, a 1,25(OH)2D3‐driven component similar to Klotho‐/‐ mice and a component driven by lack of Fgf23, causing additional accumulation of osteopontin. We found that FGF23 regulates osteopontin secretion indirectly by suppressing alkaline phosphatase transcription and phosphate production in osteoblastic cells, acting through FGF receptor‐3 in a Klotho‐independent manner. Hence, FGF23 secreted from osteocytes may form an autocrine/paracrine feedback loop for the local fine‐tuning of bone mineralization. © 2015 American Society for Bone and Mineral Research.
In vivo discrimination of hip fracture with quantitative computed tomography: Results from the prospective European Femur Fracture Study (EFFECT)

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case‐control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework—Femur option (MIAF‐Femur)] in differentiating hip fracture and non–hip fracture subjects. One‐hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low‐energy hip fractures and 60 female non–hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF‐Femur. Areal BMD (aBMD) was assessed using dual‐energy X‐ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non–hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable—a trabecular BMD (measured in the femoral head or in the trochanteric region)—and one geometric variable—a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. © 2011 American Society for Bone and Mineral Research.
Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix

Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long‐term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2. 3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X‐ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age‐related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. © 2015 American Society for Bone and Mineral Research.
Depth-kymography: high-speed calibrated 3D imaging of human vocal fold vibration dynamics

We designed and developed a laser line-triangulation endoscope compatible with any standard high-speed camera for a complete three-dimensional profiling of human vocal fold vibration dynamics. With this novel device we are able to measure absolute values of vertical and horizontal vibration amplitudes, length and width of vocal folds as well as the opening and closing velocities from a single in vivo measurement. We have studied, for the first time, the generation and propagation of mucosal waves by locating the position of its maximum vertical position and the propagation velocity. Precise knowledge about the absolute dimensions of human vocal folds and their vibration parameters has significant importance in clinical diagnosis and treatment as well as in fundamental research in voice. The new device can be used to investigate different kinds of pathological conditions including periodic or aperiodic vibrations. Consequently, the new device has significant importance in investigating vocal fold paralysis and in phonosurgical applications.
Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength

The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild‐type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild‐type mice. A micro‐CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone‐formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU‐positive osteoblastic cell numbers were increased, TUNEL‐positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three‐point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild‐type mice. The frequency of TUNEL‐positive primary osteoblasts was lower in BCLXL transgenic mice than in wild‐type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. © 2016 American Society for Bone and Mineral Research.
Chest diameter ratios for detecting static hyperinflation in children using photogrammetry.

OBJECTIVES To develop a photogrammetric method capable of identifying increases in anteroposterior chest diameters suggestive of pulmonary hyperinflation, and to test it with both asthmatic and asthma-free children. METHODS Two distinct study designs were used to achieve these two objectives. The first was a descriptive analysis of diameters measured at the height of the axilla and of the xiphoid on digital images of 56 children aged 8 to 12 years photographed in the orthostatic position. The second was a case-control study of (a) 19 asthmatic children in treatment for at least 12 months; and (b) 37 children free from asthma with no prior history of complaints of respiratory/allergic disease. Diameters were measured on images of the front and left side views using CorelDRAW, and the ratio between the front and side diameters was calculated for the axillary and xiphoid measurements, providing the diameter ratios. Diameter ratios close to or greater than 1 represent geometry tending towards a cylindrical shape, typical of hyperinflation on radiographs. RESULTS Analysis with the t test for independent samples revealed a mean diameter ratio at the sternum that was significantly greater in the group of asthmatic children (p < 0.01) than the mean for the whole sample and also than the mean for the children without asthma. CONCLUSIONS Despite the existence of disagreement on the best instruments, methods and times for identifying hyperinflation, results indicate that a system using diameter ratios obtained by photogrammetry is a promising tool for the identification of a kinesiopathological manifestation that is known to determine air entrapment in asthma patients. Research that combines clinical data with longitudinal intrapatient follow-up will be necessary to establish the strength of the evidence found in this study.
The Reduction of Catheter-Related Blood Stream Infections through the Implementation of an Interdisciplinary Healthcare Team

In December 2012, a multidisciplinary task force was implemented to address the elevated number of central line associated boodstream infections (CLABSIs) at Newark Beth Israel Medical Center from January 2012 to December 2012. Sixty-eight CLABSIs were documented within the adult inpatient population, resulting in a rate of 14.7 CLABSIs/1,000 central line days in the adult inpatient population. This was well above the national average of 1.87 infections per 1,000 central line days. Most of these infections were noted to be within the critical care units where the rate was at 2.86 CLABSIs/1,000 central line days. However, in 2013, the annual rate was decreased to 0.709 CLABSIs/1000 line days with similar trends observed across the critical care units. Analysis of CLASBI data indicates that the implementation of a multidisciplinary task force dedicated to appropriate central line insertion, maintenance, and the removal of unnecessary central venous catheters can have an impact on reducing rates of CLASBIs throughout the adult inpatient population, including those within critical care units.
Health Communication at the Centers for Disease Control and Prevention

Objective: To describe the diffusion of health communication in a federal agency over this past decade. Methods: Authors reviewed documents and interviewed staff. Results: CDC’s health communication agenda tools for diffusion and programmatic examples are described. Conclusions: Health communication at CDC is positioned as a means of influencing individual behaviors and environmental factors to reduce risks to health. Although virtually all CDC programs share scientific findings with the public comparatively few mount systematic health communication programs. This is due in part to health communication’s place within the epidemiological paradigm of CDC and in part to health promotion needs outstripping resources. (authors)
Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium‐Sensing Receptor‐Mediated Signaling

Abnormal feedback of serum calcium to parathyroid hormone (PTH) secretion is the hallmark of primary hyperparathyroidism (PHPT). Although the molecular pathogenesis of parathyroid neoplasia in PHPT has been linked to abnormal expression of genes involved in cell growth (e.g., cyclin D1, retinoblastoma, and β‐catenin), the molecular basis of abnormal calcium sensing by calcium‐sensing receptor (CaSR) and PTH hypersecretion in PHPT are incompletely understood. Through gene expression profiling, we discovered that an orphan adhesion G protein‐coupled receptor (GPCR), GPR64/ADGRG2, is expressed in human normal parathyroid glands and is overexpressed in parathyroid tumors from patients with PHPT. Using immunohistochemistry, Western blotting, and coimmunoprecipitation, we found that GPR64 is expressed on the cell surface of parathyroid cells, is overexpressed in parathyroid tumors, and physically interacts with the CaSR. By using reporter gene assay and GPCR second messenger readouts we identified Gαs, 3′,5′‐cyclic adenosine monophosphate (cAMP), protein kinase A, and cAMP response element binding protein (CREB) as the signaling cascade downstream of GPR64. Furthermore, we found that an N‐terminally truncated human GPR64 is constitutively active and a 15–amino acid–long peptide C‐terminal to the GPCR proteolysis site (GPS) of GPR64 activates this receptor. Functional characterization of GPR64 demonstrated its ability to increase PTH release from human parathyroid cells at a range of calcium concentrations. We discovered that the truncated constitutively active, but not the full‐length GPR64 physically interacts with CaSR and attenuates the CaSR‐mediated intracellular Ca2+ signaling and cAMP suppression in HEK293 cells. Our results indicate that GPR64 may be a physiologic regulator of PTH release that is dysregulated in parathyroid tumors, and suggest a role for GPR64 in pathologic calcium sensing in PHPT. © 2016 American Society for Bone and Mineral Research.
The Circadian Gene Clock Regulates Bone Formation Via PDIA3

The expression patterns of clock‐controlled genes (ccgs) are regulated by circadian rhythm, which is a major regulatory and physiological mechanism tied to the solar day. Disruptions in circadian rhythm contribute to the development of cardiovascular diseases, cancer, metabolic syndromes, and aging. It has been reported that bone remodeling is also regulated by circadian rhythm. However, the molecular mechanism by which the circadian gene Clock regulates bone remodeling has yet to be elucidated. Here, we show that Clock mutant mice exhibit a significant reduction in bone density as well as increased apoptosis. Protein disulfide isomerase family A member 3 (PDIA3) is a 1,25‐dihydroxy‐vitamin D3 [1α,25(OH)2D3] receptor that can regulate bone formation and apoptosis. Using luciferase and ChIP assays, we confirmed that Pdia3 is a ccg. Clock activates Pdia3 transcription by binding the E‐box promoter, and transcription is decreased in ClockΔ19 mutant mice. Forced expression of Pdia3 or of Clock completely rescues the osteogenic disorders found in the mutant background and inhibits apoptosis in vivo and in vitro. Furthermore, ablation of PDIA3 via RNA interference completely blocks the compensatory effect of forced expression of Clock in osteoblasts. Our results demonstrate that the core circadian gene Clock regulates bone formation via transcriptional control of 1,2,5(OH)2D3 receptor PDIA3. © 2016 American Society for Bone and Mineral Research.
Bone enhancement in digital dual energy radiographs from normalization with a synthetic background image

We have developed a method to enhance bone contrast in dual x-ray images. The method relies on the creation of a synthetic background image representing soft tissues and air in the image. The original image is normalized with this background image, thus enhancing bone contrast and eliminating soft tissues and air holes. The central idea of the method resides in the proper combination of information contained in equivalent aluminum and plastic thicknesses, calculated from well-known dual-energy algorithms.
Areal and volumetric bone mineral density and geometry at two levels of protein intake during caloric restriction: A randomized, controlled trial

Weight reduction induces bone loss by several factors, and the effect of higher protein (HP) intake during caloric restriction on bone mineral density (BMD) is not known. Previous study designs examining the longer‐term effects of HP diets have not controlled for total calcium intake between groups and have not examined the relationship between bone and endocrine changes. In this randomized, controlled study, we examined how BMD (areal and volumetric), turnover markers, and hormones [insulin‐like growth factor 1 (IGF‐1), IGF‐binding protein 3 (IGFBP‐3), 25‐hydroxyvitamin D, parathyroid hormone (PTH), and estradiol] respond to caloric restriction during a 1‐year trial using two levels of protein intake. Forty‐seven postmenopausal women (58.0 ± 4.4 years; body mass index of 32.1 ± 4.6 kg/m2) completed the 1‐year weight‐loss trial and were on a higher (HP, 24%, n = 26) or normal protein (NP, 18%, n = 21) and fat intake (28%) with controlled calcium intake of 1.2 g/d. After 1 year, subjects lost 7.0% ± 4.5% of body weight, and protein intake was 86 and 60 g/d in the HP and NP groups, respectively. HP compared with NP diet attenuated loss of BMD at the ultradistal radius, lumbar spine, and total hip and trabecular volumetric BMD and bone mineral content of the tibia. This is consistent with the higher final values of IGF‐1 and IGFBP‐3 and lower bone‐resorption marker (deoxypyridinoline) in the HP group than in the NP group (p < .05). These data show that a higher dietary protein during weight reduction increases serum IGF‐1 and attenuates total and trabecular bone loss at certain sites in postmenopausal women. © 2011 American Society for Bone and Mineral Research.