Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrafibrillar Collagen Mineralization Produced by Biomimetic Hierarchical Nanoapatite Assembly

Biomineralization templated by non-collagenous proteins is an example how nature uses nanotechnology to strengthen the load-bearing skeletons of vertebrates. [1–3] Mineralized collagen fibrils are responsible for the second level of hierarchy of bone structure[4] and account for its strength and toughness. [5] Calcium-deficient apatites are deposited in nanocrystalline form at the intrafibrillar and extrafibrillar spaces associated with the collagen fibrillar assembly. [6] Regulation of calcium phosphate phases during biomineralization is believed to exhibit two major characteristics. [7–9] The first is the sequestration of the calcium and phosphate ions into nanoscopic entities known as amorphous calcium phosphate (ACP). The second is the templating of mineral nucleation and growth through noncollagenous extracellular matrix proteins. These protein molecules contain polyanionic domains that are rich in polycarboxylic acid and phosphate function groups that bind to the collagen substrates at specific sites such as the gap zones of the collagen molecular assembly. [1,10] The immobilized proteins contain anionic charge sites wherein calcium binding and apatite nucleation occur at the aforementioned intrafibrillar locations. As a highly ordered manner of intrafibrillar mineralization at the nanoscale is responsible for the biomechanical properties of mineralized collagen,[11] this intricate biological process has inspired scientists to mimic its mechanism for creating mineralized type I collagen scaffolds to repair existing bone defects and/or generate new bone. Here, we demonstrate that the use of two phosphate-based templating analogs of matrix proteins in the presence of a polycarboxylic acid sequestration analog of ACPs results in a highly ordered intrafibrillar nanoapatite assembly that recapitulates the gap and overlap arrangement of collagen molecules within a collagen fibril. Adoption of a dual analog biomimetic strategy provides a means to produce advanced mineralized collagen scaffolds for tissue engineering applications.
Tardive dyskinesia and other movement disorders secondary to aripiprazole

The objective of this report is to draw attention to tardive dyskinesia (TD) caused by aripiprazole, a third generation antipsychotic. TD has been traditionally attributed to typical (first‐generation) antipsychotics, but other dopamine receptor blocking drugs and atypical (second‐ and third‐generation) neuroleptics are emerging as an important cause of TD. We reviewed the medical records of patients with TD seen at the Baylor College of Medicine Movement Disorders Clinic between 2002 and 2010 to identify patients with TD associated with aripiprazole. Among 236 patients with TD seen over the specified period, 8 (3.4%) were found to have aripiprazole‐associated TD. In 5 patients, TD occurred after exclusive exposure to aripiprazole. The mean age at onset was 55.8 ± 14.8 years with a female predominance. The average duration of treatment with aripiprazole was 18.4 ± 26.4 months. Oro‐bucco‐lingual stereotypy was seen in all patients. In most patients, TD did not spontaneously improve after stopping aripiprazole. Of the 5 patients treated with tetrabenazine, 4 improved during follow‐up. Although aripiprazole, a third generation antipsychotic, has been promoted to have a low risk of TD, the drug accounts for about 3.5% of patients with TD evaluated in a movement disorders clinic. This largest reported series draws attention to the growing incidence of TD and other drug‐induced movement disorders associated with “atypical antipsychotics. ” © 2010 Movement Disorder Society
Novel Evolutionary-conserved Role for the Activity-dependent Neuroprotective Protein (ADNP) Family That Is Important for Erythropoiesis*

Background: ADNP is vital for embryonic development. Is this function conserved for the homologous protein ADNP2? Results: Down-regulation/silencing of ADNP or ADNP2 in zebrafish embryos or mouse erythroleukemia cells inhibited erythroid maturation, with ADNP directly associating with the β-globin locus control region. Conclusion: ADNPs are novel molecular regulators of erythropoiesis. Significance: New regulators of globin synthesis are suggested. Activity-dependent neuroprotective protein (ADNP) and its homologue ADNP2 belong to a homeodomain, the zinc finger-containing protein family. ADNP is essential for mouse embryonic brain formation. ADNP2 is associated with cell survival, but its role in embryogenesis has not been evaluated. Here, we describe the use of the zebrafish model to elucidate the developmental roles of ADNP and ADNP2. Although we expected brain defects, we were astonished to discover that the knockdown zebrafish embryos were actually lacking blood and suffered from defective hemoglobin production. Evolutionary conservation was established using mouse erythroleukemia (MEL) cells, a well studied erythropoiesis model, in which silencing of ADNP or ADNP2 produced similar results as in zebrafish. Exogenous RNA encoding ADNP/ADNP2 rescued the MEL cell undifferentiated state, demonstrating phenotype specificity. Brg1, an ADNP-interacting chromatin-remodeling protein involved in erythropoiesis through regulation of the globin locus, was shown here to interact also with ADNP2. Furthermore, chromatin immunoprecipitation revealed recruitment of ADNP, similar to Brg1, to the mouse β-globin locus control region in MEL cells. This recruitment was apparently diminished upon dimethyl sulfoxide (DMSO)-induced erythrocyte differentiation compared with the nondifferentiated state. Importantly, exogenous RNA encoding ADNP/ADNP2 significantly increased β-globin expression in MEL cells in the absence of any other differentiation factors. Taken together, our results reveal an ancestral role for the ADNP protein family in maturation and differentiation of the erythroid lineage, associated with direct regulation of β-globin expression.
Altered Peptidase Activities in Thyroid Neoplasia and Hyperplasia

Background. Papillary thyroid carcinoma (PTC), follicular thyroid adenoma (FTA), and thyroid nodular hyperplasia (TNH) are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26) in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. Methods. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. Results. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP), alanyl aminopeptidase (AlaAP), prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. Conclusions. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.
Partition Bound Is Quadratically Tight for Product Distributions

Let f: {0,1}^n*{0,1}^n -> {0,1} be a 2-party function. For every product distribution mu on {0,1}^n*{0,1}^n, we show that CC^{mu}_{0.49}(f) = O(log(prt_{1/8}(f))*log(log(prt_{1/8}(f)))^2), where CC^{mu}_{epsilon}(f) is the distributional communication complexity of f with error at most epsilon under the distribution mu and prt_{1/8}(f) is the partition bound of f, as defined by Jain and Klauck [Proc. 25th CCC, 2010]. We also prove a similar bound in terms of IC_{1/8}(f), the information complexity of f, namely, CC^{mu}_{0.49}(f) = O((IC_{1/8}(f)*log(IC_{1/8}(f)))^2). The latter bound was recently and independently established by Kol [Proc. 48th STOC, 2016] using a different technique. We show a similar result for query complexity under product distributions. Let g: {0,1}^n -> {0,1} be a function. For every bit-wise product distribution mu on {0,1}^n, we show that QC^{mu}_{0.49}(g) = O((log(qprt_{1/8}(g))*log(log(qprt_{1/8}(g))))^2), where QC^{mu}_{epsilon}(g) is the distributional query complexity of f with error at most epsilon under the distribution mu and qprt_{1/8}(g) is the query partition bound of the function g. Partition bounds were introduced (in both communication complexity and query complexity models) to provide LP-based lower bounds for randomized communication complexity and randomized query complexity. Our results demonstrate that these lower bounds are polynomially tight for product distributions.
Discovery of a New Low-Latitude Milky Way Globular Cluster Using GLIMPSE

Spitzer Space Telescope imaging from the Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE) reveals a previously unidentified low-latitude rich star cluster near l = 31. °3, b = -0. °1. Near-infrared JHK′ photometry from the Wyoming Infrared Observatory indicates an extinction of AV ≃ 15 ± 3 mag for cluster members. Analysis of 13CO features along the same sight line suggests a probable kinematic distance of 3.1–5.2 kpc. The new cluster has an angular diameter of ∼1–2 pc, a total magnitude corrected for extinction of m = 2.1, and a luminosity of MK ≃ -10.3 at 3.1 kpc. In contrast to young massive Galactic clusters with ages less than 100 Myr, the new cluster has no significant radio emission. Comparison with theoretical K-band luminosity functions indicates an age of at least several gigayears and a mass of at least 105 M⊙. Unlike known old open clusters, this new cluster lies in the inner Galaxy at RGC ≃ 6.1 kpc. We designate this object "GLIMPSE-C01" and present evidence that it is a Milky Way globular cluster passing through the Galactic disk. We also identify a region of star formation and fan-shaped outflows from young stellar objects in the same field as the cluster. The cluster's passage through the Galactic molecular layer may have triggered this star formation activity.
The wounded healer.

This paper deals with the emergence, elaboration, and use of the concept of "the wounded healer. " The term refers to a person whose personal experience of illness and/or trauma has left lingering effects on him--in the form of lessons learned that later served him in ministering to other sufferers, or in the form of symptoms or characteristics that usefully influenced his therapeutic endeavors. While such persons and their actions have been noted across the ages, in other cultures, and in many contexts, it was not until the early twentieth century that the patterns in the behaviors of such persons were recognized, named, explained, and categorized as "healing. " Early in the century, the concept was commonly used in the fields of pastoral counseling and analytical psychology; by the end of the century it had been vastly expanded and extended and no longer referred mainly to a healer of psychological suffering. The term wounded healer is now in common use in areas such as rehabilitation medicine, medical-career choice, Alcoholics Anonymous and the self-help movement, and chronic-illness support groups, as well as in the original areas of psychotherapy and pastoral care.
Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy

Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin–kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies.
Volatile oil of Artemisia santolina decreased morphine withdrawal jumping in mice

Introduction: Flowered aerial parts of Artemisia santolina Schrenk (Asteraceae), which is found in the central and western regions of Iran were collected from Khorasan province and the volatile oil extracted by hydro distillation. Materials and Methods: The oil (0.5% v/w) was analyzed by GC and GC/MS using DB-5 column. The effect of this oil on the withdrawal syndrome was determined in mice. After induction of dependency by morphine, mice were intraperitoneally administered different concentrations of the oil. Morphine-withdrawal inducing by naloxone was assessed by recording the incidence of escape jumps for 60 min. Results: The results indicated that a significant difference between the essential oil received group (at dose of 3.6 mg/kg) and control group was shown but the lower doses were not effective. Essential oil analysis showed that there were forty-six components, representing 95.4% of the oil. Conclusion: The oil of A. santolina which is rich in oxygenated monoterpenes with the major components, trans-verbenol (34.6%) and p-mentha3-en-8-ol (13.1%), can decreased the number of withdrawal jumping in addicted mice.
Vancomycin dosage in overweight and obese children.

PURPOSE Vancomycin dosages in overweight and obese children were evaluated. METHODS This retrospective study evaluated data for children who were age 2-17 years, received i.v. vancomycin, and were admitted to a children's hospital from September 1, 2007, through October 31, 2009. Patients were then stratified into two groups: normal-weight patients and overweight or obese patients. The primary objective was to compare the number of vancomycin regimens between groups with a trough concentration of 5-15 μg/mL. Secondary objectives included a comparison of dosage changes and toxicities. Multivariate, conditional logistic regression was performed to assess the relationship between attaining optimal vancomycin concentrations (5-15 μg/mL) and independent variables. RESULTS Data were collected for 232 courses of vancomycin, representing 187 patients. The mean ± S.D. initial dose for the normal-weight and overweight or obese groups differed significantly (461.3 ± 303.1 mg and 658.4 ± 389.6 mg, respectively; p < 0.01); the milligram-per-kilogram initial vancomycin dose did not. The multivariate analysis revealed that every-eight-hour regimens had increased odds of achieving therapeutic concentrations (p < 0.001), while obese children had decreased odds of achieving therapeutic concentrations (p = 0.037). CONCLUSION A study of prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses (in milligrams per kilogram) given to normal-weight children compared with overweight or obese children. Regimens using every-eight-hour dosing were significantly more likely than other regimens to result in a vancomycin trough concentration of 5-15 μg/mL, and regimens for obese children, compared with regimens for nonobese children, were less likely to produce trough concentrations in the same range of 5-15 μg/mL.
Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing

Abstract Aim: To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship. Methods: Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses. Results: A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B, HNF1A, PDX1, and BLK mutations in the others. We identified five novel missense mutations – three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic. Conclusion: The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.
The use of Straumann Bone Ceramic in a maxillary sinus floor elevation procedure: a clinical, radiological, histological and histomorphometric evaluation with a 6-month healing period.

OBJECTIVES In this study, we evaluated the quality and quantity of bone formation in maxillary sinus floor elevation procedure using a new fully synthetic biphasic calcium phosphate (BCP) consisting of a mixture of 60% hydroxyapatite and 40% of beta-tricalcium phosphate (Straumann Bone Ceramic). MATERIAL AND METHODS A unilateral maxillary sinus floor elevation procedure was performed in six patients using 100% BCP. Biopsy retrieval for histological and histomorphometric analysis was carried out before implant placement after a 6-month healing period. RESULTS In this study, the maxillary sinus floor elevation procedure with the use of BCP showed uneventful healing. Radiological evaluation after 6 months showed maintenance of vertical height gained immediately after surgery. Primary stability was achieved with all Straumann SLA dental implants of 4.1 mm diameter and 10 or 12 mm length. The implants appeared to be osseointegrated well after a 3-month healing period. Histological investigation showed no signs of inflammation. Cranial from the native alveolar bone, newly formed mineralized tissue was observed. Also, osteoid islands as well as connective tissue were seen around the BCP particles, cranial from the front of newly formed mineralized tissue. Close bone-to-substitute contact was observed. Histomorphometric analysis showed an average bone volume/total volume (BV/TV) of 27.3% [standard deviation (SD) 4.9], bone surface/total volume (BS/TV) 4.5 mm(2)/mm(3) (SD 1.1), trabecula-thickness (TbTh) 132.1 mum (SD 38.4), osteoid-volume/bone volume (OV/BV) 7.5% (SD 4.3), osteoid surface/bone surface (OS/BS) 41.3% (SD 28.5), osteoid thickness (O.Th) 13.3 mum (SD 4.7) and number of osteoclasts/total area (N.Oc/Tar) 4.4 1/mm (SD 5.7). CONCLUSIONS Although a small number of patients were treated, this study provides radiological and histological evidence in humans confirming the suitability of this new BCP for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 6-month healing period. The newly formed bone had a trabecular structure and was in intimate contact with the substitute material, outlining the osteoconductive properties of the BCP material. Bone maturation was evident by the presence of lamellar bone.
Resting‐state functional connectivity of the human hypothalamus

The hypothalamus is of enormous importance for multiple bodily functions such as energy homeostasis. Especially, rodent studies have greatly contributed to our understanding how specific hypothalamic subregions integrate peripheral and central signals into the brain to control food intake. In humans, however, the neural circuitry of the hypothalamus, with its different subregions, has not been delineated. Hence, the aim of this study was to map the hypothalamus network using resting‐state functional connectivity (FC) analyses from the medial hypothalamus (MH) and lateral hypothalamus (LH) in healthy normal‐weight adults (n = 49). Furthermore, in a separate sample, we examined differences within the LH and MH networks between healthy normal‐weight (n = 25) versus overweight/obese adults (n = 23). FC patterns from the LH and MH revealed significant connections to the striatum, thalamus, brainstem, orbitofrontal cortex, middle and posterior cingulum and temporal brain regions. However, our analysis revealed subtler distinctions within hypothalamic subregions. The LH was functionally stronger connected to the dorsal striatum, anterior cingulum, and frontal operculum, while the MH showed stronger functional connections to the nucleus accumbens and medial orbitofrontal cortex. Furthermore, overweight/obese participants revealed heightened FC in the orbitofrontal cortex and nucleus accumbens within the MH network. Our results indicate that the MH and LH network are tapped into different parts of the dopaminergic circuitry of the brain, potentially modulating food reward based on the functional connections to the ventral and dorsal striatum, respectively. In obese adults, FC changes were observed in the MH network. Hum Brain Mapp 35:6088–6096, 2014. © 2014 Wiley Periodicals, Inc.
“Coming out” as an alcoholic: how former problem drinkers negotiate disclosure of their nondrinking identity

Abstract Although communication is critical for former problem drinkers to reject drinks, socialize with others, minimize stigma, and maintain their health and sobriety, recovering alcoholics’ communication has not been examined beyond alcohol self-help groups. Using a Communication Privacy Management framework and in-depth, semistructured interviews, this study examined how former problem drinkers negotiate the disclosure of their nondrinking status. As participants perceived not drinking in the United States as deviant and socially risky, the investigation found participants primarily concealed their nondrinking status in order to fit in. Participants enacted specific communicative behaviors to regulate their privacy boundaries, only disclosing their struggles with alcohol when benefits outweighed costs (e.g., inspiring others, maintaining sobriety, or building relationships). This study offers practical disclosure strategies for former problem drinkers to protect their private information, manage social interactions, and stay sober.
Cyclic behavior of reinforced concrete haunched beams failing in shear

This paper presents the research results about the testing of ten prototype reinforced concrete haunched beams subjected to cyclic loading. Beams were designed to present shear failure. Two groups of beams were tested: a) beams without shear reinforcement, and b) beams with minimum shear reinforcement. The cyclic testing allowed to fully validating a previous proposed equation to estimate the shear strength of reinforced concrete haunched beams. From the obtained results, it can be observed that haunched beams have a different shear behavior with respect to prismatic beams, having higher deformation and energy dissipation capacities, among other reasons, because nonprismatic beams exhibit an arching action along the haunched length as the main resisting mechanism, that favors smoother cracking patterns.