Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of NOD2 Mutations with Aggressive Periodontitis

Aggressive periodontitis (AgP) is characterized by rapid alveolar bone destruction and tooth loss early in life, and its etiology remains unclear. To explore the genetic risk factors of AgP, we performed genome-wide single-nucleotide polymorphism genotyping for identity-by-descent mapping and identified 32 distinct candidate loci, followed by whole exome sequencing with 2 pedigrees of AgP consisting of 3 cases and 1 control in 1 family and 2 sibling cases in the other. After variant filtering procedures and validation by targeted Sanger sequencing, we identified 2 missense mutations at 16q12 in NOD2 (p.Ala110Thr and p.Arg311Trp), which encodes nucleotide-binding oligomerization domain protein 2. We further examined 94 genetically unrelated AgP patients by targeted sequencing of NOD2 and found that 2 patients among them also carried the p.Arg311Trp variant. Furthermore, we found 3 additional missense mutations in this gene (p.His370Tyr, p.Arg459Cys, and p.Ala868Thr). These mutations either had not been previously observed or are extremely rare (frequency <0.001) in Asian populations. NOD2 plays a crucial role in innate immunity as an intracellular receptor initiating nuclear factor κB–dependent and mitogen-activated protein kinase–dependent gene transcription. These results demonstrated NOD2 as a novel gene involved in AgP.
ALLERGY DUE TO MENOTOXIN OF PREGNANCY

One hesitates to report a case of allergy due to human emanation, not only because the condition is so rare and to date experimentally unattainable, but because of the fact, recently reemphasized by Vaughan and Fowlkes,1that allergy due to cohabitation is usually traceable to a substance about the offending person other than human emanation. Encouraged by Cooper's2recent report of allergy to human semen, however, we wish to report here the occurrence of bronchial asthma in a child due to the menotoxin of the mother during her pregnancy and puerperium. Although the existence of menstrual toxin has been suspected and mentioned since Biblical times, the superstition was first put to scientific test by Dr. Bela Schick,3who in 1920 showed that freshly cut flowers held in the hand of a menstruating woman for from ten to thirty minutes on the first to the third day of
Identification of Osr2 Transcriptional Target Genes in Palate Development

Previous studies have identified the odd-skipped related 2 (Osr2) transcription factor as a key intrinsic regulator of palatal shelf growth and morphogenesis. However, little is known about the molecular program acting downstream of Osr2 in the regulation of palatogenesis. In this study, we isolated palatal mesenchyme cells from embryonic day 12.5 (E12.5) and E13.5 Osr2RFP/+ and Osr2RFP/- mutant mouse embryos and performed whole transcriptome RNA sequencing analyses. Differential expression analysis of the RNA sequencing datasets revealed that expression of 70 genes was upregulated and expression of 61 genes was downregulated by >1.5-fold at both E12.5 and E13.5 in the Osr2RFP/- palatal mesenchyme cells, in comparison with Osr2RFP/+ littermates. Gene ontology analysis revealed enrichment of signaling molecules and transcription factors crucial for skeletal development and osteoblast differentiation among those significantly upregulated in the Osr2 mutant palatal mesenchyme. Using quantitative real-time polymerase chain reaction (RT-PCR)and in situ hybridization assays, we validated that the Osr2-/- embryos exhibit significantly increased and expanded expression of many osteogenic pathway genes, including Bmp3, Bmp5, Bmp7, Mef2c, Sox6, and Sp7 in the developing palatal mesenchyme. Furthermore, we demonstrate that expression of Sema3a, Sema3d, and Sema3e, is ectopically activated in the developing palatal mesenchyme in Osr2-/- embryos. Through chromatin immunoprecipitation, followed by RT-PCR analysis, we demonstrate that endogenous Osr2 protein binds to the promoter regions of the Sema3a and Sema3d genes in the embryonic palatal mesenchyme. Moreover, Osr2 expression repressed the transcription from the Sema3a and Sema3d promoters in cotransfected cells. Since the Sema3 subfamily of signaling molecules plays diverse roles in the regulation of cell proliferation, migration, and differentiation, these data reveal a novel role for Osr2 in regulation of palatal morphogenesis through preventing aberrant activation of Sema3 signaling. Together, these data indicate that Osr2 controls multiple molecular pathways, including BMP and Sema3 signaling, in palate development.
Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice

Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves. We found that expression of Dkk2, encoding a secreted Wnt antagonist, is significantly increased whereas the levels of active β-catenin protein, the essential transcriptional coactivator of canonical Wnt signaling, is significantly decreased in the posterior regions of the palatal shelves in embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates. We show that small molecule–mediated inhibition of Dickkopf (DKK) activity in utero during palatal shelf morphogenesis partly rescued secondary palate development in Pax9-deficient embryos. Moreover, we found that genetic inactivation of Wise, which is expressed in the developing palatal shelves and encodes another secreted antagonist of canonical Wnt signaling, also rescued palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9del/del embryos exhibit defects in palatal shelf elevation/reorientation and significant reduction in accumulation of hyaluronic acid—a high molecular extracellular matrix glycosaminoglycan implicated in playing an important role in palatal shelf elevation—80% of Pax9del/del;Wise-/- double-mutant mouse embryos exhibit rescued palatal shelf elevation/reorientation, accompanied by restored hyaluronic acid accumulation in the palatal mesenchyme. Together, these data identify a crucial role for canonical Wnt signaling in acting downstream of Pax9 to regulate palate morphogenesis.
Submucosal Diclofenac for Acute Postoperative Pain in Third Molar Surgery: A Randomized, Controlled Clinical Trial

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) for relief of inflammatory pain. A recent formulation combines this drug with hydroxypropyl-β-cyclodextrin (HPβCD) to improve its solubility and to enable subcutaneous administration. Previous studies confirmed the efficacy of this combination. This study’s aim was to evaluate the efficacy, safety, and local tolerability of diclofenac HPβCD administered as a local submucosal injection prior to lower third molar surgery. We conducted a prospective, randomized, double-blind, placebo-controlled, parallel-group phase II single-center study. Seventy-five patients requiring mandibular third molar surgery were randomized into 1 of 5 groups: 5 mg/1 mL diclofenac HPβCD, 12.5 mg/1 mL diclofenac HPβCD, 25 mg/1 mL diclofenac HPβCD, 50 mg/1 mL diclofenac HPβCD, or 1 mL placebo. The respective study drug was injected into the mucosal tissue surrounding the surgical site prior to surgery following achievement of local anesthesia. The primary outcome measure was the area under the curve (AUC) of cumulative pain scores from end of surgery to 6 h postsurgery. This demonstrated a global treatment effect between the active groups and placebo, hence confirming the study drug’s efficacy (P = 0.0126). Secondary outcome measures included the time until onset of pain and the time until patients required rescue medication, both showing statistical significance of the study drug compared to placebo (P < 0.0161 and P < 0.0001, respectively). The time until rescue medication ranged between 7.8 h (for 25 mg/1 mL diclofenac HPβCD) and 16 h (for 50 mg/1 mL diclofenac HPβCD). Interestingly, the 5-mg/1-mL solution appeared superior to the 12.5-mg/1-mL and 25-mg/1-mL solutions (time until rescue medication = 12.44 h). A total of 14% of patients experienced minor adverse drug reactions (ADRs), of which 2 cases demonstrated flap necrosis. These resolved without further intervention. The study results overall indicate efficacy, safety, and relative tolerability of diclofenac HPβCD used locally as a submucosal injection prior to third molar surgery (ClinicalTrials.gov NCT01706588).
Appearance of Bony Bridging of the Hypoglossal Canal during the Fetal Period

Bony bridging of the hypoglossal canal was observed in 10% of 160 Japanese fetal crania. The incidence was slightly lower than that in any Japanese adult cranial series compared. The anatomical nature of the bridging in fetuses was substantially the same as that in adults. It was inferred that in the majority of cases the bridging trait makes its appearance during the fetal period. These findings were discussed from the anthropological point of view.
CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels

Summary Monocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16+ monocytes than controls (13.6% versus 11.4%; p<0.001). Logistic regression analysis including quartiles of CD14+CD16+ monocytes showed that CD14+CD16+ monocytes were associated with prevalence of CAD (OR 4.9, 95% CI 2.5–19.1, for subjects in the fourth quartile in comparison to subjects in the first quartile). The association between CD14+CD16+ monocytes and CAD remained independently significant after adjustment for most potential confounders (OR 5.0, 95% CI 1.2-20.0). Serum concentrations of TNF-α were elevated in subjects within the highest quartiles of CD14+CD16+ monocytes (p=0.018). Our study showed that increased numbers of CD14+CD16+ monocytes are associated with coronary atherosclerosis and TNF-α. In accordance, recent animal studies suggest a possibly important role of these monocytes in the development of atherosclerosis.
Meta-analysis of Trials Comparing β-Blockers, Calcium Antagonists, and Nitrates for Stable Angina

ContextWhich drug is most effective as a first-line treatment for stable angina is not known.ObjectiveTo compare the relative efficacy and tolerability of treatment with β-blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina.Data SourcesWe identified English-language studies published between 1966 and 1997 by searching the MEDLINE and EMBASE databases and reviewing the bibliographies of identified articles to locate additional relevant studies.Study SelectionRandomized or crossover studies comparing antianginal drugs from 2 or 3 different classes (β-blockers, calcium antagonists, and long-acting nitrates) lasting at least 1 week were reviewed. Studies were selected if they reported at least 1 of the following outcomes: cardiac death, myocardial infarction, study withdrawal due to adverse events, angina frequency, nitroglycerin use, or exercise duration. Ninety (63%) of 143 identified studies met the inclusion criteria.Data ExtractionTwo independent reviewers extracted data from selected articles, settling any differences by consensus. Outcome data were extracted a third time by 1 of the investigators. We combined results using odds ratios (ORs) for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration and type of drug (nifedipine vs nonnifedipine). Data SynthesisRates of cardiac death and myocardial infarction were not significantly different for treatment with β-blockers vs calcium antagonists (OR, 0.97; 95% confidence interval [CI], 0.67-1.38; P=.79). There were 0.31 (95% CI, 0.00-0.62; P=.05) fewer episodes of angina per week with β-blockers than with calcium antagonists. β-Blockers were discontinued because of adverse events less often than were calcium antagonists (OR, 0.72; 95% CI, 0.60-0.86; P<.001). The differences between β-blockers and calcium antagonists were most striking for nifedipine (OR for adverse events with β-blockers vs nifedipine, 0.60; 95% CI, 0.47-0.77). Too few trials compared nitrates with calcium antagonists or β-blockers to draw firm conclusions about relative efficacy. Conclusionsβ-Blockers provide similar clinical outcomes and are associated with fewer adverse events than calcium antagonists in randomized trials of patients who have stable angina.
Drinking, Socioemotional Functioning, and Academic Progress in Secondary School

Secondary schools are sites of academic instruction but also contexts of socioemotional development, and the intertwining of these two functions has consequences for adolescents’ future health and education. Drawing on nationally representative data from the National Longitudinal Study of Adolescent Health (n = 8,271), this study explored the bidirectional associations among indicators of adolescents’ alcohol use and their feelings of social integration at school. Socioemotional problems did not predict increased drinking over time, but drinking predicted declining socioemotional functioning, with negative implications for adolescents’ academic grades by the end of high school. These associations, however, were conditioned by aspects of school context, with drinkers feeling more marginalized in schools characterized by dense networks with low rates of drinking.
Generating Connected Textured Fractal Patterns Using Markov Random Fields

An algorithm that yields textured and connected binary fractals is presented. The texture is imposed by modelling the fractal as a Markov random field (MRF) at every resolution level. The model size and the parameters specify the texture. The generation starts at a coarser level and continues at finer levels. Connectivity, which is a global property, is maintained by restricting the flow of the sample generating Markov chain within a limited subset of all possible outcomes of the Markov random field. The texture is controlled by the parameters of the MRF model being used. Sample patterns are shown. >
Biometric Identification through Hand Geometry Measurements

A work in defining and implementing a biometric system based on hand geometry identification is presented here. Hand features are extracted from a color photograph taken when the user has placed his hand on a platform designed for such a task. Different pattern recognition techniques have been tested to be used in classification and/or verification from Euclidean distance to neural networks. Experimental results, up to a 97 percent rate of success in classification, will show the possibility of using this system in medium/high security environments with full acceptance from all users.
Least-Squares Estimation of Transformation Parameters Between Two Point Patterns

In many applications of computer vision, the following problem is encountered. Two point patterns (sets of points) (x/sub i/) and (x/sub i/); i=1, 2, . , n are given in m-dimensional space, and the similarity transformation parameters (rotation, translation, and scaling) that give the least mean squared error between these point patterns are needed. Recently, K.S. Arun et al. (1987) and B.K. P. Horn et al. (1987) presented a solution of this problem. Their solution, however, sometimes fails to give a correct rotation matrix and gives a reflection instead when the data is severely corrupted. The proposed theorem is a strict solution of the problem, and it always gives the correct transformation parameters even when the data is corrupted. >
What Does Self-rated Health Mean? Changes and Variations in the Association of Obesity with Objective and Subjective Components Of Self-rated Health

There are concerns about the meaning of self-rated health (SRH) and the factors individuals consider. To illustrate how SRH is contextualized, we examine how the obesity–SRH association varies across age, periods, and cohorts. We decompose SRH into subjective and objective components and use a mechanism-based age–period–cohort model approach with four decades (1970s to 2000s) and five birth cohorts of National Health and Nutrition Examination Survey data (N = 26,184). Obese adults rate their health more negatively than non-obese when using overall SRH with little variation by age, period, or cohort. However, when we decomposed SRH into objective and subjective components, the obesity gap widened with increasing age in objective SRH but narrowed in subjective SRH. Additionally, the gap narrowed for more recently born cohorts for objective SRH but widened for subjective SRH. The results provide indirect evidence that the relationship between obesity and SRH is socially patterned according to exposure to information about obesity and the availability of resources to manage it.
Review: Jordanian nurses’ perceptions of their roles toward the families of hospitalised critically ill patients

This paper presents an exploratory study which uses the survey approach to examine Jordanian nurses’ perceptions of their roles toward families of hospitalised critically ill patients. The relationship between nurses’ role expectations and perceived role performance toward these families is then explored. The paper is written as a research report which is appropriate for this type of study. The findings apply to critical care nurses but there are parallels which resonate with all providers of healthcare to patients. The clinical significance of examining this issue is well argued. The literature review highlights the evidence showing the importance of supporting the families of patients in the critical care environment, nurses’ roles in doing this and how good familial support can improve the experiences of patients’ relatives. However, there are barriers for nurses in providing good support and these are discussed. The aims of the study are justified as most previous studies were conducted in the UK, USA and Canada and little is known about Jordanian nurses’ perceptions and role performance. Themethodology is described in detail and ethical and consent issues are addressed. Nurses (n1⁄4 127) were surveyed from four different hospitals and potential bias was decreased as the researcher was not known to the nurses. Detail is given about data collection, the survey questionnaire and analysis methods. Correlational analysis was appropriate to examine the relationship between nurses’ perceptions of their role expectations and role performance. The main finding that, for Jordanian nurses, roles which required more time, emotion and communication skills were performed less than roles which required less time and emotional effort will resonate with many nurses. Some of the roles nurses expected to perform were rarely or never done as part of clinical practice.
FC14 First-line Dacarbazine (DTIC) plus Bevacizumab (B) combination therapy in advanced melanoma (MM) patients (pts): a phase II study

Background Advanced melanoma patients have a poor prognosis (median survival-time of < 9 months; 5-year survival-rate < 5%). Neither of the 2 FDA-approved agents for the treatment of stage IV melanoma [Dacarbazine (DTIC) and Interleukin-2 (IL-2)] has resulted in an improved overall-survival, but a modest increase in tumour response-rate. Single-agent DTIC showed average response-rate of 10% and median response-duration of 5–6 months, being poly-chemotherapy never proven as superior to mono-chemotherapy. To improve such sober results, different DTIC-combinations have been proposed. Several melanoma in vitro models showed a transcriptional up-regulation of Vascular Endothelial Growth-Factor (VEGF) by DTIC, suggesting the combination of DTIC/anti-VEGF therapy as an intriguing exploiting path.
Deconstructing Barriers

This phenomenological study investigated barriers to higher education faced by 11 college students labeled with learning disabilities (LD) using their voice as the primary data. Data were analyzed and interpreted through a disability theory perspective revealing barriers stemmed largely from external social causes rather than individual pathology. Barriers included being misunderstood by faculty, being reluctant to request accommodations for fear of invoking stigma, and having to work considerably longer hours than nonlabeled peers. Findings indicated barriers could be overcome through raising faculty awareness about LD issues, engaging the assistance of the college LD specialist, and participation in a LD democratic empowerment community on campus.
From home treatment to crisis resolution: the impact of national targets

Aims and method The home treatment service in central Manchester was established in 1997 to provide an alternative to in-patient care: referrals were only taken from secondary care services. In order to meet national crisis resolution and home treatment (CRHT) activity targets, referral routes were extended to primary care from 2008. To examine the impact of these changes, details of all referrals to the service were collected for a 6-month period in 2008/2009. Referral sources, demographic details and diagnosis were compared with similar data from 2005. Results There was a marked increase in the number of individuals accepted by the service in 2008/2009 with a corresponding reduction in duration of contact. Primary care referrals were not accepted in 2005 but accounted for 20% of people treated in 2008/2009. This was mirrored by a change in diagnostic profile, with the proportion of individuals with mild to moderate illness increasing from 25 to 50%. In 2005, 70% of individuals treated had complex care needs compared with 39% in 2008/2009. Clinical implications The strict imposition of numerical activity targets can have a significant impact on service delivery. Although more individuals have been treated under the new arrangements, the emphasis has shifted away from the intensive care of those with severe mental illness.