Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic regulation of the imprinted U2af1‐rs1 gene during retinoic acid‐induced differentiation of embryonic stem cells

Epigenetic modifications such as DNA methylation and changes in chromatin structure are changes in the chemical composition or structure of DNA that work by regulating gene expression. Their mechanisms of action have been generally studied in imprinted genes. The present work analyzes the involvement of these mechanisms in the expression of the U2af1‐rs1 imprinted gene during the differentiation process of embryonic stem (ES) cells induced by retinoic acid. By DNA digestion with methylation‐dependent or independent restriction enzymes and consecutive Southern blot, we have found that methylation of the U2af1‐rs1 gene increases in differentiated ES cells and in embryoid bodies. However, northern blot and real‐time reverse transcription–polymerase chain reaction analysis showed a higher expression of the U2af1‐rs1 gene in differentiated ES cells and in embryoid bodies than in undifferentiated ones. On the other hand, the sensitivity to DNase‐I assay demonstrated an open chromatin conformation for differentiated cells with regard to undifferentiated ES cells. Our results suggest that the expression of the U2af1‐rs1 gene would be regulated by changes in chromatin structure rather than by DNA methylation during the RA‐induced process of differentiation of ES cells.
Availability of and attitudes toward resources on alternative medicine products in the community pharmacy setting.

OBJECTIVE To examine the availability of resources on dietary supplements in the community pharmacy setting and to assess the attitudes of community pharmacists toward these resources. DESIGN Cross-sectional study. SETTING Community pharmacies in New York and New Jersey that serve as experiential sites for senior student pharmacists at the Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University. PARTICIPANTS Preceptors or full-time pharmacists. INTERVENTION Mailed survey. MAIN OUTCOME MEASURES Frequency of use, availability of, and pharmacists' satisfaction with resources on alternative medicines, defined in the survey as any product including herbal remedies, vitamins, minerals, and natural products that may be purchased at a health food store, pharmacy, supermarket, alternative medicine store/magazine for the purpose of self-treatment. RESULTS A total of 64 pharmacists characterized their frequency of use of resources on alternative medicines while formulating responses to questions as: never (n = 5; 7.8%), seldom (n = 31; 48.4%), often (n = 24; 37.5%), or always (n = 4; 6.3%). A total of 30 different resources were available to 40 respondents. The most commonly available resources were the PDR for Herbal Medicines (42.5%), The Review of Natural Products (20.0%), and the Web site of the National Center for Complementary and Alternative Medicine (12.5%). Of 54 respondents, 4 (7.1%) reported being completely dissatisfied with the available resources; 17 (31.5%) were somewhat dissatisfied; 25 (46.3%) were somewhat satisfied; and 8 (14.8%) were completely satisfied with the resources available to them. Topics the pharmacists most commonly wanted to see improved included safety (72.7%), interactions (70.9%), and uses (69.1%). CONCLUSION Community pharmacists do not use information resources on alternative medicine products frequently, and many are not satisfied with the resources available to them.
Metacarpophalangeal Joint Arthroplasty with a Metallic Hinged Prosthesis

A long-term clinical study of 41 Flatt metallic hinged prostheses inserted in the metacarpopha-langeal joints of ten rheumatoid patients was completed to provide a historic and clinical perspective of the ongoing clinical performance of this prosthesis. Postsurgical analysis performed an average of 138 months after operation demonstrated an average active range of metacarpophalangeal joint motion of 24°, with average maximum active extension of 16° and flexion of 40°. Motion through this device in the metacarpophalangeal joint was relatively well preserved with time and was within a functional range. Recurrent digital ulnar deviation was observed in 58% of patients, digital malrotation in 50%, and extensor tendon redislocation in 45%. The prosthesis failed by screw or prong failure (47%). Periprosthetic radiolucency was common (87%), indicating poor host bone tolerance. With net bone resorption the prosthesis migrated, often perforating the cortex of the metacarpal (44%) or proximal phalanx (59%). Patient satisfaction, despite suboptimal clinical results, was high. All patients considered the appearance of the operated hand and pain relief improved. These advantages must be considered relative to the disadvantages of recurrent digital deformity, poor host tolerance, and unpredictability of clinical results.
Dorsal retinal pigment epithelium differentiates as neural retina in the microphthalmia (mi/mi) mouse.

PURPOSE Microphthalmia, a bHLH-zip transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigment epithelial (RPE) compartment during optic vesicle and optic cup development. To determine a role for microphthalmia (mi) during eye development, the effects of an mi loss of function mutation on RPE and neural retinal were investigated in the mi/mi mouse. METHODS A series of embryonic and postnatal mi/mi and wild-type eyes were sectioned and labeled with neural retina- and RPE cell type-specific antibodies. Photoreceptor loss was quantified by counting the number of photoreceptor nuclei spanning the outer nuclear layer throughout postnatal retinal development. RESULTS Early neural retinal differentiation is not affected in the mi/mi mouse. The mi/mi ventral retinal pigment epithelial layer begins to develop normally, but does not pigment or attain a differentiated cuboidal morphology. The dorsal region of mi/mi retinal pigment epithelium expands and forms an ectopic retina, which develops all major retinal cell types along a similar time course as the wild type. After birth, mi/mi photoreceptors begin to form rosettes, outer segments fail to elongate, and over an extended time period, the retina degenerates. CONCLUSIONS Together these results suggest that early retinal development can proceed normally in the mi/mi mutant, but later retinal histogenesis is dependent on the presence of a differentiated retinal pigment epithelium. Most importantly, loss of mi function permits a change in cell fate from RPE to retina in the dorsal eye.
Macroeconomic Risk and Idiosyncratic Risk-Taking

We develop and estimate a dynamic model of risk-shifting over the business cycle. First, equity holders with Epstein-Zin preferences increase their taking of idiosyncratic risk substantially more than the standard model in repeated games, because they perceive the arrival probability of bad states to be higher than the actual probability and prefer an early resolution of macroeconomic uncertainty. Second, sudden switches to bad states and large shocks in the bad states induce the countercyclical and “synchronized” idiosyncratic risk. Third, combined with the high market risk premium in the bad states, clustered risk-taking generates a countercyclical idiosyncratic volatility discount on equity returns.Received July 1, 2017; editorial decision January 22, 2018 by Editor Stijn Van Nieuwerburgh. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Functional neuroimaging correlates of thinking flexibility and knowledge structure in memory: Exploring the relationships between clinical reasoning and diagnostic thinking

Abstract Background: Diagnostic reasoning involves the thinking steps up to and including arrival at a diagnosis. Dual process theory posits that a physician’s thinking is based on both non-analytic or fast, subconscious thinking and analytic thinking that is slower, more conscious, effortful and characterized by comparing and contrasting alternatives. Expertise in clinical reasoning may relate to the two dimensions measured by the diagnostic thinking inventory (DTI): memory structure and flexibility in thinking. Aim: Explored the functional magnetic resonance imaging (fMRI) correlates of these two aspects of the DTI: memory structure and flexibility of thinking. Methods: Participants answered and reflected upon multiple-choice questions (MCQs) during fMRI. A DTI was completed shortly after the scan. The brain processes associated with the two dimensions of the DTI were correlated with fMRI phases – assessing flexibility in thinking during analytical clinical reasoning, memory structure during non-analytical clinical reasoning and the total DTI during both non-analytical and analytical reasoning in experienced physicians. Results: Each DTI component was associated with distinct functional neuroanatomic activation patterns, particularly in the prefrontal cortex. Conclusion: Our findings support diagnostic thinking conceptual models and indicate mechanisms through which cognitive demands may induce functional adaptation within the prefrontal cortex. This provides additional objective validity evidence for the use of the DTI in medical education and practice settings.
Dynamic Status Effects, Savings, and Income Inequality

This article advances the hypothesis that the intensity of status preferences depends negatively on the average wealth of society (endogenous dynamic status effect), in accordance with empirical evidence. Our theory replicates the contradictory historical facts of an increasing saving rate along with declining returns to capital over time. By affecting the dynamics of the saving rate, the dynamic status effect raises inequality, thereby providing a behavioral mechanism for the observed diverse dynamics of income inequality across countries. In countries in which the dynamic status effect is strong (weak), inequality rises (declines) over time in response to a positive productivity shock.
Survival signaling and terminal differentiation in cholesteatoma epithelium

Conclusion: There is a strong indication that epithelial keratinocytes in cholesteatoma are protected against apoptosis. The late terminal differentiation program in cholesteatoma epithelium is disturbed. Objectives: Previously, minimal apoptosis has been demonstrated in cholesteatoma epithelium. The phosphoinositide 3-kinase/Akt/protein kinase B (PI3K/Akt/PKB) and the mitogen activated protein kinases (MAPK) signaling transduction pathways have been reported to protect epithelial cells against apoptosis. Both pathways have also been proven to regulate late terminal differentiation of keratinocytes. In cholesteatoma epithelium, MAPK activation has been shown to be associated with terminal differentiation. The purpose of this study was to investigate whether in human cholesteatoma epithelium protection against programmed cell death by means of PI3K/Akt survival signaling is present and associated with MAPK activation and terminal differentiation. Materials and methods: Fifteen human cholesteatoma and patient-matched retro-auricular skin samples were immunohistochemically stained for pAkt/PKB, phosphorylated extracellular regulated kinase1/2 (pERK1/2), phosphorylated JNK/SAPK, phosphorylated p38, involucrin and filaggrin. Positive cells were counted by computer-assisted digital image analysis. Results: Protein expressions of pAkt/PKB, pERK1/2, pp38, and involucrin in cholesteatoma epithelium were significantly increased when compared with retro-auricular skin (p<0.01). Filaggrin expression was significantly decreased (p=0.03). The positive correlation was confirmed between both pERK1/2 and pp38, and involucrin (p≤0.05).
A Revision of What Life Cycle Sustainability Assessment Should Entail: Towards Modeling the Net Impact on Human Well‐Being

The main goal of a sustainability assessment is to evaluate the impact of systems (e.g., human or natural ones) on areas sought to be protected and maintained over time (e.g., human well‐being, ecosystems, etc.). These are called areas of protection (AoPs). Life cycle sustainability assessment is a type of sustainability assessment that focuses on the impact of industrial production systems on AoPs. To further this field, three conceptual challenges should be tackled: (1) framing which areas should primarily be sustained and hence on which the impact should be assessed, that is, (re)defining of the AoPs; (2) accounting for the interconnectedness among AoPs (e.g., influence of ecosystems on human well‐being); and (3) the assessment of both benefit and damage to the AoPs (e.g., benefit of industrial products and damage of their production). The aim of this study is to provide a first roadmap to address these three issues and to suggest potential solutions. Regarding the first issue, our conclusion is that human well‐being, encompassing health and happiness, is the primary AoP. This is based on the argument that the sustainability concept is inherently anthropocentric. In this regard, other entities such as ecosystems as a whole are sustained in light of human well‐being. The well‐being adjusted life years, interpreted as years of perfect well‐being, is pinpointed as the most promising holistic indicator. To conduct a respective sustainability assessment that tackles the remaining two issues—integrated system modeling of the earth and its support to well‐being—is argued as the most suitable approach.
The Effect of a T Cell-Specific NF-κB Inhibitor on In Vitro Cytokine Production and Collagen-Induced Arthritis1

NF-κB plays a key role in the production of cytokines in inflammatory diseases. The effects of a novel T cell-specific NF-κB inhibitor, SP100030, were evaluated in cultured Jurkat cells and in murine collagen-induced arthritis (CIA). Chemical libraries were screened for NF-κB-inhibitory activity. SP100030, a compound identified in this process, inhibited NF-κB activation in PMA/PHA-activated Jurkat cells by EMSA at a concentration of 1 μM. Jurkat cells and the monocytic cell line THP-1 were transfected with an NF-κB promotor/luciferase construct and activated. SP100030 inhibited luciferase production in the Jurkat cells (IC50 = 30 nM). ELISA and RT-PCR confirmed that IL-2, IL-8, and TNF-α production by activated Jurkat and other T cell lines were inhibited by SP100030. However, cytokine expression was not blocked by the compound in THP-1 cells, fibroblasts, endothelial cells, or epithelial cells. Subsequently, DBA/1J mice were immunized with type II collagen. Treatment with SP100030 (10 mg/kg/day i.p. beginning on day 21) significantly decreased arthritis severity from onset of clinical signs to the end of the study on day 34 (arthritis score, 5.6 ± 1.7 for SP100030 and 9.8 ± 1.5 for control; p < 0.001). Histologic evaluation demonstrated a trend toward improvement in SP100030-treated animals. EMSA of arthritic mouse ankles in CIA showed that synovial NF-κB binding was suppressed in the SP100030-treated mice. SP100030 inhibits NF-κB activation in T cells, resulting in reduced NF-κB-regulated gene expression and decreased CIA. Its selectivity for T cells could provide potent immunosuppression with less toxicity than other NF-κB inhibitors.
The effect of osteotomy dimension on osseointegration to resorbable media-treated implants: A study in the sheep

The drilling technique and the surface characteristics are known to influence the healing times of oral implants. The influence of osteotomy dimension on osseointegration of microroughned implant surfaces treated with resorbable blasting media was tested in an in vivo model. Ninety-six implants (ø4.5 mm, 8 mm in length) with resorbable blasting media-treated surfaces were placed in the ileum of six sheep. The final osteotomy diameters were 4.6 mm (reamer), 4.1 mm (loose), 3.7 mm (medium), and 3.2 mm (tight). After three and six weeks of healing, the implants were biomechanically tested and histologically evaluated. Statistical analysis was performed using Page L trend test for ordered and paired sample and linear regression, with significance level at p < 0.05. An overall increase in all dependent variables was observed with the reduction of osteotomy diameter. In addition, all osseointegration scores increased over time. At three weeks, the retention was significantly higher for smaller osteotomies. The histological sections depicted intimate contact of bone with all the implant surfaces and osteoblast lines were visible in all sections. The resorbable blasting media microroughed surfaces achieved successful osseointegration for all the instrumentation procedures tested, with higher osseointegration scores for the high insertion torque group.
KIAA0495/PDAM Is Frequently Downregulated in Oligodendroglial Tumors and Its Knockdown by siRNA Induces Cisplatin Resistance in Glioma Cells

Co‐deletion of chromosomes 1p and 19q is a common event in oligodendroglial tumors (OTs), suggesting the presence of OT‐related genes. The aim of this study was to identify the target genes residing in the minimally deleted regions on chromosome 1p36.31–p36.32 that might be involved in OTs. A novel gene KIAA0495/p53‐dependent apoptosis modulator (PDAM) was found frequently deregulated, with 37 of 58 (63.8%) OTs examined showing reduced expression compared with normal brain. Chromosome 1p loss and epigenetic modifications were the major mechanisms contributing to PDAM downregulation. The role of PDAM in chemosensitivity was also evaluated. PDAM knockdown had no effect on sensitivity to vincristine, lomustine, temozolomide and paclitaxel, but could induce cisplatin resistance in glioma cells harboring wild‐type p53. B‐cell CCL/lymphoma 2 (BCL2)‐like 1 (BCL2L1) exhibited significant upregulation, while BCL2 showed partial derepression in PDAM‐silenced cells after cisplatin treatment, suggesting that alteration of anti‐apoptotic genes contributed in part to cisplatin resistance. Knockdown of BCL2L1 abrogated the induced cisplatin‐resistant phenotype. Moreover, our data suggested that PDAM might function as a non‐protein‐coding RNA. Collectively, these findings suggest that PDAM deregulation may play a role in OT development and that PDAM may possess the capacity to modulate apoptosis via regulation of p53‐dependent anti‐apoptotic genes.
The presence of post-traumatic stress disorder symptoms in adolescents three months after an 8·0 magnitude earthquake in southwest China.

AIMS AND OBJECTIVES The aims of the study were to describe the post-traumatic stress disorder symptoms in adolescent survivors three months after Wenchuan 5·12 Earthquake and to explore its contributing or preventing factors. BACKGROUND Adolescents are more vulnerable to be affected by natural disasters because of their special growth stage. Post-traumatic stress disorder symptoms are common responses in adolescents after disasters, and its occurrence is related to some psychosocial factors. DESIGN The study used a cross-sectional design in a large sample. METHODS A total of 1976 subjects aged 12-20 were evaluated at three months after the earthquake by using the Post-traumatic stress disorder Checklist-Civilian Version. The Internality, Powerful others and Chance scale and the Coping Styles Scale were also administered to the subjects at the same time. RESULTS The mean total score of Post-traumatic Stress Disorder Checklist-Civilian Chinese Version was 33·64 (SD 11·15; range of score 17-85). The boys with a higher level of initial exposure to the earthquake had lower symptoms scores than girls with a lower level of initial exposure. Chance locus of control and power other locus of control were the powerful risk factors of post-traumatic stress disorder symptoms, while the protective factors included withdrawing skill, internality locus of control, junior high grade and social supports. CONCLUSIONS Post-traumatic stress disorder symptoms are prevalent psychiatric reactions in adolescents after earthquakes. Locus of control and coping strategy could play an important role in its occurrence and severity besides demographic factors, exposure characteristics and social support factors. RELEVANCE TO CLINICAL PRACTICE This study reveals that adolescents are the vulnerable group for suffering psychological stress responses to catastrophic events. Healthcare professionals, especially school nurses, should pay more attention to adolescents after trauma. Prompt and effective intervention should be carried out to mitigate the impact of initial exposure and reduce the occurrence of post-traumatic stress disorder symptoms.
Age and Third Molar Extraction as Risk Factors for Temporomandibular Disorder

This study investigated third molar removal as a risk factor for temporomandibular disorder (TMD) in all age groups. We compared 2217 Kaiser Permanente Northwest health plan enrollees with a history of third molar extraction with 2217 age-and gender-matched enrollees with radiographic confirmation of no lifetime third molar removal. Common Dental Terminology codes were used to identify information on third molar removal, and International Classification of Disease codes were used to identify TMD. Relative risks were calculated overall, and by each decade of life, in univariate and multivariate analyses. The incidence of TMD in subjects with and without third molar removal were 7 and 5 per thousand person-years, respectively. Third molar removal among subjects of all ages resulted in a statistically insignificant increased relative risk for TMD (1.4, 95% confidence interval (CI): 0.9–2.2). The relative risk was slightly higher in those under 21, but was also not statistically significant (1.6, CI: 0.8–3.1).
Chest radiograph reading and recording system: evaluation for tuberculosis screening in patients with advanced HIV.

SETTING An antiretroviral treatment (ART) service in Gugulethu township, Cape Town, South Africa. OBJECTIVE To assess the inter-observer agreement when using the chest radiographic reading and reporting system (CRRS) to detect radiographic abnormalities in patients with advanced human immunodeficiency virus (HIV) associated immunodeficiency being actively screened for tuberculosis (TB). Second, to assess the associated performance characteristics of radiology as a routine screening test for detection of culture-confirmed pulmonary TB. DESIGN Radiographs from a study in which patients were actively screened for TB just before starting ART were independently reported by two CRRS-certified readers blinded to clinical status. RESULTS Good kappa statistic agreements between observers were found when reporting any radiological abnormality consistent with TB among all patients (n = 203, kappa = 0.63, 95%CI 0.52-0.73) and among those with culture-confirmed TB (n = 53, kappa = 0.61, 95%CI 0.40-0.83). However, in comparison with sputum culture, the sensitivity (0.68, 95%CI 0.54-0.79) and specificity (0.53, 95%CI 0.45-0.61) of radiology in this patient group were low. CONCLUSION This study provides evidence of the good inter-observer agreement using the CRRS standardised reporting methodology when used among patients with advanced HIV-associated immunodeficiency and a high prevalence of culture-proven pulmonary TB. The utility of radiology as a screening test for TB in this patient group, however, remains limited.