Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation by p38 Mitogen-Activated Protein Kinase Promotes Estrogen Receptor α Turnover and Functional Activity via the SCFSkp2 Proteasomal Complex

ABSTRACT The nuclear hormone receptor estrogen receptor α (ERα) mediates the actions of estrogens in target cells and is a master regulator of the gene expression and proliferative programs of breast cancer cells. The presence of ERα in breast cancer cells is crucial for the effectiveness of endocrine therapies, and its loss is a hallmark of endocrine-insensitive breast tumors. However, the molecular mechanisms underlying the regulation of the cellular levels of ERα are not fully understood. Our findings reveal a unique cellular pathway involving the p38 mitogen-activated protein kinase (p38MAPK)-mediated phosphorylation of ERα at Ser-294 that specifies its turnover by the SCFSkp2 proteasome complex. Consistently, we observed an inverse relationship between ERα and Skp2 or active p38MAPK in breast cancer cell lines and human tumors. ERα regulation by Skp2 was cell cycle stage dependent and critical for promoting the mitogenic effects of estradiol via ERα. Interestingly, by the knockdown of Skp2 or the inhibition of p38MAPK, we restored functional ERα protein levels and the control of gene expression and proliferation by estrogen and antiestrogen in ERα-negative breast cancer cells. Our findings highlight a novel pathway with therapeutic potential for restoring ERα and the responsiveness to endocrine therapy in some endocrine-insensitive ERα-negative breast cancers.
A Hydroxyapatite Graft Substitute Reduces Subsidence in a Femoral Impaction Grafting Model

Synthetic bone graft substitutes have been developed for impaction grafting revision hip surgery in response to concerns about the availability and potential infection risk of allograft. We performed an in vitro experiment to determine whether a synthetic porous hydroxyapatite material might improve resistance to cumulative subsidence and cyclic (elastic) movement on loading. We impacted different ratios of hydroxyapatite and allograft (0%, 50%, 70%, and 90% hydroxyapatite) into composite femoral models (eight per group) and implanted tapered, polished stems with cement. Models were loaded for 18,000 cycles on a servohydraulic materials testing machine. Migration of the femoral prostheses and the distal cement was determined using radiostereometric analysis, and cyclic movement was measured mechanically by the testing machine. Hydroxyapatite decreased overall subsidence and subsidence at the prosthesis-cement interface, but there was no difference at the cement-femur interface. This decrease may have occurred because the hydroxyapatite-containing graft was more rigid, or because it resulted in a thicker cement mantle. Cyclic prosthesis movement also was lower with hydroxyapatite. While the biologic response to porous hydroxyapatite remains to be determined, its mechanical properties appear promising.
The Use of Information Technology as Value Co-creation : The Role of Contextual Variety and Means Drivenness

This paper proposes a service dominant logic view of technology use as value cocreation in context. We argue that individuals, as value co-creators, are resource integrators and such resource integration in technology use is determined by the degree of variability of the context within which the individual faces. We also posit that where contexts are varied to the extent that goals are unknown, individuals could be means driven rather than goals driven. Our paper develops two new constructs, contextual variety and means drivenness, and investigate its impact on technology use and the technology adoption model (TAM) through four focus groups and a survey of 1526 smartphone users. Our results indicate that contextual variety and means drivenness impacted on use behaviors and the two constructs mediated the impact of the original TAM perceived ease of use (fully) and perceived usefulness (partially) constructs towards use. We also showed that increased contextual variety drives means drivenness. Our study demonstrates the role of context within co-creation that is set apart from the role of the individual's enduring traits. We also show the influence of effectual reasoning, as opposed to causal reasoning on technology use and propose that future research could focus on contexts, as well as users.
Role of Temporal Resolution in Selection of the Appropriate Strain Technique for Evaluation of Subclinical Myocardial Dysfunction

Objective: To assess the effects of frame and volume rate on the concordance between two‐dimensional speckle tracking strain (2DS) and three‐dimensional speckle tracking strain (3DS), and between 2DS and triplane imaging of speckle tracking (Tri‐P). Methods: Global longitudinal strains (GLSs) derived from 2DS, 3DS, and Tri‐P were compared among 142 prospectively recruited patients who underwent evaluation of subclinical left ventricle (LV) function. Results: Feasibility to obtain GLS of 3DS was significantly higher than that of Tri‐P (76% vs. 47%, P < 0.001). The correlation between 2DS and 3DS was only modest (r = 0.47) whereas that of 2DS and Tri‐P was better (r = 0.67). The difference in frame/volume rate between two methods also affected their correlation. A volume rate between 34 and 50 volumes/sec had the highest correlation between 2DS and 3DS (r = 0.72). The correlation between 2DS and Tri‐P was better with a difference in frame‐rate ≤20 per second than with a difference >20 per second. Likewise, there was a better correlation between 2DS and 3DS when the difference between 2D frame rate and 3D volume rate was ≤40 per second, compared to when it was >40 per second. These associations differed from segment to segment and the apical segments had the highest correlation and the basal the lowest. Conclusions: The feasibility of each means of strain calculation showed important differences, with 2DS being the most attainable. Strain values were not interchangeable among 2DS, Tri‐P, and 3DS. Importantly, poor correlations seemed to be driven by differences in acquisition rate. Currently, 2DS offers the most robust measurement of subclinical myocardial dysfunction. (Echocardiography 2012;29:334‐339)
Guard Cell- and Phloem Idioblast-Specific Expression of Thioglucoside Glucohydrolase 1 (Myrosinase) in Arabidopsis1

Thioglucoside glucohydrolase 1 (TGG1) is one of two known functional myrosinase enzymes in Arabidopsis. The enzyme catalyzes the hydrolysis of glucosinolates into compounds that are toxic to various microbes and herbivores. Transgenic Arabidopsis plants carrying β-glucuronidase and green fluorescent protein reporter genes fused to 0.5 or 2.5 kb of the TGG1 promoter region were used to study spatial promoter activity. Promoter activity was found to be highly specific and restricted to guard cells and distinct cells of the phloem. No promoter activity was detected in the root or seed. All guard cells show promoter activity. Positive phloem cells are distributed in a discontinuous pattern and occur more frequent in young tissues. Immunocytochemical localization of myrosinase in transverse and longitudinal sections of embedded material show that the TGG1 promoter activity reflects the position of the myrosinase enzyme. In the flower stalk, the myrosinase-containing phloem cells are located between phloem sieve elements and glucosinolate-rich S cells. Our results suggest a cellular separation of myrosinase enzyme and glucosinolate substrate, and that myrosinase is contained in distinct cells. We discuss the potential advantages of locating defense and communication systems to only a few specific cell types.
Adapting to the challenge of psychosis: personal resilience and the use of sealing-over (avoidant) coping strategies

Background Avoidance coping (e.g. sealing over) is common in people recovering from psychosis, but it is not understood why some individuals ‘seal over’. Aims We examined the hypothesis that individuals who ‘seal over’ do not have the personal resilience to withstand this major life event. Method Fifty participants were interviewed during an acute episode of psychosis and reassessed at 3-month and 6-month follow-up. Measures included psychotic symptoms, recovery style, service engagement, parental and adult attachment and self-evaluative beliefs. Results Sealing-over recovery styles are associated with negative early childhood experience, insecure adult attachment, negative self-evaluative beliefs and insecure identity. Insecure adult attachment was associated with less engagement with services. Conclusions Sealing over was associated with multiple signs of low personal resilience in adapting to psychosis.
Tumor seeding after endoscopic ultrasound-guided fine-needle aspiration of cancer in the body of the pancreas

fine-needle aspiration of cancer in the body of the pancreas The use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been rapidly expanding as a useful examination technique which enables highly accurate histological diagnosis. Reports of tumor dissemination induced by EUS-FNA are rare [1–5]. We recently encountered a case in which tumor cells were observed in the puncture line in a surgically resected specimen after EUS-FNA, and in which dissemination in the posterior wall of the upper gastric body was later observed. The patient was a 68-year-old woman. A computed tomography (CT) scan revealed a 2-cmmass in the pancreatic body, which was suspected to be pancreatic cancer. We scheduled distal pancreatectomy, and to obtain a definitive diagnosis the patient underwent preoperative EUS-FNA with a 22-gauge needle (Olympus Medical Systems, Tokyo, Japan) inserted four times, which yielded a diagnosis of adenocarcinoma. No clinical complications developed after EUS-FNA. Distal pancreatectomy was performed 20 days after the EUS-FNA and, intraoperatively, bleeding and adhesion were observed at the puncture sites (●" Fig.1). Histopathology of the surgically resected specimen confirmed adenocarcinoma (T2N0M0). A small number of tumor cells were found within the lymphatic vessels of the resected specimen, similar to the areas of bleeding and adhesion (●" Fig.2). At 22 months after distal pancreatectomy, upper gastrointestinal endoscopy revealed a submucosal tumor-like mass in the posterior wall of the upper gastric body (●" Fig.3a), which was subsequently confirmed to be adenocarcinoma by biopsy (●" Fig.3b). An abdominal CT scan did not reveal any local recurrence at the resected site of the pancreas or lymph node metastasis around the stomach, but a tumor was observed on the posterior wall of the gastric body (●" Fig.4). In the present case, bleeding was seen at the puncture sites and tumor cells were observed within the lymphatic vessels in these areas. As similar findings were absent in the areas whichwere free of bleeding or adhesion, we speculated that the punctures caused the bleeding and adhesion, and that subsequent reactive changes facilitated the survival of tumor cells within the lymphatic vessels. Moreover, it is possible that similar changes occurred in the gastric wall.
Web Content Accessibility of Consumer Health Information Web Sites for People with Disabilities: A Cross Sectional Evaluation

Background The World Wide Web (WWW) has become an increasingly essential resource for health information consumers. The ability to obtain accurate medical information online quickly, conveniently and privately provides health consumers with the opportunity to make informed decisions and participate actively in their personal care. Little is known, however, about whether the content of this online health information is equally accessible to people with disabilities who must rely on special devices or technologies to process online information due to their visual, hearing, mobility, or cognitive limitations. Objective To construct a framework for an automated Web accessibility evaluation; to evaluate the state of accessibility of consumer health information Web sites; and to investigate the possible relationships between accessibility and other features of the Web sites, including function, popularity and importance. Methods We carried out a cross-sectional study of the state of accessibility of health information Web sites to people with disabilities. We selected 108 consumer health information Web sites from the directory service of a Web search engine. A measurement framework was constructed to automatically measure the level of Web Accessibility Barriers (WAB) of Web sites following Web accessibility specifications. We investigated whether there was a difference between WAB scores across various functional categories of the Web sites, and also evaluated the correlation between the WAB and Alexa traffic rank and Google Page Rank of the Web sites. Results We found that none of the Web sites we looked at are completely accessible to people with disabilities, i.e., there were no sites that had no violation of Web accessibility rules. However, governmental and educational health information Web sites do exhibit better Web accessibility than the other categories of Web sites (P < 0.001). We also found that the correlation between the WAB score and the popularity of a Web site is statistically significant (r = 0.28, P < 0.05), although there is no correlation between the WAB score and the importance of the Web sites (r = 0.15, P = 0.111). Conclusions Evaluation of health information Web sites shows that no Web site scrupulously abides by Web accessibility specifications, even for entities mandated under relevant laws and regulations. Government and education Web sites show better performance than Web sites among other categories. Accessibility of a Web site may have a positive impact on its popularity in general. However, the Web accessibility of a Web site may not have a significant relationship with its importance on the Web.
Afi1p Functions as an Arf3p Polarization-specific Docking Factor for Development of Polarity*

ADP-ribosylation factors (Arfs) are highly conserved small GTPases and are critical components of vesicle trafficking. Yeast Arf3p, despite its similarity to mammalian Arf6, is not required for endocytosis but is involved in polarity development. In this study, we identified an Arf3p interacting protein 1 (Afi1p), which, through its N-terminal conserved region, specifically interacts with GTP-bound Arf3p. Afi1p is distributed asymmetrically at the plasma membrane and is required for polarized distribution of Arf3p but not of an Arf3p guanine nucleotide-exchange factor, Yel1p. However, Afi1p is not required for targeting of Arf3p or Yel1p to the plasma membrane. Like arf3 mutant yeast, afi1 mutant yeast exhibited an abnormal budding pattern and partially delayed actin patch polarization. An Afi1p, 38KLGP4A-Afi1p, mutated at the Arf3p-binding region, loses its ability to interact with Arf3p and maintain the polarized distribution of Arf3p. Although 38KLGP4A-Afi1p still possessed a proper polarized distribution, it lost its ability to rescue actin patch polarization in afi1 mutant cells. Our findings demonstrate that Afi1p functions as an Arf3p polarization-specific adapter and participates in development of polarity.
Retention of family medicine faculty development fellows in academic medicine.

OBJECTIVE This study measured the retention of family medicine faculty development fellows in academic medicine. METHODS Surveys were sent, in two stages, to 1) fellowship program directors and 2) fellows. These surveys were about full-time faculty development fellowships with new or continued Title VII funding during the interval of 1993-1996. Retention as faculty was the primary outcome. Likelihood of leaving academics and service in a federally designated medically underserved area were secondary outcomes. RESULTS The fellowship program directors survey produced an 88% response rate and identified 105 alumni. The survey of fellows yielded a response rate of 73% (n = 77). The retention rate of these newly graduated family medicine fellows in academic positions was 75% (n = 58). A total of 37% (n = 21) of alumni in full- and part-time teaching positions reported being likely to leave their current position within the next 2 years. CONCLUSIONS Retention rates of newly graduated family medicine fellows in academic positions are similar to rates reported in the 1980s. This group anticipates a high job turnover within the next 2 years.
Application of minimax Distribution Free Procedure and Chebyshev Approach in mixed inventory Model involving Reducible lead-Time and setup Cost with Imprecise Demand

In this paper, we extend Lin [Lin, YJ (2008). Minimax distribution free procedure with backorder price discount. International Journal of Production Economics, 111, 118–128] model by fuzzifying the demand rate, based on triangular fuzzy number to increase its applicability and solve the problem by using an alternative approach i.e., Chebyshev approach. We prove the concavity and convexity of the estimate of total variable cost per unit time in fuzzy sense. To compare the expected annual cost of proposed model, defuzzification is performed by two different methods namely signed distance and centroid method. We provide a solution procedure to find the optimal values of lead-time, the order quantity and the backorder price discount by using minimax distribution free procedure and Chebyshev approach. Through numerical example it is shown that there is a significant saving in cost due to crashing cost to reduce the lead-time and the setup cost. We also compare our results with Cheng et al. [Cheng, TL, CK Huang and KC Chen (2004). Inventory model involving lead-time and setup cost as decision variables. Journal of Statistics and Management Systems, 7, 131–141] model and show that Ben-Daya and Raouf's [Ben-Daya, M and A Raouf (1994). Inventory model involving lead-time as a decision variable. Journal of the Operational Research Society, 45, 579–582] model is the special case of our proposed model.
Activity of hydrolysed lactoferrin against foodborne pathogenic bacteria in growth media: the effect of EDTA

Lactoferrin was hydrolysed with pepsin and the antimicrobial activity of the resulting hydrolysate (HLF) was studied in 1% peptone, 0·05% yeast extract, 1% glucose (PYG) medium and tryptic soy broth (TSB). HLF was effective against Listeria monocytogenes, enterohaemorrhagic Escherichia coli and Salmonella enteritidis in PYG, however, the highest studied concentration (1·6 mg ml−1) did not inhibit growth of any of these organisms in TSB. The addition of EDTA enhanced the activity of HLF in TSB, indicating that the decreased activity of HLF may have been due, in part, to excess cations in the medium.
Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19

Background and objective: Until recently, there has been little agreement between conflicting results of osteoarthritis (OA) linkage. The purpose of this study was to conduct a whole-genome linkage scan to identify susceptibility loci for idiopathic hand OA in a large, population-based sample of females. Methods: Two OA-related radiographic phenotypes DIP (distal interphalangeal joints)-OA and Tot-KL (Kellgren-Lawrence score for both hands) chosen a priori were examined on 538 (269 pairs) monozygous and 1256 (628 pairs) dizygous (DZ) females. A genome-wide scan using microsatellite markers spaced 10 cM apart was performed on 1028 DZ twins. First, the heritability of the two OA phenotypes was estimated. Next, multipoint linkage analysis was conducted using a modified version of the Haseman–Elston method in a generalised linear model. Results: Heritability for DIP-OA and Tot-KL was found to be 47.6% and 67.4%, respectively. A genome-wide scan produced reliable evidence of significant linkage of DIP-OA on chromosome 2 at 90 cM (logarithmic odds ratio (LOD) = 2.90) and for Tot-KL on chromosome 19 at 65 cM (LOD = 4.26). These results are in agreement with data published previously. Several other significant linkage peaks were observed—for example, on chromosome 1 at 250 cM and on chromosome 3 at 30 cM—but were confirmed less reliably. Conclusion: This is one of the largest OA linkage studies performed to date and provides clear evidence for linkage at two quantitative trait loci (on chromosome 2 at 90 cM and on chromosome 19 at 65 cM). As the results were robust and replicated in previous smaller studies, the fine mapping of these regions is a logical next step to pinpoint potential susceptibility gene(s) of interest.
Role of Noninsulin Therapies Alone or in Combination in Chromosome 6q24-Related Transient Neonatal Diabetes: Sulfonylurea Improves but Does Not Always Normalize Insulin Secretion

Chromosome 6q24-related transient neonatal diabetes (6q24-TND) is a rare form of diabetes caused by an overexpression of PLAGL1 and HYMAI (1). After remitting in infancy, diabetes recurs in most patients later in life. While the best treatment remains unknown, many patients are managed with insulin (1). We sought to characterize β-cell function and glucose homeostasis in patients with 6q24-TND and assess their response to sulfonylurea (SU) therapy. Adults with 6q24-TND and recurrence of hyperglycemia requiring insulin therapy later in life were identified through The University of Chicago Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu/registry) and invited to participate in a trial of SU therapy. Four patients with insulin doses of 0.41–0.76 units/kg/day attempted the trial. Three were available for a mixed-meal test (MMT) and arginine stimulation test (AST) on day one and day five of SU treatment. All insulin products were withheld on the morning of day one. Subjects ingested 7 mL/kg (maximal 360 mL) of BOOST High Protein (http://www.boost.com) within 5 …
Repeatability of central corneal thickness and ocular anterior chamber depth measurements with the Orbscan topography system

The Orbscan topography system is a new anatomical noncontact system that allows study of central corneal thickness and ocular anterior chamber depth. It is currently important to know if there are significant differences among different observers when morphometric studies are carried out with the Orbscan System. Following on from this, the present work focuses on the repeatability of the new Orbscan Topography System II measurements. At the Rahhal Ophthalmology Clinic and the Faculty of Medicine of Valencia (Spain), we carried out a prospective study involving 46 eyes of 46 healthy patients: 27 were women (58.59%) and 19 were men (41.30%). The mean age of the sample was 29.93 ± 6.6 years (range: 18-47 years). One physician carried out central corneal thickness and ocular anterior chamber depth measurements with the Orbscan Topography System II (Bausch & Lomb Surg, Barcelona, Spain), while a second physician measured the corneal thickness and ocular anterior chamber depth again. The means of two consecutive measurements were used. Only one eye per patient was considered for the statistical analysis. The repeatability of the Orbscan measurements was analysed by comparing the results obtained by physicians 1 and 2. The mean central corneal thickness of the sample (mean ±SD) was 549.39 ±46.65 µm (physician 1) and 549.32 ±47 µm (physician 2). Thus, no significant differences were found between physicians (p=0.994). The mean ocular anterior chamber depth (mean ±SD) was 3.14 ±0.27 mm (physician 1) and 3.14 ±0.26 mm (physician 2). No significant differences were found between the physicians (p=0.978). Women had significantly greater corneal thickness values than men (p=0.003 for physician 1, and p=0.004 for physician 2). No significant differences between the sexes were found for ocular anterior chamber depth. In sum, the Orbscan Topography System II offers a high degree of repeatability for central corneal thickness and ocular anterior chamber depth measurements. This situation should facilitate the study of corneal and ocular anatomy in vivo