Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes.

CONTEXT Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM. OBJECTIVE To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM. DESIGN, SETTING, AND PARTICIPANTS Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States. MAIN OUTCOME MEASURE Self-reported incident fractures, which were verified by radiology reports. RESULTS Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66). CONCLUSIONS Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.
Expert Cognitive Control and Individual Differences Associated with Frontal and Parietal White Matter Microstructure

Although many functional imaging studies have reported frontal activity associated with “cognitive control” tasks, little is understood about factors underlying individual differences in performance. Here we compared the behavior and brain structure of healthy controls with fighter pilots, an expert group trained to make precision choices at speed in the presence of conflicting cues. Two different behavioral paradigms—Eriksen Flanker and change of plan tasks—were used to assess the influence of distractors and the ability to update ongoing action plans. Fighter pilots demonstrated superior cognitive control as indexed by accuracy and postconflict adaptation on the Flanker task, but also showed increased sensitivity to irrelevant, distracting choices. By contrast, when pilots were examined on their ability to inhibit a current action plan in favor of an alternative response, their performance was no better than the control group. Diffusion weighted imaging revealed differences in white matter radial diffusivity between pilots and controls not only in the right dorsomedial frontal region but also in the right parietal lobe. Moreover, analysis of individual differences in reaction time costs for conflict trials on the Flanker task demonstrated significant correlations with radial diffusivity at these locations, but in different directions. Postconflict adaptation effects, however, were confined to the dorsomedial frontal locus. The findings demonstrate that in humans expert cognitive control may surprisingly be mediated by enhanced response gain to both relevant and irrelevant stimuli, and is accompanied by structural alterations in the white matter of the frontal and parietal lobe.
External and internalized heterosexism, meaning in life, and psychological distress.

In the current study, we examined the mediating role of internalized heterosexism in the link between heterosexist discrimination and psychological distress among 361 lesbian, gay, and bisexual (LGB) persons who completed an online survey. We also examined the potential moderating role of meaning in life (both search for and presence of) in the links between heterosexist discrimination and psychological distress and between the heterosexist discrimination and internalized heterosexism. As such, we examined a moderated mediation model. We hypothesized that search for meaning would play an exacerbating role and presence of meaning would play a buffering role in these relationships. Results revealed internalized heterosexism mediated the heterosexist discrimination and psychological distress link. In addition, presence of meaning moderated and buffered the heterosexist discrimination-psychological distress link. Findings from the moderation analyses also revealed that the direct effect of heterosexist discrimination on internalized heterosexism and the conditional indirect effect of heterosexist discrimination on psychological distress were contingent on search for meaning such that these relationships were only significant among LGB persons with moderate to high levels of search for meaning. Finally, search for meaning did not moderate the heterosexist discrimination–psychological distress link and presence of meaning did not moderate the heterosexist discrimination–internalized heterosexism link.
Overexpression of the far upstream element binding protein 1 in hepatocellular carcinoma is required for tumor growth

We identified the far upstream element binding protein 1 (FBP1), an activator of transcription of the proto‐oncogene c‐myc, in a functional yeast survival screen for tumor‐related antiapoptotic proteins and demonstrated strong overexpression of FBP1 in human hepatocellular carcinoma (HCC). Knockdown of the protein in HCC cells resulted in increased sensitivity to apoptotic stimuli, reduced cell proliferation, and impaired tumor formation in a mouse xenograft transplantation model. Interestingly, analysis of gene regulation in these cells revealed that c‐myc levels were not influenced by FBP1 in HCC cells. Instead, we identified the cell cycle inhibitor p21 as a direct target gene repressed by FBP1, and in addition, expression levels of the proapoptotic genes tumor necrosis factor α, tumor necrosis factor–related apoptosis‐inducing ligand, Noxa, and Bik were elevated in the absence of FBP1. Conclusion: Our data establish FBP1 as an important oncoprotein overexpressed in HCC that induces tumor propagation through direct or indirect repression of cell cycle inhibitors and proapoptotic target genes. (HEPATOLOGY 2009.)
The Status of Maculopathy in Diabetes and Prediabetes Patients in a Population-Based Study Detected by Optical Coherence Tomography: The 2011 Health Examination Survey in Beijing

Objective The aim of the study was to investigate the prevalence and the risk factors of maculopathy detected by optical coherence tomography (OCT) in a Chinese population with diabetes or prediabetes. Methods. 8,155 people were randomly selected to participate in the 2011 annual Health Examination Survey in Beijing. A 75 g oral glucose tolerance test (OGTT) was tested in 3760 subjects with fasting plasma glucose (FPG) ≥ 5.6 mmol/L. Of 3,760 subjects, 583 were also randomly selected to take OCT. Results In this study population, 21 (3.95%) patients had maculopathy. Eight patients had diabetes macular edema (DME) and the prevalence was 6.72% in diabetes patients and 1.51% in all subjects. Eleven patients had age-related macular degeneration (AMD) and the prevalence was 3.36% in diabetes patients and 2.07% in all subjects. Logistic regression model confirmed that elevated HbA1c (p < 0.001) and systolic pressure (p < 0.05) made significant contributions to DME. Stepwise regression analysis revealed that HbA1c and blood creatinine were significantly independent influence factors for central subfield thickness (CST) (p = 0.01, p < 0.001). Conclusions High prevalence of maculopathy was found in patients with diabetes in a Chinese population. Maculopathy poses a significant public health problem in China with rapid rising trend of diabetes.
Tracking Young Adults' Attitudes Toward Tobacco Marketing Using Ecological Momentary Assessment (EMA)

ABSTRACT Background: Decades of research demonstrate the pernicious effects of targeted cigarette marketing on young people. Now, with tobacco marketing shifting toward greater incorporation of alternative products, it is critical to identify current attitudes toward the new landscape of tobacco advertisements. Objectives: The purpose of this study was to understand the present landscape of tobacco marketing to which young adults are exposed, and to assess how they respond to it. Method: During 2015–2016, we used ecological momentary assessment (EMA), in which 44 young adults (aged 18–28) carried smartphones equipped with a survey app. Seventy-seven percent were ever-users of tobacco and 29.5% were intermittent users of tobacco (someday users of cigarettes and/or those who used another tobacco product >5 times within the past year). For ten days, participants were prompted at three random times/day to complete a brief survey about their exposures and responses to tobacco-related advertising. Analyses used t-test and multilevel modeling. Results: Intermittent users reported greater exposure than non-intermittent users to tobacco advertising. Further, both intermittent and ever-users reported more positive attitudes toward the tobacco advertising. Of the tobacco advertisements reported, 22% were for products unregulated by the FDA at the time of data collection. Conclusions/Importance: These findings indicate that young adults, and especially young adults who use tobacco, are exposed to a fair amount of tobacco advertising on a weekly basis. As the tobacco users in our sample were largely experimental and occasional users, these marketing exposures could put young adults at risk for progression toward regular use.
Accounting for perception, placebo and unmasking effects in estimating treatment effects in randomised clinical trials

There is a rich literature on the role of placebos in experimental design and evaluation of therapeutic agents or interventions. The importance of masking participants, investigators and evaluators to treatment assignment (treatment or placebo) has long been stressed as a key feature of a successful trial design. Nevertheless, there is considerable variability in the technical definition of the placebo effect and the impact of treatment assignments being unmasked. We suggest a formal concept of a ‘perception effect’ and define unmasking and placebo effects in the context of randomised trials. We employ modern tools from causal inference to derive semi-parametric estimators of such effects. The methods are illustrated on a motivating example from a recent pain trial where the occurrence of treatment-related side effects acts as a proxy for unmasking.
Twenty-Year Review of a Single Surgeon's Experience Using a Unique Surgical Technique to Correct Lambdoidal Synostosis

Background: Numerous techniques for the surgical management of lambdoidal synostosis have been previously described; however, no best practice technique currently exists. Surgical procedures range from complete posterior calvarial reconstruction to distraction osteogenesis techniques. Our primary purpose is to describe a novel approach to correct unilateral or bilateral lambdoidal synostosis. Methods: A retrospective review was performed on a single surgeon's experience with craniosynostosis (1994–2014). Specifically, craniosynostosis cases involving the lambdoidal suture, which were repaired using a novel ‘tongue and groove’ technique, were identified. Results: A total of 664 craniosynostosis cases were retrieved, with 21 primarily involving the lambdoidal suture (3.2%). Of these, 18 were unilateral and 3 were bilateral lambdoidal synostosis. Male-to-female ratio was 3:1. Average age of first encounter with a craniofacial physician was 33 weeks (8 months). Average age at time of surgery was 43 weeks (10.75 months). Complications of this technique included 1 patient who experienced refusion of his lambdoidal suture and fusion of his sagittal suture, and 4 who returned for bone graft coverage of full-thickness calvarial defects owing to a lack of complete reossification. Conclusion: The “tongue and groove” technique represents a novel method for the management of lambdoidal synostosis with good esthetic outcomes, allowing immediate cranial stabilization with increased skull volume. This technique, used by the senior author for >20 years, provides a reproducible and reliable method of correcting lambdoidal synostosis.
Detection of Equine Herpesvirus (EHV) ‐1, ‐2, ‐4 and ‐5 in Ethiopian Equids with and without Respiratory Problems and Genetic Characterization of EHV‐2 and EHV‐5 Strains

Infections with equine herpesviruses (EHVs) are widespread in equine populations worldwide. Whereas both EHV-1 and EHV-4 produce well-documented respiratory syndromes in equids, the contribution of EHV-2 and EHV-5 to disease of the respiratory tract is still enigmatic. This study describes the detection and genetic characterization of EHVs from equids with and without clinical respiratory disease. Virus-specific PCRs were used to detect EHV-1, -2, -4 and -5. From the total of 160 equids with respiratory disease, EHV-5 was detected at the highest prevalence (23.1%), followed by EHV-2 (20.0%), EHV-4 (8.1%) and EHV-1 (7.5%). Concurrent infections with EHV-2 and EHV-5 were recorded from nine (5.2%) diseased horses. Of the total of 111 clinically healthy equids, EHV-1 and EHV-4 were never detected whereas EHV-2 and EHV-5 were found in 8 (7.2%) and 18 (16.2%) horses, respectively. A significantly higher proportion of EHV-2-infected equids was observed in the respiratory disease group (32/160, 20.0%; P = 0.005) compared to those without disease (8/111; 7.2%). EHV-2-positive equids were three times more likely to display clinical signs of respiratory disease than EHV-2-negative equids (OR 3.22, 95% CI: 1.42-7.28). For EHV-5, the observed difference was not statistically significant (P = 0.166). The phylogenetic analysis of the gB gene revealed that the Ethiopian EHV-2 and EHV-5 strains had a remarkable genetic diversity, with a nucleotide sequence identity among each other that ranged from 94.0 to 99.4% and 95.1 to 100%, respectively. Moreover, the nucleotide sequence identity of EHV-2 and EHV-5 with isolates from other countries acquired from GenBank ranged from 92.9 to 99.1% and 95.1 to 99.5%, respectively. Our results suggest that besides EHV-1 and EHV-4, EHV-2 is likely to be an important contributor either to induce or predispose equids to respiratory disease. However, more work is needed to better understand the contribution of EHV-2 in the establishment of respiratory disease.
Patient-completed, preoperative web-based anaesthetic assessment questionnaire (electronic Personal Assessment Questionnaire PreOperative): Development and validation

BACKGROUND Worldwide, guidelines support the routine use of anaesthetic preoperative assessment (POA), a process that is frequently supported by pro formas and unvalidated questionnaires. Electronic questionnaires can provide reliable data. A local initiative has seen the development of a computerised electronic Personal Assessment Questionnaire (ePAQ). OBJECTIVE To develop and validate a novel electronic instrument for POA. DESIGN The content and face validity were evaluated in 30 patients. The questionnaire was then modified and completed by a further 300 patients, evaluating the reliability of its items and scoring algorithms for BMI and American Society of Anesthesiologists (ASA) physical status. The study was approved by the South Yorkshire Regional Ethics Committee (REC 09/H1308/127). SETTING The study was conducted in a tertiary teaching hospital in the United Kingdom between January 2011 and February 2012 and was funded by a research grant from the Charitable Trustees of Sheffield Teaching Hospitals National Health Service Foundation Trust. PATIENTS A total of 330 patients aged 18 years or older, listed for surgery and able to read and understand English, were recruited. Neurosurgery; ear, nose and throat; orthopaedics; gynaecology; general and plastic surgery; ophthalmology and urology patients were included. All participants provided written consent. MAIN OUTCOME MEASURES Validation including test–retest analysis, assessment of patient value and burden, assessment of accuracy, mean score difference of BMI estimation and comparison of inter-rater ASA grading. RESULTS In all, 77% of patients reported that the ePAQ helped with communication, 99% that it was easy to complete and 98% that they would be happy to use it again. ePAQ preoperative assigned ASA grades matched consultant-assigned grades more frequently than nurse-assigned grades. Self-reported BMI classification was correct in 78% of patients and within one WHO category in a further 21%. Test–retest scores were good. CONCLUSION Initial evaluation suggests that ePAQ is acceptable to patients. Data collected using the system were found to be reliable, and its intrinsic scoring systems for ASA and BMI are comparable with values assigned by clinicians.
Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations

Abstract Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r2ncv and q2loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r2Pred) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.
Biomarkers in Early-Stage Non–Small-Cell Lung Cancer: Current Concepts and Future Directions

Advances in molecular biology and bioinformatics have resulted in the identification of a number of potential biomarkers that could be relevant in the management of patients with non–small-cell lung cancer (NSCLC). Although there is an increasing amount of literature related to these biomarkers, major issues need to be resolved including validity and reproducibility of results. Additionally, in order to interpret the existing literature accurately, a clear distinction must be made between the prognostic and predictive value of biomarkers. The practical applicability of biomarker discovery for patients with lung cancer includes the identification of patients with early-stage NSCLC who are most likely to benefit from adjuvant therapy. Information gleaned from biomarkers has the potential to help in evaluating the role of targeted therapies including immunotherapy in the neoadjuvant and adjuvant setting. The role of gene signatures and the use of newer platforms such as RNA, methylation, and protein signatures is being explored in patients with early-stage NSCLC. This review focuses on the applications of biomarker discovery in patients with early-stage NSCLC.
Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin

Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen‐induced arthritis (AIA) mouse model with methylated bovine serum albumin (mBSA) as well as a modified model with mutated citrullinated vimentin (MCV) alone or in combination with mBSA. Periarticular bone loss, subchondral osteoclastogenesis, as well as local expression of cytokines, osteoclast genes, and peptidyl‐arginine deiminase (PAD) enzymes were assessed after arthritis induction. Immune cell and osteoclast precursor infiltration were detected in the periarticular bone marrow and local lymph nodes. In addition, periarticular bone loss was assessed upon challenge of mice with purified anti‐MCV antibody. Despite inducing a milder form of arthritis than mBSA, MCV triggered significant periarticular bone loss associated with an increased infiltration of osteoclast precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced the expression of the osteoclast inducers RANKL and M‐CSF, the cytokines IL‐8, IL‐1, IL‐6, and TNF‐α, as well as PAD2 and PAD4 enzymes in the periarticular bone marrow. Furthermore, also anti‐MCV antibody challenge induced significant periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity against citrullinated vimentin triggers periarticular bone loss by osteoclast activation in the bone marrow. These findings may explain why periarticular bone loss is already found very early in the disease course of patients with rheumatoid arthritis. © 2017 American Society for Bone and Mineral Research.
Productive vocabulary among three groups of bilingual American children: Comparison and prediction

The importance of input factors for bilingual children’s vocabulary development was investigated. Forty-seven Argentine, 42 South Korean, 51 European American, 29 Latino immigrant, 26 Japanese immigrant, and 35 Korean immigrant mothers completed checklists of their 20-month-old children’s productive vocabularies. Bilingual children’s vocabulary sizes in each language separately were consistently smaller than their monolingual peers but only Latino bilingual children had smaller total vocabularies than monolingual children. Bilingual children’s vocabulary sizes were similar to each other. Maternal acculturation predicted the amount of input in each language, which then predicted children’s vocabulary size in each language. Maternal acculturation also predicted children’s English-language vocabulary size directly.