Miracle-dz/UniFAR-FTUs huggingface dataset:
A Chronic Model for Experimental Investigation of Epidural Anesthesia in the Rabbit

Background and Objectives A rabbit chronic model has been developed for investigation of epidural anesthesia without surgery. Methods A catheter was implanted via a non-traumatic route in the lumbar epidural space between the apex coccis sacri and the first vertebra coccygea after a 1-cm incision was made in the skin at the root of the tail. The ligamentum was punctured to allow the catheter to slide gently 10 cm into the epidural space and avoid subperiosteal soft tissue dissection. The motor block effects of epidural lidocaine and bupivacaine were studied 1 week after implantation. Three injections of lidocaine 1% (group I) or 2% (group II) or bupivacaine 0.25% (group III) or 0.5% (group IV) were given at 48-hour intervals to four rabbits in each group. Increasing concentrations (0.5%, 1.0%, and 2.0%) of lidocaine and bupivacaine (0.125, 0.25, and 0.5%) were injected into eight rabbits in each of groups V and VI. The spinal cord and meninges were examined histopathologically in eight other chronically implanted rabbits that received no drugs. Results Catheters were kept in place during 2 months in 40 rabbits without neurologic disturbance, discomfort, infection or weight loss. Complete motor block was observed during a mean 27, 43, and 51 minutes with increasing doses of lidocaine. Administration of bupivacaine 0.125% led to incomplete motor deficit in three rabbits, whereas all other rabbits exhibited complete motor block, lasting a mean of 26, 53, and 93 minutes for increasing doses. Linear relationships were found between the concentration of each drug and the duration of motor block (r = .902, P < .001 for lidocaine; and r = .857, P < .001 for bupivacaine). Repeated injections of local anesthetics produced consistent durations of motor block (Bland and Altman test). No significant histologic changes were observed. Conclusion This rabbit model appears to be a suitable tool for evaluating motor block of epidural agents under standardized experimental conditions.
Three scenarios to teach difficult discussions in pediatric emergency medicine: sudden infant death, child abuse with domestic violence, and medication error.

Within an emergency medicine (EM) environment, the pace of clinical care delivery rarely allows time to stop and observe extended interactions between trainees and patients, or to provide feedback on communication skills. Once residency and fellowship conclude, however, these same trainees will be required to manage complicated medical and social interactions independently. In particular, unique challenges in the realm of patient-doctor interaction arise in the field of pediatric emergency medicine (PEM), with most clinical encounters involving both a child and their caregiver. Whether delivering bad news to a family or screening and managing cases of suspected child abuse, child neglect or domestic violence, many physicians report having no formal training in communicating effectively and compassionately under difficult conditions.1–4 It is imperative to consider and prepare future physicians for the emotional relationship between the (pediatric) patient and the family when caring for the family unit, especially in emergent situations and times of crisis. The occurrence of medical error presents another tremendously challenging situation for physicians and requires sophisticated communications skills. Despite clinicians’ best preventive and conscientious efforts, various elements can lead to a medical error, and the physicians involved will need to disclose and discuss the event with the family. Once again, few physicians have had formal training in managing these situations.5 To improve training in PEM physician communications during difficult discussions, we created a hybrid medical simulation program, a combination of standardized patients and high-fidelity medical simulation. The primary objective was to educate EM residents and PEM fellows on the communication skills necessary to engage in difficult discussions when caring for children in an emergency department setting. Authors will present three scenarios developed for an educational activity designed to focus on difficult discussion communication skills in PEM.
Molecular tools in understanding the evolution of Vibrio cholerae

Vibrio cholerae, the etiological agent of cholera, has been a scourge for centuries. Cholera remains a serious health threat for developing countries and has been responsible for millions of deaths globally over the past 200 years. Identification of V. cholerae has been accomplished using a variety of methods, ranging from phenotypic strategies to DNA based molecular typing and currently whole genomic approaches. This array of methods has been adopted in epidemiological investigations, either singly or in the aggregate, and more recently for evolutionary analyses of V. cholerae. Because the new technologies have been developed at an ever increasing pace, this review of the range of fingerprinting strategies, their relative advantages and limitations, and cholera case studies was undertaken. The task was challenging, considering the vast amount of the information available. To assist the study, key references representative of several areas of research are provided with the intent to provide readers with a comprehensive view of recent advances in the molecular epidemiology of V. cholerae. Suggestions for ways to obviate many of the current limitations of typing techniques are also provided. In summary, a comparative report has been prepared that includes the range from traditional typing to whole genomic strategies.
Stochastic Conjugate Gradient Algorithm With Variance Reduction

Conjugate gradient (CG) methods are a class of important methods for solving linear equations and nonlinear optimization problems. In this paper, we propose a new stochastic CG algorithm with variance reduction<xref rid="fn1" ref-type="fn"><sup>1</sup></xref> and we prove its linear convergence with the Fletcher and Reeves method for strongly convex and smooth functions. We experimentally demonstrate that the CG with variance reduction algorithm converges faster than its counterparts for four learning models, which may be convex, nonconvex or nonsmooth. In addition, its area under the curve performance on six large-scale data sets is comparable to that of the LIBLINEAR solver for the <inline-formula> <tex-math notation="LaTeX">$L2$ </tex-math></inline-formula>-regularized <inline-formula> <tex-math notation="LaTeX">$L2$ </tex-math></inline-formula>-loss but with a significant improvement in computational efficiency. <fn id="fn1"><label><sup>1</sup></label><p>CGVR algorithm is available on github: <uri>https://github.com/xbjin/cgvr</uri></p></fn>
Apoptotic body–loaded dendritic cells efficiently cross‐prime cytotoxic T lymphocytes specific for NA17‐A antigen but not for Melan‐A/MART‐1 antigen

DCs hold promise for cancer immunotherapy due to their functional ambivalence: iDCs internalize antigens, then mDCs trigger naive T‐cell activation. However, no consensus has been reached concerning the optimal mode of antigen acquisition for efficient cross‐priming of TAA‐specific CTLs, and this remains a field of investigation. Here, we used highly purified apobodies derived from an HLA‐A*0201‐negative melanoma line as a source of tumor antigens for HLA‐A*0201 DCs. We compared in vitro mDCs loaded with apobodies to DCs loaded with antigenic peptides, NA17‐A1–9 and Melan‐A/MART‐126–35 A27L analogue, for their capacity to stimulate melanoma antigen‐specific T cells from autologous PBLs. Apobody phagocytosis did not induce spontaneous DC maturation, but phagocytic DCs were still responsive to maturation signals, resulting in a functional ability to activate antigen‐specific lymphocytes. NA17‐A‐specific T lymphocytes were activated by both types of stimulation, whereas only peptide‐pulsed DCs stimulated the growth of Melan‐A/MART‐1‐specific lymphocytes. We also observed a lack of staining of melanoma‐derived apobodies with a Melan‐A‐specific MAb, suggesting protein alteration during apoptosis induction. After HLA‐A*0201/NA17‐A multimer sorting, antigen‐specific lymphocytes induced by mature DCs loaded with either peptide or apobodies displayed similar functional capacity against peptide‐pulsed T2 cells and melanoma cells. Therefore, apobody‐loaded DCs can achieve T‐cell priming similar to that induced by peptide‐pulsed DCs, provided that the apoptotic process allows the preservation of antigen expression. © 2002 Wiley‐Liss, Inc.
Structural analysis of the human immunodeficiency virus-binding domain of CD4. Epitope mapping with site-directed mutants and anti-idiotypes

The CD4 molecule, a differentiation marker expressed primarily by T lymphocytes, plays an important role in lymphocyte activation. CD4 is also the receptor for HIV. A number of recent studies have localized the high affinity binding site of the HIV envelope glycoprotein, gp120, to the NH2-terminal (V1) domain of CD4, a region with sequence and predicted structural homology with Ig kappa chain V domains (V kappa). In this report, we show that V1 bears structural similarities with V kappa regions through detailed epitope mapping of 26 CD4 mAbs. The binding sites of these mAbs were initially defined relative to one another by crossblocking analysis and were then localized to specific domains of CD4 in blocking studies with truncated, soluble CD4 proteins. The epitopes within the V1 domain were mapped in detail with a panel of 17 substitution mutants, and the specificities of several mAbs that appear to recognize very similar epitopes were examined in crossblocking studies with anti-idiotype antibodies. The location of the epitopes is consistent with a V kappa-like structure of V1. Most of the epitopes lie within regions of predicted exposed loops. A number of these epitopes span discontinuous residues in the linear sequence that lies in close proximity in an Ig fold. Alignment of CD4 V1 with the Ig V kappa chains places these epitopes within stretches corresponding to the complimentarity-determining regions. This epitope analysis is relevant for a vaccine strategy for HIV based on anti-idiotype antibodies to CD4 mAbs and for studies with CD4 antibodies on the role of CD4 in T lymphocyte activation.
Echocardiographic epicardial fat thickness is associated with coronary artery calcification - results from the CAESAR study.

BACKGROUND Few studies have addressed the relationship between echocardiographic epicardial fat thickness (EFT) and coronary artery calcification in an apparently healthy Asian population, and those that have, are inconsistent. METHODS AND RESULTS A total of 2,299 individuals (1,871 men; mean age, 45±8.9 years) were enrolled in the CArdiometabolic risk, Epicardial fat, and Subclinical Atherosclerosis Registry (CAESAR) study and underwent CT for measurement of coronary artery calcium score (CACS) and echocardiography for EFT. According to EFT quartiles, the prevalence of CAC >0 was 8.3%, 16.8%, 24.6%, and 28.3% in the lowest, second, third, and highest EFT quartiles, respectively (P<0.001). On multivariate logistic regression after adjusting for variables with a univariate relationship (P<0.05), the second, third, and highest quartile groups of EFT had higher odds ratios (OR) for the presence of CAC compared with those of the lowest quartile (OR, 1.634; 95% confidence interval (CI): 0.940-2.839; 1.762, 1.019-3.048; and 1.924, 1.107-3.342, respectively), and the increase in absolute EFT was also independently associated with higher OR for the presence of CAC (1.842; 95% CI: 1.057-3.208, P=0.031). Moreover, increasing absolute EFT was associated with increasing CACS on multivariate linear regression (standardized β=0.081, P=0.005). CONCLUSIONS There was an independent relationship between EFT and coronary artery calcification in Korean adults, suggesting that echocardiographic EFT might be an easily accessible tool for early detection of subclinical coronary atherosclerosis.
Integrating Embedded Computing Systems Into High School and Early Undergraduate Education

Early exposure to embedded computing systems is crucial for students to be prepared for the embedded computing demands of today's world. However, exposure to systems knowledge often comes too late in the curriculum to stimulate students' interests and to provide a meaningful difference in how they direct their choice of electives for future education and careers. This paper describes an experience with integrating embedded computing systems education into high school and early undergraduate curricula to give students that needed early exposure. It provides assessment data that illustrates the success and limitations of the efforts described as well as the lessons they hold for a reform of the undergraduate curriculum and its impact on high school education.
D-galactan II is an immunodominant antigen in O1 lipopolysaccharide and affects virulence in Klebsiella pneumoniae: implication in vaccine design

In the O1 strain of Klebsiella, the lipopolysaccharide (LPS) O-antigen is composed of D-galactan I and D-galactan II. Although the composition of the O1 antigen of Klebsiella was resolved more than two decades, the genetic locus involved in the biosynthesis of D-galactan II and the role of D-galactan II in bacterial pathogenesis remain unclear. Here, we report the identification of the D-galactan II-synthesizing genes by screening a transposon mutant library of an acapsulated Klebsiella pneumoniae O1 strain with bacteriophage. K. pneumoniae strain deleted for wbbY exhibited abrogated D-galactan II production; altered serum resistance and attenuation of virulence. Serologic analysis of K. pneumoniae clinical isolates demonstrated that D-galactan II was more prevalent in community-acquired pyogenic liver abscess (PLA)—causing strains than in non-tissue-invasive strains. WbbY homologs, WbbZ homologs, and lipopolysaccharide structures based on D-galactan II also were present in several Gram-negative bacteria. Immunization of mice with the magA-mutant (K−1 O1) (that is, with a LPS D-galactan II-producing strain) provided protection against infection with an O1:K2 PLA strain. Our findings indicate that both WbbY and WbbZ homologs are sufficient for the synthesis of D-galactan II. D-galactan II represents an immunodominant antigen; is conserved among multiple species of Gram-negative bacteria and could be a useful vaccine candidate.
Periodontal repair in dogs: rhBMP-2 significantly enhances bone formation under provisions for guided tissue regeneration.

BACKGROUND Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to support the regeneration of alveolar bone and periodontal attachment in surgically created periodontal defects and in defects with a history of dental plaque and calculus exposure. Periodontal regeneration has also been shown following guided tissue regeneration using space-providing expanded polytetrafluoroethylene (ePTFE) devices. The objective of this study was to evaluate the influence of rhBMP-2 on regeneration of alveolar bone and periodontal attachment used in conjunction with a space-providing ePTFE device. METHODS Routine, critical-size, 5-6 mm, supra-alveolar, periodontal defects were created around the third and fourth mandibular premolar teeth in four young adult Hound Labrador mongrel dogs. rhBMP-2 (0.2 mg/ml) in an absorbable collagen sponge (rhBMP-2/ACS) or buffer/ACS (control) implants were randomly assigned to be placed around the premolar teeth in the left and right jaw quadrants in subsequent animals. Space-providing ePTFE devices with 300-microm laser-drilled pores, 0.8 mm apart, were used to cover the rhBMP-2 and control implants. The gingival flaps were advanced for primary wound closure. The animals were euthanized at 8 weeks postsurgery for histologic and histometric analyses. RESULTS Bone regeneration and ankylosis were significantly increased in jaw quadrants receiving rhBMP-2/ACS compared to control (bone height 4.8+/-0.3 versus 2.0+/-0.2 mm, p=0.001; bone area 10.9+/-1.3 versus 1.4+/-0.1 mm2; p=0.009, and ankylosis 2.2+/-0.2 versus 0.04+/-0.7 mm; p=0.01). No differences between groups were found for cementum regeneration and root resorption. CONCLUSIONS rhBMP-2 significantly enhances regeneration of alveolar bone in conjunction with a space-providing, macroporous ePTFE device for GTR.
Dementia among the Elderly in a Rural Korean Community

The age-specific prevalence of dementia, its sex difference, and the relative prevalence of important types of dementia were studied in the elderly people in a Korean rural community. A two-stage approach was employed, involving screening and clinical assessment. The prevalence among individuals aged 65 and over was found to be 10.8%, with rates of 7.2% in men and 14.5% in women. The dementia was of the Alzheimer type in 60.0% of cases, multi-infarct dementia in 12.0%, mixed dementia of Alzheimer type and multi-infarct in 10.7%, alcoholic dementia in 8.0%, and others and unclassifiable in 9.3%. The prevalence of dementia of the Alzheimer type was significantly higher in women and rapidly increased with age in both sexes. The prevalence of multi-infarct dementia was not related to sex or age. Alcoholic dementia was identified only in men. These findings indicate that the prevalence of dementia in rural Korea is similar to that reported in Western countries and that the prevalence of dementia of the Alzheimer type in rural Korea is greater than that of multi-infarct dementia.
Interaction between Transform Faults and Rift Systems: A Combined Field and Experimental Approach

We present a detailed field structural survey of the area of interaction between the active NW-striking transform Husavik-Flatey Fault (HFF) and the N-S Theystareykir Fissure Swarm (TFS), in North Iceland, integrated by analogue scaled models. Field data contribute to a better understanding of how transform faults work, at a much higher detail than classical marine geophysical studies. Analogue experiments are conducted to analyse the fracture patterns resulting from different possible cases where transform faulting accompanies or postpones the rift motions; different tectonic block configurations are also considered. West of the intersection between the transform fault (HFF) and the rift zone (TFS), the former splays with a gradual bending giving rise to a leading extensional imbricate fan. The westernmost structure of the rift, the N-S Gudfinnugja Fault (GF), is divided into two segments: the southern segment makes a junction with the HFF and is part of the imbricate fan; north of the junction instead, the northern GF appears right-laterally offset by about 20 m. Southeast of the junction, along the possible prolongation of the HFF across the TFS, the strike of the rift faults rotates in an anticlockwise direction, attaining a NNW-SSE orientation. Moreover, the TFS faults north of the HFF prolongation are fewer and have smaller offsets than those located to the south. Through the comparison between the structural data collected in the field at the HFF-TFS connection zone and a set of scaled experiments, we confirm a prolongation of the HFF through the rift, although here the transform fault has a much lower slip-rate than west of the junction. Our data suggest that transform fault terminations may be more complex than previously known, and propagate across a rift through a modification of the rift pattern.
Autophagy-Dependent Survival of Mutant B-Raf Melanoma Cells Selected for Resistance to Apoptosis Induced by Inhibitors against Oncogenic B-Raf

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 (IC50<0.5 μM), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 (IC50>20 μM). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at G0/G1 with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.
The Role of Intelligence Quotient and Emotional Intelligence in Cognitive Control Processes

The relationship between intelligence quotient (IQ) and cognitive control processes has been extensively established. Several studies have shown that IQ correlates with cognitive control abilities, such as interference suppression, as measured with experimental tasks like the Stroop and Flanker tasks. By contrast, there is a debate about the role of Emotional Intelligence (EI) in individuals' cognitive control abilities. The aim of this study is to examine the relation between IQ and EI, and cognitive control abilities evaluated by a typical laboratory control cognitive task, the Stroop task. Results show a negative correlation between IQ and the interference suppression index, the ability to inhibit processing of irrelevant information. However, the Managing Emotions dimension of EI measured by the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), but not self-reported of EI, negatively correlates with the impulsivity index, the premature execution of the response. These results suggest that not only is IQ crucial, but also competences related to EI are essential to human cognitive control processes. Limitations and implications of these results are also discussed.