Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcatheter Aortic Valve Replacement: A Review Article

Transcatheter aortic valve replacement (TAVR) is a novel therapeutic intervention for the replacement of severely stenotic aortic valves in high-risk patients for standard surgical procedures. Since the initial PARTNER trial results, use of TAVR has been on the rise each year. New delivery methods and different valves have been developed and modified in order to promote the minimally invasive procedure and reduce common complications, such as stroke. This review article focuses on the current data on the indications, risks, benefits, and future directions of TAVR. Recently, TAVR has been considered as a standard-of-care procedure. While this technique is used frequently in high-risk surgical candidates, studies have been focusing on the application of this method for younger patients with lower surgical risk. Moreover, several studies have proposed promising results regarding the use of valve-in-valve technique or the procedure in which the valve is placed within a previously implemented bioprosthetic valve. However, ischemic strokes and paravalvular leak remain a matter of debate in these surgeries. New methods and devices have been developed to reduce the incidence of post-procedural stroke. While the third generation of TAVR valves (i.e., Edwards Sapien 3 and Medtronic Evolut R) addresses the issue of paravalvular leak structurally, results on their efficacy in reducing the risk of paravalvular leak are yet to be obtained. Furthermore, TAVR enters the field of hybrid methods in the treatment of cardiac issues via both surgical and catheter-based approaches. Finally, while TAVR is primarily performed on cases with aortic stenosis, new valves and methods have been proposed regarding the application of this technique in aortic regurgitation, as well as other aortic pathologies. TAVR is a suitable therapeutic approach for the treatment of aortic stenosis in high-risk patients. Considering the promising results in the current patient population, recent studies have been conducted to evaluate the efficacy of this approach as a standard-of-care procedure. Â Â
Generation of Red-Shifted Cameleons for Imaging Ca2+ Dynamics of the Endoplasmic Reticulum

Cameleons are sophisticated genetically encoded fluorescent probes that allow quantifying cellular Ca2+ signals. The probes are based on Förster resonance energy transfer (FRET) between terminally located fluorescent proteins (FPs), which move together upon binding of Ca2+ to the central calmodulin myosin light chain kinase M13 domain. Most of the available cameleons consist of cyan and yellow FPs (CFP and YFP) as the FRET pair. However, red-shifted versions with green and orange or red FPs (GFP, OFP, RFP) have some advantages such as less phototoxicity and minimal spectral overlay with autofluorescence of cells and fura-2, a prominent chemical Ca2+ indicator. While GFP/OFP- or GFP/RFP-based cameleons have been successfully used to study cytosolic and mitochondrial Ca2+ signals, red-shifted cameleons to visualize Ca2+ dynamics of the endoplasmic reticulum (ER) have not been developed so far. In this study, we generated and tested several ER targeted red-shifted cameleons. Our results show that GFP/OFP-based cameleons due to miss-targeting and their high Ca2+ binding affinity are inappropriate to record ER Ca2+ signals. However, ER targeted GFP/RFP-based probes were suitable to sense ER Ca2+ in a reliable manner. With this study we increased the palette of cameleons for visualizing Ca2+ dynamics within the main intracellular Ca2+ store.
Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma

The molecular basis for the inverse relationship between differentiation and tumorigenesis is unknown. The function of runx2, a master regulator of osteoblast differentiation belonging to the runt family of tumor suppressor genes, is consistently disrupted in osteosarcoma cell lines. Ectopic expression of runx2 induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and leading to the dephosphorylation of the retinoblastoma tumor suppressor protein (pRb) and a G1 cell cycle arrest. Runx2 physically interacts with the hypophosphorylated form of pRb, a known coactivator of runx2, thereby completing a feed-forward loop in which progressive cell cycle exit promotes increased expression of the osteoblast phenotype. Loss of p27KIP1 perturbs transient and terminal cell cycle exit in osteoblasts. Consistent with the incompatibility of malignant transformation and permanent cell cycle exit, loss of p27KIP1 expression correlates with dedifferentiation in high-grade human osteosarcomas. Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is mediated through runx2 and p27KIP1, and these processes are disrupted in osteosarcoma.
Occupation and Personality in Television Dramas

In recent years, the possibility that the speech and actions of people in television's dramatic world might influence viewers' understanding of the personalities of others and themselves has received little attention. The first step to exploring that possibility is to chart the personality types which populate television, and to understand the reasons for their existence. This study examines television industry's view of the various personality dimen sions the audience will attribute to characters. The method is to apply an established personality inventory to descriptions creators of prime-time dramas share regarding criminals, law enforcement agents, blue-collar workers, and other citizens. The one-sided view of human nature that is disclosed raises important questions about the consequences of television's portrayals for people using them for social comparison or as indicators of the human condition.
Expression of a bacterial gene in plants mediated by infectious geminivirus DNA

A viable coat protein deletion mutant of cassava latent virus (CLV) DNA 1 has been isolated, suggesting that this geminivirus might be exploited as a gene replacement vector. An extensive deletion of 727 nucleotides within the coat protein gene renders DNA 1 non‐infectious. Chimeric clones have been constructed in which the deleted coat protein open reading frame has been replaced by the coding region of the bacterial chloramphenicol acetyl transferase (CAT) gene. Infectivity is restored to DNA 1 when the CAT gene is inserted in either orientation, producing symptoms typical of CLV infection. The results demonstrate that the coat protein plays no essential role in virus spread throughout the host. Levels of CAT expression of 80 U/mg soluble protein occur in systemically infected Nicotiana benthamiana leaves when the CAT gene is fused in‐frame to the amino terminus of the coat protein, providing a sensitive assay for viral DNA replication.
Groupthink: Hypothesis in Need of Testing

This article reviews the major tenets of the groupthink hypothesis of Irving Janis, as well as the research on which it is based. In addition, previous research on group dynamics related to groupthink is briefly reviewed and compared to groupthink propositions. Finally, guidelinesfor research to test the propositions of groupthink are proposed.
Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine.

Minimal residual disease (MRD) can be detected in bone marrow core biopsies of patients with hairy cell leukemia (HCL) after treatment with 2-chlorodeoxyadenosine (2-CdA) using immunohistochemical (IHC) techniques. The purpose of this study was to determine whether the presence of MRD predicts bone marrow relapse. We studied paraffin-embedded bone marrow core biopsies from 39 patients with HCL in complete remission (CR) 3 months after a single cycle of 2-CdA. Biopsies performed 3 months posttherapy and annually thereafter were examined by routine hematoxylin and eosin (H&E) staining and IHC using the monoclonal antibodies (MoAbs) anti-CD45RO, anti-CD20, and DBA.44. At 3 months after therapy, 5 of 39 (13%) patients had MRD detectable by IHC that was not evident by routine H&E staining. Two of the five patients (40%) with MRD at 3 months have relapsed, whereas only 2 of 27 (7%) patients with no MRD and at least 1 year of follow up relapsed (P = .11). Over the 3-year follow-up period, two additional patients developed MRD. Overall, three of six (50%) patients with MRD detected at any time after therapy have relapsed, whereas only 1 of 25 (4%) patients without MRD has relapsed (P = .016). These data suggest that the presence of MRD after treatment with 2-CdA may predict relapse.
The moderating effect of tenure in person—environment fit: A field study in educational organizations

This study investigated the role of employee tenure in the relationship between person and environment factors whereby person factors were represented by personal orientations of teachers and environment factors by organizational climates in schools. Questionnaires assessing personal orientations and tenure were completed by 597 employees from 29 organizations. Climate scores were assessed based on the perceptions of a separate sample of 581 employees from the same organizations. Consistent with Schneider's ASA framework, results suggest that tenure moderates the relationship between person and environment; teachers with longer tenure generally fit the school better than their colleagues with shorter tenure. The effects were stronger at the aggregate group level than at the individual level. Implications of these findings are discussed.
Identification of medium/high-threshold extrinsic mechanosensitive afferent nerves to the gastrointestinal tract.

BACKGROUND & AIMS Large distentions reliably evoke sensation from the noninflamed, nonischemic bowel, but the specialized afferent axonal structures responsible have not been morphologically identified. We investigated whether their transduction sites are located on major blood vessels close to and within the gut wall. METHODS In vitro extracellular recordings were made from mesenteric nerve trunks in guinea pig ileum, combined with rapid axonal dye filling and immunohistochemical analysis of nerve trunks. RESULTS Recordings revealed sensory fibers with focal mechanosensitive sites in the mesenteries that could be activated by von Frey hairs and by stretch. Dye filling revealed varicose branching sensory axons on mesenteric blood vessels but no other anatomically specialized structures in mesenteric membranes or the serosa. Large-amplitude stretch and von Frey hairs also activated sensory endings within the gut wall itself but only if the submucosa was present; mechanotransduction sites in the serosa or outer muscle layers were sparse. Mechanosensitive sites in submucosa were exclusively associated with submucosal blood vessels. Submucosal endings had significantly higher thresholds to stretch than specialized low-threshold mechanoreceptors characterized previously in the rectum (P < .05) and were therefore classified as medium/high-threshold mechanoreceptors. Capsaicin (0.3-1 micromol/L) activated most mechanosensitive mesenteric (68%) and submucosal (85%) afferent endings. Similar intramural mechanosensitive afferent endings on blood vessels also exist in the colon and bladder. CONCLUSIONS Varicose branching axons of sensory neurons on intramural blood vessels, previously shown to mediate sensory vasodilation, are transduction sites for medium/high-threshold, stretch-sensitive mechanoreceptors, encoding large distentions in hollow viscera.
‘A Place of Our Own'? Teenage Mothers’ Views on Housing Needs and Support Models

Since 2003, government policy has required local authorities to provide support when they house lone teenage parents seeking accommodation. This qualitative study addresses young mothers’ routes into housing need and their experiences of housing access and support, drawing on interview and focus group data collected in 2003. The findings emphasise mothers’ preferences for forms of support which facilitate moves towards increased choice and independence. Reinforcing messages from other research, these findings also show a gap between concepts of ‘support’ embodied in government policy and those which inform practice, within agencies and among young people. © 2006 The Author(s). Journal compilation Copyright © 2006 National Children's Bureau.
Combination Treatment With N-Acetyl-Seryl-Aspartyl-Lysyl-Proline and Tissue Plasminogen Activator Provides Potent Neuroprotection in Rats After Stroke

Background and Purpose— N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), an endogenously produced circulating peptide in humans and rodents, exerts anti-inflammatory and cardioprotective activities in various cardiovascular diseases. Methods— The present study evaluated the neuroprotective effect of AcSDKP alone and in combination with thrombolytic therapy in a rat model of embolic focal cerebral ischemia. Results— We found that treatment with AcSDKP alone at 1 hour or the combination treatment with AcSDKP and tissue plasminogen activator (tPA) at 4 hours after stroke onset substantially increased AcSDKP levels in plasma and cerebrospinal fluid and robustly reduced infarct volume and neurological deficits, without increasing the incidence of brain hemorrhage compared with ischemic rats treated with saline, AcSDKP alone at 4 hours, and tPA alone at 4 hours. Moreover, the combination treatment considerably reduced the density of nuclear transcription factor-&kgr;B (NF-&kgr;B), transforming growth factor &bgr; (TGF-&bgr;), and plasminogen activator inhibitor-1 (PAI-1) positive cerebral blood vessels in the ischemic brain, all of which were associated with reduced microvascular fibrin extravasation and platelet accumulation compared with tPA monotherapy. In vitro, AcSDKP blocked fibrin-elevated TGF-&bgr;1, PAI-1, and NF-&kgr;B proteins in primary human brain microvascular endothelial cells. Conclusions— Our data indicate that AcSDKP passes the blood–brain barrier, and that treatment of acute stroke with AcSDKP either alone at 1 hour or in combination with tPA at 4 hours of the onset of stroke is effective to reduce ischemic cell damage in a rat model of embolic stroke. Inactivation of TGF-&bgr; and NF-&kgr;B signaling by AcSDKP in the neurovascular unit may underlie the neuroprotective effect of AcSDKP.
The Association between Chronic Widespread Musculoskeletal Pain, Depression and Fatigue Is Genetically Mediated

Background Chronic widespread muscoloskeletal pain (CWP) is prevalent in the general population and associated with high health care costs, so understanding the risk factors for chronic pain is important for both those affected and for society. In the present study we investigated the underlying etiological structure of CWP to understand better the association between the major clinical features of fatigue, depression and dihydroepiandrosterone sulphate (DHEAS) using a multivariate twin design. Methodology/Principle Findings Data were available in 463 UK female twin pairs including CWP status and information on depression, chronic fatigue and serum DHEAS levels. High to moderate heritabilities for all phenotypes were obtained (42.58% to 74.24%). The highest phenotypic correlation was observed between fatigue and CWP (r = 0.45), and the highest genetic correlation between CWP and fatigue (rg = 0.78). Structural equation modeling revealed the AE Cholesky model to provide the best model of the observed data. In this model, two additive genetic factors could be detected loading heavily on CWP—A2 explaining 40% of the variance and A3 20%. The factor loading heaviest on DHEAS showed only a small loading on the other phenotypes and none on fatigue at all. Furthermore, one distinct non-shared environmental factor loading specifically on CWP—but not on any of the other phenotypes—could be detected suggesting that the association between CWP and the other phenotypes is due only to genetic factors. Conclusions/Significance Our results suggest that CWP and its associated features share a genetic predisposition but that they are relatively distinct in their environmental determinants.
Use of a prediction paradigm to evaluate proficient decision making

The contrast between proficient and novice chess players was examined. A chess game played between two experts was used as the target. Subjects were never shown the actual game but were asked to predict the moves played. Feedback was given after each prediction. The proficient players were significantly more accurate than novices. They also were more likely to generate the correct option as the first one they considered and made fewer guesses about the predicted move. The data are interpreted as supporting a recognitional model of decision making. In addition, the findings suggest the value of using the prediction paradigm to study decision making in ill-defined tasks where there are no criteria for correct responses. Implications for training are discussed.
The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis

Background Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. Methods We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm3, and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). Results Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. Conclusions Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.
The use of computer aided lung sound analysis to characterise adventitious lung sounds : a potential outcome measure for respiratory therapy

A barrier to assessing the effectiveness of respiratory physiotherapy has been insufficient accurate, reliable and sensitive outcome measures. Lung sounds provide useful, specific information for assessing and monitoring respiratory patients. However, standard auscultation techniques are too subjective to allow them to be used as an outcome measure. In this research, Computer Aided Lung Sound Analysis (CALSA) was used to assess whether adventitious lung sounds’ characteristics could be quantified clinically and used as a new objective, non-invasive, bedside clinical outcome measure for physiotherapy alveolar recruitment and airway clearance techniques. Two experimental studies were conducted incorporating ‘before-and-after’ and ‘repeated measures’ components. Fifty four participants with productive lung disorders (cystic fibrosis and bronchiectasis) were recruited from out-patient clinics. Demographic, anthropometric, lung function, oxygen saturation, breathlessness and lung sound data were collected at baseline and after a single intervention (selfintervention in the first study and intervention applied by a physiotherapist in the second study). The intra-subject reliability of crackle frequency (f) within each session was found to be ‘good’ to ‘excellent’, estimated by the Analysis of Variance, Intraclass Correlation Coefficient, Smallest Real Difference and Bland and Altman 95% limits of agreement. Crackle initial deflection width (IDW) and crackle two cycles deflection width (2CD) were reliable over short time periods. The f of crackles increased in the majority of participants post interventions. Agreement on the number (N) and timing (T) of crackles between CALSA and a physiotherapist‘s auscultatory findings was found to be poor in anterior chest sites, but higher in posterior sites. Conclusion: the use of CALSA to identify the type and f of adventitious lung sounds collected clinically is feasible; crackle IDW and 2CD are both reliable measures but crackle 2CD is more consistent; crackle f was more responsive than the N or T of crackles per breathing cycle to the interventions. In future, CALSA may provide an objective and responsive tool for assessing and monitoring respiratory interventions in clinical settings.
Micro-crowdfunding: achieving a sustainable society through economic and social incentives in micro-level crowdfunding

This paper introduces a new approach, named micro-crowdfunding, for motivating people to participate in achieving a sustainable society. Increasing people's awareness of how they participate in maintaining the sustainability of common resources, such as public sinks, toilets, shelves, and office areas, is central to achieving a sustainable society. Micro-crowdfunding, as proposed in the paper, is a new type of community-based crowdsourcing architecture that is based on the crowdfunding concept and uses the local currency idea as a tool for encouraging people who live in urban environments to increase their awareness of how important it is to sustain small, common resources through their minimum efforts. Because our approach is lightweight and uses a mobile phone, people can participate in micro-crowdfunding activities with little effort anytime and anywhere. We present the basic concept of micro-crowdfunding and a prototype system. We also describe our experimental results, which show how economic and social factors are effective in facilitating micro-crowdfunding. Our results show that micro-crowdfunding increases the awareness about social sustainability, and we believe that micro-crowdfunding makes it possible to motivate people for achieving a sustainable society.
Recent progress in targeting cancer

In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer.