Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonmuscle myosin II localizes to the Z-lines and intercalated discs of cardiac muscle and to the Z-lines of skeletal muscle.

To understand the role of nonmuscle myosin II in cardiac and skeletal muscle, we used a number of polyclonal antibodies, three detecting nonmuscle myosin heavy chain II-B (NMHC II-B) and two detecting NMHC II-A, to examine the localization of these two proteins in fresh-frozen, acetone-fixed sections of normal human and mouse hearts and human skeletal muscles. Results were similar in both species and were confirmed by examination of fresh-frozen sections of human hearts subjected to no fixation or to treatment with either 4% p-formaldehyde or 50% glycerol. NMHC II-B was diffusely distributed in the cytoplasm of cardiac myocytes during development, but after birth it was localized to the Z-lines and intercalated discs. Dual labeling showed almost complete colocalization of NMHC II-B with alpha-actinin. Whereas endothelial cells, smooth muscle cells and fibroblasts showed strong immunoreactivity for NMHC II-A and NMHC II-B, cardiac myocytes only showed reactivity for the latter. The Z-lines of human skeletal muscle cells, in contrast to those of cardiac myocytes, gave positive reactions for both NMHC II-A and NMHC II-B. The presence of a motor protein in the Z-lines and intercalated discs raises the possibility that these structures may play a more dynamic role in the contraction/relaxation mechanism of cardiac and skeletal muscle than has been previously suspected.
Impact of Adjunct Immunotherapy with Multi-herbal Supplement Dzherelo (Immunoxel) on Treatment Outcomes in End-stage TB/HIV Patients

Prognosis for TB/HIV co-infection is very unfavourable. In terminally-ill patients treatment options are often limited to palliative care. In our salvage, 2-month therapy of 40 late-stage TB/HIV patients we administered to half of the patients TB drugs along with over-the-counter botanical immunomodulator Dzherelo (Immunoxel). Despite best possible care 6 patients had died. Remaining 14 patients experienced marked clinical improvements and one patient was discharged due to full recovery. Among 20 matched subjects on conventional TB regimen, 12 died and only one was slightly better-off. These results indicate that Dzherelo might reduce mortality (P=0.055) and improve significantly the quality of life (P=0.00002). Improvement in quality of life is also supported by substantial weight gain (mean/median 3.3/4 kg) in much higher proportion of patients than among those who received TB drugs only, i.e., 16 vs. 1 (P=0.000001). At the end of two months 13 (65%) patients became sputum smear negative versus only one individual (5%) in ATT group (P=0.00007). These results suggest that adjuvant immunotherapy improves significantly therapy outcome and reduces mortality. Larger study is warranted to confirm the benefit of Dzherelo.
Certain aspects of cell lineage and morphogenesis studied in embryos of Drosophila melanogaster with an ultra-violet micro-beam.

Recent developments in the study of the biosynthetic processes Of OOgenesis in Drosophila melanogaster (Jacob & Sirlin, 1959; King & Sang, 1959; Zalokar, 1960; Sirlin & Jacob, 1960) and a more extensive knowledge of the submicroscopic structure of the developing egg (King & Devine, 1958; Waddington & Okada, 1960) have renewed interest in the ‘mosaic’ character of the freshly deposited egg. This has long been a subject of investigation for insect embryologists, but the available experimental techniques have not provided the necessary refinement for detailed studies. Previously, the most successful method of experimental investigation was that of partial egg irradiation with ultra-violet light (Geigy, 1931 a , b ). The ultraviolet was particularly suitable for this type of work because of its comparatively low penetration into protoplasm: roughly 85 per cent, absorption occurred in 50 μ at a wavelength of 300 mμ (from data of Bachem & Read, 1931, for the stratum malpighii), and stronger absorption was obtained at shorter wavelengths.
Multidrug resistance is a component of V79 cell resistance to the alkylating agent adozelesin.

Adozelesin is a highly potent alkylating agent which has entered clinical trials based on its unique mechanisms of action and broad-spectrum antitumor activity in vivo. V79 cells resistant to adozelesin (V79/AdoR) were not resistant to the alkylating agent cisplatin but showed the phenotypic and genotypic characteristics of multidrug resistance. Thus V79/AdoR was cross-resistant to several structurally and functionally unrelated drugs, resistance was reversed by verapamil, and the resistant cell line expressed mdr mRNA and p170 glycoprotein. Also, adozelesin uptake and the amount of drug alkylated to DNA was much lower in the resistant cell line as compared to the sensitive parent. However, even with the same amount of drug bound to DNA (10 fmol/micrograms DNA) the survival of V79/S approximately 15% survival) was much lower than that of V79/AdoR (approximately 80%). Therefore the resistance of V79/AdoR cannot be explained solely by the multidrug resistance mechanism (i.e., lower drug uptake and less drug alkylation to DNA), which suggests that multiple mechanisms may account for resistance to adozelesin. V79/AdoR showed different levels of cross-resistance to several adozelesin analogues. The analogues could be divided into 2 groups; those with very low partition coefficients (log P < 2 as compared to 2.74 for adozelesin) had low levels of cross-resistance, whereas analogues with higher partition coefficients (log P > 2.4) were cross-resistant to adozelesin.
Mechanical characterization of bioprinted in vitro soft tissue models

Recent development in bioprinting technology enables the fabrication of complex, precisely controlled cell-encapsulated tissue constructs. Bioprinted tissue constructs have potential in both therapeutic applications and nontherapeutic applications such as drug discovery and screening, disease modelling and basic biological studies such as in vitro tissue modelling. The mechanical properties of bioprinted in vitro tissue models play an important role in mimicking in vivo the mechanochemical microenvironment. In this study, we have constructed three-dimensional in vitro soft tissue models with varying structure and porosity based on the 3D cell-assembly technique. Gelatin/alginate hybrid materials were used as the matrix material and cells were embedded. The mechanical properties of these models were assessed via compression tests at various culture times, and applicability of three material constitutive models was examined for fitting the experimental data. An assessment of cell bioactivity in these models was also carried out. The results show that the mechanical properties can be improved through structure design, and the compression modulus and strength decrease with respect to time during the first week of culture. In addition, the experimental data fit well with the Ogden model and experiential function. These results provide a foundation to further study the mechanical properties, structural and combined effects in the design and the fabrication of in vitro soft tissue models.
Why has productivity growth stagnated in most Latin American countries since the neo-liberal reforms? The economic consequences of a rentier-dominated power structure and a narcissistic ideology

Latin America’s economic performance since the beginning of neo-liberal reforms has been poor; this not only contrasts with its own performance pre-1980, but also with what has happened in Asia since 1980. I shall argue that the weakness of the region’s new paradigm is rooted as much in its intrinsic flaws as in the particular way it has been implemented. Latin America’s economic reforms were undertaken primarily as a result of the perceived economic weaknesses of the region — i.e., there was an attitude of ‘throwing in the towel’ vis-a-vis the previous state-led import substituting industrialisation strategy, because most politicians and economists interpreted the 1982 debt crisis as conclusive evidence that it had led the region into a cul-de-sac. As Hirschman has argued, policymaking has a strong component of ‘path-dependency’; as a result, people often stick with policies after they have achieved their aims, and those policies have become counterproductive. This leads to such frustration and disappointment with existing policies and institutions that is not uncommon to experience a ‘rebound effect’. An extreme example of this phenomenon is post-1982 Latin America, where the core of the discourse of the economic reforms that followed ended up simply emphasising the need to reverse as many aspects of the previous development (and political) strategies as possible. This helps to explain the peculiar set of priorities, the rigidity and the messianic attitude with which the reforms were implemented in Latin America, as well as their poor outcome. Something very different happened in Asia, where economic reforms were often intended (rightly or wrongly) as a more targeted and pragmatic mechanism to overcome specific economic and financial constraints. Instead of implementing reforms as a mechanism to reverse existing industrialisation strategies, in Asia they were put into practice in order to continue and strengthen ambitious processes of industrialisation.
Practice of Epidemiology Controlling for Informed Presence Bias Due to the Number of Health Encounters in an Electronic Health Record

Electronic health records (EHRs) are an increasingly utilized resource for clinical research. While their size allows for many analytical opportunities, as with most observational data there is also the potential for bias. One of the key sources of bias in EHRs is what we term informed presence—the notion that inclusion in an EHR is not random but rather indicates that the subject is ill, making people in EHRs systematically different from those not in EHRs. In this article, we use simulated and empirical data to illustrate the conditions under which such bias can arise and how conditioning on the number of health-care encounters can be one way to remove this bias. In doing so, we also show when such an approach can impart M bias, or bias from conditioning on a collider. Finally, we explore the conditions under which number of medical encounters can serve as a proxy for general health. We apply these methods to an EHR data set from a university medical center covering the years 2007–2013.
Exercise and myotonic dystrophy: A 31P magnetic resonance spectroscopy and magnetic resonance imaging case study

We thank Dr Poser for his thoughtful comments expressing his concern for misdiagnosis of multiple sclerosis (MS) using the McDonald Diagnostic Criteria. The fundamental principle of the McDonald Diagnostic Criteria is identical with the 1983 diagnostic criteria that bears Dr Poser’s name, namely, the demonstration of dissemination of lesions characteristic of MS in both space and time. Although magnetic resonance imaging (MRI)–detected lesions may be nonspecific, clinical symptoms can also be nonspecific and the rigorous application of both MRI and clinical criteria is essential. MRI has introduced new challenges in separating lesions that are specific from those that are not specific for MS, but there is little doubt that imaging has substantially enhanced both the specificity and sensitivity of the diagnosis. The MRI criteria for dissemination in space used in the McDonald Criteria were selected for their specificity in predicting conversion from “clinically isolated syndrome” to an established diagnosis of MS, rather than for their sensitivity. In fact, contrary to Dr. Poser’s view, these imaging criteria have been criticized for being overly restrictive. However, in a recent study, Nielsen and colleagues show that careful application of these MRI criteria protects against false-positive diagnosis in almost all cases where an alternative diagnosis was subsequently made. The MRI criteria for dissemination in time, slightly modified in the revised version of the McDonald Criteria, still require objective evidence of new disease activity at least 30 days after the onset of the initial clinical event, to distinguish between MS and monophasic disease. Brinar has proposed that some patients with recurrent demyelinating disease have recurrent disseminated encephalomyelitis, a condition that is distinct from MS. Whether recurrent disseminated encephalomyelitis can be adequately defined, however, remains controversial. In summary, the McDonald Criteria provide an early, objective diagnosis of MS with a low likelihood of a falsepositive diagnosis.
Multiple states of U3 RNA in Novikoff hepatoma nucleoli.

U3 RNA, a capped small nuclear RNA found thus far only in the nucleolus, has been implicated in the processing and/or transport of preribosomal RNA [Busch, H. , Reddy, R. , Rothblum, L. , & Choi, Y. C. (1982) Annu. Rev. Biochem. 51, 617-654]. Tris(hydroxymethyl)aminomethane (Tris) (10 mM, pH 7.0) extracts of Novikoff hepatoma nucleoli, which contained about 80% of total nucleolar U3 RNA, were analyzed by sucrose density gradient centrifugation. Approximately 65% of the U3 RNA was bound to greater than 60S preribosomal ribonucleoprotein (RNP) particles, and about 15% sedimented at less than 20 S. The association between the 65% of U3 RNA that was bound to the preribosomal RNP particles was stable up to 55 degrees C. About 10% of U3 RNA was base paired to preribosomal RNA after deproteinization at 22 degrees C. The base-paired fraction of U3 RNA was released from the preribosomal RNA by heating to 45 degrees C or treating with 4 M urea. These results show that of the total nucleolar U3 RNP, (a) about 55% is bound to preribosomal RNP particles primarily by protein interactions, (b) about 10% is base paired to preribosomal RNA, (c) approximately 15% sedimented slowly and consisted presumably of free U3 RNP particles, and (d) the remaining 20% of U3 RNP was not extractable using 10 mM Tris buffer. On the basis of the different association states of U3 RNP particles, a model is proposed for the binding and dissociation events which take place between U3 RNP and preribosomal RNP particles.
Retrospective Analysis of the Risk Factors and Pathogens Associated With Early-onset Ventilator-associated Pneumonia in Surgical-ICU Head-trauma Patients

Background Early-onset ventilator associated pneumonia (EOVAP) are frequent in head-trauma patients, but specific risk factors are poorly studied in this population. Methods We conducted a retrospective cohort study in a surgical intensive care unit. Consecutive severe head-trauma patients admitted from January 2000 to December 2002 were studied. Microorganisms, and risks factors for EOVAP were analyzed. Results During the 3-year period, 161 patients were studied; 21.1% of them developed an EOVAP. On univariate analysis 6 variables were associated with EOVAP: early enteral feeding, barbiturate use, immunosuppression, mean Simplified Acute Physiology Score 2, acute respiratory distress syndrome, and initial neurosurgery procedures. On multivariate analysis, enteral feeding >2000 Kcal before day 5 [odds ratio (OR): 0.33, 95% confidence interval (CI): 0.21-0.85] and initial neurosurgical procedure (OR: 0.36, 95% CI: 0.15-0.89) remained protective factors for EOVAP, whereas immunosuppression (OR: 7.15, 95% CI: 1.66-30.73) and barbiturate use (OR: 2.68, 95% CI: 1.06-6.80) remained risk factors for EOVAP. EOVAP was also significantly associated with a longer duration of mechanical ventilation (14.0 vs. 11.0 d, P=0.024), and a longer sedation duration (8.3 vs. 5.8 d P=0.005). Methicillin-susceptible Staphylococcus aureus was the most common pathogen involved in EOVAP (46%). Conclusions We demonstrate for the first time that early enteral feeding is a protective factor for EOVAP, and this result could have clinical implications for the prevention of EOVAP after traumatic brain injury. This study also confirms that barbiturate use is an important risk factor of EOVAP whereas Methicillin-susceptible S. aureus was found to be the main pathogen involved in EOVAP.
Approach for Identifying Human Leukocyte Antigen (HLA)-DR Bound Peptides from Scarce Clinical Samples *

Immune-mediated diseases strongly associating with human leukocyte antigen (HLA) alleles are likely linked to specific antigens. These antigens are presented to T cells in the form of peptides bound to HLA molecules on antigen presenting cells, e.g. dendritic cells, macrophages or B cells. The identification of HLA-DR-bound peptides presents a valuable tool to investigate the human immunopeptidome. The lung is likely a key player in the activation of potentially auto-aggressive T cells prior to entering target tissues and inducing autoimmune disease. This makes the lung of exceptional interest and presents an ideal paradigm to study the human immunopeptidome and to identify antigenic peptides. Our previous investigation of HLA-DR peptide presentation in the lung required high numbers of cells (800 × 106 bronchoalveolar lavage (BAL) cells). Because BAL from healthy nonsmokers typically contains 10–15 × 106 cells, there is a need for a highly sensitive approach to study immunopeptides in the lungs of individual patients and controls. In this work, we analyzed the HLA-DR immunopeptidome in the lung by an optimized methodology to identify HLA-DR-bound peptides from low cell numbers. We used an Epstein-Barr Virus (EBV) immortalized B cell line and bronchoalveolar lavage (BAL) cells obtained from patients with sarcoidosis, an inflammatory T cell driven disease mainly occurring in the lung. Specifically, membrane complexes were isolated prior to immunoprecipitation, eluted peptides were identified by nanoLC-MS/MS and processed using the in-house developed ClusterMHCII software. With the optimized procedure we were able to identify peptides from 10 × 106 cells, which on average correspond to 10.9 peptides/million cells in EBV-B cells and 9.4 peptides/million cells in BAL cells. This work presents an optimized approach designed to identify HLA-DR-bound peptides from low numbers of cells, enabling the investigation of the BAL immunopeptidome from individual patients and healthy controls in order to identify disease-associated peptides.
DARES: A Distributed Automated REasoning System

In many domains of interest to distributed artificial intelligence, the problem solving environment may be viewed as a collection of loosely coupled intelligent agents, each of which reasons based on its own incomplete knowledge of the state of the world. No agent has sufficient knowledge to solve the problem at hand so that coordinated cooperative problem solving is required to satisfy system goals. In this paper, we present DARES, a distributed reasoning system in which agents have the ability to focus their attention on selective information interchange to facilitate cooperative problem solving. The experimental results we present demonstrate that agents in a loosely coupled network of problem solvers can work semi-independently, yet focus their attention with the aid of relatively simple heuristics when cooperation is appropriate. These results suggest that we have developed an effective cooperation strategy which is largely independent of initial knowledge distribution.
Rethinking the research-practice gap: relevance of the RCT to practice.

The research-practice gap is not a new phenomenon in nursing. It was first observed about 50 years ago.The results of surveys conducted in various countries and at different points in time have consistently indicated that a small percentage of nurses use research-based evidence to guide their practice (e.g., Brett, 1987; Coyle & Sokop, 1990; Ketefian, 1975; Kirchhoff, 1982; Parahoo, Barr, & McCaughan, 2000; Rodgers, 2000). Attention to the research-practice gap has resurfaced at a time when evidence-based practice is viewed as a means for enhancing the quality of health and nursing care.The implementation of evidence-based nursing practice requires that nurses critically review the research evidence supporting the effectiveness of interventions, synthesize it, and translate it into practice guidelines.Yet, anecdotal and empirical observation suggests that the updating and use of research findings in everyday practice is rather limited (Naylor, 2003). Barriers to research utilization have been identified in four areas: the social system in which nurses are employed, nurses’ research values and skills, quality of research, and methods for communicating research (Funk,Tornquist, & Champagne, 1995). Various strategies have been proposed to address these barriers and subsequently the research-practice gap. For instance, unit-based journal clubs and workshops focusing on the critical appraisal of research have been established in an effort to increase nurses’ research knowledge and skills. Other organizational strategies to support the research-utilization endeavours of nurses include the following: pairing of researchers and clinicians to work on developing practice guidelines, making computers available in the practice setting to facilitate access to research literature, and using research or evidencebased practice as a key value (Estabrooks, 2003; Funk et al.; LeMay, Mulhall, & Alexander, 1998). Another strategy is to improve the methods for disseminating research findings to practitioners (Oxman,Thomson, & Davis, 1995). CJNR 2004,Vol. 36 No 3, 7–18
Clinical Significance of Serum Anti-Human Papillomavirus 16 and 18 Antibodies in Cervical Neoplasia

OBJECTIVE: To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. METHODS: The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. RESULTS: Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43–5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01–0.94], P=.044). CONCLUSION: Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. LEVEL OF EVIDENCE: II
PORTNEUF - a framework for continuous user involvement

In practice, developers often ignore user feedback, especially if its volume is high. We describe Portneuf, a framework which consolidates user feedback with a hybrid recommender system, and a novel algorithm allowing developers to assess the importance of collected user feedback. In an experiment, we demonstrate that Portneuf increases developers’ efficiency when working with user feedback. Our results show that Portneuf significantly reduces the amount of user feedback duplicates by over 67%.