Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G

Toward the end of the 20th and beginning of the 21st centuries, clever in vitro biochemical complementation experiments and genetic screens from the laboratories of Xiaodong Wang, Shigekazu Nagata, and Ding Xue led to the discovery of two major apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase‐activated DNase (CAD) and endonuclease G (Endo G). Both endonucleases attack chromatin to yield 3′‐hydroxyl groups and 5′‐phosphate residues, first at the level of 50–300 kb cleavage products and next at the level of internucleosomal DNA fragmentation, but these nucleases possess completely different cellular locations in normal cells and are regulated in vastly different ways. In non‐apoptotic cells, DFF exists in the nucleus as a heterodimer, composed of a 45 kD chaperone and inhibitor subunit (DFF45) [also called inhibitor of CAD (ICAD‐L)] and a 40 kD latent nuclease subunit (DFF40/CAD). Apoptotic activation of caspase‐3 or ‐7 results in the cleavage of DFF45/ICAD and release of active DFF40/CAD nuclease. DFF40's nuclease activity is further activated by specific chromosomal proteins, such as histone H1, HMGB1/2, and topoisomerase II. DFF is regulated by multiple pre‐ and post‐activation fail‐safe steps, which include the requirements for DFF45/ICAD, Hsp70, and Hsp40 proteins to mediate appropriate folding during translation to generate a potentially activatable nuclease, and the synthesis in stoichiometric excess of the inhibitors (DFF45/35; ICAD‐S/L). By contrast, Endo G resides in the mitochondrial intermembrane space in normal cells, and is released into the nucleus upon apoptotic disruption of mitochondrial membrane permeability in association with co‐activators such as apoptosis‐inducing factor (AIF). Understanding further regulatory check‐points involved in safeguarding non‐apoptotic cells against accidental activation of these nucleases remain as future challenges, as well as designing ways to selectively activate these nucleases in tumor cells. © 2005 Wiley‐Liss, Inc.
Protease inhibitor‐based triple therapy in chronic hepatitis C: guidelines by the French Association for the Study of the Liver

The recent marketing authorizations and hence availability of the new protease inhibitors, telaprevir and boceprevir, have profoundly changed the management of chronic hepatitis C patients. Guidelines for the use of these new drugs as part of a triple therapy, in combination with the standard therapy of peginterferon plus ribavirin, are proposed. The guidelines have been drawn up and evaluated by a meeting of the French Association for the Study of the Liver, posted online for comments, and extensively reviewed by international experts. The current published data on the various treatment strategies are reviewed.
[Bech-Rafaelsen Mania Scale and Young Mania Rating Scale--comparison of psychometric properties of the two instruments for rating a manic syndrome].

AIM The Bech-Rafaelsen Mania Rating Scale (BRMAS) and Young Mania Rating Scale (YMRS) are both popular rating scales for mania. Until now BRMAS has not had a Polish language version BRMAS, although it may be particularly useful because of its twin depression (melancholia) rating scale (BRMES). No attempt of evaluation of the scales were made in Poland until now. Attempts to compare their worth are rare in the literature. The aim of this study was to evaluate and compare the two scales. METHOD Thirty-five patients hospitalised for mania in the course of affective, schizophrenic and organic disorders were assessed by means of two mania rating scales (BRMAS, YRMS), as well as with clinical global impression (CGI) scale, and its parallel versions for mania (CGI-M) and treatment adverse events (CGI-SE). Two rating scales for psychotic syndromes (PANSS, KOSS-S) was also used. Patients were assessed three times. First three diagnosticians evaluated simultaneously and independently the patients' mental state, and then--after one and two weeks--one of them. As reliability measures, inter-rater, test-retest, and internal consistency indices were analysed. As validity measures, a clinical meaning of descriptive characteristics of the scales (external validity), and a comparison with alternative tools for mania rating (criterion, diagnostic validity) were performed. Specificity and sensitivity of BRMAS and YMRS in relation to clinical criterion of severe mania (CGI > or = 5) was analysed by means of ROC curve. As feasibility measure observations made during assessments were used. RESULTS BRMAS and YMRS revealed satisfactory convergence between assessments of the three diagnosticians (Spearman's rho > 0.72, no significant difference in non-parametric Friedman test), repeatability after a week (rho > 0.52) and internal consistency (Cronbach's alpha for BRMAS > 0.86, for YMRS > 0.73). Profile and dynamics of symptoms in the three successive assessments (each week) depicted changes consistent with expectations, which proved external validity of the scales. Mutual, high correlations between the BRMAS and YMRS (rho > 0.90), between them and CGI-M scale (rho >77), and between them and some meaningful items of psychosis rating scales (PANSS, KOSS-S) may be a mark of their diagnostic validity. ROC for both scales revealed similar, extensive areas under curve (AUC > 0.947; p < 0.000). BRMAS score above 24 points predicted severe mania with 92% sensitivity and 91% specificity. By analogy, YRMAS score above 29 points allowed this diagnosis with 83% sensitivity and 91% specificity. Practically no difficulties in application of the scale under study were noted. CONCLUSIONS Both compared mania scales revealed satisfactory indices of reliability and validity. They are also feasible tools. However limited size of the group under study has not allowed more penetrating analysis, particularly that of validity. This is why the study requires continuation.
Periodontal disease and preterm birth: results of a pilot intervention study.

BACKGROUND Previous case-control and prospective studies have shown an association between the presence of periodontitis and the risk of preterm birth (PTB). The goal of this pilot trial was to determine the feasibility of conducting a trial to determine whether treatment of periodontitis reduces the risk of spontaneous preterm birth (SPTB). METHODS Three hundred sixty-six (366) women with periodontitis between 21 and 25 weeks' gestation were recruited and randomized to one of three treatment groups with stratification on the following two factors: 1) previous SPTB at <35 weeks and 2) body mass index <19.8 or bacterial vaginosis as assessed by Gram stain. The treatment groups consisted of: 1) dental prophylaxis plus placebo capsule; 2) scaling and root planing (SRP) plus placebo capsule; and 3) SRP plus metronidazole capsule (250 mg t.i.d. for one week). An additional group of 723 pregnant women meeting the same criteria for periodontitis and enrolled in a prospective study served as an untreated reference group. RESULTS The rate of PTB at <35 weeks was 4.9% in the prophylaxis group, compared to 3.3% in the SRP plus metronidazole group and 0.8% in the SRP plus placebo group (P = 0.75 and 0.12, respectively). The rate of PTB at <35 weeks was 6.3% in the reference group. CONCLUSIONS This trial indicates that performing SRP in pregnant women with periodontitis may reduce PTB in this population. Adjunctive metronidazole therapy did not improve pregnancy outcome. Larger trials will be needed to achieve statistical significance, especially at less than 35 weeks gestational age.
Virus-Induced Airway Dysfunction: Pathogenesis and Biomechanisms

Background: Viral respiratory tract infections cause significant morbidity and mortality. Respiratory viruses are suspected to play a role in the inception of asthma early in life. Respiratory syncytial virus (RSV) is the most common cause of infant bronchiolitis, which is associated with the development of childhood wheezing and asthma. However, it is not clear whether this association is “causal” or “circumstantial. ” Methods: Animal models have been pivotal in studying the pathophysiology of viral respiratory infections. Various approaches to assessing airway inflammation and function have been used to define the mechanisms of virus-induced airway dysfunction and to address clinically relevant questions regarding the role of RSV in wheezing and asthma after bronchiolitis. Results: Viral lower respiratory tract infections alter airway function in humans and animals. The extent and duration of the alterations may depend on the virus itself, host factors and environmental factors. Animal studies demonstrated that viral infection induces airway hyperresponsiveness and enhances this alteration in the allergen-sensitized and exposed host. This altered airway function is mediated by immune and neurogenic inflammatory mechanisms. Recent studies in mice show that neonatal RSV infection sensitizes the newborn to develop an asthma-like phenotype on reinfection, providing further opportunities to investigate the role of RSV in postbronchiolitis wheezing and asthma in this animal model. Conclusions: Further studies are needed to fully establish the mechanisms underlying the pathophysiology of viral respiratory tract infections and to clarify their role in the inception and/or progression of chronic airway diseases such as asthma. The results of ongoing therapeutic studies promise to minimize the impact of such viral infections.
Examining cross-database global training to evaluate five different methods for ventricular beat classification

The detection of ventricular beats in the holter recording is a task of great importance since it can direct clinicians toward the parts of the electrocardiogram record that might be crucial for determining the final diagnosis. Although there already exists a fair amount of research work dealing with ventricular beat detection in holter recordings, the vast majority uses a local training approach, which is highly disputable from the point of view of any practical—real-life—application. In this paper, we compare five well-known methods: a classical decision tree approach and its variant with fuzzy rules, a self-organizing map clustering method with template matching for classification, a back-propagation neural network and a support vector machine classifier, all examined using the same global cross-database approach for training and testing. For this task two databases were used—the MIT–BIH database and the AHA database. Both databases are required for testing any newly developed algorithms for holter beat classification that is going to be deployed in the EU market. According to cross-database global training, when the classifier is trained with the beats from the records of one database then the records from the other database are used for testing. The results of all the methods are compared and evaluated using the measures of sensitivity and specificity. The support vector machine classifier is the best classifier from the five we tested, achieving an average sensitivity of 87.20% and an average specificity of 91.57%, which outperforms nearly all the published algorithms when applied in the context of a similar global training approach.
FISH Chromosome Aberration Analysis on Retired Radiation Workers from the Sellafield Nuclear Facility

Abstract Tawn, E. J., Whitehouse, C. A. and Tarone, R. E. FISH Chromosome Aberration Analysis on Retired Radiation Workers from the Sellafield Nuclear Facility. Radiat. Res. 162, 249–256 (2004). Chromosome analysis using fluorescence in situ hybridization was undertaken on 294 retired workers from the British Nuclear Fuels plc facility at Sellafield, 95 with external occupational exposure <50 mSv, 108 with 50–499 mSv, and 91 with >500 mSv. In univariate analyses, external dose (P < 10−5) and age (P = 0.0075) were significantly associated with translocation frequency, but no effect was found for smoking status. In a multivariate analysis with age and external dose as continuous variables, the slopes were 0.017 ± 0.0075 × 10−2 translocations per cell per year for age (P = 0.024) and 1.11 ± 0.190 × 10−2 translocations per cell per sievert for external dose (P < 10−5). The dose response for translocation induction for occupational workers is similar to the linear component of in vitro dose–response curves, thus supporting the use of translocation frequency for retrospective biological dosimetry in situations of chronic low-dose exposure occurring over many years. The dose response obtained in this study is lower than the linear component of the dose response for stable chromosome aberrations obtained for the Japanese atomic bomb survivors. Thus, if chromosome aberration levels are indicative of cancer risk, this would suggest that low-dose risks derived from the Japanese atomic bomb survivor data will overestimate the risks associated with the occupational exposure encountered by the men in this study.
Mechanisms of inhibition in cat visual cortex.

1. Neurones from layers 2‐6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long‐lasting (200‐400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5‐20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non‐optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition.
Five-Level Diode Clamped Inverter to EliminateCommon Mode Voltage and Reduce $dv/dt$ inMedium Voltage Rating Induction Motor Drives

The High power induction machines are designed at medium voltage (MV) rating for better performance. The multilevel inverters (MLI) are able to provide medium voltage with high quality output at low switching frequency as compared to conventional two-level inverter. In addition to this, MLI reduces dv/dt, switching losses and leakage current. In this paper, approaches to reduce and eliminate the common mode voltage (CMV) using five- level diode clamped multilevel inverter (DCMLI) are presented. The CMV spikes are also eliminated by shifting dead-time across the phase pole. A novel technique for the selection of switching states to synthesize the desire vector is proposed. This paper realizes the implementation of five-level diode clamped MLI for three phase induction motor. Experimental results demonstrate the feasibility of the proposed solution.
Oil Extraction from Microalgae Dunalliela sp. by Polar and Non-Polar Solvents

 Abstract — Microalgae are tiny photosynthetic plants. Nowadays, microalgae are being used as nutrient-dense foods and sources of fine chemicals. They have significant amounts of lipid, carotenoids, vitamins, protein, minerals, chlorophyll, and pigments. Oil extraction from algae is a hotly debated topic currently because introducing an efficient method could decrease the process cost. This can determine the sustainability of algae-based foods. Scientific research works show that solvent extraction using chloroform/methanol (2:1) mixture is one of the efficient methods for oil extraction from algal cells, but both methanol and chloroform are toxic solvents, and therefore, the extracted oil will not be suitable for food application. In this paper, the effect of two food grade solvents (hexane and hexane/ isopropanol) on oil extraction yield from microalgae Dunaliella sp. was investigated and the results were compared with chloroform/methanol (2:1) extraction yield. It was observed that the oil extraction yield using hexane, hexane/isopropanol (3:2) and chloroform/methanol (2:1) mixture were 5.4, 13.93, and 17.5 (% w/w, dry basis), respectively. The fatty acid profile derived from GC illustrated that the palmitic (36.62%), oleic (18.62%), and stearic acids (19.08%) form the main portion of fatty acid composition of microalgae Dunalliela sp. oil. It was concluded that, the addition of isopropanol as polar solvent could increase the extraction yield significantly. Isopropanol solves cell wall phospholipids and enhances the release of intercellular lipids, which improves accessing of hexane to fatty acids.
STOP-like Protein 21 Is a Novel Member of the STOP Family, Revealing a Golgi Localization of STOP Proteins*

Neuronal microtubules are stabilized by two calmodulin-regulated microtubule-associated proteins, E-STOP and N-STOP, which when suppressed in mice induce severe synaptic and behavioral deficits. Here we show that mature neurons also contain a 21-kDa STOP-like protein, SL21, which shares calmodulin-binding and microtubule-stabilizing homology domains with STOP proteins. Accordingly, in different biochemical or cellular assays, SL21 has calmodulin binding and microtubule stabilizing activity. However, in cultured hippocampal neurons, SL21 antibodies principally stain the somatic Golgi and punctate Golgi material in neurites. In cycling cells, transfected SL21 decorates microtubules when expressed at high levels but is otherwise principally visible at the Golgi. The Golgi targeting of SL21 depends on the presence of cysteine residues located within the SL21 N-terminal domain, suggesting that Golgi targeting may require SL21 palmitoylation. Accordingly we find that SL21 is palmitoylated in vivo. N-STOP and E-STOP, which contain the Golgi targeting sequences present in SL21, also display distinct Golgi staining when expressed at low level in cycling cells. Thus neuronal proteins of the STOP family have the capacity to associate with Golgi material, which could be important for STOP synaptic functions.
Hearing Aid Use for Children With Hearing Loss: A Literature Review

Purpose The purpose of this study was to complete a comprehensive literature review related to hearing aid use during early childhood. Method A rapid evidence assessment was completed to provide a summary of information published or presented between 1980 and 2012. A qualitative assessment was completed for all eligible material, emergent themes related to hearing aid use were synthesized, and a narrative summary was generated. Results Eight publications, one conference proceeding, and one presentation were identified. Three themes emerged from the review: hours of hearing aid use, factors influencing use, and suggestions about how to increase use from parents and professionals. Conclusion Minimal research has been done related to hearing aid use for young children with hearing loss. Further research is needed to address influences such as quality of fit, parent factors, multiple disabilities, and cultural differences and to investigate effective strategies for increasing hearing aid use.
Atypical exanthems related to human herpesvirus‐6 reactivations in transplant recipients

To the Editor We read with interest the article by Schlaweck et al. (1) about a case of human herpesvirus-6 (HHV-6) reactivation, defined as exanthem subitum, after autologous stem cell transplantation, and we would like to make a few observations. In the last 5 years, we observed 21 patients who developed atypical exanthems after hematopoietic stem cell transplantation (HSCT): 14 allogeneic and 7 autologous. HHV-6 plasma viremia (2), marker of virus reactivation, was found in 9 of them (3). The HHV-6 reactivation rate found in our series was comparable with other studies (4), confirming that rash is significantly associated with post-transplantation HHV-6 viremia. In 7 of these 9 patients, the simultaneous presence of HHV-6 DNA in plasma and skin lesions suggested the role of HHV-6 in causing the exanthem (4). Remarkably, only 1 of 9 patients with systemic HHV-6 reactivation and 5 of 21 patients with atypical exanthems developed a clinically and histopathologically confirmed acute graft-versus-host disease (aGVHD) (3). Indeed, HHV-6 reactivation in transplant patients may be associated with fever and skin rash resembling aGVHD and may play an important role in the development of the disease (5, 6). It is noteworthy that the reactivation of HHV-6 within 30 days after HSCT seems a predictive marker for aGVHD (4, 7). However, it is difficult to distinguish whether the skin eruption is a viral exanthem or the earliest sign of aGVHD (8). Nonethless, in HSCT patients, distinguishing the eruptions related to HHV-6 reactivation, as pityriasis rosea (9) and/or atypical exanthems (10), from eruptions related to GVHD (11) is crucial for proper treatment. The clinical involvement of other organs and histopathological findings can help in the diagnosis: an interface dermatitis of varying severity appears in all aGVHDs and can aid in the correct diagnosis. Immunosuppressive drugs, which should be reserved for true aGVHD, could be inappropriate for an exanthem caused by HHV-6 reactivation, a condition that may be associated with severe complications (hepatitis, encephalitis). Conversely, in viral reactivations, patients may benefit from antiviral drugs. Therefore, in the absence of life-threatening GVHD symptoms/signs, an effort to search for HHV6 reactivation should be made, and immunosuppressive treatment should be delayed until the results of viral investigations and skin biopsy are known. Incidentally, we would like to point out that the diagnosis of “exanthem subitum” attributed by Schlaweck
Exposing Privacy Concerns in mHealth

Mobile health (mHealth) sensing devices can help individuals work towards a healthier lifestyle or allow them to share the collected information with their doctor to diagnose health issues or manage a chronic disease. If these sensors are collecting personal health information while patients are at home or at their workplace, the sensors might record other sensitive information – like the location of their home, when they leave for work, or who they interact with – information that may in some cases be misused. Patients may be concerned about where that information is stored or who has access to it. In this paper, we refer to the users of an mHealth device as Patients, whether they use it for disease management or for personal wellness applications, and we refer to the recipient of the shared information as a consumer. We conducted several exploratory focus groups to understand what privacy concerns Patients might have with the collection, storage and sharing of their personal health information, when using mHealth devices. We found that Patients want control over their health information, and we noticed privacy trends that were particular to Patients in the same age group and with similar health experiences.