Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple recurrences and risk of disease progression in patients with primary low-grade (TaG1) non–muscle-invasive bladder cancer and with low and intermediate EORTC-risk score

Aim To assess the prognostic value of multiple recurrences on the risk of progression in a large cohort of TaG1 bladder cancer of low and intermediate risk based on the EORTC score and to evaluate prognostic factors of multiple recurrences. Materials and methods We retrospectively analyzed a French cohort of 470 patients with primary TaG1 bladder cancer diagnosed between 1986 and 2010 and followed until 2012. They were classified at low and intermediate risk using the EORTC risk score. Associations between the number of recurrences and the risk of progression to high grade Ta/T1 bladder cancer and progression to muscle-invasive disease were assessed. The characteristics of recurrences, as occurrence time or localization, and risk of other recurrences were evaluated. Results Out of 470 patients, 251 had recurrence, 34 progressed to high grade Ta/T1 and 17 to muscle-invasive disease, including 4 who had non muscle-invasive progression first. The median follow-up was 7.2 years (interquartile range: 4.2–10.9). In half the progressions, no previous recurrence was observed. No association between the number of recurrences and the risk of progression was detected. Even after 5 years free of event, patients had a 15% risk of recurrence. History of two or more recurrences increased by 4.5 the risk of subsequent recurrence. Time between two recurrences inferior to six months and multifocal localization increased the risk of recurrence. Conclusion Surveillance of patients with TaG1 should be continued beyond 5 years of follow-up. However, cystoscopy exams could be spaced after 5 years. Multiple TaG1 recurrences did not appear to be prognostic for disease progression, but increased significantly the risk of subsequent recurrences. Short time between two recurrences and multifocal localization may serve to adapt monitoring of patients with TaG1 Bladder cancer.
A Study on the Effects of Rumen Acidity on Rumination Time and Yield, Composition, and Technological Properties of Milk from Early Lactating Holstein Cows

Simple Summary The increase in milk yield achieved in recent decades by the dairy sector has been sustained by feeding dairy cows with more concentrates and less forage. This leads to increasing rumen acidity, a status widespread in high-producing dairy cows that may affect feed intake, impair ruminal digestion, and cause diarrhea, laminitis, inflammation, and liver abscesses. The effects of rumen acidity on milk yield and composition are controversial, while those on milk coagulation properties and cheese yield have not yet been explored. This study investigated whether the rumen acidity status affects rumination time, and the production, composition, coagulation properties and cheese yield of milk obtained by 100 early-lactating Holstein cows. The variation in rumen acidity was associated with changes in the cows’ rumen fluid composition and circadian pattern of rumination time. Moreover, daily milk yield linearly decreased as the rumen acidity increased. Conversely, the composition and technological properties of milk were unaffected, even when there were differences in rumen acidity, suggesting that variation in rumen acidity has little impact on cheese-making traits. Abstract The use of high grain rations in dairy cows is related to an increase in rumen acidity. This study investigated whether the rumen acidity status affects rumination time (RT), and the production, composition, coagulation properties (MCPs) and cheese yield (CY) of milk. One hundred early-lactating Holstein cows with no clinical signs of disease and fed total mixed rations were used. Rumen fluid was collected once from each cow by rumenocentesis to determine pH and volatile fatty acid (VFA) content. The cows were classified according to the quartile of rumen acidity (QRA), a factor defined by multivariate analysis and associated with VFA and pH. Rumen fluid pH averaged 5.61 in the first quartile and 6.42 in the fourth, and total VFA content increased linearly with increasing rumen acidity. In addition, RT increased as rumen acidity increased, but only in the daily time interval from 08:00 to 12:00. Milk yield linearly decreased as rumen acidity increased, whereas QRA did not affect pH, fat or protein contents of milk. Furthermore, the MCPs, assessed by lactodynamograph, and CY were unaffected by QRA. It is suggested that differences in rumen acidity have little influence on the nutrient content, coagulation properties and CY of milk.
Early Prediction of Breast Cancer Therapy Response using Multiresolution Fractal Analysis of DCE-MRI Parametric Maps

We aimed to determine whether multiresolution fractal analysis of voxel-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parametric maps can provide early prediction of breast cancer response to neoadjuvant chemotherapy (NACT). In total, 55 patients underwent 4 DCE-MRI examinations before, during, and after NACT. The shutter-speed model was used to analyze the DCE-MRI data and generate parametric maps within the tumor region of interest. The proposed multiresolution fractal method and the more conventional methods of single-resolution fractal, gray-level co-occurrence matrix, and run-length matrix were used to extract features from the parametric maps. Only the data obtained before and after the first NACT cycle were used to evaluate early prediction of response. With a training (N = 40) and testing (N = 15) data set, support vector machine was used to assess the predictive abilities of the features in classification of pathologic complete response versus non-pathologic complete response. Generally the multiresolution fractal features from individual maps and the concatenated features from all parametric maps showed better predictive performances than conventional features, with receiver operating curve area under the curve (AUC) values of 0.91 (all parameters) and 0.80 (Ktrans), in the training and testing sets, respectively. The differences in AUC were statistically significant (P < .05) for several parametric maps. Thus, multiresolution analysis that decomposes the texture at various spatial-frequency scales may more accurately capture changes in tumor vascular heterogeneity as measured by DCE-MRI, and therefore provide better early prediction of NACT response.
A computational scheme for internal models not requiring precise system parameters

Utilization by humans of a precise and adaptable internal model of the dynamics of the body in generating movements is a well-supported concept. The prevailing opinion is that such an internal model ceaselessly develops through long-term repetition and accumulation in the central nervous system (CNS). However, a long-term learning process would not be absolutely necessary for the formation of internal models. It is possible to estimate the dynamics of the system by using a motor command and its resulting output, instead of constructing a model of the dynamics with precise parameters. In this study, a computational model is proposed that uses a motor command and its corresponding output to estimate the dynamics of the system and it is examined whether the proposed model is capable of describing a series of empirical movements. The proposed model was found to be capable of describing humans’ fast movements which require compensation for system dynamics as well as sensory delays. In addition, the proposed model shows equifinality under inertial perturbations as seen in several experimental studies. This satisfactory reproducibility of the proposed computation raises the possibility that humans make a movement by estimating the system dynamics with a copy of motor command and sensory output on a momentary basis, without the need to identify precise system parameters.
Cardiac and mitochondrial function in HIV-uninfected fetuses exposed to antiretroviral treatment

Background Mitochondrial toxicity related to maternal combined antiretroviral treatment (cART) may have an impact on the heart of HIV-exposed uninfected (HEU) fetuses. Our objective was to evaluate fetal cardiovascular and mitochondrial biomarkers in HIV pregnancies. Methods Prospective cohort including 47 HIV-infected and 47 non HIV-infected pregnancies. Fetal echocardiography was performed at 26–32 weeks of pregnancy. Umbilical cord blood and placental tissue were collected to study mitochondrial DNA content (mtDNA) (ratio 12SrRNA/RNAseP) and mitochondrial function (cytochrome c oxidase, COX, enzymatic activity) normalized by mitochondrial content (citrate synthase, CS). Results HEU fetuses showed hypertrophic hearts (left myocardial wall thickness: HIV mean 3.21 mm (SD 0.81) vs. non-HIV 2.72 (0.42), p = 0.012), with signs of systolic and diastolic dysfunction (isovolumic relaxation time: HIV 52.2 ms (8.85) vs. non-HIV 42.5 ms (7.30); p<0.001). Cord blood mitochondrial content was significantly increased in HIV-exposed fetuses (CS activity: HIV 82.9 nmol/min.mg of protein (SD 40.5) vs. non-HIV 56.7 nmol/min.mg of protein (28.4); p = 0.007), with no differences in mtDNA content and COX activity. Both myocardial and mitochondrial mass parameters were significantly associated with zidovudine exposure. Conclusions HEU fetuses showed signs of increased myocardial and mitochondrial mass associated with maternal zidovudine treatment, suggesting a fetal adaptive response to cART toxicity.
Finite time dissipativity-based reliable control for time-varying system with delay and linear fractional uncertainties

ABSTRACT This paper is concerned with the problem of finite time dissipativity-based reliable control for a time-varying system with linear fractional uncertainty (LFU) and time delay. An actuator fault model consisting of both linear and nonlinear faults is considered during the time-varying control process. By implementing an augmented time-varying Lyapunov functional and using the Wirtinger-type integral inequality, delay-dependent finite time dissipative conditions are established in forms of derivative linear matrix inequalities (DLMIs), which can guarantee the closed-loop system is finite time dissipative for all admissible uncertainties. Then, the DLMIs are transformed into a series of recursive linear matrix inequalities (RLMIs) based on the discretization method. And an algorithm is given to solve the RLMIs to obtain the state feedback gain. Simulation results demonstrate the validity of the proposed approach.
Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse

Background Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. Methods Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40–41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. Results Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. Conclusions Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors.
Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants

Live attenuated vaccines (LAVs), if sufficiently safe, provide the most potent and durable anti-pathogen responses in vaccinees with single immunizations commonly yielding lifelong immunity. Historically, viral LAVs were derived by blind passage of virulent strains in cultured cells resulting in adaptation to culture and a loss of fitness and disease-causing potential in vivo. Mutations associated with these phenomena have been identified but rarely have specific attenuation mechanisms been ascribed, thereby limiting understanding of the attenuating characteristics of the LAV strain and applicability of the attenuation mechanism to other vaccines. Furthermore, the attenuated phenotype is often associated with single nucleotide changes in the viral genome, which can easily revert to the virulent sequence during replication in animals. Here, we have used a rational approach to attenuation of eastern equine encephalitis virus (EEEV), a mosquito-transmitted alphavirus that is among the most acutely human-virulent viruses endemic to North America and has potential for use as an aerosolized bioweapon. Currently, there is no licensed antiviral therapy or vaccine for this virus. Four virulence loci in the EEEV genome were identified and were mutated individually and in combination to abrogate virulence and to resist reversion. The resultant viruses were tested for virulence in mice to examine the degree of attenuation and efficacy was tested by subcutaneous or aerosol challenge with wild type EEEV. Importantly, all viruses containing three or more mutations were avirulent after intracerebral infection of mice, indicating a very high degree of attenuation. All vaccines protected from subcutaneous EEEV challenge while a single vaccine with three mutations provided reproducible, near-complete protection against aerosol challenge. These results suggest that informed mutation of virulence determinants is a productive strategy for production of LAVs even with highly virulent viruses such as EEEV. Furthermore, these results can be directly applied to mutation of analogous virulence loci to create LAVs from other viruses.
Irreversible climate change will also change environmental assessment and management

Environmental and management methods and procedures developed for the planet’s present climate will not be effective after irreversible climate change occurs. To quote Rubin (2009, p 17) ‘‘Suddenly the text books seem to be describing some other world than the one we live in. ’’ Because the results of climate change cannot be known until they do occur, the focus of new environmental and management methods and procedures is unknown at present, but professionals should be prepared to act when they are known. Anthropogenic greenhouse gas emissions are still rising, and reaching zero discharge of carbon dioxide is not probable as long as fossil fuels (petroleum, coal, natural gas) are a major source of energy. As a consequence, environmental changes that have already occurred are not likely to be reversed. ‘‘The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility . the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop’’ (Solomon et al. 2009, p 1704). ‘‘Global average temperatures increase while CO2 is increasing and then remain approximately constant (within __ 0.58C) until the end of the millennium despite zero further emissions . ’’ (Solomon et al. 2009, p 1705). Therefore, humankind is likely to experience climate change for 1000 years after anthropogenic carbon dioxide emissions cease. Nonanthropogenic carbon is in the atmosphere—e.g., drying wetlands, thawing permafrost—and these positive feedback loops are likely to accelerate. Rapid climate change may soon become the norm, and all humankind must adjust to it effectively. Obviously, global problems require global collaborations from the world’s nations. Failure to do so effectively will ensure that climate change continues. The encouraging aspect of collaboration and improvisation is that ‘‘carbon dioxide is the only greenhouse gas whose falloff displays multiple rather than single time constraints . Current emissions of major non-CO2 greenhouse gases such as methane or nitrous oxide are significant for climate change in the next few decades or century, but these gases do not persist over time in the same way as carbon dioxide’’ (Solomon et al. 2009, p 1705).
Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development

Cytomegalovirus (CMV) infection causes birth defects and life-threatening complications in immunosuppressed patients. Lack of vaccine and need for more effective drugs have driven widespread ongoing therapeutic development efforts against human CMV (HCMV), mostly using murine CMV (MCMV) as the model system for preclinical animal tests. The recent publication (Yu et al., 2017, DOI: 10.1126/science.aam6892) of an atomic model for HCMV capsid with associated tegument protein pp150 has infused impetus for rational design of novel vaccines and drugs, but the absence of high-resolution structural data on MCMV remains a significant knowledge gap in such development efforts. Here, by cryoEM with sub-particle reconstruction method, we have obtained the first atomic structure of MCMV capsid with associated pp150. Surprisingly, the capsid-binding patterns of pp150 differ between HCMV and MCMV despite their highly similar capsid structures. In MCMV, pp150 is absent on triplex Tc and exists as a “Λ”-shaped dimer on other triplexes, leading to only 260 groups of two pp150 subunits per capsid in contrast to 320 groups of three pp150 subunits each in a “Δ”-shaped fortifying configuration. Many more amino acids contribute to pp150-pp150 interactions in MCMV than in HCMV, making MCMV pp150 dimer inflexible thus incompatible to instigate triplex Tc-binding as observed in HCMV. While pp150 is essential in HCMV, our pp150-deletion mutant of MCMV remained viable though with attenuated infectivity and exhibiting defects in retaining viral genome. These results thus invalidate targeting pp150, but lend support to targeting capsid proteins, when using MCMV as a model for HCMV pathogenesis and therapeutic studies.
Exploring Community Smokers’ Perspectives for Developing a Chat-Based Smoking Cessation Intervention Delivered Through Mobile Instant Messaging: Qualitative Study

Background Advances in mobile communication technologies provide a promising avenue for the delivery of tobacco dependence treatment. Although mobile instant messaging (IM) apps (eg, WhatsApp, Facebook messenger, and WeChat) are an inexpensive and widely used communication tool, evidence on its use for promoting health behavior, including smoking cessation, is scarce. Objective This study aims to explore the perception of using mobile IM as a modality to deliver a proposed chat intervention for smoking cessation in community smokers in Hong Kong, where the proportion of smartphone use is among the highest in the world. Methods We conducted 5 focus group, semistructured qualitative interviews on a purposive sample of 15 male and 6 female current cigarette smokers (age 23-68 years) recruited from the community in Hong Kong. All interviews were audiotaped and transcribed. Two investigators independently analyzed the transcripts using thematic analyses. Results Participants considered mobile IM as a feasible and acceptable platform for the delivery of a supportive smoking cessation intervention. The ability to provide more personalized and adaptive behavioral support was regarded as the most valued utility of the IM–based intervention. Other perceived utilities included improved perceived psychosocial support and identification of motivator to quit. In addition, participants provided suggestions on the content and design of the intervention, which may improve the acceptability and usability of the IM–based intervention. These include avoiding health warning information, positive messaging, using former smokers as counselors, and adjusting the language style (spoken vs written) according to the recipients’ preference. Conclusions This qualitative study provides the first evidence that mobile IM may be an alternative mobile health platform for the delivery of a smoking cessation intervention. Furthermore, the findings inform the development of a chat-based, IM smoking cessation program being evaluated in a community trial.
Prehospital Management of Pediatric Hanging

Objectives Hanging may inflict laryngotracheal injuries and increase the potential for difficult airway management. We describe the management of pediatric hangings attended by an urban physician-led prehospital trauma service to provide information on a clinical situation encountered infrequently by most acute care clinicians. Methods Retrospective trauma registry-based observational study of all children younger than 16 years attended with hanging as mechanism of injury in the period between 2000 and 2014. Results Twenty-three thousand one hundred thirty patients were attended; 2415 (10%) of which were children. Of these, 32 cases (<1%) were pediatric hanging (1 case excluded due to missing data). There were 22 (71%) boys and 9 (29%) girls. Median age was 13 years. There was suicidal intent in 23 (74%) cases, and in 8 (26%) cases, hanging was accidental. There were 17 (55%) deaths, of which 14 (82%) were suicides. The doctor-paramedic team intubated 25 (80%) patients, with a 100% success rate. One (3%) patient was managed with a supraglottic airway device, and 5 (16%) patients did not require any advanced airway management. Conclusions Pediatric hanging is rare, but has a high mortality rate. Attempted suicide is the leading cause of hangings in children and preventive measures should target psychiatric morbidity. Despite concerns about airway edema or laryngeal injury, experienced doctor-paramedic teams had no failed airway attempts.
Creating objects with 3D printers to stimulate reminiscence in memory loss: A mixed-method feasibility study

ABSTRACT Objective. The objective of the current project was to determine the feasibility of using 3D printed technology to facilitate reminiscence-related activities for persons with memory loss (PWMLs). Methods. A parallel convergent mixed methods design was used. Fifteen PWMLs, 13 family members, and six staff from two residential long-term care facilities participated. Participants were observed and interviewed initially, during a 2-week reminiscence session, and again during a 1-month reminiscence session. Staff participants also completed a 1-month focus group, and staff and family members were administered a 3D printing review checklist at 1-month. Results. The integrated qualitative and quantitative data strongly suggested that PWMLs enjoyed using the 3D objects, were engaged while doing so and appeared to value the objects due to their personalized nature. The use of 3D printed objects also appeared to encourage family involvement as well as family and staff interactions with PWMLs. Barriers to use included memory impairment and behavioral issues. Conclusions. The use of 3D printed objects could provide an easy-to-use, well-received, person-centered approach that augments current reminiscence strategies for PWMLs.