Miracle-dz/UniFAR-FTUs huggingface dataset:
Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage/repair factors (γH2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells—the defining feature of neoplasia.
Sesame Lignans Suppress Age-Related Cognitive Decline in Senescence-Accelerated Mice

Sesame lignans, which are biologically active compounds present in sesame seeds and oil, are known to have neuroprotective effects in several models of brain dysfunction. However, the effects of sesame lignans on age-related brain dysfunction are not clear and were thus investigated in the present study using a senescence-accelerated mouse (SAMP10). Two-month-old male SAMP10 mice were administrated a basal diet with 0% or 0.05% sesame lignans for two months, or with 0%, 0.02%, or 0.05% sesame lignans for 10 months and subjected to step-through passive avoidance tasks and forced swim tests. Reactive carbonyl species (RCs) were evaluated as markers of oxidative stress using a recently developed comprehensive analytical method. Both learning time in passive avoidance tasks and immobile time in forced swim tests became longer with aging (p < 0.05). However, the administration of sesame lignans significantly ameliorated age-related effects in both tests (p < 0.05). Age-related increases in RCs such as 4-hydroxy-2-nonenal in the cerebral cortex and liver were reduced in mice fed sesame lignans. These results suggest that sesame lignans can prevent age-related brain dysfunction via anti-oxidative activity.
A Review of the Capacitive MEMS for Seismology

MEMS (Micro Electro-Mechanical Systems) sensors enable a vast range of applications: among others, the use of MEMS accelerometers for seismology related applications has been emerging considerably in the last decade. In this paper, we provide a comprehensive review of the capacitive MEMS accelerometers: from the physical functioning principles, to the details of the technical precautions, and to the manufacturing procedures. We introduce the applications within seismology and earth sciences related disciplines, namely: earthquake observation and seismological studies, seismic surveying and imaging, structural health monitoring of buildings. Moreover, we describe how the use of the miniaturized technologies is revolutionizing these fields and we present some cutting edge applications that, in the very last years, are taking advantage from the use of MEMS sensors, such as rotational seismology and gravity measurements. In a ten-year outlook, the capability of MEMS sensors will certainly improve through the optimization of existing technologies, the development of new materials, and the implementation of innovative production processes. In particular, the next generation of MEMS seismometers could be capable of reaching a noise floor under the lower seismic noise (few tenths of ng/Hz) and expanding the bandwidth towards lower frequencies (∼0.01 Hz).
PTEN expression and mutations in TSC1, TSC2 and MTOR are associated with response to rapalogs in patients with renal cell carcinoma

The mammalian target of rapamycin (mTOR) pathway inhibitors are key drugs for the treatment of many tumor types, however, there are no predictive biomarkers in clinical use. Here, we performed a molecular and immunohistochemical characterization of key mTOR pathway components in a series of 105 renal cell carcinoma patients treated with rapalogs, aimed at identifying markers of treatment response. Mutational analysis in MTOR, TSC1 and TSC2 was performed through targeted next‐generation sequencing (NGS), and immunohistochemistry (IHC) was performed for PTEN, pAKT, pS6K1, pS6 and p21. Among patients with NGS data, 11 of 87 (13%) had mTOR pathway mutations (8 in MTOR, 1 in TSC1 and 2 in TSC2). When comparing the molecular data to the response of the patients, we found that partial response was more frequent in cases with mTOR pathway mutations than in those without mutations (odds ratio [OR] = 0.08, 95% confidence interval [CI] = 0.008–0.79, p = 0.030 univariate; p = 0.038 multivariable). Regarding IHC, negative PTEN staining was detected in 58% of the tumors, and it was more frequent in rapalog responder patients (OR = 0.24, 95% CI = 0.065–0.86, p = 0.029 univariate; p = 0.029 multivariable). Mutations and PTEN IHC were not mutually exclusive events and its combination improved response prediction (OR = 0.16, 95% CI = 0.04–0.62, p = 0.008 univariate; p = 0.013 multivariable). The staining of other proteins did not show and association with response and no association with PFS was observed in unselected patients. In conclusion, our findings suggest that mTOR pathway mutations, negative PTEN IHC and their combination are potential markers of rapalog response.
A Mutation in Histone H2B Represents a New Class of Oncogenic Driver.

By examination of the cancer genomics database we identified a new set of mutations in core histones that frequently recur in cancer patient samples and are predicted to disrupt nucleosome stability. In support of this idea, we characterized a glutamate to lysine mutation of histone H2B at amino acid 76 (H2B-E76K) found particularly in bladder and head and neck cancer that disrupts the interaction between H2B and H4. Although H2B-E76K forms dimers with H2A, it does not form stable histone octamers with H3 and H4 in vitro and when reconstituted with DNA forms unstable nucleosomes with increased sensitivity to nuclease. Expression of the equivalent H2B mutant in yeast restricted growth at high temperature and led to defective nucleosome-mediated gene repression. Significantly, H2B-E76K expression in the normal mammary epithelial cell line MCF10A increased cellular proliferation, cooperated with PIK3CA to promote colony formation, caused a significant drift in gene expression and fundamental changes in chromatin accessibility particularly at gene regulatory elements. Taken together, these data demonstrate that mutations in the globular domains of core histones may give rise to an oncogenic program due to nucleosome dysfunction and deregulation of gene expression.
Statistical Workflow for Feature Selection in Human Metabolomics Data

High-throughput metabolomics investigations, when conducted in large human cohorts, represent a potentially powerful tool for elucidating the biochemical diversity underlying human health and disease. Large-scale metabolomics data sources, generated using either targeted or nontargeted platforms, are becoming more common. Appropriate statistical analysis of these complex high-dimensional data will be critical for extracting meaningful results from such large-scale human metabolomics studies. Therefore, we consider the statistical analytical approaches that have been employed in prior human metabolomics studies. Based on the lessons learned and collective experience to date in the field, we offer a step-by-step framework for pursuing statistical analyses of cohort-based human metabolomics data, with a focus on feature selection. We discuss the range of options and approaches that may be employed at each stage of data management, analysis, and interpretation and offer guidance on the analytical decisions that need to be considered over the course of implementing a data analysis workflow. Certain pervasive analytical challenges facing the field warrant ongoing focused research. Addressing these challenges, particularly those related to analyzing human metabolomics data, will allow for more standardization of as well as advances in how research in the field is practiced. In turn, such major analytical advances will lead to substantial improvements in the overall contributions of human metabolomics investigations.
Non-Invasive Ambient Intelligence in Real Life: Dealing with Noisy Patterns to Help Older People

This paper aims to contribute to the field of ambient intelligence from the perspective of real environments, where noise levels in datasets are significant, by showing how machine learning techniques can contribute to the knowledge creation, by promoting software sensors. The created knowledge can be actionable to develop features helping to deal with problems related to minimally labelled datasets. A case study is presented and analysed, looking to infer high-level rules, which can help to anticipate abnormal activities, and potential benefits of the integration of these technologies are discussed in this context. The contribution also aims to analyse the usage of the models for the transfer of knowledge when different sensors with different settings contribute to the noise levels. Finally, based on the authors’ experience, a framework proposal for creating valuable and aggregated knowledge is depicted.
NMR Based Metabolomics Comparison of Different Blood Sampling Techniques in Awake and Anesthetized Rats

The composition of body fluids has become one of the most commonly used methods for diagnosing various diseases or monitoring the drug responses, especially in serum/plasma. It is therefore vital for investigators to find an appropriate way to collect blood samples from laboratory animals. This study compared blood samples collected from different sites using the NMR based metabolomics approach. Blood samples were collected from the saphenous vein (awake state), tail vein (awake and anesthetized states after administration of sevoflurane or pentobarbital) and the inferior thoracic vena cava (ITVC, anesthetized state). These approaches from the saphenous and tail veins have the potential to enable the collection of multiple samples, and the approach from ITVC is the best method for the collection of blood for the terminate state. The compositions of small molecules in the serum were determined using the 1H-NMR method, and the data were analyzed with traditional correlation analysis, principle component analysis (PCA) and OPLS-DA methods. The results showed that acute anesthesia significantly influenced the composition of serum in a very short period, such as the significant increase in glucose, and decrease in lactate. This indicates that it is better to obtain blood samples under the awake state. From the perspective of animal welfare and multiple sampling, the current study shows that the saphenous vein and tail vein are the best locations to collect multiple blood samples for a reduced risk of injury in the awake state. Furthermore, it is also suitable for investigating pharmacokinetics and the effects of drug intervention on animals.
Linear periodization of strength training in blocks attenuates hypertension and diastolic dysfunction with normalization of myocardial collagen content in spontaneously hypertensive rats.

BACKGROUND AND METHOD This study evaluated the effects of a linear block strength training programme on the parameters of cardiac remodelling in spontaneously hypertensive rats. Thirty-nine rats were equally distributed in four groups: normotensive sedentary (N), normotensive trained, hypertensive sedentary (H) and hypertensive trained. The strength training protocol was organized in three mesocycles of 4 weeks, with an increase in the training load organized in a linear fashion for each block, considering the weight established in the maximum loaded load test. The following parameters were evaluated: ventricular function assessed by echocardiogram, caudal blood pressure, ventricular haemodynamics and cardiac masses. Two-way analysis of variance was used to determine the differences between the group and time. RESULTS After 12 weeks of training, the hypertensive trained group presented the following results: increased muscle strength, reduced blood pressure, reduced heart rate, isovolumetric relaxation time and total collagen content, with increased cardiac function, without promoting changes in the mass and nuclear volume of cardiomyocytes. Also, blood pressure reduction seems to be associated with both muscle strength adjustments and total load progress. CONCLUSION The findings of this study showed that the training programme carried out attenuated systemic arterial pressure and preserved the ventricular function of spontaneously hypertensive rats without cardiac mass change.
Selection of the Optimal Puncture Needle for Induction of a Rat Intervertebral Disc Degeneration Model.

BACKGROUND The incidence of intervertebral disc (IVD) degeneration has increased in recent years. A simple, reliable, and reproducible animal model is critical for understanding the underlying mechanisms of IVD degeneration. The caudal discs of rats have been proposed as a common puncture model in which to induce IVD degeneration. However, there is still no consensus on the size of needle to be used. OBJECTIVES The present study aimed to identify the appropriate needle size to establish an IVD degeneration model. STUDY DESIGN A randomized, experimental trial. SETTING Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, China. METHODS Validity was verified by magnetic resonance imaging (MRI) and histology. RESULTS From T2-weighted MRI imaging and histological examination, the IVD punctured by the 16-gauge needle degenerated acutely one week after the operation, whereas the 26-gauge needle puncture did no harm to the IVD. An 18-gauge needle showed a progressive degeneration in IVD. LIMITATIONS The observation period was not very long (4 weeks). CONCLUSIONS An 18-gauge needle can be used to induce IVD degeneration in rats. Therefore, an 18-gauge needle is the optimal selection to establish the degenerative IVD model on rats, whereas the 26-gauge needle failed to cause IVD degeneration. Thus, to study the prevention and treatment of IVD degeneration, a 26-gauge needle can be used for IVD injection of growth factors, plasmids, and drugs. A 16-gauge needle may be used to induce acute disc injury, but not IVD degeneration. KEY WORDS Low back pain, degenerative intervertebral disc, animal model, puncture needle, rat model, optimal choice.
Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease

ABSTRACT Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. More high-throughput in vivo systems are required to rapidly evaluate therapeutic agents. We visualize, in zebrafish, the effects on epithelial barrier function and intestinal autophagy of one-course and repetitive injury. Repetitive injury induces increased mortality, impaired recovery of intestinal barrier function, failure to contain bacteria within the intestine and impaired autophagy. Prostaglandin E2 (PGE2) administration protected against injury by enhancing epithelial barrier function and limiting systemic infection. Effects of IBD therapeutic agents were defined: mesalamine showed protective features during injury, whereas 6-mercaptopurine displayed marked induction of autophagy during recovery. Given the highly conserved nature of innate defense in zebrafish, it represents an ideal model system with which to test established and new IBD therapies targeted to the epithelial barrier. This article has an associated First Person interview with the first author of the paper. Summary: As IBD attempts to enter the era of precision medicine, our models provide an opportunity for the rapid and sophisticated determination of time course, cellular contributions and mechanisms of new drugs.
Exploring mental illness stigma among Asian men mobilized to become Community Mental Health Ambassadors in Toronto Canada

ABSTRACT Background Stigma of mental illness contributes to silence, denial and delayed help seeking. Existing stigma reduction strategies seldom consider gender and cultural contexts. Purpose The Strengths in Unity study was a multi-site Canadian study that engaged Asian men in three stigma reduction interventions (ACT, CEE, psychoeducation) and mobilized them as Community Mental Health Ambassadors. Our participants included both men living with or affected by mental illness (LWA) as well as community leaders (CL). This paper will: (1) describe the baseline characteristics of the Toronto participants including their sociodemographic information, mental illness stigma (CAMI and ISMI), attitudes towards social change (SJS), and intervention-related process variables (AAQ-II, VLQ, FMI, Empowerment); (2) compare the differences among these variables between LWA and CL; and (3) explore factors that may correlate with socio-economic status and mental health stigma. Results A total of 609 Asian men were recruited in Toronto, Canada. Both CL and LWA had similar scores on measures of external and internalized stigma and social change attitudes, except that LWA had more positive views about the acceptance and integration of those with mental illness into the community on the CAMI, while CL had a higher level of perceived behavioral control on the SJS. Group differences were also observed between LWA and CL in some process-related variables. Exploratory analysis suggests that younger and more educated participants had lower stigma. Conclusion Our findings underscore the importance of engaging both community leaders and people with lived experience as mental health advocates to address stigma.
Comparative efficacy of gypsy moth (Lepidoptera: Erebidae) entomopathogens on transgenic blight‐tolerant and wild‐type American, Chinese, and hybrid chestnuts (Fagales: Fagaceae)

American chestnut (Castanea dentata [Marsh.] Borkh.) was once the dominant hardwood species in Eastern North America before an exotic fungal pathogen, Cryphonectria parasitica (Murrill) Barr, functionally eliminated it across its range. One promising approach toward restoring American chestnut to natural forests is development of blight‐tolerant trees using genetic transformation. However, transformation and related processes can result in unexpected and unintended phenotypic changes, potentially altering ecological interactions. To assess unintended tritrophic impacts of transgenic American chestnut on plant–herbivore interactions, gypsy moth (Lymantria dispar L.) caterpillars were fed leaf disks excised from two transgenic events, Darling 54 and Darling 58, and four control American chestnut lines. Leaf disks were previously treated with an LD50 dose of either the species‐specific Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) or the generalist pathogen Bacillus thuringiensis subsp. kurstaki (Btk). Mortality was quantified and compared to water blank controls. Tree genotype had a strong effect on the efficacies of both pathogens. Larval mortality from Btk‐treated foliage from only one transgenic event, Darling 54, differed from its isogenic progenitor, Ellis 1, but was similar to an unrelated wild‐type American chestnut control. LdMNPV efficacy was unaffected by genetic transformation. Results suggest that although genetic modification of trees may affect interactions with other nontarget organisms, this may be due to insertion effects, and variation among different genotypes (whether transgenic or wild‐type) imparts a greater change in response than transgene presence.
Deep Multi-Layer Perception Based Terrain Classification for Planetary Exploration Rovers

Accurate classification and identification of the detected terrain is the basis for the long-distance patrol mission of the planetary rover. But terrain measurement based on vision and radar is subject to conditions such as light changes and dust storms. In this paper, under the premise of not increasing the sensor load of the existing rover, a terrain classification and recognition method based on vibration is proposed. Firstly, the time-frequency domain transformation of vibration information is realized by fast Fourier transform (FFT), and the characteristic representation of vibration information is given. Secondly, a deep neural network based on multi-layer perception is designed to realize classification of different terrains. Finally, combined with the Jackal unmanned vehicle platform, the XQ unmanned vehicle platform, and the vibration sensor, the terrain classification comparison test based on five different terrains was completed. The results show that the proposed algorithm has higher classification accuracy, and different platforms and running speeds have certain influence on the terrain classification at the same time, which provides support for subsequent practical applications.
Value-based Healthcare: Can Artificial Intelligence Provide Value in Orthopaedic Surgery?

Artificial intelligence (AI), broadly defined as a “branch of computer science that simulates intelligent behavior in computers” [9], has expanded into the healthcare sector with the promise of enhanced predictive, diagnostic, and decision-making capabilities [11]. The accelerating allure of AI in health care has been fueled by growing datasets, algorithmic innovation, storage capacity, and the steep rise in affordable computational power [11]. But can AI-related applications provide value in orthopaedic surgery? Famed physicist, author, and cosmologist Stephen Hawking stated that AIwill either be the best orworst thing to happen to humanity [3]. While we may be a long way off from a Hollywoodstyled “rise of the machines,” focusing our AI efforts on value may help us to transform orthopaedic health care. We believe value-oriented AI-related applications in orthopaedics might best focus on three domains: (1) Advanced data discovery and extraction, (2) improved diagnostics and prediction, and (3) enhanced clinical and decision support.