Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificial Intelligence for the Artificial Kidney: Pointers to the Future of a Personalized Hemodialysis Therapy

Background: Current dialysis devices are not able to react when unexpected changes occur during dialysis treatment or to learn about experience for therapy personalization. Furthermore, great efforts are dedicated to develop miniaturized artificial kidneys to achieve a continuous and personalized dialysis therapy, in order to improve the patient’s quality of life. These innovative dialysis devices will require a real-time monitoring of equipment alarms, dialysis parameters, and patient-related data to ensure patient safety and to allow instantaneous changes of the dialysis prescription for the assessment of their adequacy. The analysis and evaluation of the resulting large-scale data sets enters the realm of “big data” and will require real-time predictive models. These may come from the fields of machine learning and computational intelligence, both included in artificial intelligence, a branch of engineering involved with the creation of devices that simulate intelligent behavior. The incorporation of artificial intelligence should provide a fully new approach to data analysis, enabling future advances in personalized dialysis therapies. With the purpose to learn about the present and potential future impact on medicine from experts in artificial intelligence and machine learning, a scientific meeting was organized in the Hospital Universitari Bellvitge (L’Hospitalet, Barcelona). As an outcome of that meeting, the aim of this review is to investigate artificial intel ligence experiences on dialysis, with a focus on potential barriers, challenges, and prospects for future applications of these technologies. Summary and Key Messages: Artificial intelligence research on dialysis is still in an early stage, and the main challenge relies on interpretability and/or comprehensibility of data models when applied to decision making. Artificial neural networks and medical decision support systems have been used to make predictions about anemia, total body water, or intradialysis hypotension and are promising approaches for the prescription and monitoring of hemodialysis therapy. Current dialysis machines are continuously improving due to innovative technological developments, but patient safety is still a key challenge. Real-time monitoring systems, coupled with automatic instantaneous biofeedback, will allow changing dialysis prescriptions continuously. The integration of vital sign monitoring with dialysis parameters will produce large data sets that will require the use of data analysis techniques, possibly from the area of machine learning, in order to make better decisions and increase the safety of patients.
Osteophytes and fracture calluses share developmental milestones and are diminished by unloading

Osteophytes are a typical radiographic finding during osteoarthritis (OA), but the mechanisms leading to their formation are not well known. Comparatively, fracture calluses have been studied extensively; therefore, drawing comparisons between osteophytes and fracture calluses may lead to a deeper understanding of osteophyte formation. In this study, we compared the time courses of osteophyte and fracture callus formation, and investigated mechanisms contributing to development of these structure. Additionally, we investigated the effect of mechanical unloading on the formation of both fracture calluses and osteophytes. Mice underwent either transverse femoral fracture or non‐invasive anterior cruciate ligament rupture. Fracture callus and osteophyte size and ossification were evaluated after 3, 5, 7, 14, 21, or 28 days. Additional mice were subjected to hindlimb unloading after injury for 3, 7, or 14 days. Protease activity and gene expression profiles after injury were evaluated after 3 or 7 days of normal ambulation or hindlimb unloading using in vivo fluorescence reflectance imaging (FRI) and quantitative PCR. We found that fracture callus and osteophyte growth achieved similar developmental milestones, but fracture calluses formed and ossified at earlier time points. Hindlimb unloading ultimately led to a threefold decrease in chondro/osteophyte area, and a twofold decrease in fracture callus area. Unloading was also associated with decreased inflammation and protease activity in injured limbs detected with FRI, particularly following ACL rupture. qPCR analysis revealed disparate cellular responses in fractured femurs and injured joints, suggesting that fracture calluses and osteophytes may form via different inflammatory, anabolic, and catabolic pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:699–710, 2018.
Predictive control of plastic melt in heated zones with insulation

The control of plastic melt temperature is important for maintaining product quality and for reducing injection molding production costs. Insulating the heated zones of an injection molding machine can significantly reduce the energy requirements of the polymer melting process. Conventional control approaches do not always provide good control of these machines. This has also limited the use of insulation of the heated zones. It has been shown previously that the model predictive control approach can provide an improved control of plastic melt temperature for the injection molding process. However, the past work was conducted on un-insulated machines. This paper investigates the model predictive control of plastic melt temperature on an insulated injection molding machine barrel. The experimental results show that this approach results in good control of the melt temperature, and that the energy consumption can be reduced by as much as 30% when barrel insulation is used.
Fetal heart rate feature extraction from cardiotocographic recordings through autoregressive model's power spectral- and pole-based analysis

The main objective of this work is to perform an autoregressive model (AR)-based power spectral analysis of the fetal heart rate (FHR) signal for the extraction of significant features for fetal welfare assessment. A group of features is directly computed from the AR-based spectrum while another group is computed from the poles representation. The presented method is applied to real cardiotocographic (CTG) signals and for different frequency bands, and the obtained results are very promising as they exhibit direct correlations between the extracted features and the fetal welfare in terms of umbilical pH.
Job-Related Stress in Forensic Interviewers of Children with Use of Therapy Dogs Compared with Facility Dogs or No Dogs

Sexually abused children providing essential testimony regarding crimes in forensic interviews now sometimes are provided facility dogs or therapy dogs for comfort. Facility dogs are extensively trained to work with forensic interviewers; when using therapy dogs in interviews, volunteers are the dog handlers. Interviews can impact child welfare workers’ mental health causing secondary traumatic stress (STS). To investigate this stress, first data were gathered on stress retrospectively for when interviewers initially started the job prior to working with a dog, and then currently, from forensic interviewers using a facility dog, a therapy or pet dog, or no dog. These retrospective and secondary traumatic stress scale (STSS) data compared job stress among interviewers of children using: a certified, workplace facility dog (n = 16), a volunteer’s trained therapy dog or the interviewer’s pet dog (n = 13/3), or no dog (n = 198). Retrospective scores of therapy dog and no dog interviewers’ stress were highest for the first interviewing year 1 and then declined. Extremely or very stressful retrospective scores differed among the three groups in year 1 (p < 0.038), and were significantly elevated for the therapy dog group as compared with the facility dog group (p < 0.035). All interviewing groups had elevated STSS scores; when compared with other healthcare groups that have been studied, sub-scores were especially high for Avoidance: a psychological coping mechanism to avoid dealing with a stressor. STSS scores differed among groups (p < 0.016), primarily due to Avoidance sub-scores (p < 0.009), reflecting higher Avoidance scores for therapy dog users than no dog users (p < 0.009). Facility dog users more consistently used dogs during interviews and conducted more interviews than therapy/pet dog users; both groups favored using dogs. Interviewers currently working with therapy dogs accompanied by their volunteers reported they had experienced heightened stress when they began their jobs; their high stress levels still persisted, indicating lower inherent coping skills and perhaps greater empathy among interviewers who later self-selected to work with therapy dogs. Results reveal extreme avoidant stress for interviewers witnessing children who are suffering and their differing coping approaches.
A multi-criteria evaluation method for assessing the defibrillation outcome of different electrode placements in swine

Compared with clinical and experimental approaches, numerical modeling of defibrillation offers a great opportunity to optimize the defibrillation strategy in a more individualized way. Through numerical simulation of the shock-induce electric field distribution, the outcome of a certain defibrillation shock could be predicted according to several different metrics. In this paper, we propose a novel evaluation method, in which four defibrillation criteria are assigned with separate weighting factors to quantitatively assess the efficiency of a certain defibrillation shock. Three anatomically realistic finite element models of swine were constructed for the evaluation study of 8 electrode pairs in different placements. In addition, corresponding animal experiments were performed to determine the defibrillation threshold of 8 electrode placements. Both computational and experimental results suggest that the clinical recommended anterior-lateral position is the most efficient electrode displacement for transthoracic defibrillation in swine. In conclusion, the good agreement between stimulations and experiments indicates that the present multi-criteria evaluation method would be potentially useful for optimizations of cardiac defibrillation outcome.
Mutual Interplay between the Human Cytomegalovirus Terminase Subunits pUL51, pUL56, and pUL89 Promotes Terminase Complex Formation

ABSTRACT Human cytomegalovirus (HCMV) genome encapsidation requires several essential viral proteins, among them pUL56, pUL89, and the recently described pUL51, which constitute the viral terminase. To gain insight into terminase complex assembly, we investigated interactions between the individual subunits. For analysis in the viral context, HCMV bacterial artificial chromosomes carrying deletions in the open reading frames encoding the terminase proteins were used. These experiments were complemented by transient-transfection assays with plasmids expressing the terminase components. We found that if one terminase protein was missing, the levels of the other terminase proteins were markedly diminished, which could be overcome by proteasome inhibition or providing the missing subunit in trans. These data imply that sequestration of the individual subunits within the terminase complex protects them from proteasomal turnover. The finding that efficient interactions among the terminase proteins occurred only when all three were present together is reminiscent of a folding-upon-binding principle leading to cooperative stability. Furthermore, whereas pUL56 was translocated into the nucleus on its own, correct nuclear localization of pUL51 and pUL89 again required all three terminase constituents. Altogether, these features point to a model of the HCMV terminase as a multiprotein complex in which the three players regulate each other concerning stability, subcellular localization, and assembly into the functional tripartite holoenzyme. IMPORTANCE HCMV is a major risk factor in immunocompromised individuals, and congenital CMV infection is the leading viral cause for long-term sequelae, including deafness and mental retardation. The current treatment of CMV disease is based on drugs sharing the same mechanism, namely, inhibiting viral DNA replication, and often results in adverse side effects and the appearance of resistant virus strains. Recently, the HCMV terminase has emerged as an auspicious target for novel antiviral drugs. A new drug candidate inhibiting the HCMV terminase, Letermovir, displayed excellent potency in clinical trials; however, its precise mode of action is not understood yet. Here, we describe the mutual dependence of the HCMV terminase constituents for their assembly into a functional terminase complex. Besides providing new basic insights into terminase formation, these results will be valuable when studying the mechanism of action for drugs targeting the HCMV terminase and developing additional substances interfering with viral genome encapsidation.
Tick-Borne Viruses and Biological Processes at the Tick-Host-Virus Interface

Ticks are efficient vectors of arboviruses, although less than 10% of tick species are known to be virus vectors. Most tick-borne viruses (TBV) are RNA viruses some of which cause serious diseases in humans and animals world-wide. Several TBV impacting human or domesticated animal health have been found to emerge or re-emerge recently. In order to survive in nature, TBV must infect and replicate in both vertebrate and tick cells, representing very different physiological environments. Information on molecular mechanisms that allow TBV to switch between infecting and replicating in tick and vertebrate cells is scarce. In general, ticks succeed in completing their blood meal thanks to a plethora of biologically active molecules in their saliva that counteract and modulate different arms of the host defense responses (haemostasis, inflammation, innate and acquired immunity, and wound healing). The transmission of TBV occurs primarily during tick feeding and is a complex process, known to be promoted by tick saliva constituents. However, the underlying molecular mechanisms of TBV transmission are poorly understood. Immunomodulatory properties of tick saliva helping overcome the first line of defense to injury and early interactions at the tick-host skin interface appear to be essential in successful TBV transmission and infection of susceptible vertebrate hosts. The local host skin site of tick attachment, modulated by tick saliva, is an important focus of virus replication. Immunomodulation of the tick attachment site also promotes co-feeding transmission of viruses from infected to non-infected ticks in the absence of host viraemia (non-viraemic transmission). Future research should be aimed at identification of the key tick salivary molecules promoting virus transmission, and a molecular description of tick-host-virus interactions and of tick-mediated skin immunomodulation. Such insights will enable the rationale design of anti-tick vaccines that protect against disease caused by tick-borne viruses.
Variations on the theme of musical expertise: cognitive and sensory processing in percussionists, vocalists and non‐musicians

Comparisons of musicians and non‐musicians have revealed enhanced cognitive and sensory processing in musicians, with longitudinal studies suggesting these enhancements may be due in part to experience‐based plasticity. Here, we investigate the impact of primary instrument on the musician signature of expertise by assessing three groups of young adults: percussionists, vocalists, and non‐musician controls. We hypothesize that primary instrument engenders selective enhancements reflecting the most salient acoustic features to that instrument, whereas cognitive functions are enhanced regardless of instrument. Consistent with our hypotheses, percussionists show more precise encoding of the fast‐changing acoustic features of speech than non‐musicians, whereas vocalists have better frequency discrimination and show stronger encoding of speech harmonics than non‐musicians. There were no strong advantages to specialization in sight‐reading vs. improvisation. These effects represent subtle nuances to the signature since the musician groups do not differ from each other in these measures. Interestingly, percussionists outperform both non‐musicians and vocalists in inhibitory control. Follow‐up analyses reveal that within the vocalists and non‐musicians, better proficiency on an instrument other than voice is correlated with better inhibitory control. Taken together, these outcomes suggest the more extensive engagement of motor systems during instrumental practice may be an important factor for enhancements in inhibitory control, consistent with evidence for overlapping neural circuitry involved in both motor and cognitive control. These findings contribute to the ongoing refinement of the musician signature of expertise and may help to inform the use of music in training and intervention to strengthen cognitive function.
Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling

Based on the latest gnomAD dataset, the prevalence of symptomatic hereditary cerebral cavernous malformations (CCMs) prone to cause epileptic seizures and stroke-like symptoms was re-evaluated in this review and calculated to be 1:5,400-1:6,200. Furthermore, state-of-the-art molecular genetic analyses of the known CCM loci are described which reach an almost 100% mutation detection rate for familial CCMs if whole genome sequencing is performed for seemingly mutation-negative families. An update on the spectrum of CCM1, CCM2, and CCM3 mutations demonstrates that deep-intronic mutations and submicroscopic copy-number neutral genomic rearrangements are rare. Finally, this review points to current guidelines on genetic counselling, neuroimaging, medical as well as neurosurgical treatment and highlights the formation of active patient organizations in various countries.
Ipilimumab: An Anti-CTLA-4 Antibody for Metastatic Melanoma

Ipilimumab (MDX-010, Yervoy; Bristol-Myers Squibb), a fully human monoclonal antibody against CTL antigen 4 (CTLA-4), was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. In both early- and late-phase trials, ipilimumab has shown consistent activity against melanoma. For example, in a randomized phase III trial that enrolled patients with previously treated metastatic disease, ipilimumab, with or without a peptide vaccine, improved overall survival: Median overall survival was 10.1 and 10.0 months in the ipilimumab and ipilimumab plus vaccine arms, respectively, versus 6.4 months in the vaccine-alone group (hazard ratio, 0.68; P ≤ 0.003). Serious (grade 3–5) immune-related adverse events occurred in 10% to 15% of patients. Thus, although it provides a clear survival benefit, ipilimumab administration requires careful patient monitoring and sometimes necessitates treatment with immune-suppressive therapy. Here, we review the mechanism of action, preclinical data, and multiple clinical trials that led to FDA approval of ipilimumab for metastatic melanoma. Clin Cancer Res; 17(22); 6958–62. ©2011 AACR.
Patterns of motor branching of the musculocutaneous nerve in human fetuses and clinical significance

The purpose of this morphologic study is to investigate the course and the branching pattern of motor branches of musculocutaneous nerve (MCN) in human fetuses. Twenty upper limbs (10 right, 10 left) of spontaneously aborted formalin‐fixed fetuses were dissected under a stereomicroscope to determine motor branches for the biceps brachii and brachialis and the communicating branches between the MCN and median nerve (MN). The MCN entered the proximal and middle part of coracobrachialis in 13/20 and 5/20 of arms, respectively, and the remaining 2/20 did not pierce coracobrachialis. The communication between MCN and MN was observed in 5/20 of the arms and detected only in the distal part of the coracobrachialis. The most frequently observed innervation is the type wherein a single branch to biceps brachii, which bifurcated for supplying the short and long heads (12/20). For the innervation of brachialis, the most frequent type was a single branch from the main trunk of the MCN (15/20). During the dissections, the distance between the acromion and the emerging point of the motor branches was measured. The mean distance between the acromion and the emerging point of the all motor branches for biceps brachii in all types of specimens was 33.8 ± 6.1% of acromion‐lateral epicondyle length and for brachialis was 50.6 ± 11.5% of acromion‐lateral epicondyle length. The data of the MCN variations in the human fetus may be useful for the clinicians and pediatric surgery. Clin. Anat. 24:168–178, 2011. © 2011 Wiley‐Liss, Inc.
Quantitative Assessments of Mechanical Responses upon Radial Extracorporeal Shock Wave Therapy

Although radial extracorporeal shock wave therapy (rESWT) has been widely used to treat orthopedic disorders with promising clinical results, rESWT largely relies on clinicians' personal experiences and arbitrary judgments, without knowing relationships between administration doses and effective doses at target sites. In fact, practitioners lack a general and reliable way to assess propagation and distribution of pressure waves inside biological tissues quantitatively. This study develops a methodology to combine experimental measurements and computational simulations to obtain pressure fields from rESWT through calibrating and validating computational models with experimental measurements. Wave pressures at the bottom of a petri dish and inside biological tissues are measured, respectively, by attaching and implanting flexible membrane sensors. Detailed wave dynamics are simulated through explicit finite element analyses. The data decipher that waves from rESWT radiate directionally and can be modeled as acoustic waves generated from a vibrating circular piston. Models are thus established to correlate pressure amplitudes at the bottom of petri dishes and in the axial direction of biological tissues. Additionally, a pilot simulation upon rESWT for human lumbar reveals a detailed and realistic pressure field mapping. This study will open a new avenue of personalized treatment planning and mechanism research for rESWT.
INVITED REVIEW SERIES: SEEKING INNOVATIVE SOLUTIONS IN SEVERE ASTHMA

Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e.g. anti-IL-5 and anti-IgE). These therapies are effective in relevant subsets of severe asthma patients. Unfortunately, non-allergic/noneosinophilic asthma, steroid resistance and disease exacerbation remain areas of unmet clinical need. No mouse model encompasses all features of severe asthma. However, mouse models can provide insight into pathogenic pathways that are relevant to severe asthma. In this review, as examples, we highlight models relevant to understanding steroid resistance, chronic tissue remodelling and disease exacerbation. Although these models highlight the complexity of the immune pathways that may underlie severe asthma, they also provide insight into new potential therapeutic approaches.