Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of Life and Traditional Outcome Results at 1 Year in Elderly Patients Having Critical Limb Ischemia and the Role of Conservative Treatment

Introduction: Revascularization is the cornerstone of the treatment of critical limb ischemia (CLI), but the number of elderly frail patients increase. Revascularization is not always possible in these patients and conservative therapy seems to be an option. The goals of this study are to analyze the 1-year quality of life (QoL) results and mortality rates of elderly patients with CLI and to investigate if conservative treatment could be an acceptable treatment option. Methods: Patients with CLI ≥70 years old were included in a prospective observational cohort study in 2 hospitals in the Netherlands between 2012 and 2016 and were divided over 3 treatment modalities: endovascular therapy, surgical revascularization, and conservative treatment. The World Health Organization Quality of Life (WHOQoL-Bref) instrument, a generic QoL assessment tool that includes components of physical, psychological, social relationships and environment, was used to evaluate QoL at baseline, 6 months, and 1 year. Results: In total, 195 patients (56% male, 33% Rutherford 4, mean age of 80) were included. Physical QoL significantly increased after surgical (10.4 vs 14.9, P < .001), endovascular (10.9 vs 13.7, P < .001), and conservative therapy (11.6 vs 13.2, P = .01) at 1 year. One-year mortality was relatively low after surgery (10%) compared to endovascular (40%) and conservative therapy (37%). Conclusion: The results of this study could not be used to designate the superior treatment used in elderly patients with CLI. Conservative treatment could be an acceptable treatment option in selected patients with CLI unfit for revascularization. Treatment of choice in elderly patients with CLI is based on multiple factors and should be individualized in a shared decision-making process.
Do Changes in Blood Nutrient Levels Mediate Treatment Response in Children and Adults With ADHD Consuming a Vitamin–Mineral Supplement?

Objective: We investigated whether changes in serum nutrient levels mediate clinical response to a micronutrient intervention for ADHD. Method: Data were compiled from two ADHD trials (8-10 weeks), one in adults (n = 53) and one in children (n = 38). Seven outcomes included change in ADHD symptoms, mood, overall functioning (all clinician-rated) as well as response status. Change in serum/plasma nutrient levels (vitamins B12 and D, folate, ferritin, iron, zinc, and copper) were considered putative mediators. Results: A decrease in ferritin and an increase in copper were weakly associated with greater likelihood of being identified as an ADHD responder; none of the other nutrient biomarkers served as mediators. Conclusion: Further research looking at nutrients more broadly from other tissues are required to confirm these initial observations of the limited value of nutrient levels in deciphering mechanism of action. Monitoring these biomarkers on their own is unlikely helpful in understanding clinical response to a broad-spectrum micronutrient approach.
Stratification based on adverse laboratory/pathological features for predicting overall survival in patients undergoing radical prostatectomy

Abstract When making clinical decisions concerning additional treatment for patients who have undergone radical prostatectomy (RP), adverse laboratory/pathological features are considered major factors. We investigated and compared the prognostic efficacy of adverse laboratory/pathological features in predicting overall survival (OS) and biochemical failure (BCF) in these patients. The Korean Prostate Cancer Database was used to identify patients undergoing RP between May 2001 and April 2013. Patients with incomplete clinicopathological data or positive lymphadenectomy results were excluded. Finally, 4486 patients included in the final analysis were categorized based on their adverse laboratory/pathological features. Adverse pathological features and detectable prostate-specific antigen (PSA) levels 6 weeks after surgery were observed in 1977 (44.1%) and 634 (14.1%) patients, respectively. PSA levels, pathological Gleason score ≥8, adverse pathological features [positive surgical margin (PSM), seminal vesicle invasion (SVI), and extracapsular extension (ECE)], and adverse laboratory features (detectable PSA levels after 6 weeks) together were significant predictors of BCF-free survival (BCFFS). SVI was identified as a predictor of OS. Additionally, patients with ECE, PSM, and detectable PSA levels after 6 weeks, but without SVI, showed similar OS to those without ECE, PSM, and detectable PSA levels after 6 weeks and with SVI (log-rank test, P = .976). We successfully stratified patients based on adverse laboratory/pathological features after RP and demonstrated that these are important prognostic factors for OS and BCFFS. Additionally, we identified the criteria for selecting appropriate patients for undergoing additional treatment based on OS and BCFFS.
Use of a Blast Dominance–Hematogone Index for the Flow Cytometric Evaluation of Myelodysplastic Syndrome (MDS)

OBJECTIVES We tested whether combined flow cytometric assessment of loss of blast heterogeneity and decreased hematogones is a diagnostically useful approach for evaluation of myelodysplastic syndrome (MDS). METHODS Bone marrow samples from patients with known MDS were analyzed by 10-color flow cytometric immunophenotyping and compared with normal bone marrow samples. RESULTS There was loss of blast heterogeneity in patients with MDS compared with normal bone marrow samples, based on the relative size of the dominant blast population (83.0% vs 64.8%) and fewer hematogones (0.08% vs 1.39%). The size of the largest blast population divided by the fraction of hematogones (blast dominance-hematogone [BDH] index) was significantly larger in MDS compared with normal cases (27,084 vs 190, P < .0001; receiver operating characteristic area under the curve = 0.96). CONCLUSIONS The BDH index is more sensitive and specific than loss of blast heterogeneity or decrease in hematogones for detecting MDS in bone marrow samples and may be useful in clinical practice.
Endothelial miR-30c suppresses tumor growth via inhibition of TGF-&bgr;–induced Serpine1

In tumors, extravascular fibrin forms provisional scaffolds for endothelial cell (EC) growth and motility during angiogenesis. We report that fibrin-mediated angiogenesis was inhibited and tumor growth delayed following postnatal deletion of Tgfbr2 in the endothelium of Cdh5-CreERT2 Tgfbr2fl/fl mice (Tgfbr2iECKO mice). ECs from Tgfbr2iECKO mice failed to upregulate the fibrinolysis inhibitor plasminogen activator inhibitor 1 (Serpine1, also known as PAI-1), due in part to uncoupled TGF-&bgr;–mediated suppression of miR-30c. Bypassing TGF-&bgr; signaling with vascular tropic nanoparticles that deliver miR-30c antagomiRs promoted PAI-1–dependent tumor growth and increased fibrin abundance, whereas miR-30c mimics inhibited tumor growth and promoted vascular-directed fibrinolysis in vivo. Using single-cell RNA-Seq and a NanoString miRNA array, we also found that subtypes of ECs in tumors showed spectrums of Serpine1 and miR-30c expression levels, suggesting functional diversity in ECs at the level of individual cells; indeed, fresh EC isolates from lung and mammary tumor models had differential abilities to degrade fibrin and launch new vessel sprouts, a finding that was linked to their inverse expression patterns of miR-30c and Serpine1 (i.e., miR-30chi Serpine1lo ECs were poorly angiogenic and miR-30clo Serpine1hi ECs were highly angiogenic). Thus, by balancing Serpine1 expression in ECs downstream of TGF-&bgr;, miR-30c functions as a tumor suppressor in the tumor microenvironment through its ability to promote fibrin degradation and inhibit blood vessel formation.
Identification of etiologic agents and clinical characteristics for patients suspected of having pertussis in a large Children's Hospital in China.

Background In China, pertussis is a major health problem with an increasing incidence despite immunization efforts. Timely and accurate diagnosis is essential for the optimal management of pertussis, especially in severe cases. Methods Nasopharyngeal swabs or sputum specimens were obtained from patients suspected of having pertussis on the day of hospitalization at Shanghai Children's Medical Center from December 01, 2016, to November 30, 2017. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction (PCR) assay that detects 16 viruses, Bordetella pertussis (B. pertussis), Mycoplasma pneumoniae (M. pneumoniae), and Chlamydophila pneumoniae (C. pneumoniae). Results Among the 140 children studied, 50.0% (70/140) were detected with a single pathogen, 45.0% (63/140) were detected with multiple pathogens, and 5.0% (7/140) had no detected pathogens. Forty-nine (35%, 49/140) patients tested positive for B. pertussis. Respiratory syncytial virus (RSV), parainfluenza virus (Para) and rhinovirus/enterovirus (Rhino/Entero) were the most prevalent pathogens in patients with pertussis-like syndrome. No significant differences between the groups with pertussis and pertussis-like syndrome were observed regarding the clinical symptoms. Severe cases were more frequently observed in unvaccinated, premature and pertussis/RSV co-infection patients. Conclusions Our study highlights the importance of the timely and accurate diagnosis of pertussis based on both clinical symptoms and laboratory methods.
Ventral tegmental area disruption in Alzheimer’s disease

In the last World Alzheimer Report the global economic impact of Alzheimer’s Disease (AD) and dementias was estimated to be US$818 billion, with 47 million people suffering from AD and representing the 0.5% of the global population [1]. Despite the urgent need for interventions, currently there are no available therapies with the ability to modify the clinical course of AD. No tailored drugs for AD have been approved over the past 15 years, despite massively expensive trials aimed at tackling the disease. An often-cited explanation for the clinical trials’ failure is that they are set too late in the disease course. The cholinergic hypothesis of AD has been extensively investigated and prompted the current use of anticholinesterase inhibitors, whose efficacy is however extremely limited. It has been recently put forward the hypothesis that other neurotransmitter pathways are involved in AD pathophysiology with a special focus on the monoaminergic systems [2-4]. A recent work in a transgenic mice, harbouring human Amyloid Precursor Protein (APP) mutant allele linked to familial AD, demonstrated that degeneration of dopaminergic neurons in the ventral tegmental area (VTA) precedes the deposition of Aβ-plaques in the hippocampus [2]. VTA is a brainstem nucleus containing dopaminergic neurons that project diffusively to the brain cortex by direct and indirect pathways [2]. Interestingly, an association between measures of VTA disruption and memory impairment was previously shown in patients with early AD [3]. The dopaminergic system is known to be implicated in several cognitive and behavioural functions [5] and, importantly, may be modulated by pharmacological interventions [5]. Behavioural symptoms are known to be present since the early clinical stages of AD [6]. They strongly impact on patients’ global disability by causing high distress for the patients themselves and their caregivers. Against this background we recently investigated the potential relationship between disruption of VTA projections and behavioural disorders in patients with AD at different clinical stages [4]. We used functional brain magnetic resonance imaging (MRI) at rest, which has been previously shown to be highly sensitive to AD pathology [7], to selectively investigate the VTA-driven modulation of connectivity in AD brains and its impact on behavioural symptoms. Strikingly, when comparing AD patients to controls, we identified a pattern of disconnection between VTA and the rest of the brain that Editorial
Efficacy of exercise for improving functional outcomes for patients undergoing total hip arthroplasty

Background: The objective of this meta-analysis was aimed to illustrate the functional outcomes of exercise for total hip arthroplasty (THA) patients. Methods: In July, 2018, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on exercise for functional outcomes for THA patients were retrieved. The primary endpoint was walking speed. Other outcomes included physical activity scale, Harris hip score, pain scores, abduction strength, and the length of hospital stay. After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary. Results: Ten clinical studies with 441 patients were ultimately included in the meta-analysis. Compared with the control group, exercise was associated with an increase of the walking speed by 0.15 m/s than control group (weighted mean difference [WMD] 0.15; 95% confidence interval [CI] 0.08, 0.22; P = .000). Also, exercise group could also increase Harris hip score (WMD 8.49; 95% CI 5.19, 11.78; P = .000) and abduction strength than control group (WMD 9.75; 95% CI 5.33, 14.17; P = .000). What is more, exercise has a beneficial role in reducing the pain scores (WMD −1.32; 95% CI −2.07, −0.57; P = .001) and the length of hospital stay (WMD −0.68; 95% CI −1.07, −0.29; P = .001) than the control group. However, there was no significant difference between the physical activity scale (WMD −2.13; 95% CI −6.31, 2.05; P = .317). Conclusions: Compared with control group in the management of THA, postoperative exercise has a better pain relief and clinical outcomes. Considering the beneficial of the postoperative exercise, we take a positive attitude toward use exercise for patients with THA.
Fusing autonomy and sociality via embodied emergence and development of behaviour and cognition from fetal period

Human-centred AI/Robotics are quickly becoming important. Their core claim is that AI systems or robots must be designed and work for the benefits of humans with no harm or uneasiness. It essentially requires the realization of autonomy, sociality and their fusion at all levels of system organization, even beyond programming or pre-training. The biologically inspired core principle of such a system is described as the emergence and development of embodied behaviour and cognition. The importance of embodiment, emergence and continuous autonomous development is explained in the context of developmental robotics and dynamical systems view of human development. We present a hypothetical early developmental scenario that fills in the very beginning part of the comprehensive scenarios proposed in developmental robotics. Then our model and experiments on emergent embodied behaviour are presented. They consist of chaotic maps embedded in sensory–motor loops and coupled via embodiment. Behaviours that are consistent with embodiment and adaptive to environmental structure emerge within a few seconds without any external reward or learning. Next, our model and experiments on human fetal development are presented. A precise musculo-skeletal fetal body model is placed in a uterus model. Driven by spinal nonlinear oscillator circuits coupled together via embodiment, somatosensory signals are evoked and learned by a model of the cerebral cortex with 2.6 million neurons and 5.3 billion synapses. The model acquired cortical representations of self–body and multi-modal sensory integration. This work is important because it models very early autonomous development in realistic detailed human embodiment. Finally, discussions toward human-like cognition are presented including other important factors such as motivation, emotion, internal organs and genetic factors. This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction’.
Deep cerebellar stimulation reduces ataxic motor symptoms in the shaker rat

Degenerative cerebellar ataxias (DCAs) affect up to 1 in 5,000 people worldwide, leading to incoordination, tremor, and falls. Loss of Purkinje cells, nearly universal across DCAs, dysregulates the dentatothalamocortical network. To address the paucity of treatment strategies, we developed an electrical stimulation‐based therapy for DCAs targeting the dorsal dentate nucleus.
Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio‐facio‐cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r‐FLACC, Wang‐Baker scale, NPSI, BPI, NCCPC‐R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs‐QL, SF‐36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle‐skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level.
Warming impacts on boreal fen CO2 exchange under wet and dry conditions

Northern peatlands form a major soil carbon (C) stock. With climate change, peatland C mineralization is expected to increase, which in turn would accelerate climate change. A particularity of peatlands is the importance of soil aeration, which regulates peatland functioning and likely modulates the responses to warming climate. Our aim is to assess the impacts of warming on a southern boreal and a sub‐arctic sedge fen carbon dioxide (CO2) exchange under two plausible water table regimes: wet and moderately dry. We focused this study on minerotrophic treeless sedge fens, as they are common peatland types at boreal and (sub)arctic areas, which are expected to face the highest rates of climate warming. In addition, fens are expected to respond to environmental changes faster than the nutrient poor bogs. Our study confirmed that CO2 exchange is more strongly affected by drying than warming. Experimental water level draw‐down (WLD) significantly increased gross photosynthesis and ecosystem respiration. Warming alone had insignificant impacts on the CO2 exchange components, but when combined with WLD it further increased ecosystem respiration. In the southern fen, CO2 uptake decreased due to WLD, which was amplified by warming, while at northern fen it remained stable. As a conclusion, our results suggest that a very small difference in the WLD may be decisive, whether the C sink of a fen decreases, or whether the system is able to adapt within its regime and maintain its functions. Moreover, the water table has a role in determining how much the increased temperature impacts the CO2 exchange.
An evidence-based approach to evaluate the accuracy of amide proton transfer-weighted MRI in characterization of gliomas

Backgroud: To perform a meta-analysis to evaluate the diagnostic accuracy of the amide proton transfer (APT) technique in differentiating high-grade gliomas (HGGs) from low grade gliomas (LGGs). Methods: Medical literature databases were searched for studies that evaluated the diagnostic accuracy of APT in patients suspected of brain tumor who underwent APT MRI and surgery. Only English language studies and published before September 2018 were considered to be included in this project. Homogeneity was assessed by the inconsistency index. Mean difference (MD) at 95% confidence interval (CI) of all parameters derived from APT was calculated. Publication bias was explored by Egger's funnel plot. Results: Six eligible studies were included in the meta-analysis, comprising 144 HGGs and 122 LGGs. The APT-related parameter signal intensity (SI) was significantly higher in the HGG than the LGG (WMD = 0.86 (0.61–1.1), P < . 0001); A significant difference was also found between grade II and grade III (WMD = 0.6 (0.4–0.8), P < . 0001), and between grade II and grade IV (WMD = 1.07 (0.65–1.49), P < . 0001). Conclusions: APT imaging may be a useful imaging biomarker for discriminating between LGGs and HGGs. However, large randomized control trials (RCT) were necessary to evaluate its clinical value.
Values, quality, and evaluation in ethics consultation

ABSTRACT Background: The American Society for Bioethics and Humanities has recommended regular evaluation of the quality of health care ethics consultation. This article discusses the impact of ethics consultation on clinicians' perceptions of a patient's plan of care and on the personal values of clinicians who participated in an ethics consultation. Methods: Following institutional review board (IRB) approval, select data points were abstracted from case file report forms for ethics consultations over a 12-month period. Clinicians involved in the care of a patient who was the focus of an ethics consultation were invited to participate in an anonymous online survey. Clinicians who initiated an ethics consultation, were interviewed during the course of an ethics consultation, or were present at a patient care conference attended by an ethics consultant were invited to participate. A purposive sampling approach was used to invite clinicians to participate in an in-person interview. Results: The survey response rate was 44.4% (123 respondents from 277 invited). More than 60% of participants felt the consultation helped clarify the values of the patient and/or patient's family and helped them clarify their own values. Only 32% of participants indicated the patient's plan of care changed as a result of the ethics consultation, yet 75% indicated their confidence in the plan of care increased as a result of the ethics consultation. Preliminary findings from the qualitative interviews support the overall positive assessments reported by survey respondents. Conclusions: Ethics consultation can help clinicians clarify their own values and helps them clarify the values of patients and patients' families. Ethics consultation offers meaningful support when clinicians face ethically challenging cases, provides an opportunity to address moral distress, and is viewed favorably by those who experience the resource.