Miracle-dz/UniFAR-FTUs huggingface dataset:
Manual Cultivation Operations in Poplar Stands: A Characterization of Job Difficulty and Risks of Health Impairment

Short rotation poplar forests are a viable alternative in producing high quality wood for industrial applications. Their success depends on timely and high-quality implementation of a series of operations. Weed control operations are implemented to favor the trees in their competition for soil resources, and cultivation is an option typically used in many European countries. For the moment, a complete mechanization of such operations is virtually impossible, and they still require an intensive use of manual labor. Since information on work difficulty and risks in manual cultivation operations is limited, this study aimed to characterize this job. Evaluation was made in terms of work efficiency, cardiovascular workload, work intensity and postural risks by implementing a time and motion study combined with heart rate measurements, accelerometry and whole-body postural analysis. Work efficiency was particularly low even if the share of effective work time was high (70% of the observation time). Job was characterized as moderate to high intensity, which resulted into a moderate to high cardiovascular strain. While the postural analysis indicated rather small risks, the main problem was found for the back postures assumed during the work. Improvements should aim to extend mechanization, train the workers and appropriately design rest breaks.
Neuroplasticity of Sensorimotor Control in Low Back Pain.

SYNOPSIS Low back pain (LBP) is an important medical and socioeconomic problem. Impaired sensorimotor control has been suggested to be a likely mechanism underlying development and/or maintenance of pain. Although early work focused on the structural and functional abnormalities within the musculoskeletal system, in the past 20 years there has been an increasing realization that patients with LBP might also have extensive neuroplastic changes within the central nervous system. These include changes related to both the structure (eg, gray matter changes) and function (eg, organization of the sensory and motor cortices) of the nervous system as related to processing of pain and nociception and to motor and somatosensory systems. Moreover, clinical interventions increasingly aim to drive neuroplasticity with treatments to improve pain and sensorimotor function. This commentary provides a contemporary overview of neuroplasticity of the pain/nociceptive and sensorimotor systems in LBP. This paper addresses (1) defining neuroplasticity in relation to control of the spine and LBP, (2) structural and functional nervous system changes as they relate to nonspecific LBP and sensorimotor function, and (3) related clinical implications. Individuals with recurrent and persistent LBP differ from those without LBP in several markers of the nervous system's function and structure. Neuroplastic changes may be addressed by top-down cognitive-based interventions and bottom-up physical interventions. An integrated clinical approach that combines contemporary pain neuroscience education, cognition-targeted sensorimotor control, and physical or function-based treatments may lead to better outcomes in patients with recurrent and persistent LBP. This approach will need to consider variation among individuals, as no single finding/mechanism is present in all individuals, and no single treatment that targets neuroplastic changes in the sensorimotor system is likely to be effective for all patients with LBP. J Orthop Sports Phys Ther 2019;49(6):402-414. doi:10.2519/jospt.2019. 8489.
Intracellular iron deficiency in pulmonary arterial smooth muscle cells induces pulmonary arterial hypertension in mice

Significance Pulmonary arterial hypertension (PAH) is a disease in which lung blood pressure is raised chronically, causing right heart failure. It has been shown that iron deficiency also raises lung blood pressure. However, we don’t know the mechanisms because we don’t understand precisely how cells of the lung blood vessels are affected by iron levels. The smooth muscle cells of the lung blood vessels are important for controlling lung blood pressure. Our study shows that iron deficiency specifically within these cells is sufficient to cause PAH, even against a background of normal iron levels in other tissues. Iron deficiency augments hypoxic pulmonary arterial pressure in healthy individuals and exacerbates pulmonary arterial hypertension (PAH) in patients, even without anemia. Conversely, iron supplementation has been shown to be beneficial in both settings. The mechanisms underlying the effects of iron availability are not known, due to lack of understanding of how cells of the pulmonary vasculature respond to changes in iron levels. The iron export protein ferroportin (FPN) and its antagonist peptide hepcidin control systemic iron levels by regulating release from the gut and spleen, the sites of absorption and recycling, respectively. We found FPN to be present in pulmonary arterial smooth muscle cells (PASMCs) and regulated by hepcidin cell autonomously. To interrogate the importance of this regulation, we generated mice with smooth muscle-specific knock in of the hepcidin-resistant isoform fpn C326Y. While retaining normal systemic iron levels, this model developed PAH and right heart failure as a consequence of intracellular iron deficiency and increased expression of the vasoconstrictor endothelin-1 (ET-1) within PASMCs. PAH was prevented and reversed by i.v. iron and by the ET receptor antagonist BQ-123. The regulation of ET-1 by iron was also demonstrated in healthy humans exposed to hypoxia and in PASMCs from PAH patients with mutations in bone morphogenetic protein receptor type II. Such mutations were further associated with dysregulation of the HAMP/FPN axis in PASMCs. This study presents evidence that intracellular iron deficiency specifically within PASMCs alters pulmonary vascular function. It offers a mechanistic underpinning for the known effects of iron availability in humans.
Effects of epidural analgesia on cancer recurrence and long-term mortality in patients after non-small-cell lung cancer resection: a propensity score-matched study

Objectives Previous studies showed reductions in recurrence and mortality rate of several cancer types in patients receiving perioperative epidural analgesia. This study aimed to investigate the effects of thoracic epidural analgesia on oncological outcomes after resection for lung cancer. Design Retrospective study using propensity score matching methodology. Setting Single medical centre in Taiwan. Participants Patients with stages I–III non-small-cell lung cancer undergoing primary tumour resection between January 2005 and December 2015 and had either epidural analgesia, placed preoperatively and used intra- and postoperatively, or intravenous analgesia were evaluated through May 2017. Primary and secondary outcome measures Primary endpoint was postoperative recurrence-free survival and secondary endpoint was overall survival. Results The 3-year recurrence-free and overall survival rates were 69.8% (95% CI 67.4% to 72.2%) and 92.4% (95% CI 91% to 93.8%) in the epidural group and 67.4% (95% CI 62.3% to 72.5%) and 89.6% (95% CI 86.3% to 92.9%) in the non-epidural group, respectively. Multivariable Cox regression analysis before matching demonstrated no significant difference in recurrence or mortality between groups (adjusted HR: 0.93, 95% CI 0.76 to 1.14 for recurrence; 0.81, 95% CI 0.58 to 1.13 for mortality), similar to the results after matching (HR: 0.97, 95% CI 0.71 to 1.31; 0.94, 95% CI 0.57 to 1.54). Independent risk factors for both recurrence and mortality were male, higher pretreatment carcinoembryonic antigen level, advanced cancer stage, poor differentiation, lymphovascular invasion, microscopic necrosis and postoperative radiotherapy. Conclusions Thoracic epidural analgesia was not associated with better recurrence-free or overall survival in patients receiving surgical resection for stages I–III non-small-cell lung cancer.
A 205-Nucleotide Deletion in the 3′ Untranslated Region of Avian Leukosis Virus Subgroup J, Currently Emergent in China, Contributes to Its Pathogenicity

ABSTRACT In the past 5 years, an atypical clinical outbreak of avian leukosis virus subgroup J (ALV-J), which contains a unique 205-nucleotide deletion in its 3′ untranslated region (3′UTR), has become epidemic in chickens in China. To determine the role of the 205-nucleotide deletion in the pathogenicity of ALV-J, a pair of viruses were constructed and rescued. The first virus was an ALV-J Chinese isolate (designated HLJ09SH01) containing the 205-nucleotide deletion in its 3′UTR. The second virus was a chimeric clone in which the 3′UTR contains a 205-nucleotide sequence corresponding to a region of the ALV-J prototype virus. The replication and pathogenicity of the rescued viruses (rHLJ09SH01 and rHLJ09SH01A205) were investigated. Compared to rHLJ09SH01A205, rHLJ09SH01 showed a moderate growth advantage in vitro and in vivo, in addition to exhibiting a higher oncogenicity rate and lethality rate in layers and broilers. Increased vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth receptor subtype 2 (VEGFR-2) expression was induced by rHLJ09SH01 more so than by rHLJ09SH01A205 during early embryonic vascular development, but this increased expression disappeared when the expression levels were normalized to the viral levels. This finding suggests that the expression of VEGF-A and VEGFR-2 is associated with viral replication and may also represent a novel molecular mechanism underlying the oncogenic potential of ALV-J. Overall, our findings not only indicate that the unique 205-nucleotide deletion in the ALV-J genome occurred naturally in China and contributes to increased pathogenicity but also point to the possible mechanism of ALV-J-induced oncogenicity.
Microtubule-associated Protein-dependent Binding of Phagosomes to Microtubules (*)

In macrophages, phagosome movement is microtubule-dependent. Microtubules are a prerequisite for phagosome maturation because they facilitate interactions between phagosomes and organelles of the endocytic pathway. We have established an in vitro assay that measures the binding of purified phagosomes to microtubules. This binding depends on the presence of membrane proteins, most likely integral to the surface of phagosomes, and on macrophage cytosol. The cytosolic binding factor can interact with microtubules prior to the addition of phagosomes to the assay, suggesting that it is a microtubule-associated protein (MAP). Consistent with this, depletion of MAPs from the cytosol by microtubule affinity removes all binding activity. Microtubule motor proteins show no binding activity, whereas a crude MAP preparation is sufficient to support binding and to restore full binding activity to MAP-depleted cytosol. We show that the activating MAP factor is a heat-sensitive protein(s) that migrates at around 150 kDa by gel filtration.
Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy‐Naive Metastatic Castrate‐Resistant Prostate Cancer

Abstract Lessons Learned. The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate‐resistant prostate cancer (mCRPC). The negative data underscore that, despite a sound biological rationale and supportive early‐phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge. Background. Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor‐induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate‐resistant prostate cancer (mCRPC). Methods. This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy‐naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6‐month progression‐free survival (PFS) rate between the two arms. Secondary endpoints included 6‐month overall survival (OS), objective tumor and prostate‐specific antigen (PSA) response rates, biomarkers, and adverse events. Results. The 6‐month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6‐month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL‐6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm). Conclusion. Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.
In situ prevascularization designed by laser-assisted bioprinting: effect on bone regeneration

Vascularization plays a crucial role in bone formation and regeneration process. Development of a functional vasculature to improve survival and integration of tissue-engineered bone substitutes remains a major challenge. Biofabrication technologies, such as bioprinting, have been introduced as promising alternatives to overcome issues related to lack of prevascularization and poor organization of vascular networks within the bone substitutes. In this context, this study aimed at organizing endothelial cells in situ, in a mouse calvaria bone defect, to generate a prevascularization with a defined architecture, and promote in vivo bone regeneration. Laser-assisted bioprinting (LAB) was used to pattern Red Fluorescent Protein-labeled endothelial cells into a mouse calvaria bone defect of critical size, filled with collagen containing mesenchymal stem cells and vascular endothelial growth factor. LAB technology allowed safe and controlled in vivo printing of different cell patterns. In situ printing of endothelial cells gave rise to organized microvascular networks into bone defects. At two months, vascularization rate (vr) and bone regeneration rate (br) showed statistically significant differences between the ‘random seeding’ condition and both ‘disc’ pattern (vr = +203.6%; br = +294.1%) and ‘crossed circle’ pattern (vr = +355%; br = +602.1%). These results indicate that in vivo LAB is a valuable tool to introduce in situ prevascularization with a defined configuration and promote bone regeneration.
Effects of Feed Particle Size and Hydro-Thermal Processing Methods on Starch Modification, Nutrient Digestibility and the Performance and the Gastrointestinal Tract of Broilers

Simple Summary Technological benefits of feed processing methods are well defined but not their benefits and disadvantages for broiler feeding. The current study tested the impact of feed particle size and various hydro-thermal processing methods (HTPM) on feed value, broiler performance and alterations of the digestive tract. It was shown that HTPM influences physico-chemical characteristics of the feed including starch modifications. The compaction process during pelleting contributes to the reduction of feed wastage and selection. However, the high daily feed intake caused by pellet feeding is also a main risk factor for proventricular dilatation. Abstract Influences of feed particle size (coarse, fine) and hydro-thermal processing methods (HTPM) (without–non-compacted feed, pelleting, expanding and pelleting) on feeding value and the performance and digestive tract of 624 broilers were studied. HTPM increased the starch disintegration of feed. Starch disintegration and electron microscopy indicated the highest degree of starch modification in expanded and pelleted feed. HTPM affected ether extract digestibility (p < 0.05). A grinding-by-HTPM interaction was found in case of crude protein digestibility (p = 0.008). Non-compacted feed reduced daily feed intake (DFI) and body weight gain and increased the feed to gain ratio compared to compacted feeds (p < 0.001). Compacted feeds increased proventricular size and the risk of Isthmus gastrici dilatation compared to coarsely ground non-compacted feed, except for finely ground expanded and pelleted feed. Finely ground feed reduced proventricular weights compared to coarsely ground feed and pelleted feed compared to other feeds. Non-compacted feed increased gizzard weights compared to compacted feeds. Relationships between proventricular size and Isthmus gastrici dilatation and the DFI were detected. Summarizing, the beneficial effects of pelleted feed were mainly based on the reduction of feed wastage and selection. However, the high DFI caused by pellet feeding is also a main risk factor for proventricular dilatation.
Aversive Imagery Causes De Novo Fear Conditioning

In classical fear conditioning, neutral conditioned stimuli that have been paired with aversive physical unconditioned stimuli eventually trigger fear responses. Here, we tested whether aversive mental images systematically paired with a conditioned stimulus also cause de novo fear learning in the absence of any external aversive stimulation. In two experiments (N = 45 and N = 41), participants were first trained to produce aversive, neutral, or no imagery in response to three different visual-imagery cues. In a subsequent imagery-based differential-conditioning paradigm, each of the three cues systematically coterminated with one of three different neutral faces. Although the face that was paired with the aversive-imagery cue was never paired with aversive external stimuli or threat-related instructions, participants rated it as more arousing, unpleasant, and threatening and displayed relative fear bradycardia and fear-potentiated startle. These results could be relevant for the development of fear and related disorders without trauma.
Exploring reasons for differences in performance between UK and international medical graduates in the Membership of the Royal College of General Practitioners Applied Knowledge Test: a cognitive interview study

Objectives International medical graduates (IMGs) perform less well in national postgraduate licensing examinations compared with UK graduates, even in computer-marked multiple-choice licensing examinations. We aimed to investigate thought processes of candidates answering multiple- choice questions, considering possible reasons for differential attainment between IMGs and UK graduates. Design We employed a semistructured qualitative design using cognitive interviews. Systematic grounded theory was used to analyse data from ‘think aloud’ interviews of general practitioner specialty trainees (GPSTs) while answering up to 15 live questions from the UK Membership of the Royal College of General Practitioners Applied Knowledge Test (AKT). Setting East Midlands, UK. Participants 21 GPSTs including 13IMGs and 8 UK-trained doctors. Outcomes Perceptions of participants on how they answered AKT questions together with strategies used or difficulties experienced. Results We interviewed 21 GPSTs (8 female, 13 male, 13 IMGs, 14 from black and minority ethnic groups, age 24–64 years) in years 1–3 of training between January and April 2017. Four themes were identified. ‘Theoretical versus real-life clinical experience’: participants reported difficulties recalling information and responding to questions from theoretical learning compared with clinical exposure; rote learning helped some IMGs recall rare disease patterns. Recency, frequency, opportunity and relevance: participants reported greater difficulty answering questions not recently studied, less frequently encountered or perceived as less relevant. Competence versus insight: some participants were over optimistic about their performance despite answering incorrectly. Cultural barriers: for IMGs included differences in undergraduate experience, lack of familiarity with UK guidelines and language barriers which overlapped with the other themes. Conclusions The difficulties we identified in candidates when answering AKT questions may be addressed through training. IMGs face additional difficulties which impede examination success due to differences in educational experience, content familiarity and language, which are also potentially amenable to additional training support.
QoS improvement with an optimum controller selection for software-defined networks

The software-defined networking (SDN) paradigm has simplified the management of computer networks by decoupling data and control planes. Moreover, the separation of the data and control planes has transitioned network complexity from traditional devices to controllers; therefore, controllers have become indispensable entities in SDN. Controllers have multiple features and direct the network from a central point and respond to updates to topological changes. However, the supportive capability of these features is strong in one controller but weak in another. Due to several controllers and each controller having a set of features, selecting an optimal SDN controller can be considered to be a multi-criteria decision-making (MCDM) problem. Herein, a two-step approach is proposed for SDN controller selection. First, the controllers are ranked with analytical network process (ANP) according to their qualitative features which influence the performance of these controllers and then a performance comparison is performed to check for the QoS improvement. The controller with a high-weight value from the feature-based comparison is quantitatively analysed by experimental analysis. The main contribution of this paper is checking the applicability of the ANP for controller selection in SDN considering its features and performance analysis in real-world Internet and Brite topologies. The simulation results show that the controller computed through the proposed approach outperforms the controller selected with existing approaches. The selection of an optimum controller with ANP results in a reduction of topology discovery time and delay in the normal and traffic load scenario. Similarly, an increase in throughput with a reasonable utilization of the central processing unit (CPU) is observed for the proposed controller.