Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization

Abstract Aims Mesenchymal stromal cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischaemia/reperfusion (I/R) and its implications in cardiac injury repair. Methods and results Exosomes were isolated from the supernatant of MSCs using gradient centrifugation method. Administration of MSC-Exo to mice through intramyocardial injection after myocardial I/R reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and toll-like receptor 4 (TLR4) as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial I/R. Conclusion Our data indicate that MSC-Exo attenuates myocardial I/R injury in mice via shuttling miR-182 that modifies the polarization status of macrophages. This study sheds new light on the application of MSC-Exo as a potential therapeutic tool for myocardial I/R injury.
Morphology and Molecular Phylogeny of Two New Terrestrial Ciliates, Australocirrus rubrus n. sp. and Notohymena gangwonensis n. sp. (Ciliophora: Oxytrichidae), from South Korea

Two new soil oxytrichids, Australocirrus rubrus n. sp. and Notohymena gangwonensis n. sp. , were discovered from South Korea. Morphologically, A. rubrus shares many features with A. australis, and these two species form a single clade in a molecular tree based on nuclear small subunit ribosomal RNA (SSU rRNA) gene sequences. Australocirrus rubrus mainly differs from A. australis in the color (citrine color vs. reddish) and distribution of the cortical granules. Additionally, we confirm that the genus Australocirrus is not a monophyletic group, as A. shii is separated from the clade comprising the other Australocirrus species, being clustered instead with other taxa. Notohymena gangwonensis n. sp. mainly differs from its congeners by the following combination of features: irregularly distributed cortical granules (vs. arranged in groups associated with cirri and dorsal kineties), variable four or five (usually four) transverse cirri (vs. invariable five), and the anteriormost pretransverse cirrus V/2 on 13.2–16.1% of cell length (vs. on or above 18.9% of cell length). Currently, there are no available gene sequences for members of the genus Notohymena, thus we provide SSU rRNA gene sequences from the new species of Notohymena, as well as detailed morphological descriptions of the novel species.
Romantic functioning mediates prospective associations between childhood abuse and neglect and parenting outcomes in adulthood

Abstract Research suggests intergenerational links between childhood abuse and neglect and subsequent parenting quality, but little is known about the potential mechanisms underlying intergenerational continuities in parenting. Adult romantic functioning may be one plausible mechanism, given its documented associations with both adverse caregiving in childhood and parenting quality in adulthood. The present study used data from the Minnesota Longitudinal Study of Risk and Adaptation to (a) investigate prospective associations between childhood experiences of abuse and neglect and multiple parenting outcomes in adulthood, and (b) evaluate the degree to which adult romantic functioning mediates those associations. Information regarding childhood abuse and neglect was gathered prospectively from birth through age 17.5 years. Multimethod assessments of romantic functioning were collected repeatedly through early adulthood (ages 20 to 32 years), and parenting quality was assessed as participants assumed a parenting role (ages 21 to 38 years). As expected, childhood abuse and neglect experiences predicted less supportive parenting (observed and interview rated) and higher likelihood of self-reported Child Protective Services involvement. The association with interview-rated supportive parenting was partially mediated by lower romantic competence, whereas the association with Child Protective Services involvement was partially mediated by more relational violence in adult romantic relationships. Implications of these novel prospective findings for research and clinical intervention are discussed.
Possible prediction of patterns of cervical lymph node spread based on primary tumor location in papillary thyroid carcinomas*

Backround/aim Papillary thyroid carcinomas (PTC) frequently metastasize to regional lymph nodes. Our purpose was to investigate the predictive role of tumor location for lymph node metastasis pattern in PTCs. Materials and methods Medical records of 110 PTC patients were reviewed retrospectively. Tumor location was determined as upper, middle, and lower pole according to ultrasonography (USG) findings. The effects of age, sex, tumor size, and location on lymph node metastasis were investigated. Results The series comprised 87% females (n = 96) and 13% males (n = 14). Forty-three patients had central neck metastasis (CNM) and 14 had lateral neck metastasis (LNM). Upper pole tumors (UPT) metastasized to the central neck (CN) at a lower rate (17.6%) than middle (40.0%) or lower (48.5%) poles overall (P = 0.104), while it was at a significantly lower rate (13.3%) in the PTC group (P < 0.05). UPTs (n = 17) metastasized to the lateral neck (LN) almost 2-fold more. It was observed that 3 of 4 UPTs spread directly to the LN without CNM. Conclusion In our opinion, UPTs have propensity to demonstrate metastasis to LN rather than the CN in PTCs. Therefore, UPTs should be evaluated meticulously in terms of LNM. New studies could suggest that CN dissection is not performed for low-risk PTCs in UPTs.
Parkinson's disease: Is it a consequence of human brain evolution?

Department of Neurosciences, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA Neurology Clinic with Neuromorphomics Laboratory, Nitobe Memorial Nakano General Hospital, Tokyo, Japan Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Neuroscience, Karolinska Institut, Stockholm, Sweden Department of Neurological Sciences, Rush University, Chicago, Illinois, USA
Measuring calprotectin in plasma and blood with a fully automated turbidimetric assay

Abstract Calprotectin in plasma and blood might prove to be a useful biomarker of inflammation and infection; however, automated methods for analysing the concentration of calprotectin in those materials are lacking. We have validated a fully automated turbidimetric method and present health-related reference limits. Calprotectin was measured by Siemens Advia XPT with the Bühlmann fCAL® turbo test (Bühlmann Laboratories AG, Schönenbuch, Switzerland), a particle enhanced turbidimetric immunoassay for quantification of calprotectin in fecal extracts. Plasma and serum samples were analysed directly, while whole blood was first extracted with M-PER® Mammalian Protein Extraction Reagent (ThermoFisher) and diluted with B-CAL-EX (Bühlmann). We studied analytical imprecision, estimated health-related reference limits and examined the correlation between neutrophil-calprotectin (blood-calprotectin adjusted for plasma-calprotectin) and the neutrophil count. The intermediate (‘day-to-day’) coefficient of variation was 3.5 and 1.0% for heparin-plasma-calprotectin at 0.52 mg/L and 3.53 mg/L, respectively, and 4.9% for heparin-blood-calprotectin at 50.2 mg/L. Health-related reference limits were 0.470–3.02 mg/L for calprotectin in heparin-plasma, 50.8–182 mg/L for calprotectin in heparin-blood, 0.534–2.41% for the ratio between them and 24.7–33.3 pg for the mean amount of calprotectin per neutrophil. Compared to heparin-plasma, calprotectin concentrations were significantly lower in EDTA-plasma and higher in serum (p < .05). Correlation between neutrophil-calprotectin and the neutrophil count was excellent. We have shown that the Bühlmann fCAL® turbo test can be used to measure calprotectin in plasma and blood.
Oral Morphine Effectiveness in Nigerian Patients With Advanced Cancer

ABSTRACT Oral morphine elixir in the immediate release form became available in Nigeria in the year 2006 after decades of use in the treatment of cancer pain in many other countries. In order to determine the effectiveness of oral morphine in Nigerian patients, 182 patients presenting with severe cancer pain at the Radiotherapy Clinic, University College Hospital (UCH), Ibadan, Nigeria, were recruited in a prospective descriptive observational study. Information on patient's demography, diagnosis, baseline intensity and character of pain, morphine dosages, and effects were collected using a semistructured questionnaire administered at recruitment and biweekly in the follow-up period. Mean (+ SD) age of the patients was 47 (+ 14.6) years and the most common types of cancer diagnosed in the study participants included cancer of the breast and uterine cervix. The pretreatment pain intensity score mean (+ SD) was 8.09 (+ 1.51). Of the 166 patients whose data were analyzed, 84.3% (95% confidence interval [CI] 77.8–89.5%) achieved a 3-point reduction in pain intensity using the 11-point Numerical Rating Scale at the end of the first week of treatment. Twenty-six patients (15.7%) required adjuvant therapy. The reduction in pain intensity was maintained throughout the 3 months follow-up period, with the mean 24-hour morphine consumption of 55.54 mg in the first month and 61.54 mg in the third month. Oral morphine significantly reduced cancer pain in Nigerian patients (P < .01). Increasing dose as required was found to enhance the effectiveness of oral morphine.
Hierarchical Transcription Factor and Chromatin Binding Network for Wood Formation in Populus trichocarpa[OPEN]

A hierarchical transcriptional regulatory network for wood formation in Populus contains 57 direct transcription factor (TF)–DNA interactions linking 17 TFs regulating 27 cell wall biosynthetic genes. Wood remains the world’s most abundant and renewable resource for timber and pulp and is an alternative to fossil fuels. Understanding the molecular regulation of wood formation can advance the engineering of wood for more efficient material and energy productions. We integrated a black cottonwood (Populus trichocarpa) wood-forming cell system with quantitative transcriptomics and chromatin binding assays to construct a transcriptional regulatory network (TRN) directed by a key transcription factor (TF), PtrSND1-B1 (secondary wall-associated NAC-domain protein). The network consists of four layers of TF–target gene interactions with quantitative regulatory effects, describing the specificity of how the regulation is transduced through these interactions to activate cell wall genes (effector genes) for wood formation. PtrSND1-B1 directs 57 TF–DNA interactions through 17 TFs transregulating 27 effector genes. Of the 57 interactions, 55 are novel. We tested 42 of these 57 interactions in 30 genotypes of transgenic P. trichocarpa and verified that ∼90% of the tested interactions function in vivo. The TRN reveals common transregulatory targets for distinct TFs, leading to the discovery of nine TF protein complexes (dimers and trimers) implicated in regulating the biosynthesis of specific types of lignin. Our work suggests that wood formation may involve regulatory homeostasis determined by combinations of TF–DNA and TF–TF (protein–protein) regulations.
Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population.

OBJECTIVE There has been debate whether polymorphisms within the serotonin transporter-linked polymorphic region (5-HTTLPR) moderate susceptibility to posttraumatic stress disorder (PTSD). The authors investigated 5-HTTLPR genotypes and their interaction with the number of traumatic events in the prediction of PTSD in a general population sample. METHOD Analyses were based on data from 3,045 subjects who participated in the Study of Health in Pomerania. All participants were assessed with the PTSD module of the Structured Clinical Interview for DSM-IV. The short (S)/long (L) polymorphism of 5-HTTLPR (rs4795541) and the A-G polymorphism (rs25531) were genotyped. RESULTS Among the participants, 1,663 had been exposed to at least one traumatic event, and 67 (4.0%) developed PTSD. Among those who had experienced less than three traumatic events, the lifetime prevalence of PTSD was 2.6%, 3.5%, and 4.3% for those with zero, one, and two L(A) alleles, respectively, but the lifetime prevalence was 0%, 7.3%, and 19.6%, respectively, among those with three or more traumatic experiences. This finding suggests that there is an additive excess risk for frequent trauma in the L(A)/L(A) genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 3.3. Thus, the odds ratio for PTSD in L(A) allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the L(A) allele. CONCLUSIONS An additive gene-environment interaction with the high expression L(A) allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all L(A) allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure.
A Novel Dual Successive Projection-Based Model-Free Adaptive Control Method and Application to an Autonomous Car

In this paper, a novel model-free adaptive control (MFAC) algorithm based on a dual successive projection (DuSP)-MFAC method is proposed, and it is analyzed using the introduced DuSP method and the symmetrically similar structures of the controller and its parameter estimator of MFAC. Then, the proposed DuSP-MFAC scheme is successfully implemented in an autonomous car “Ruilong” for the lateral tracking control problem via converting the trajectory tracking problem into a stabilization problem by using the proposed preview-deviation-yaw angle. This MFAC-based lateral tracking control method was tested and demonstrated satisfactory performance on real roads in Fengtai, Beijing, China, and through successful participation in the Chinese Smart Car Future Challenge Competition held in 2015 and 2016.
SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

In this study, microarray data analysis, real‐time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure‐specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan‐Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype‐related molecules were assessed. The growth of xenograft tumours in nude mice was also assessed. MiRNAs that potentially targeted SSRP1 were determined by bioinformatic analysis, Western blotting and luciferase reporter assays. We showed that SSRP1 mRNA levels were significantly increased in CRC tissue. We also confirmed that this upregulation was related to the terminal tumour stage in CRC patients, and high expression levels of SSRP1 predicted shorter disease‐free survival and faster relapse. We also found that SSRP1 modulated proliferation, metastasis, cellular energy metabolism and the epithelial‐mesenchymal transition in CRC. Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5‐fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA‐28‐5p (miR‐28‐5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR‐28‐5p.
Cardiovascular stress biomarker assessment of middle-aged non-athlete marathon runners

Background Cardiovascular safety of marathon running in recreational runners remains unclear. We set up this study to comprehensively evaluate the effects of a marathon run on the profile of cardiovascular stress biomarkers in connection with transthoracic echocardiography. Design and methods Thirty-three healthy male amateur runners, aged ≥50 years (mean age 57 ± 7) were enrolled. Venous blood samples were obtained before the marathon, just after the race, 2–4 and seven days after the marathon. Using novel single molecule counting technology we measured: plasma concentrations of high-sensitivity cardiac troponin I (hs-cTnI) and endothelin-1. N-terminal pro B-type natriuretic peptide was measured using electrochemiluminescence. Each participant had transthoracic echocardiography before and immediately after the race. Results We observed a sharp rise in the levels of all biomarkers after the race (all p < 0.01), which subsequently normalized after 2–4 days and stayed within normal range after seven days. Runners with intensive training programmes (>169 km/month, a median for the studied group) had lower hs-cTnI leak after the race (median 15.11 ng/ml and 31.2 ng/ml, respectively; p < 0.05). Neither transthoracic echocardiography measures of ventricles nor strain rates changed after the run. We observed a decrease in the left atrial volume index and increase in the maximal right atrial volumes (all p < 0.05). Changes in Doppler indices of diastolic function suggestive of alteration in left ventricular relaxation were observed. Conclusions Marathon run is associated with sharp and significant rises in the biomarkers of cardiovascular stress. The profile of these changes, however, along with echocardiographic parameters, does not suggest irreversible myocardial damage.
Patient-reported Health-related Quality of Life with Apremilast for Psoriatic Arthritis: A Phase II, Randomized, Controlled Study

Objective. Apremilast, a specific inhibitor of phosphodiesterase 4, modulates proinflammatory and antiinflammatory cytokine production. A phase IIb randomized, controlled trial (RCT) evaluated the effect of apremilast on patient-reported outcomes (PRO) in psoriatic arthritis (PsA). Methods. In this 12-week RCT, patients with active disease (duration > 6 mo, ≥ 3 swollen and ≥ 3 tender joints) received apremilast (20 mg BID or 40 mg QD) or placebo. PRO included pain and global assessment of disease activity [visual analog scale (VAS)], Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Medical Outcomes Study Short-Form 36 Health Survey (SF-36) assessing health-related quality of life (HRQOL). Percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and correlations between SF-36 domains and pain VAS, HAQ-DI, and FACIT-F were determined. Results. Among the 204 randomized patients (52.5% men; mean age 50.6 yrs), baseline SF-36 scores reflected large impairments in HRQOL. Apremilast 20 mg BID resulted in statistically significant and clinically meaningful improvements in physical and mental component summary scores and 7 and 6 SF-36 domains, respectively, compared with no change/deterioration in placebo group. Patients receiving apremilast 20 mg BID and 40 mg QD reported significant improvements ≥ MCID in global VAS scores and FACIT-F versus placebo, and significant improvements in pain VAS scores. Moderate-high, significant correlations were evident between SF-36 domains and other PRO. Conclusion. Apremilast resulted in statistically significant and clinically meaningful improvements in HRQOL, pain and global VAS, and FACIT-F scores.
Multimillijoule coherent terahertz bursts from picosecond laser-irradiated metal foils

Significance Terahertz (THz) radiation, with frequencies spanning from 0.1 to 10 THz, has long been the most underdeveloped frequency band in electromagnetic waves, mainly due to the dearth of available high-power THz sources. Although the last decades have seen a surge of electronic and optical techniques for generating intense THz radiation, all THz sources reported until now have failed to produce above-millijoule (mJ) THz pulses. We present a THz source that enables a THz pulse energy up to tens of mJ, by using an intense laser pulse to irradiate a metal foil. Ultrahigh-power terahertz (THz) radiation sources are essential for many applications, for example, THz-wave-based compact accelerators and THz control over matter. However, to date none of the THz sources reported, whether based upon large-scale accelerators or high-power lasers, have produced THz pulses with energies above the millijoule (mJ) level. Here, we report a substantial increase in THz pulse energy, as high as tens of mJ, generated by a high-intensity, picosecond laser pulse irradiating a metal foil. A further up-scaling of THz energy by a factor of ∼4 is observed when introducing preplasmas at the target-rear side. Experimental measurements and theoretical models identify the dominant THz generation mechanism to be coherent transition radiation, induced by the laser-accelerated energetic electron bunch escaping the target. Observation of THz-field-induced carrier multiplication in high-resistivity silicon is presented as a proof-of-concept application demonstration. Such an extremely high THz energy not only triggers various nonlinear dynamics in matter, but also opens up the research era of relativistic THz optics.