Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabinoids induce latent sensitization in a preclinical model of medication overuse headache

Aim Evaluation of cannabinoid receptor agonists in a preclinical model of medication overuse headache. Methods Female Sprague Dawley rats received graded intraperitoneal doses of WIN55,212-2 or Δ-9-tetrahydrocannabinol (Δ-9-THC). Antinociception (tail-flick test), catalepsy and hypomotility (open field test) and impairment of motor function (rotarod test) were assessed to establish effective dosing. Rats were then treated twice daily with equianalgesic doses of WIN55,212-2 or Δ-9-THC, or vehicle, for 7 days and cutaneous tactile sensory thresholds were evaluated during and three weeks following drug discontinuation. Rats then received a one-hour period of bright light stress (BLS) on two consecutive days and tactile sensory thresholds were re-assessed. Results WIN55,212-2 and Δ-9-THC produced antinociception as well as hypomotility, catalepsy and motor impairment. Repeated administration of WIN55,212-2 and Δ-9-THC induced generalized periorbital and hindpaw allodynia that resolved within 3 weeks after discontinuation of drug. Two episodes of BLS produced delayed and long-lasting periorbital and hindpaw allodynia selectively in rats previously treated with WIN55,212-2, and Δ-9-THC. Interpretation Cannabinoid receptor agonists including Δ-9-THC produce a state of latent sensitization characterized by increased sensitivity to stress, a presumed migraine trigger. Overuse of cannabinoids including cannabis may increase the risk of medication overuse headache in vulnerable individuals.
Acute Response to Aerobic Exercise on Autonomic Cardiac Control of Patients in Phase III of a Cardiovascular Rehabilitation Program Following Coronary Artery Bypass Grafting

Objective The aim of the present study was to investigate the acute response to aerobic exercise on autonomic cardiac control of patients undergoing coronary artery bypass grafting (CABG). Methods The study sample consisted of eight patients (age: 58.6±7.7 years; body mass index: 26.7±3.5 kg.m2) who underwent a successful CABG (no complications during surgery and/or in the following weeks). To assess heart rate variability (HRV), participants remained in a supine position with a 30-degree head elevation for 20 minutes. Electrocardiographic signal (protocol with three derivations) was collected from 600 Hz sample rate to obtain beat-to-beat intervals (R-R interval). This assessment was performed before, after one hour and after 24 hours of the exercise session. All patients underwent a 35 minutes aerobic exercise session (AES) (low-moderate intensity) on the cycle ergometer. Results Significant differences were found in the time domain, with positive changes in root mean square of successive RR interval differences (rMSSD) (ms) (parasympathetic component) (one [P=0.017] and 24 hours [P=0.007] post-session). In the frequency domain, we found a significant difference in high frequency (HF) (ms2) (parasympathetic component) (one hour [P=0.048] post-session). The low frequency (LF)/HF ratio (sympathetic and parasympathetic components with a predominance of the sympathetic component) reached statistical significance only 24 hours (P=0.018) post-session. Additionally, the largest effect size was observed only for the LF/HF ratio at one (d=-0.8) and 24 hours (d=-1.3) after one AES. Conclusion The practice of (acute) aerobic exercise improved autonomic cardiac control in patients undergoing CABG.
Paramedic versus physician-staffed ambulances and prehospital delays in the management of patients with ST-segment elevation myocardial infarction

Background Time delays to reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) still remain a considerable drawback in many healthcare systems. Emergency medical service (EMS) has a critical role in the early management of STEMI. Under investigation herein, was whether the use of physician-staffed ambulances leads to shorter pre-hospital delays in STEMI patients. Methods This was an observational and retrospective study, using data from the registry of the Silesian regional EMS system in Katowice, Poland and the Polish Registry on Acute Coronary Syndromes (PL-ACS) for a study period of January 1, 2013 to December 31, 2016. The study population (n = 717) was divided into two groups: group 1 (n = 546 patients) — physician-staffed ambulances and group 2 (n = 171 patients) — paramedic-staffed ambulances. Results Responses during the day and night shifts were similar. Paramedic-led ambulances more often transmitted 12-lead electrocardiogram (ECG) to the percutaneous coronary intervention centers. All EMS time intervals were similar in both groups. The type of EMS dispatched to patients (physician-staffed vs. paramedic/nurse-only staffed ambulance) was adjusted for ECG transmission, sex had no impact on in-hospital mortality (odds ratio [OR] 1.41; 95% confidence interval [CI] 0.79–1.95; p = 0.4). However, service time exceeding 42 min was an independent predictor of in-hospital mortality (OR 4.19; 95% CI 1.27–13.89; p = 0.019). In-hospital mortality rate was higher in the two upper quartiles of service time in the entire study population. Conclusions These findings suggest that both physician-led and paramedic-led ambulances meet the criteria set out by the Polish and European authorities. All EMS time intervals are similar regardless of the type of EMS unit dispatched. A physician being present on board did not have a prognostic impact on outcomes.
Left Ventricular Reconstruction Surgery in Candidates for Heart Transplantation

Objective To report our center’s experience in the surgical treatment of ventricular reconstruction, an effective and efficient technique that allows patients with end-stage heart failure of ischemic etiology to have clinical improvement and increased survival. Methods Observational, clinical-surgical, sequential, retrospective study. Patients with ischemic cardiomyopathy and left ventricular aneurysm were attended at the Heart Failure, Ventricular Dysfunction and Cardiac Transplant outpatient clinic of the Dante Pazzanese Cardiology Institute, from January 2010 to December 2016. Data from 34 patients were collected, including systemic arterial hypertension, ejection fraction, New York Heart Association (NYHA) functional classification (FC), European System for Cardiac Operative Risk Evaluation (EuroSCORE) II value, Society of Thoracic Surgeons (STS) score, ventricular reconstruction technique, and survival. Results Overall mortality of 14.7%, with hospital admission being 8.82% and late death being 5.88%. Total survival rate at five years of 85.3%. In the preoperative phase, NYHA FC was Class I in five patients, II in 18, III in eight, and IV in three vs. NYHA FC Class I in 17 patients, II in eight, III in six, and IV in three, in the postoperative period. EuroSCORE II mean value was 6.29, P≤0.01; hazard ratio (HR) 1.16 (95% confidence interval [CI] 1.02-1.31). STS mortality/morbidity score mean value was 18.14, P≤0.004; HR 1.19 (95% CI 1.05-1.33). Surgical techniques showed no difference in survival among Dor 81% vs. Jatene 91.7%. Conclusion Surgical treatment of left ventricular reconstruction in candidates for heart transplantation is effective, efficient, and safe, providing adequate survival.
Effects of Genetically Determined Iron Status on Risk of Venous Thromboembolism and Carotid Atherosclerotic Disease: A Mendelian Randomization Study

Background Systemic iron status has been implicated in atherosclerosis and thrombosis. The aim of this study was to investigate the effect of genetically determined iron status on carotid intima‐media thickness, carotid plaque, and venous thromboembolism using Mendelian randomization. Methods and Results Genetic instrumental variables for iron status were selected from a genome‐wide meta‐analysis of 48 972 subjects. Genetic association estimates for carotid intima‐media thickness and carotid plaque were obtained using data from 71 128 and 48 434 participants, respectively, and estimates for venous thromboembolism were obtained using data from a study incorporating 7507 cases and 52 632 controls. Conventional 2‐sample summary data Mendelian randomization was performed for the main analysis. Higher genetically determined iron status was associated with increased risk of venous thromboembolism. Odds ratios per SD increase in biomarker levels were 1.37 (95% CI 1.14‐1.66) for serum iron, 1.25 (1.09‐1.43) for transferrin saturation, 1.92 (1.28‐2.88) for ferritin, and 0.76 (0.63‐0.92) for serum transferrin (with higher transferrin levels representing lower iron status). In contrast, higher iron status was associated with lower risk of carotid plaque. Corresponding odds ratios were 0.85 (0.73‐0.99) for serum iron and 0.89 (0.80‐1.00) for transferrin saturation, with concordant trends for serum transferrin and ferritin that did not reach statistical significance. There was no Mendelian randomization evidence of an effect of iron status on carotid intima‐media thickness. Conclusions These findings support previous work to suggest that higher genetically determined iron status is protective against some forms of atherosclerotic disease but increases the risk of thrombosis related to stasis of blood.
Male-Specific Long Noncoding RNA TTTY15 Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis via TBX4

Gender affects cancer susceptibility. Currently, there are only a few studies on Y chromosome-linked long noncoding RNAs (lncRNAs), and the potential association between lncRNAs and cancers in males has not been fully elucidated. Here, we examined the expression of testis-specific transcript Y-linked 15 (TTTY15) in 37 males with non-small cell lung cancer (NSCLC), and performed circular chromosome conformation capture with next-generation sequencing to determine the genomic interaction regions of the TTTY15 gene. Our results showed that the expression levels of TTTY15 were lower in NSCLC tissues. Lower TTTY15 expression levels were associated with Tumor-Node-Metastasis (TNM) stage. A TTTY15 knockdown promoted malignant transformation of NSCLC cells. Based on the bioinformatics analysis of circular chromosome conformation capture data, we found that T-box transcription factor 4 (TBX4) may be a potential target gene of TTTY15. The RNA immunoprecipitation and chromatin immunoprecipitation results showed that TTTY15 may interact with DNA (cytosine-5)-methyltransferase 3A (DNMT3A), and the TTTY15 knockdown increased the binding of DNMT3A to the TBX4 promoter. We concluded that low TTTY15 expression correlates with worse prognosis among patients with NSCLC. TTTY15 promotes TBX4 expression via DNMT3A-mediated regulation. The identification of lncRNAs encoded by male-specific genes may help to identify potential targets for NSCLC therapy.
Current understanding and treatment of intra‐amniotic infection with Ureaplasma spp.

Considerable evidence has shown that intra‐amniotic infection with Ureaplasma spp. increases the risk of chorioamnionitis and preterm labor. Ureaplasma spp. are among the smallest organisms, and their isolation is uncommon in routine clinical practice because of their size and high auxotrophy. Although Ureaplasma spp. have been reported as causative agents of preterm birth, they also have a high incidence in vaginal swabs collected from healthy reproductive‐age women; this has led to questions on the virulence of Ureaplasma spp. and to them being considered as harmless commensal bacteria. Therefore, many efforts have been made to clarify the pathogenicity of Ureaplasma spp. at the molecular level. Ureaplasma spp. are surrounded by lipoproteins, including multiple‐banded antigen. Both multiple‐banded antigen and its derivative, that is, the synthetic lipopeptide, UPM‐1, induce an inflammatory response in a preterm mice model, which was adequate to cause preterm birth or stillbirth. In this review, we present an overview of the virulence mechanisms of Ureaplasma spp. and treatment of ureaplasma infection during pregnancy to prevent possible serious sequelae in infants. In addition, relevant mechanisms underlying antibiotic resistance in Ureaplasma spp. are discussed. Ureaplasma spp. are naturally resistant against β‐lactam antibiotics because of the lack of a cell wall. Azithromycin is one of the effective agents that can control intrauterine ureaplasma infection. In fact, macrolide‐ and fluoroquinolone‐resistant isolates of Ureaplasma spp. have already been observed in perinatal practice in Japan.
Control of pathogens in fresh pork sausage by inclusion of Lactobacillus sakei BAS0117.

A pork sausage was produced with low sodium content (1.64%) and added of Lactobacillus sakei. The aim was to develop a meat pork sausage destined to be cooked and having technological, sensory and hygiene advantages. The LAB L. sakei, Lactococcus sp. and Pediococcus pentosaceus were submitted to extremes conditions of pH, temperature and NaCl. L. sakei was used in pork sausage based on its resistance to different culture conditions and antimicrobial potential. The foodborne pathogens Listeria monocytogenes Scott A, Enterococcus faecalis and Staphylococcus aureus were used as indicator microorganisms to evaluate the antimicrobial activity of selected LAB strains. Salmonella enterica serotype Choleraesuis is a common pathogen of pigs. In raw sausage product containing L. sakei and non-pathogenic endogenous microbiota, we added about ˃104 and <105 CFU/g S. enterica of serotype Choleraesuis to evaluate the inhibitory potential of L. sakei in relation to the pathogen. This one was inhibited in the presence of L. sakei over 7 days of storage of the meat product (about 3.0 Log cycles reduction). This inhibition provided by L. sakei was significantly higher than non-fermented sausage. Thus, L. sakei BAS0117 had an important role as an additional hurdle in the fermented meat pork sausage during storage.
Application Scenarios in Streaming-Oriented Embedded System Design

In the past decade real-time embedded systems became more and more complex and pervasive. From the user perspective, these systems have stringent requirements regarding size, performance and energy consumption, and due to business competition, their time-to-market is a crucial factor. Therefore, much work has been done in developing design methodologies for embedded systems to cope with these tight requirements. In this paper, we introduce the concept of application scenarios that group operation modes of an application that are similar from the resource usage perspective, and we describe how to incorporate them in the overall real-time embedded system design process. A case study shows the use of application scenarios for low energy design, under both soft and hard real-time constraints.
Rehabilitation in Children With Sclerodermoid Chronic Graft-Versus-Host Disease: Case Series

Joint contracture in chronic graft-versus-host disease (cGVHD) is refractory to treatment, and tends to deteriorate gradually over time. There is scant clinical research focusing on timing and intensity of rehabilitation on joint contractures in children with sclerodermoid cGVHD after hematopoietic stem cell transplantation. We retrospectively reviewed rehabilitative therapeutic effects in 6 children with sclerodermoid cGVHD, whose clinical records documented their condition, before and after rehabilitation therapies. Three children who started treatment within a mean of 2 months after the onset of joint symptoms, and who underwent home-based exercise twice daily for 30 minutes showed more prominent improvement in range of motion compared with the other 3 children, who started rehabilitation therapy later than 6 months after onset of joint symptoms, without regular home-based exercise.
Detection of dynamic form in faces and fire

Moving natural scenes pose a challenge to the human visual system, containing diverse objects, clutter, and backgrounds. Well-known models of object recognition do not fully explain natural scene perception, ignoring segmentation or the recognition of dynamic objects. In this thesis, we use a familiar natural stimulus, moving flames, to evaluate the human visual system’s ability to match and search for complex examples of dynamic form. What can analysis in the image domain tell us about dynamic flame? Using image statistics, Fourier analysis and motion evaluation algorithms, we analysed a highresolution dataset typical of moving flame. We characterise it as a motion-rich stimulus with an exponential power spectrum and few long-range spatial or temporal correlations. Are observers able to effectively encode and recognise dynamic flame stimuli? What visual features play an important role in matching? To investigate, we set observers matching tasks using clips from the same dataset. Colour changes do not affect matching on short clips, but inversion and reversal do. We show that dynamic edges are a key component of flame representations. Can observers search well for flame stimuli? Can they detect targets (short flame clips) in equally-sized longer clips? Using temporal search tasks, we show that observers’ accuracy drops quickly as the search space grows; there is no pop-out. Accuracy is not so strongly affected by a blank ISI, however, showing that search difficulties, rather than representational decay, are to blame. In conclusion, we find that the human visual system is capable of matching the complex motion patterns of dynamic flame, but finds search much harder. We find no evidence of category orientation specialisation. Combining several experimental results, we suggest that the representation of dynamic flame is neither snapshot-based nor dedicated and high-level, but relies on the encoding of sparse, local spatiotemporal features.
Effective desensitization for a strong donor‐specific HLA antibody in a case of HLA‐mismatched allogeneic hematopoietic cell transplantation

We describe a unique ABO compatible and 9/10 HLA‐matched case of successful allogeneic hematopoietic cell transplantation (HCT) after effective desensitization of a strong anti‐HLA‐A24 donor‐specific antibody (DSA) with mean fluorescence intensity of approximately 18 000. Due to absence of a suitable matched unrelated donor the patient sibling was considered the best available donor, and it was decided to desensitize patient prior to transplant. The strength of HLA‐A24 DSA slowly decreased over the course of treatment, necessitating a total of 23 sessions of therapeutic plasma exchange in order to bring the DSA strength to undetectable levels, followed by a successful transplant. In summary, the outcome of this case shows effective application of desensitization treatment to remove strong DSA in HCT patients.
Syndrome d’antidiurèse inappropriée néphrogénique

Les troubles de l'équilibre de l'eau représentent une pathologie fréquente dans notre pratique clinique. L'étude du récepteur V2R est importante pour la compréhension de la physiologie de l'équilibre hydrique et a servi de prototype pour la biologie des récepteurs G couplés aux protéines. Le syndrome d'antidiurèse inappropriée néphrogénique (NSIAD) est un syndrome de sécrétion inappropriée d'hormone antidiurétique (SIADH)-like avec un dosage plasmatique de vasopressine bas. La preuve du rôle du récepteur V2R et de l'aquaporine (AQP) dans le mode d'action de l'hormone antidiurétique (ADH) est venue de l'identification de mutations dans les gènes de ces protéines dans le diabète insipide néphrogénique et dans le syndrome NSIAD. Des mutations activatrices du V2R ont été retrouvées dans le NSIAD, à l'opposé des nombreuses mutations inactivatrices du V2R liées à l'X décrites dans le diabète insipide néphrogénique.
Phthalate plasticizer di(2‐ethyl‐hexyl) phthalate induces cyclooxygenase‐2 expression in gastric adenocarcinoma cells

The phthalate plasticizer, di(2‐ethyl‐hexyl) phthalate (DEHP), and its derived metabolites are common anthropogenic environmental toxins, which are known to act as endocrine disruptors. Numerous studies have associated DEHP with disruption of sex hormones, abnormal development of reproductive organs, allergies, and inflammation. Its role in promoting inflammation has been reported by both human epidemiological and animal studies. In stomach tissue, chronic inflammation is known to accompany mucosal damage, and pave the way to gastritis, stomach ulcers, and ultimately gastric cancer. Eastern Asian populations possess the highest gastric cancer incidences in the world. Coincidentally, East Asia is one of the world's major sites for plastics manufacture and export. Thus, possible correlations between DEHP, a common plasticizer, and gastric cancer are of great interest. Our study revealed several critical findings. First, even at very low dosage, mimicking the residual plasticizer exposure, detrimental effects of DEHP on gastric cells can be detected. Second, gastric cells treated with DEHP increased cyclooxygenase‐2 (COX‐2) in a time‐dependent manner. Third, promoter deletion studies revealed a critical role of nuclear factor‐kappa B (NF‐κB) for COX‐2 gene responses. Finally, our results indicated that a low concentration of DEHP is able to trigger COX‐2 activation via the extracellular signal–regulated kinase (ERK1/2) and NF‐κB signaling pathway. Taken together, we demonstrate that very low doses of DEHP enhance the expression of the prototypical inflammatory gene, COX‐2, in gastric cancer cells via ERK1/2 and NF‐κB activation. This study provides important insights into the inflammatory process and damages associated with phthalate plasticizers exposure.
The role of p53 in reproduction, an unexpected function for a tumor suppressor

At the beginning of the 21st century, the role of p53 as a tumor suppressor was well-established; however, the function of p53 other than tumor suppression, especially its function under physiological conditions, was poorly understood. Here, we revisited the journey of a multi-disciplinary team of researchers that revealed an unexpected and important function of p53 in regulating maternal reproduction at that time. This finding of p53 in maternal reproduction helped us gain important insights about the p53 protein and expanded our understanding of p53 protein functions in addition to its tumor suppressive function. This finding also provided a possible clue to explain the observed evolutionary selection on some alleles of the p53 pathway.
Inhibition of p53 inhibitors: progress, challenges and perspectives

Abstract p53 is the major tumor suppressor and the most frequently inactivated gene in cancer. p53 could be disabled either by mutations or by upstream negative regulators, including, but not limited to MDM2 and MDMX. p53 activity is required for the prevention as well as for the eradication of cancers. Restoration of p53 activity in mouse models leads to the suppression of established tumors of different origin. These findings provide a strong support to the anti-cancer strategy aimed for p53 reactivation. In this review, we summarize recent progress in the development of small molecules, which restore the tumor suppressor function of wild-type p53 and discuss their clinical advance. We discuss different aspects of p53-mediated response, which contribute to suppression of tumors, including non-canonical p53 activities, such as regulation of immune response. While targeting p53 inhibitors is a very promising approach, there are certain limitations and concerns that the intensive research and clinical evaluation of compounds will hopefully help to overcome.