Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting the NLRP3 Inflammasome With Inhibitor MCC950 Prevents Aortic Aneurysms and Dissections in Mice

Background Aortic aneurysms and dissections are highly lethal diseases for which an effective treatment strategy is critically needed to prevent disease progression. The nucleotide‐binding oligomerization domain–like receptor pyrin domain containing 3 (NLRP3)–caspase‐1 inflammasome cascade was recently shown to play an important role in aortic destruction and disease development. In this study, we tested the effects of MCC950, a potent, selective NLRP3 inhibitor, on preventing aortic destruction and aortic aneurysm and dissection formation. Methods and Results In a model of sporadic aortic aneurysm and dissection induced by challenging wild‐type mice with a high‐fat, high‐cholesterol diet and angiotensin II infusion, MCC950 treatment significantly inhibited challenge‐induced aortic dilatation, dissection, and rupture in different thoracic and abdominal aortic segments in both male and female mice. Aortic disease reduction by MCC950 was associated with the prevention of NLRP3–caspase‐1 upregulation, smooth muscle cell contractile protein degradation, aortic cell death, and extracellular matrix destruction. Further investigation revealed that preventing matrix metallopeptidase 9 (MMP‐9) expression and activation in macrophages is an important mechanism underlying MCC950's protective effect. We found that caspase‐1 directly activated MMP‐9 by cleaving its N‐terminal inhibitory domain. Moreover, the genetic knockdown of Nlrp3 or Casp‐1 in mice or treatment of mice with MCC950 diminished the challenge‐induced N‐terminal cleavage of MMP‐9, MMP‐9 activation, and aortic destruction. Conclusions Our findings suggest that the NLRP3–caspase‐1 inflammasome directly activates MMP‐9. Targeting the inflammasome with MCC950 is a promising approach for preventing aortic destruction and aortic aneurysm and dissection development.
Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia

Abstract Background In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. Methods The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. Results Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. Conclusions Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.
Dual epidemics of deaths by heroin overdose and suicide

Introduction: Dual epidemics of deaths by heroin overdose and suicide were recorded in US from 2000 to 2014. Also from 2000 to 2014 an estimated 11.342 physicians -accused of overprescribing opiates and treating some estimated 8 million people with chronic pain, addiction or psychiatric disorders-were forced out of medical practice. The aim of this study is to determine whether there is a correlation between the dual epidemics and possible adverse influences mediating access to opiate treatment. Method: We have reviewed CDC vital statistics from 2000 to 2014. We also studied diverse influences on populations with increased risk of heroin addiction and suicide from 2000 to 2014. Results: From 2000 to 2014 the US heroin deaths rate jumped from 0.7 to 3,4 and deaths by suicide from 10.1 to 13 per 100.000 population. There was a statistically strong correlation (r = 0.9) between the suicides and heroin deaths. From 2000 to 2014 the accidental overdose deaths rose from 3 to 14 per 100.000 population. The percentage of deaths associated with prescription opiates declined from 38,1% to 28% while the percentage of heroin deaths jumped from 11% to 28%. From 2000 to 2014 some estimated 11.342 accused of over prescribing opiates were forced out of practice with some estimated 6.8 million opiate dependent patients enduring disruption and or discontinuation of stable treatment. Discussion: Reduction of access to prescription opiates by disrupting stable treatment of a population vulnerable to mood instability might have been an independent contributor to the dual epidemics of heroin overdose deaths and suicides from 2000 to 2014. Correspondence to: Alen J Salerian, Salerian Centre for Neuroscience and Pain, 5325 Westbard Avenue, 08 Bethesda Maryland 20816, USA, Tel: 3012049004; E-mail: alensalerian@Gmail.com
A Multiparametric Study of Internalization of Fullerenol C60(OH)36 Nanoparticles into Peripheral Blood Mononuclear Cells: Cytotoxicity in Oxidative Stress Induced by Ionizing Radiation

The aim of this study was to investigate the uptake and accumulation of fullerenol C60(OH)36 into peripheral blood mononuclear cells (PBMCs). Some additional studies were also performed: measurement of fullerenol nanoparticle size, zeta potential, and the influence of fullerenol on the ionizing radiation-induced damage to PMBCs. Fullerenol C60(OH)36 demonstrated an ability to accumulate in PBMCs. The accumulation of fullerenol in those cells did not have a significant effect on cell survival, nor on the distribution of phosphatidylserine in the plasma membrane. However, fullerenol-induced depolarization of the mitochondrial membrane proportional to the compound level in the medium was observed. Results also indicated that increased fullerenol level in the medium was associated with its enhanced transport into cells, corresponding to its influence on the mitochondrial membrane. The obtained results clearly showed the ability of C60(OH)36 to enter cells and its effect on PBMC mitochondrial membrane potential. However, we did not observe radioprotective properties of fullerenol under the conditions used in our study.
The enzymatic debridement for the treatment of burns of in-determinate depth.

The rapid eschar removal by surgical debridement is currently considered the standard of care for the treatment of burned patients. However, the excision of viable dermal residues can frequently occurs when this procedure is applied affecting, in turn, the possible spontaneous re-epithelialization of the lesion area and increasing the amount of autologous skin grafts required for its treatment. To overcome these problems, the use of enzymatic debridement by proteolytic enzymes enriched in Bromelain has aroused great interest in the clinical field as a valid alternative to surgical procedure for the treatment of burns when they appear of in-determinate depth. With the aim to evaluate the effectiveness of this new approach in comparison with surgical procedure for the treatment of these type of burns we performed a retrospective data analysis taking into account patients hospitalized in our Burns Center from 2014 to 2017. The results obtained show a significant reduction in the time frame to perform debridement when enzymatic approach is chosen, with the maintenance of viable dermal tissue on the superficial areas of the wounds, their spontaneous re-epithelialization and a reduction of the bleeding in the treated patients. A reduced amount of autologous skin grafts is also used when enzymatic treatment is applied. The length of stay of the patients treated with enzymatic debridement did not show significant differences compared to that treated with surgery, with excellent aesthetic results after 1-3 years.
Adopciones rotas en Andalucía: caracterización y propuestas para la intervención

La presente investigación trata de conocer la incidencia y los principales factores de riesgo asociados a las rupturas adoptivas así como realizar algunas propuestas de mejora de cara a la intervención profesional. En el estudio se analizaron los 93 casos de ruptura detectados en Andalucía en la década de 2003-2012. La incidencia acumulada de rupturas en el periodo considerado fue de 1.32%, siendo más frecuentes en la adopción nacional que en la internacional. Así mismo, los principales factores de riesgo asociados a tales rupturas fueron la presencia de problemas de conducta en el menor, la violencia intrafamiliar y los problemas de vinculación emocional. En cuanto a la intervención profesional, lo más frecuente fueron las intervenciones de asesoramiento y tratamiento familiar al inicio de la adopción, disminuyendo su presencia en los momentos de la ruptura. La intervención profesional se caracterizó por ser esporádica y realizada por profesionales no especializados en la adopción, con una baja colaboración por parte de los adoptantes y los chicos y chicas adoptados. Entre las propuestas de mejora de la intervención profesional ante estas situaciones destaca la creaciónde un registro que permita identificar los casos de ruptura en el sistema de protección infantil.
Diagnosing COVID-19: The Disease and Tools for Detection

COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.
Ideal implant choice for proximal interphalangeal joint arthrodesis in hammer toe/claw toe deformity correction: A systematic review

Intramedullary devices have been developed to reduce the problems associated with Kirschner (K)-wire fixation in proximal interphalangeal joint (PIPJ) arthrodesis. The purpose of this systematic review is to compare the surgical outcomes of K-wires versus novel internal fixation devices in PIPJ arthrodesis in claw/hammer toe surgery. The databases searched were PubMed, Scopus, Cochrane, and Embase with keywords “claw toe OR hammer toe” AND “proximal interphalangeal OR PIP” AND “fusion OR arthrodesis. ” Clinical trials published in English with evidence levels I, II, and III were included. Five studies, including one randomized controlled trial and four case-controlled studies, were identified to meet the inclusion criteria. Overall, the studies showed promising results in union rates using the novel internal devices compared to K-wires. However, the novel internal devices seem not to present advantages in clinical parameters such as pain levels, patient satisfaction, foot-related function, or surgical complication rates.
Platinum Atoms and Nanoparticles Embedded Porous Carbons for Hydrogen Evolution Reaction

Due to the growing demand for energy and imminent environmental issues, hydrogen energy has attracted widespread attention as an alternative to traditional fossil energy. Platinum (Pt) catalytic hydrogen evolution reaction (HER) is a promising technology to produce hydrogen because the consumed electricity can be generated from renewable energy. To overcome the high cost of Pt, one effective strategy is decreasing the Pt nanoparticle (NP) size from submicron to nano-scale or even down to single atom level for efficient interacting water molecules. Herein, atomically dispersed Pt and ultra-fine Pt NPs embedded porous carbons were prepared through the pyrolysis of Pt porphyrin-based conjugated microporous polymer. As-prepared electrocatalyst exhibit high HER activity with overpotential of down to 31 mV at 10 mA cm−2, and mass activity of up to 1.3 A mgPt−1 at overpotential of 100 mV, which is double of commercial Pt/C (0.66 A mgPt−1). Such promising performance can be ascribed to the synergistic effect of the atomically dispersed Pt and ultra-fine Pt NPs. This work provides a new strategy to prepare porous carbons with both atomically dispersed metal active sites and corresponding metal NPs for various electrocatalysis, such as oxygen reduction reaction, carbon dioxide reduction, etc.
Mycobacterium tuberculosis exploits host ATM kinase for survival advantage through SecA2 secretome

(Mtb) produces inflections in the host signaling networks to create a favorable milieu for survival. The virulent Mtb strain, Rv caused double strand breaks (DSBs), whereas the non-virulent Ra strain triggered single-stranded DNA generation. The effectors secreted by SecA2 pathway were essential and adequate for the genesis of DSBs. Accumulation of DSBs mediated through Rv activates ATM-Chk2 pathway of DNA damage response (DDR) signaling, resulting in altered cell cycle. Instead of the classical ATM-Chk2 DDR, Mtb gains survival advantage through ATM-Akt signaling cascade. Notably, in vivo infection with Mtb led to sustained DSBs and ATM activation during chronic phase of tuberculosis. Addition of ATM inhibitor enhances isoniazid mediated Mtb clearance in macrophages as well as in murine infection model, suggesting its utility for host directed adjunct therapy. Collectively, data suggests that DSBs inflicted by SecA2 secretome of Mtb provides survival niche through activation of ATM kinase.
Osteoporosis: Mechanism, Molecular Target, and Current Status on Drug Development.

Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone formation, including PTH analogues and sclerostin inhibitors, are current treatments for osteoporosis. Despite their efficacy, severe side effects and loss of potency may limit the long term usage of a single drug. Sequential and combinational use of current drugs, such as switching from an anabolic to an anti-resorptive agent, may provide an alternative approach. Moreover, there are novel drugs being developed against emerging new targets such as Cathepsin K and 17β-HSD2 that may have less side effects. This review will summarize the molecular mechanisms of osteoporosis, current drugs for osteoporosis treatment, and new drug development strategies.
Diagnostic Stability of Mild Cognitive Impairment, and Predictors of Reversion to Normal Cognitive Functioning

Objective: Studies that investigate predictive factors for spontaneous recovery (reversion) from mild cognitive impairment (MCI) are only beginning to emerge, and the long-term course of MCI is not properly understood. We aimed to investigate stability of the MCI diagnosis, predictors for reversion, as well as the trajectory of MCI over the course of 12 years. Materials and Methods: Data were drawn from the Swedish population study: Good Aging in Skåne with MCI defined according to the expanded Mayo Clinic criteria. A total of 331 participants, aged 60–95 years with MCI, were used to investigate 6-year MCI stability and reversion, and 410 participants were used to inspect 12-year MCI trajectory. Predictors for reversion included demographical factors, psychological status, and factors tied to the cognitive testing session and the operationalization of the MCI criteria. Results: Over half (58%, 95% CI 52.7–63.3) of the participants reverted back to normal cognitive functioning at 6-year follow-up. Of those with stable MCI, 56.5% (95% CI 48.2–64.8) changed subtype. A total of 23.9% (95% CI 13.7–34.1) of the 6-year follow-up reverters re-transitioned back to MCI at 12-year follow-up. ORs for reversion were significantly higher in participants with lower age (60-year-olds: OR 2.19, 95% CI 1.08–4.43, 70-year-olds: OR 3.11, 95% CI 1.27–7.62), better global cognitive functioning (OR 1.15, 95% CI 1.03–1.29), good concentration (OR 2.53, 95% CI 1.06–6.05), and single-domain subtype (OR 2.68, 95% CI 1.51–4.75). Conclusion: Our findings provide further support that MCI reversion to normal cognitive functioning as well as re-transitioning to MCI is fairly common, suggesting that the MCI trajectory does not necessarily lead straight to dementia. Additionally, assessment of factors associated with reversion can aid clinicians to make accurate MCI progression prognosis.
Gender-based vulnerability in women who inject drugs in a harm reduction setting

Background and aims In comparison with men, women who use drugs (WWUD) have considerably more frequent and intense experiences with interpersonal violence, sexual abuse and trauma. The aim of this study was to identify issues related to gender-based vulnerability in a group of WWUD attended in a harm reduction facility in Madrid, Spain. Material and methods A cross-sectional study was conducted during a screening of blood borne infections. We included WWUD (smoked or injected heroin/cocaine) who were actively screened for HIV, HBV and HCV in a harm reduction setting in Madrid (Spain) from January to December 2017. WWUD were interviewed for gender-based abuse or violence using a face-to-face questionnaire by a trained interviewer. Aspects related to their social-epidemiological condition and gender-based vulnerability were collected. Results We included 109 women who were actively using drugs. The median age was 39 (IQR 35–47) years, 84.4% were Spanish born, 22.9% were homeless, 43 (41.7%) had ever used injected drugs, 29 (26.6%) were currently using injected drugs, and 27.1% had mental health disorders. Aspects related to gender-based vulnerability were collected. Among those surveyed, they reported having ever suffered emotional or psychological damage (88%), having experienced at least one incident of serious physical injury by a male partner (71%), and having ever suffered sexual abuse (49%). In addition, 28% had ever exchanged sex for money/drugs. When compared to women that did not use injecting drugs, those who injected drugs had more frequently exchanged sex for money/drugs (55% vs 21%, p = 0.003). Conclusions A high proportion of WWUD suffer psychological or physical violence by partners denoting gender-based vulnerability. Interventions in harm reduction settings with a multidisciplinary and gender-based approach should be implemented.
Recovery from pathological skin picking and dermatodaxia using a revised decoupling protocol

Pathological skin picking (PSP) is characterized by repetitive scratching, biting, and picking of the skin. The disorder is subsumed under the section “obsessive‐compulsive and related disorders” in the DSM‐5. A related body‐focused repetitive disorder, which has received less empirical attention so far, is dermatophagia or dermatodaxia (eating or biting/gnawing of the skin). Habit reversal training (HRT) is regarded as the treatment of choice demonstrating improvement at a medium effect size relative to control conditions.
TARGET: a survey of real‐world management of chronic myeloid leukaemia across 33 countries

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real‐world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. Of the 1008 haematologists invited (33 countries), 614 completed the survey. Gaps regarding treatment efficacy and molecular monitoring were identified. Half of the physicians did not perform three‐monthly testing of during the initial 12 months of treatment, citing cost as the major barrier, although they know it should be done. Treatment‐free remission was not considered a primary treatment goal or as a priority factor influencing treatment decisions. European Leukemia Net guidelines interpretation was generally acceptable, but awareness regarding management of persistent adverse events was poor. Practical solutions proposed by the SC were mostly focused on enhancing physician education and awareness, or encouraging hospitals to work with the government, in order to improve the quality of BCR‐ABL testing. Gaps in current CML management were identified compared with international recommendations, which the proposed practical solutions would help to address.
Does Labor Augmentation with Oxytocin Increase the Risk of Postpartum Hemorrhage? A Randomized Controlled Trial

Labour augmentation aims to shorten labour so prevent complications related to prolonged labour. There is evidence that a significant proportion of women with uncomplicated pregnancies are subjected to routine augmentation of labour with oxytocin in spite of the general rule that labour augmentation should only be performed for valid indications. Obstetric hemorrhage is one of the leading causes of maternal mortality in developing countries, accounting for 10%-30% of direct maternal deaths. The aim of the study was to compare between labour augmentation with oxytocin and no augmentation on the total volume of blood loss during vaginal delivery. The study included 250 cases admitted to the emergency department in El-Shatby maternity university hospital, group A (Oxytocin group) 125 cases received augmentation by oxytocin infusion using 2.5 IU oxytocin in 500 cc saline with a slow rate of 20-30 drops/minute, group B (Control group) 125 cases received only 500 cc saline. The amount of blood loss during the 3rd stage of labor and the 1st hour after delivery of the placenta (4th stage) have been estimated. Results showed that the total volume of blood loss in group A ranged from 100 to 700 ml with the mean of 230.9 ± 99.3 ml, on the other hand it ranged from 100 to 650 ml with mean of 181.5 ± 83.1 ml in group B. the calculated p value was 0.001, so there was a significant statistical difference between both groups regarding the total volume of blood loss, so we concluded that use of oxytocin in labor augmentation increase the volume of blood loss.
First report of Bursaphelenchus fungivorus (Nematoda: Aphelenchida) in Italy and an overview of nematodes associated with Crocus sativus L.

Abstract Saffron is one of the most precious spices in the world. It is derived from the dried stigmas of the Crocus sativus L. flowers. This plant is triploid sterile and propagated by corms. As a subterranean organ, the corm can come into contact with different nematodes. In this contribution Bursaphelenchus fungivorus was reported for the first time in Italy. It was found associated with C. sativus corms and characterized based on morphological and morphometrical characteristics for this species. The identification was confirmed using molecular analyses. Moreover, a review of nematodes associated with C. sativus worldwide is also provided.