Miracle-dz/UniFAR-FTUs huggingface dataset:
Micro-dislodgement during transcatheter aortic valve implantation with a contemporary self-expandable prosthesis

Objectives To evaluate the incidence, risk factors and the clinical outcome of micro-dislodgement (MD) with a contemporary self-expandable prosthesis during transcatheter aortic valve implantation. Methods MD was defined as movement of the prosthesis of at least 1.5 mm upwards or downwards from its position directly before release compared to its final position. Patients were grouped according to the occurrence (+MD) or absence (-MD) of MD. Baseline characteristics, imaging data and outcome parameters were retrospectively analyzed. Results We identified 258 eligible patients. MD occurred in 31.8% (n = 82) of cases with a mean magnitude of 2.8 mm ± 2.2 in relation to the left coronary cusp and 3.0 mm ± 2.1 to the non-coronary cusp. Clinical and hemodynamic outcomes were similar in both groups with consistency over a follow-up period of three months. A larger aortic valve area (AVA) (-MD vs. +MD: 0.6 cm2 ± 0.3 vs. 0.7cm2 ± 0.2; p = 0.014), was the only independent risk factor for the occurrence of MD in a multivariate regression analysis (OR 5.3; 95% CI: 1.1–24.9; p = 0.036). Conclusions MD occurred in nearly one third of patients and did not affect clinical and hemodynamic outcome. A larger AVA seems to be a potential risk factor for MD.
Characteristics of graft‐versus‐host disease occurring after alemtuzumab‐containing allogeneic stem cell transplants: incidence, organ involvement, risk factors and survival

T‐cell depletion with alemtuzumab represents an effective form of graft‐versus‐host disease (GVHD) prophylaxis after allogeneic haematopoietic stem cell transplantation (allo‐HSCT); however, little is known regarding the impact of in vivo alemtuzumab on either the incidence or clinical characteristics of acute and chronic GVHD. We therefore studied 201 consecutive adult patients who received an alemtuzumab‐based, reduced‐intensity conditioned (RIC) allograft. With a median follow‐up of 24 months, the cumulative incidence of classic acute and late acute (persistent, recurrent and late onset) GVHD grades II–IV (grades III–IV) was 34% (13%) and 20% (8%) respectively; the cumulative incidence of classic chronic GVHD and overlap syndrome were 4% and 7% respectively. A previous diagnosis of classic acute GVHD is a risk factor for chronic GVHD (hazard ratio 10·91, 95% confidence interval 2·35–50·63, P = 0·0023) while late onset acute GVHD is not a risk factor for later development of chronic GVHD. Unrelated donor transplant is a risk factor for the development of classic acute GVHD but not for late onset or chronic GVHD. In conclusion, this study describes a distinctive pattern of GVHD following alemtuzumab‐RIC allografts, identifies the risk factors for GVHD development and provides prognostic information of patients with GVHD.
Time intervals experienced between first symptom recognition and pathologic diagnosis of breast cancer in Addis Ababa, Ethiopia: a cross-sectional study

Objectives This study aimed to estimate the magnitude of patient and diagnostic delays and associated factors among women with breast cancer in Addis Ababa. Design This is a cross-sectional study. Settings and participants All women newly diagnosed with breast cancer in seven major healthcare facilities in Addis Ababa (n=441) were included in the study. Main outcomes and measures Patient interval (time from recognition of first symptom to medical consultation) and diagnostic interval (time from first consultation to diagnosis). Patient intervals >90 days and diagnostic intervals >30 days were considered delays, and associated factors were determined using multivariable Poisson regressions with robust variance. Results Thirty-six percent (95% CI [31.1%, 40.3%]) of the patients had patient intervals of >90 days, and 69% (95% CI [64.6%, 73.3%]) of the patients had diagnostic intervals of >30 days. Diagnostic interval exceeded 1 year for 18% of patients. Ninety-five percent of the patients detected the first symptoms of breast cancer by themselves, with breast lump (78.0%) as the most common first symptom. Only 8.0% were concerned about cancer initially, with most attributing their symptoms to other factors. In the multivariable analysis, using traditional medicine before consultation was significantly associated with increased prevalence of patient delay (adjusted prevalence ratio (PR) = 2.13, 95% CI [1.68, 2.71]). First consultation at health centres (adjusted PR = 1.19, 95% CI [1.02, 1.39]) and visiting ≥4 facilities (adjusted PR = 1.24, 95% CI [1.10, 1.40]) were associated with higher prevalence of diagnostic delay. However, progression of symptoms before consultation (adjusted PR = 0.73, 95% CI [0.60, 0.90]) was associated with decreased prevalence of diagnostic delay. Conclusions Patients with breast cancer in Addis Ababa have prolonged patient and diagnostic intervals. These underscore the need for public health programme to increase knowledge about breast cancer symptoms and the importance of early presentation and early diagnosis among the general public and healthcare providers.
Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles

Abstract Iron nanoparticles (NPs) have been proposed as a tool in very different fields such as environmental remediation and biomedical applications, including food fortification against iron deficiency, even if there is still concern about their safety. Here, we propose Xenopus laevis embryos as a suitable model to investigate the toxicity and the bio-interactions at the intestinal barrier of Fe3O4 and zerovalent iron (ZVI) NPs compared to Fe(II) and (III) salts in the 5 to 100 mg Fe/L concentration range using the Frog Embryo Teratogenesis Assay in Xenopus (FETAX). Our results demonstrated that, at concentrations at which iron salts induce adverse effects, both iron NPs do not cause acute toxicity or teratogenicity even if they accumulate massively in the embryo gut. Prussian blue staining, confocal and electron microscopy allowed mapping of iron NPs in enterocytes, along the paracellular spaces and at the level of the basement membrane of a well-preserved intestinal epithelium. Furthermore, the high bioaccumulation factor and the increase in embryo length after exposure to iron NPs suggest greater iron intake, an essential element for organisms. Together, these results improve the knowledge on the safety of orally ingested iron NPs and their interaction with the intestinal barrier, useful for defining the potential risks associated with their use in food/feed fortification.
Riding the Wave: The SINE-Specific V Highly-Conserved Domain Spread into Mammalian Genomes Exploiting the Replication Burst of the MER6 DNA Transposon

Transposable elements are widely distributed within genomes where they may significantly impact their evolution and cell functions. Short interspersed elements (SINEs) are non-autonomous, fast-evolving elements, but some of them carry a highly conserved domain (HCD), whose sequence remained substantially unchanged throughout the metazoan evolution. SINEs carrying the HCD called V are absent in amniote genomes, but V-like sequences were found within the miniature inverted-repeat transposable element (MITE) MER6 in Homo sapiens. In the present work, the genomic distribution and evolution of MER6 are investigated, in order to reconstruct the origin of human V domain and to envisage its possible functional role. The analysis of 85 tetrapod genomes revealed that MER6 and its variant MER6A are found in primates, while only the MER6A variant was found in bats and eulipotyphlans. These MITEs appeared no longer active, in line with literature data on mammalian DNA transposons. Moreover, they appeared to have originated from a Mariner element found in turtles and from a V-SINE from bony fishes. MER6 insertions were found within genes and conserved in mRNAs: in line with previous hypothesis on functional role of HCDs, the MER6 V domain may be important for cell function also in mammals.
Coenzyme Q10 and male infertility

We had previously demonstrated that Coenzyme Q10 [(CoQ10) also commonly called ubiquinone]is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10 concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10 content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). The physiological role of this molecule was further clarified by inquiring into its variations in concentrations induced by different medical or surgical procedures used in male infertility treatment. We therefore evaluated CoQ10 concentration and distribution between seminal plasma and spermatozoa in VAR, before and after surgical treatment, and in infertile patients after recombinant human FSH therapy. The effect of CoQ10 on sperm motility and function had been addressed only through some in vitro experiments. In two distinct studies conducted by our group, 22 and 60 patients affected by idiopathic asthenozoospermia were enrolled, respectively. CoQ10 and its reduced form, ubiquinol, increased significantly both in seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, at baseline and after treatment, of seminal plasma or intracellular CoQ10, ubiquinol levels and kinetic parameters was found in the treated group. Patients with lower baseline value of motility and CoQ10 levels had a statistically significant higher probability to be responders to the treatment. In conclusion, the exogenous administration of CoQ10 increases both ubiquinone and ubiquinol levels in semen and can be effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia
Lamivudine vs placebo or no treatment in preventing the transmission of hepatitis B virus during pregnancy: a systematic review and meta-analysis.

BACKGROUND Hepatitis B virus (HBV) infection is a severe health problem, especially in developing countries. Almost 45% of the population lives in highly endemic areas, where the most common form of transmission is mother to child transmission (MTCT). Administration of antiviral therapy has been established. Nevertheless, its efficacy still remains controversial. METHODS We conducted the current study to fully evaluate the effectiveness of lamivudine in preventing the MTCT of HBV based on randomized controlled trials (RCTs). Four English electronic databases and four Chinese electronic databases were searched from the inception of each database to 26 September 2017. Studies were included if they (1) were human RCT studies, (2) indicated exposure to lamivudine, (3) explicitly indicated control to placebo or no treatment, (4) indicated the participants were pregnant women infected with HBVand (5) compared the outcome of interest as the MTCT. Extracted data were tabulated and analyzed using Review Manager. RESULTS Eleven RCTs were included and analyzed. Compared with controls (placebo or no treatment), lamivudine significantly reduced the probability of MTCT, as indicated by newborn HBsAg seropositivity (RR=0.44, 95% CI 0.26 to 0.74, I2=41%), HBeAg seropositivity (RR=0.66, 95% CI 0.36 to 1.19, I2=0%) and HBV DNA seropositivity (RR=0.29, 95% CI 0.18 to 0.4`6, I2=0%) within 24 h after birth. Similar results were noted pertaining to infant HBsAg seropositivity and HBV DNA seropositivity within 6-7 and 12 mo. CONCLUSIONS Lamivudine can significantly reduce the MTCT of HBsAg and HBV DNA of neonates during the third trimester of pregnancy without severe adverse events.
[Long-term results of perifocal defocus spectacle lens correction in children with progressive myopia].

Peripheral defocus plays a significant role in the formation of refraction. Perifocal spectacles allow differentiating correction of central and peripheral refraction of the eye along the horizontal meridian and can correct or reduce peripheral hyperopia. PURPOSE To study the long-term results of wearing perifocal spectacles on the refraction in children with progressive myopia. MATERIAL AND METHODS Perifocal spectacles were assigned to children of 7-14 years old with progressive myopia from -1.0 to -6.0 D in terms of refractive spherical equivalent. The children were examined before the prescription of perifocal spectacles and after 6 months, 12-18 months, 2 years, 3 years and 4-5 years. We measured visual acuity, the character of vision, refractive error before and after cycloplegia, performed biomicroscopy, ophthalmoscopy and biometry. Peripheral refraction was studied at 15° and 30° points in the nasal (N15 and N30) and temporal (T15 and T30) meridians without correction and while wearing perifocal spectacles. RESULTS In perifocal spectacles, in the 15° zone, 100% of the eyes formed myopic defocus, which averaged -0.05±0.1 D in T15°, -0.25±0.16 D in N15° and -0.44±0.03 D in T30°. In the N30° zone, the hypermetropic defocus decreased by 4 times and amounted to 0.38±0.03 D. The rate of progression of myopia decreased from 0.8 D of baseline values to 0.17 D at 4-5 years of follow-up. After 6 months of wearing perifocal spectacles, the refraction gain was -0.2±0.02 D (in the control group it was -0.38±0.04 D), after 12-18 months - (-)0.38±0.04 D (-0.63±0.09 D in the control group), after 2 years - (-)0,78±0,06 D (-1.18±0,15 D in the control group), after 3 years - (-)0.99±0.12 D (-1.65±0.20D in the control group). During the 4-5 years of the follow-up, the refractive error in the main group was -1.16±0.2 D, which is 60% less than in the control group (-1.95±0.2 D). CONCLUSION Constant wearing of perifocal spectacles reduces the rate of myopia progression in children by 4.5 times compared with the initial rate, and by 1.6 times (by 60%) in comparison with the control group. Perifocal spectacles are recommended as optical means to slow the progression of myopia.
Risk of Major Adverse Cardiovascular Events and Major Hemorrhage Among White and Black Patients Undergoing Percutaneous Coronary Intervention

Background Data on racial disparities in major adverse cardiovascular events (MACE) and major hemorrhage (HEM) after percutaneous coronary intervention are limited. Factors contributing to these disparities are unknown. Methods and Results PRiME‐GGAT (Pharmacogenomic Resource to Improve Medication Effectiveness–Genotype‐Guided Antiplatelet Therapy) is a prospective cohort. Patients aged ≥18 years undergoing percutaneous coronary intervention were enrolled and followed for up to 1 year. Racial disparities in risk of MACE and HEM were assessed using an incident rate ratio. Sequential cumulative adjustment analyses were performed to identify factors contributing to these disparities. Data from 919 patients were included in the analysis. Compared with white patients, black patients (n=203; 22.1% of the cohort) were younger and were more likely to be female, to be a smoker, and to have higher body mass index, lower socioeconomic status, higher prevalence of diabetes mellitus and moderate to severe chronic kidney disease, and presentation with acute coronary syndrome and to undergo urgent percutaneous coronary intervention. The incident rates of MACE (34.1% versus 18.2% per 100 person‐years, P<0.001) and HEM (17.7% versus 10.3% per 100 person‐years, P=0.02) were higher in black patients. The incident rate ratio was 1.9 (95% CI, 1.3–2.6; P<0.001) for MACE and 1.7 (95% CI, 1.1–2. 7; P=0.02) for HEM. After adjustment for nonclinical and clinical factors, black race was not significantly associated with outcomes. Rather, differences in socioeconomic status, comorbidities, and coronary heart disease severity were attributed to racial disparities in outcomes. Conclusions Despite receiving similar treatment, racial disparities in MACE and HEM still exist. Opportunities exist to narrow these disparities by mitigating the identified contributors.
Memory Complaint Is a Surrogate for Memory Decline in the Middle-Aged: A Register-Based Study

Memory complaint is one of the earliest symptoms of dementia. The causes and prognosis of memory complaint in the middle-aged population remain largely unknown. We reviewed the register-based data of 2129 patients with memory complaints. Among them, 404 participants were between 40 and 65 years old. The participants were separated into three groups: subjective cognitive decline (SCD), neurodegenerative diseases (ND), and non-neurodegenerative diseases (NND). One-year decline was defined as a decrease of ≥1 on the mini-mental state examination (MMSE). At baseline, 131 participants (32%) were diagnosed with SCD, 141 (35%) with ND, and 132 (33%) with NND. The 1-year cognitive decline rate was higher among patients with ND (36.8%) than in the SCD (7.3%, p = 1.3 × 10−8) and NND groups (7.6%, p = 1.1 × 10−7). One-year decline did not differ between the SCD and NND groups. Lower baseline MMSE score predicted increased risk of 1-year cognitive decline (odds ratio (OR) = 1.126, 95% confidence interval (CI) = 1.076–1.178, p = 2.52 × 10−7). Memory complaint in middle age carried a risk of 1-year cognitive decline, and baseline MMSE is an independent predictor of decline. An initial diagnosis of SCD held the same risk effect for decline as NND. These findings highlighted the necessity for neuropsychological tests in those with memory complaints presenting to the clinic.
Refixation of Large Osteochondral Fractures After Patella Dislocation Shows Better Mid- to Long-Term Outcome Compared With Debridement

Objective The purpose of this study was to compare results of osteochondral fractures (OCF) after first-time lateral patella dislocation, when either refixation or debridement was performed in a mid- to long-term follow-up and to analyze redislocation and reintervention rates. Design Fifty-three consecutive patients with OCF were included in this retrospective comparative study. Indication for refixation was presence of subchondral bone at the fragment. Thirty-six OCF were located at the patellar surface, and 17 at the lateral condyle of the distal femur. Refixation was performed in 28 patients while 25 patients underwent removal and debridement. Mean follow-up was 8.9 years (±4.4, range 2.0-16.7 years). For assessment of clinical outcome, the International Knee Documentation Committee (IKDC) Score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Lysholm score were used. Redislocation rate and further surgical interventions within follow-up were evaluated. Results All clinical scores in the refixation group yielded significantly better results at mid- to long term follow-up (IKDC P < 0.001, KOOS P = 0.006, Lysholm P = 0.001). Significantly more surgical reinterventions were necessary after debridement (48% vs. 7.1%, P = 0.001). The overall redislocation rate in cases with medial reefing as single stabilizing procedure was 43.3%. Conclusions Refixation of OCF after lateral patella dislocation shows improved clinical outcome at mid- to long-term follow-up compared with debridement. Therefore, effort to try fragment refixation is recommended. Redislocation rate is high without proper restoration of patellofemoral instability.
Teaching NeuroImages: 18F-FDG-PET/SPM analysis in 3 different stages from a patient with LGI-1 autoimmune encephalitis

A 50-year-old woman presented with faciobrachial dystonic seizures for about 50 days during sleeping (figure, A). Initial MRI scan was normal, but FDG-PET showed hypermetabolism in the basal ganglia (BG) and medial temporal lobes (MTLs) (figure, B). Clinical symptoms raised a strong suspicion of LGI-1 autoimmune encephalitis (AE) diagnosis, and LGI-1 antibody titer examination (serum and CSF) confirmed the suspicion.1,2 After relapse, the patient showed a previous PET abnormal pattern.
Uncommon Ehrlichia canis infection associated with morulae in neutrophils from naturally infected dogs in Brazil.

Ehrlichia and Anaplasma species are the most common tick-borne disease (TBD) pathogens in dogs worldwide. Ehrlichia canis, the aetiological agent of the Canine Monocytic Ehrlichiosis (CME), is known to replicate within the cytoplasm of mononuclear cells into clusters of organisms called morulae. However, detection of morulae in neutrophils is commonly observed in dogs infected by Ehrlichia ewingii or Anaplasma phagocytophilum. We report uncommon clinical cases of canine ehrlichiosis presenting morulae compatible with E. ewingii and A. phagocytophilum in dogs from two distinct regions of Brazil. Eight dogs were admitted to two veterinary teaching hospitals from Brazil, showing clinical or haematological signs suggestive of TBD. Blood or peritoneal fluid was withdrawn for haematological and cytologic analysis. All samples were evaluated by PCR assays for Ehrlichia and Anaplasma using genus-specific primers for dsb, 16S rRNA and groEL genes, followed by sequencing. Samples were also evaluated by nested PCR assays for the 16S rRNA gene of E. ewingii and groEL gene of A. phagocytophilum and Anaplasma platys. Seven dogs revealed thrombocytopenia, six dogs had monocytosis and five presented lymphopenia and anaemia. All dogs showed morulae structures compatible with Ehrlichia spp. in neutrophils and were PCR-positive for the dsb and 16S rRNA gene fragments of Ehrlichia, with sequences showing 100% identity with multiple E. canis sequences deposited in the GenBank™. Sequencing of 16S rRNA and groEL gene fragments from one PCR-positive dog showed 100% identity with A. platys. Overall, our data suggest that in endemic regions for E. canis, that is Brazil, the presence of morulae in neutrophils may indicate infection by this bacterium. Herein, morulae were also found in neutrophils present in the peritoneal fluid of a dog. Also, this is the first report of E. canis and Hepatozoon canis co-infection in neutrophils from naturally infected dogs confirmed by DNA sequencing.
Metabolic machinery encrypted in the Raman spectrum of influenza A virus‐inoculated mammalian cells

Raman spectroscopy was applied with a high spectral resolution to a structural study of Influenza (type A) virus before and after its inoculation into Madin–Darby canine kidney cells. This study exploits the fact that the major virus and cell constituents, namely DNA/RNA, lipid, and protein molecules, exhibit peculiar fingerprints in the Raman spectrum, which clearly differed between cells and viruses, as well as before and after virus inoculation into cells. These vibrational features, which allowed us to discuss viral assembly, membrane lipid evolution, and nucleoprotein interactions of the virus with the host cells, reflected the ability of the virus to alter host cells’ pathways to enhance its replication efficiency. Upon comparing Raman signals from the host cells before and after virus inoculation, we were also able to discuss in detail cell metabolic reactions against the presence of the virus in terms of compositional variations of lipid species, the formation of fatty acids, dephosphorylation of high‐energy adenosine triphosphate molecules, and enzymatic hydrolysis of the hemagglutinin glycoprotein.