Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study inhibitor antidepressant in a

Evidence of an association between early pregnancy exposure to Selective Serotonin Reuptake Inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n=12,876) and non-CHD signal CA (n=13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n=17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein’s anomaly (adjOR 8.23, 95% CI 2.94-23.16). Significant associations with SSRI exposure were also found for anorectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding
In Vitro and Ex Vivo Activities of Minocycline and EDTA against Microorganisms Embedded in Bioﬁlm on Catheter Surfaces

Minocycline-EDTA (M-EDTA) ﬂush solution has been shown to prevent catheter-related infection and colonization in a rabbit model and in hemodialysis patients. We undertook this study in order to determine the activities of M-EDTA against organisms embedded in fresh bioﬁlm (in vitro) and mature bioﬁlm (ex vivo). For the experiment with the in vitro model, a modiﬁed Robbin’s device (MRD) was used whereby 25 catheter segments were ﬂushed for 18 h with 10 6 CFU of bioﬁlm-producing Staphylococcus epidermidis , Staphyloccocus aureus , and Candida albicans per ml. Subsequently, each of the catheter segments was incubated in one of the following solutions: (i) streptokinase, (ii) heparin, (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii) minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose minocycline alternating with high-dose minocycline were used to study the additive and synergistic activities of M-EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54 catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline). Subsequently, all segments were examined by confocal laser electron microscopy. In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was signiﬁcantly more effective than any other agent in reducing colonization of S . epidermidis , S . aureus , and C . albicans ( P < 0.01). M-EDTA (with a high concentration of minocycline) eradicated all staphylococcal and C . albicans organisms embedded in the bioﬁlm. In the ex vivo model, M-EDTA (with a high concentration of minocycline) reduced bacterial colonization more frequently than EDTA or heparin ( P < 0.01). We concluded that M-EDTA is highly active in eradicating microorganisms embedded in fresh and mature bioﬁlm adhering to catheter surfaces.
Inﬂuence of Dexamethasone on Efﬁcacy of Ceftriaxone and Vancomycin Therapy in Experimental Pneumococcal Meningitis

Using a rabbit model of meningitis, we sought to determine whether concomitant use of dexamethasone affects the penetration and efﬁcacy of ceftriaxone or vancomycin in cerebrospinal ﬂuid. Rabbits were inoculated with a penicillin-sensitive strain of Streptococcus pneumoniae and treated with ceftriaxone or vancomycin with or without dexamethasone. In the ceftriaxone-treated groups, no statistically signiﬁcant differences were seen between the group treated with dexamethasone and that without dexamethasone; however, in the vancomycin- treated groups we found statistically signiﬁcant lower cerebrospinal ﬂuid vancomycin levels at 2 h in the dexamethasone-treated rabbits and differences in bacterial killing. Dexamethasone (DEX) has been shown to down modulate inﬂammatory activity in experimental bacterial meningitis, to reduce neurological sequelae in pediatric Haemophilus inﬂu- enzae and pneumococcal meningitis, and to reduce mortality in adult pneumococcal meningitis (5, 7, 9, 10, 12, 14). However, the routine use of DEX as adjunctive therapy in bacterial meningitis is not yet widely accepted because of (i) its potential adverse effects, especially the possibility of gastrointestinal bleeding; (ii) the difﬁculties in assessing adequately the clinical evolution of meningitis, since DEX is associated with a more rapid decrease in fever; (iii) the possibility of deleterious ef- fects in cases of viral meningitis; and (iv) the concerns of some about the possibility of DEX interfering with an adequate penetration of antibiotics in cerebrospinal ﬂuid (CSF) (1, 13). munoassay with a level of detection of bacteri- cidal activities were performed by a microdilution method (6) with cation-adjusted Mueller-Hinton broth supplemented with 2 to 5% lysed horse blood. twofold dilutions to CSF were performed, tion of (cid:51) used meningitis was 24
Sensor location for diagnosis in linear structured systems with disturbances

We consider here the fault detection and isolation (FDI) problem for linear systems. We design a set of observer-based residuals, in such a way that the transfer from the faults to the residuals is diagonal and the transfer from the disturbances to the residuals is zero. We deal with this problem when the system under consideration is structured, that is, the entries of the system matrices are either fixed zeros or free parameters. This problem was solved recently in terms of the graph that one can associate in a natural way to a structured system. We are concerned in this paper with the case where the FDI solvability conditions are not satisfied. We consider that some internal states can be measured at some cost and wonder if the problem is solvable with these new measurements. If this is possible we give solvability conditions at minimal cost for the considered sensor location problem. These problems are solved using the bipartite graph of the system. A particular attention is devoted to the complexity reduction of the optimization problem.
Maternal use of ﬂuconazole and risk of congenital malformations: a Danish population-based cohort study

Objectives : Fluconazole is widely used for the treatment of candidiasis. Although the drug is also prescribed to pregnant women, data on the safety of use of ﬂuconazole during pregnancy are limited. We examined the association between the maternal use of ﬂuconazole during pregnancy and the risk of congenital malformations. Patients and methods : In this population-based cohort study in Northern Denmark, we included 1079 women who had a live birth or a stillbirth after the 20th week of gestation and who redeemed at least one prescription for ﬂuconazole during the ﬁrst trimester. The reference cohort comprised 170 453 pregnant women who redeemed no ﬂuconazole prescription during pregnancy. The women were identiﬁed through the Danish Medical Birth Registry. Data on drug use, birth outcome and covariates were extracted from population-based healthcare databases. We used logistic regression to estimate the prevalence odds ratio (POR) for congenital malformations after ﬂuconazole exposure, while adjusting for maternal smoking, parity, maternal age and concurrent prescriptions for antiepileptics or antidiabetics. Results : Among 1079 women who ﬁlled a ﬂuconazole prescription during the ﬁrst trimester, 797 (74%) received a total of 150 mg of ﬂuconazole, 235 (22%) received 300 mg of ﬂuconazole, 24 (2%) received 350 mg of ﬂuconazole and 23 (2%) received 600 mg of ﬂuconazole. These women gave birth to 44 (4.1%) children with congenital malformations. The 170 453 women without ﬂuconazole prescriptions gave birth to 6152 (3.6%) children with congenital malformations. For congenital malformations overall, the adjusted POR associated with the ﬁrst-trimester ﬂuconazole use was 1.0 (95% conﬁdence interval: 0.8–1.4). Conclusions : We found no overall increased risk of congenital malformations after exposure to short-course treatment with ﬂuconazole in early pregnancy.
Hearing Profile of Multiple Sclerosis Patients in Jordan: A Case-Control Study

Objective: To determine and evaluate the difference in audiometric hearing status between individuals with and without Multiple Sclerosis (MS). Background: MS is a chronic degenerative disease characterized by multifocal demyelination of the Central Nervous System (CNS), and thus resulting in many neurologic findings that are disseminated in place and time. Although MS affects the CNS as a whole, MS patients rarely report any complaints about their hearing status. The estimates regarding the prevalence of pure tone hearing abnormality in this patient population vary greatly. Several studies reported conflicting results about the chronic effect of MS on hearing thresholds and while some studies concluded no significant association, other studies reported a significant association. The frequencies at which MS patients had hearing deficits were various in these studies. Methods: Using Pure Tone Audiometry (PTA), pure tone air-conduction thresholds were recorded at 0.25, 0.5, 1, 2, 4, and 8 kHz in 60 MS patients and 89 healthy controls. According to the means of the thresholds across these frequencies, the ears of each MS patient were classified to Better Hearing Ear (BE) or Worse Hearing Ear (WE). Mean thresholds of BEs and WEs were then compared to the mean thresholds of both ears of healthy controls. Results: Hearing thresholds of WEs of MS patients were significantly higher than controls at all tested frequencies (all Ps <0.01). Moreover, hearing thresholds of BEs of MS patients were significantly higher than controls at 0.5, 4, and 8 kHz (all Ps < 0.05). No correlation was found between auditory thresholds and duration of the disease. Conclusions: The study supports that MS does influence auditory thresholds unilaterally at low-mid frequencies and asymmetrically and bilateral at mid-high frequencies.
Clinical A Clinico-pathological study of Placenta percreta

Objective: We aim to review a series of placenta percreta (PP) managed in the same centre of excellence and to evaluate the risk factors and the impact of prior caesarean delivery (CD) surgical techniques used. Methods: Retrospective cohort study of 19 pregnancies with placenta percreta managed by a multidisciplinary team between January 2002 and March 2017 at Saint Luc University Hospital. Data reviewed included demographics, outcome, inter-pregnancy interval (IPI) and surgical techniques used for prior CD uterine closure. A series of non-accreta placenta praevia was used as control group. Results: The most commonly found ultrasound signs in the study group were loss of clear zone (n=14 out of 17 cases; 82.4%), placental lacunae (n=17; 100%) and subplacental hypervascularity (n=11 out of 14 cases); 78.6%). Median gravidity, parity and number of prior CD were significantly (P< 0.05) higher and IPI significantly (P<0.05) longer in the PP group than in the control group. There was no difference between the groups for the surgical techniques used for the prior CD. Conclusion: The prenatal ultrasound diagnosis of PP is accurate allowing for optimal management by a specialised multidisciplinary team. Multicentric studies are required to further evaluate the impact of prior CD surgical techniques used on the risks of PP in subsequent pregnancies.
Scaling laws for electrodynamic suspension in high-speed transportation

Electrodynamic suspension (EDS) relies on the repulsive force created by eddy currents in a stationary conductive body (rail) and a magnetic field generated by an excitation system on a moving vehicle (pod). The excitation system in this paper consists of permanent magnets in a Hallbach array. EDS generates lift forces that levitate the pod reliably at high speeds of the vehicle since no mechanical suspension is required. Therefore, it gains interest for high-speed transportation applications such as the Hyperloop project, driven by the Space Exploration Technologies Corporation (SpaceX). Electrodynamic fields and forces have been analysed in detail in the literature; however, the sophistication and/or limited applicability of analytical approaches or the computational burden of FEM/numerical methods render those impractical for the initial design of EDS systems. Therefore, power and loss scaling laws for EDS systems are derived in this study. A 3D simulation for a design example shows that the scaling law is within 10% deviation. Finally, the drag coefficient of EDS systems is compared with other forms of commercial high-speed ground and air transportation systems. A pod with EDS running in vacuum has the potential of decreasing energy consumption significantly above the cruising speeds of modern subsonic airliners.
Neuroblastoma in Vietnam: A retrospective analysis of MYCN status and clinical features to inform prognosis and improve outcome

Background: Neuroblastoma is the most common childhood cancer worldwide. While recent advances in diagnosis and treatment have resulted in dramatic improvements in patient survival, neuroblastoma recurrence and mortality rates in Vietnam are unknown. This study evaluated the survival rates of Vietnamese patients with NB and investigated the impact of clinical factors and MYCN status on prognosis. Methods: This study analysed survival rates, clinical factors and MYCN status of NB patients across three hospitals in Ho Chi Minh City. Kaplan-Meier and multivariable Cox proportional hazards models were used to describe Survival rates and determine hazard ratios. Patient samples were analysed retrospectively for MYCN amplification by fluorescence in-situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR). Results: 5-year overall survival (OS) was 39.78% ± 4.31% and event-free survival (EFS) was 56.63% ± 5.47% in our cohort, and significantly lower than OS and EFS rates in Europe, USA, Japan, China and Thailand. MYCN- amplified or Stage III and IV NB patients showed significantly decreased survival time in comparison to those without MYCN amplification (log rank P =0.000) or diagnosed at stage I, II and IVs (log rank P =0.000). Furthermore, patients older than 18 months or at stage III and IV had a significantly higher probability of recurrence ( P =0.038 and P =0.000, respectively). Conclusions: This study demonstrates poor outcome for NB patients in Vietnam. Furthermore, prognosis is significantly worsened by their MYCN status; NB stage and age at diagnosis.
OTT_A_254747 6485..6496

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, People’s Republic of China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, People’s Republic of China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, People’s Republic of China; National Clinical Research Center for Geriatric Disorders, Changsha 410008, Hunan, People’s Republic of China; Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; Department of Gynaecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha 410011, People’s Republic of China; Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410078, People’s Republic of China; Hunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha 410078, People’s Republic of China; HunanKey Laboratoryof PreciseDiagnosis and Treatment of Gastrointestinal Tumor, Changsha 410078, People’s Republic of China Purpose: Resistance is one of the main limitations of successful platinum treatment in nonsmall-cell lung cancer (NSCLC) patients. In this study, we aimed to identify somatic mutations associated with platinum response. Patients and Methods: A total of 57 patients who received platinum-based chemotherapy only and 13 patients who received neoadjuvant chemotherapy (NAC) were enrolled. Somatic mutations were obtained from targeted and whole exome sequencing (WES). Results: Somatic mutations in a total of 225 genes were observed. Nonsynonymous variants in EGFR, TTN, TP53 and KRAS, and copy number variations (SCNVs) in chromosome 8q24.3 and 22q11.21 were identified to be associated with platinum response. Based on these mutations, the mutational signature associated with the failure of DNA double-strand break and calcium signaling pathways were identified to be associated with platinum response. Besides, we observed a decrease in tumor mutational burden after chemotherapy. We also evaluated the mutation spectrum consistency between cell-free DNA (cfDNA) and tissue DNA. Somatic mutations detected in cfDNA were consistent with that in tDNA, which indicated that plasma might be used for somatic mutation detection. Conclusion: These results support that somatic mutations can affect platinum drug response and provide potential clinical biomarkers for NSCLC treatment.
Targeting Limits Virus, and

SUMMARY a strategy hosts use to suppress viral replication and a potential pan-antiviral To deﬁne the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged inﬂuenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for inﬂuenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of inﬂuenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying vi-rus-human protein-protein interactions in the context of active replication, we have identiﬁed targetable host factors for broad-spectrum antiviral therapies. folding. We show that partial depletion and chemical inhibition of Sec61 speciﬁcally affect biosynthesis of inﬂuenza virus proteins HA (and NA) and, in turn, viral biogenesis. Using loss-of-function screening (dengue virus [DENV]) and mathematical modeling of how proteins segregate in interaction networks during infection with different pathogens (HIV and inﬂuenza virus), we show that Sec61 partial depletion and chemical inhibition suppresses HIV and DENV replication with little to no effect on cellular proteostasis. We discuss the rationale of targeting essential cellular function as a strategy for developing pan-antiviral therapies.
Metamorphism of the Kangåmiut dykes and the metamorphic and structural evolution of the southern Nagssugtoqidian boundary in the Itvidleq-Ikertoq region,

The structural evolution of the Nagssugtoqidian mobile belt is characterised by re working of pre-existing Archaean rocks. At the southern Nagssugtoqidian boundary swarms of basic dykes, the Kangamiut dykes, intruded after the earliest Nagssugtoqidian movements. These dykes aet as time markers separating tectono-metamorphic events and record degree and extent of post-dyke metamorphism and deformation. The structural and metamorphic evolution at the southern Nagssugtoqidian boundary ean be summarised as follows. The rocks now exposed were stabilised in granulite and amphibolite facies in Archaean times. Uplift brought the rocks under low amphibolite facies conditions. Subsequent deformation (Nag. 1) caused the retrogression to low amphibolite facies and transformed the rocks into strongly schistose rocks along duetile, transcurrent, E-W trending shear zones. The Nag. 1 deformation was followed by intru sion of the mainly NE trending Kangamiut dykes. Later Nagssugtoqidian deformation (Nag. 2) affected country rocks with Nag. 1 fabrics as well as dykes and probably also Archaean gneisses unaffected by Nag. 1 deformation. In areas with intense Nag. 2 movements the deformation was characterised by duetile overthrusting towards the SSE along a linear zone striking ENE. New Nag. 2 fabrics were imposed on the country gneisses and dykes were transformed into strongly deformed amphibolites. The duetile overthrusting brought granulite facies rocks into juxtaposition with amphibolite facies rocks so that across the areas affected by Nag. 2 deformation a prograde metamorphic sequence with facies boundaries parallel to the overthrusting zone was established.
E ﬀ ect of High CO 2 Treatment and MA Packaging on Sensory Quality and Physiological-Biochemical Characteristics of Green Asparagus ( Asparagus o ﬃ cinalis L.) during Postharvest Storage

: Green asparagus is vulnerable to thrips that carry microorganisms and cause deterioration in quality. The e ﬀ ects of 60% CO 2 treatment, which is used to kill thrips, combined with perforated (P) or modiﬁed atmosphere (MA) packages during cold storage, on the sensory quality and physiological–biochemical characteristics of asparagus were investigated. MA packaging yielded an asparagus shelf-life ﬁve days longer than P packaging. The 60% CO 2 treatment for 48 h at 4 ◦ C packaged with MA ﬁlm (CO 2 -48 h-4 ◦ C-MA) showed a lower number of aerobic bacteria, yeast, and mold. Yellowing of asparagus was retarded, as shown by higher hue angle and chlorophyll content and lower chlorophyllase activity. Also, CO 2 -48 h-4 ◦ C-MA treatment inhibited the reduction of soluble solids content in asparagus. Likewise, all high CO 2 treatments showed lower electrolyte leakage (EL), with CO 2 -48 h-4 ◦ C-MA demonstrating the minimum EL. The e ﬀ ectiveness of high CO 2 on maintaining sensory qualities was observed, with a score higher than 3.0. In conclusion, CO 2 -48 h-4 ◦ C-MA treatment during cold storage was e ﬀ ective for maintaining post-harvest sensory qualities and physiological–biological traits of asparagus, and provided strong inhibition of microﬂora growth during the storage period.
Prevalence Gland in Dementia with Lewy

: Somatic mutations are post-zygotic mutations which may lead to mosaicism, the presence of cells with genetic differences in an organism. Their role in cancer is well established, but detailed investigation in health and other diseases has only been recently possible. This has been empowered by the improvements of sequencing techniques, including single cell sequencing, which can still be error-prone but is rapidly improving. Mosaicism appears relatively common in the human body, including the normal brain, probably arising in early development, but also potentially during ageing. In this review, we first discuss theoretical considerations and current evidence relevant to somatic mutations in the brain. We present a framework to explain how they may be integrated with current views on neurodegeneration, focusing mainly on sporadic late onset neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis). We review the relevant studies so far, with the first evidence emerging in Alzheimer’s in particular. We also discuss