Miracle-dz/UniFAR-FTUs huggingface dataset:
Hubs disruption in mesial temporal lobe epilepsy. A resting‐state fMRI study on a language‐and‐memory network

Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded language‐and‐memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure‐related damage. Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN‐FC using two methods: pairwise correlations (region of interest [ROI]‐to‐ROI) and graph theory. The cognitive efficiency of the LMN‐FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L‐mTLE) than in right (R‐mTLE) patients. The LMN‐FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of “connectome” would gain to be associated with a “cognitome” concept.
PREDICTIVE FACTORS FOR SUCCESSFUL INSULIN THERAPY IN PATIENTS WITH TYPE 2 DIABETES

Gereç ve Yöntem: Çal›flmaya WHO kriterlerine göre tip 2 diabetes mellitus tan›s› konmufl, 6 aydan uzun süredir maksimal dozda oral antidiyabetik almas›na ra¤men istenilen düzeyde kan flekeri regülasyonu sa¤lanamad›¤› için insülin tedavisine geçilen ve en az 6 ayd›r insülin tedavisi alan 145 hasta (yafl 57.00±11.05 y›l, vücut kitle indeksi (VK‹) 28.8±5.4 kg/m2, diyabet süresi 11.6±7.8 y›l) dahil edilmifltir. Açl›k kan flekeri, bazal c-peptid düzeyi, HbA1c, kan bas›nc›, vücut a¤›rl›¤› ile serum lipidleri insülin tedavisine bafllamadan önce ve takip periyodundaki son vizitte de¤erlendirilmifltir.
Congruence between Hypothetical Willingness to Use Pre-Exposure Prophylaxis (PrEP) and Eligibility: An Online Survey among Belgian Men Having Sex with Men

Men who have sex with men (MSM) are at high risk for acquiring HIV in Belgium. This study explores MSMs’ hypothetical willingness to use pre-exposure prophylaxis (PrEP), assesses it against formal PrEP eligibility criteria, and identifies factors associated with incongruence between eligibility and willingness. We used data from an online survey of n = 1444 self-reported HIV-negative MSM. Participants were recruited through social media of MSM organizations and dating apps. Univariate analysis described PrEP willingness and eligibility; bivariate analyses examined how specific co-variates (socio-demographic, knowledge-related, and attitudinal and behavioral factors) were associated with eligibility and willingness. About 44% were eligible for PrEP and about 70% were willing to use it. Those who were eligible were significantly more likely be willing to take PrEP (p < 0.001). Two incongruent groups emerged: 16% of eligible participants were unwilling and 58% of ineligible participants were willing to use PrEP. Factors associated with this incongruence were sexual risk behavior, HIV risk perception, partner status, PrEP knowledge, and attitudinal factors. Because the two groups differ in terms of profiles, it is important to tailor HIV prevention and sexual health promotion to their needs. Among those at risk but not willing to take PrEP, misconceptions about PrEP, and adequate risk perception should be addressed.
Stem Cells for Cardiovascular Diseases Revisited in 2019

cardiovascular diseases, such as refractory angina and myocardial failure, caused a frenzy in clinical research in the late 1990’s and early 2000’s. Experimental reports have shown marked improvements in myocardial contractility in heart failure models, and increased myocardial perfusion or even myocardial replacement after necrosis in ischemic models. More than 200 clinical trials were produced, but the experimental effects could not be reproduced. Indeed, an improvement in cardiac function as well as some angiogenic reperfusion have been observed at the clinical level, but those effects were light and temporary, not sufficient to represent a usable therapeutic tool. The reasons for that are an actual challenge to researchers. There are many hypotheses for stem cell therapy failure in clinical therapy. Animal experiments are done in young individuals and outcomes are evaluated invariably at short term. Cardiac diseases are present in older patients, in whom stem cells are also old and submitted to pharmacological effects of therapeutic drugs. Potent and prolonged improvements are necessary to influence clinical outcomes, differently from what can be achieved in animal research. Those could be some of several explanations. The mechanism of action of stem cell therapy is also under exploration. The elements responsible for the effects need to be better understood. Cellular proliferation, paracrine effects, and delivery of cell elements or components are theories to be studied. Proliferation has been demonstrated as not feasible in clinical level. Some considerations should be brought to mind. There are two main types of stem cells. Pluripotent stem cells, capable of differentiating in any type of mature cells, of EDITORIAL
Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis. ” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.
Efficacy and Safety of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα): Pooled Analysis of Phase 2 and 3 Studies in Dyslipidemic Patients with or without Statin Combination

Hypertriglyceridemia has emerged as an independent risk factor for cardiovascular events, despite low-density lipoprotein-cholesterol (LDL-C) well-controlled with statins. We pooled data from the first 12 weeks of six randomized double-blind placebo-controlled studies of pemafibrate in Japan and investigated its efficacy and safety with and without statins, particularly focusing on patients with renal dysfunction. Subjects were 1253 patients (677 in the “with-statin” group and 576 in the “without-statin” group). At Week 12 (last observation carried forward), triglyceride (TG) was significantly reduced at all pemafibrate doses (0.1, 0.2, and 0.4 mg/day), both with and without statin, compared to placebo (p < 0.001 vs. placebo for all groups). In the “with-statin” group, the estimated percent change from baseline was −2.0% for placebo and −45.1%, −48.5%, and −50.0%, respectively, for the pemafibrate groups. Findings for both groups showed significant decreases in TG-rich lipoproteins and atherogenic lipid parameters compared to placebo. The incidence of adverse events was similar between the pemafibrate and placebo groups and was also similar for patients with and without renal dysfunction in the “with-statin” group. Pemafibrate lowered TG and improved atherogenic dyslipidemia without a significant increase in adverse events in comparison to the placebo, even among “with-statin” patients who had renal dysfunction.
Application of Item Response Theory to Model Disease Progression and Agomelatine Effect in Patients with Major Depressive Disorder

In this paper, we studied the effect over time of agomelatine, an antidepressant drug administered in patient with major depressive disorder, through item response theory (IRT), taking into account a strong placebo effect and missing not at random. We also assessed the informativeness of the HAMD-17 scale’s item. The data includes five phase III clinical trials sponsored by Servier Institute, totalling 1549 patients followed during a maximum of 1 year. At each observation, individual scores for the 17 items of the HAMD scale were recorded. The probability for each score was modelled with IRT. A non-linear mixed effects model was used to describe the evolution of the disease and was coupled with a time to event model to predict dropout. Clinical trial simulations were then used to compare placebo and active treatment. Informativeness of each item was evaluated using the Fisher information theory. The best model combined an IRT model, a longitudinal model for underlying depression which describes the remission and then a possible relapse, and a hazard model for dropout depending on the evolution from baseline. The drug effect was best modelled as an effect on the remission and the relapse phases. The median predicted drop in HAMD between baseline and 6 weeks was 8.8 (90% PI, 8.3–9.2) when on placebo and 13.1 (90% PI, 12.8–13.4) when treated. Nine items were found to be the most informative. The IRT framework allowed to characterise the evolution of depression with time and estimate the effect of agomelatine, as well as the link between symptoms and disease.
The metabolic clinical risk score as a new prognostic model for surgical decision‐making in patients with colorectal liver metastases

Selection for surgery in patients with colorectal liver metastases (CRLM) remains inaccurate. We evaluated if CRLM baseline metabolic characteristics, assessed by [18]F‐fluorodeoxyglucose‐positron emission tomography/computed tomography (18FDG‐PET/CT), could predict postoperative outcomes.
The Safety of Single and Multi-level Cervical Total Disc Replacement in Ambulatory Surgery Centers.

STUDY DESIGN Retrospective cohort OBJECTIVE. : Evaluate the safety profile of single and multilevel cervical artificial disc replacement (ADR) performed in an outpatient setting. SUMMARY OF BACKGROUND DATA As healthcare costs rise, attempts are made to perform an increasing proportion of spine surgery in ambulatory surgery centers (ASCs). ASCs are more efficient, economically and functionally. Few studies have published on the safety profile of multi-level cervical ADR. METHODS We have performed an analysis of all consecutive cervical ADR surgeries that we performed in an ASC over a 9-month period, including multi-level and revision surgery. The pre-, intra- and post-op data recorded included age, gender, BMI, tobacco use and the presence of diabetes; level and procedure, OR time, EBL, complications; discharge site, occurrence of re-operation, hospital admission or any medical complication or infection over a 90-day period. RESULTS 147 patients underwent 231 treated levels: 71 single-level, 76 multi-level: 69 two-level, 6 three-level, 1 four-level. Average age was 50 +/-10 years; 71 female, 76 males. None of the patients were insulin-dependent diabetics, 4 were current smokers, 16 were former smokers. Average BMI was 26.8 +/-4.6 (range 18-40). Average total anesthesia time was 88 minutes (range 39-168 minutes). Average EBL was 15 ml (range 5-100 ml). 90.3% of patients were discharged directly home, 9.7% to an after-care facility. In the 90-day post-op period there were zero deaths, two hospital admissions (1.4%) - one for medical complication (0.7%) and one for a surgical site infection (0.7%). CONCLUSION In this consecutive case series we performed 231 ADRs in 147 patients in the outpatient setting, including multi-level and revision procedures, with 2 minor post-operative complications resulting in hospital unplanned admissions within 90 days. We believe these procedures are safe to perform in an ASC. An efficient surgical team and careful patient selection criteria are critical in making this possible. LEVEL OF EVIDENCE 3.
Axo-glial interdependence in peripheral nerve development

ABSTRACT During the development of the peripheral nervous system, axons and myelinating Schwann cells form a unique symbiotic unit, which is realized by a finely tuned network of molecular signals and reciprocal interactions. The importance of this complex interplay becomes evident after injury or in diseases in which aspects of axo-glial interaction are perturbed. This Review focuses on the specific interdependence of axons and Schwann cells in peripheral nerve development that enables axonal outgrowth, Schwann cell lineage progression, radial sorting and, finally, formation and maintenance of the myelin sheath. Summary: This Review focuses on the specific interdependence of axons and Schwann cells that enables peripheral nerve development and maintenance.
Play enhances visual form perception in infancy–an active training study

Abstract Motor experiences and active exploration during early childhood may affect individual differences in a wide range of perceptual and cognitive abilities. In the current study, we suggest that active exploration of objects facilitates the ability to process object forms and magnitudes, which in turn impacts the development of numerosity perception. We tested our hypothesis by conducting a preregistered active exploration intervention with 59 8‐month‐old infants. The minimal intervention consisted of actively playing with and exploring blocks once a day for 8 weeks. In order to control for possible training effects on attention, we used book reading as a control condition. Pre‐ and post‐test assessments using eye‐tracking showed that block play improved visual form perception, where infants became better at detecting a deviant shape. Furthermore, using three control tasks, we showed that the intervention specifically improved infants' ability to process visual forms and the effect could not be explained by a domain general improvement in attention or visual perception. We found that the intervention did not improve numerosity perception and suggest that because of the sequential nature of our hypothesis, a longer time frame might be needed to see improvements in this ability. Our findings indicate that if infants are given more opportunities for play and exploration, it will have positive effects on their visual form perception, which in turn could help their understanding of geometrical concepts.
Emerging neuromorphic devices

Artificial intelligence (AI) has the ability of revolutionizing our lives and society in a radical way, by enabling machine learning in the industry, business, health, transportation, and many other fields. The ability to recognize objects, faces, and speech, requires, however, exceptional computational power and time, which is conflicting with the current difficulties in transistor scaling due to physical and architectural limitations. As a result, to accelerate the progress of AI, it is necessary to develop materials, devices, and systems that closely mimic the human brain. In this work, we review the current status and challenges on the emerging neuromorphic devices for brain-inspired computing. First, we provide an overview of the memory device technologies which have been proposed for synapse and neuron circuits in neuromorphic systems. Then, we describe the implementation of synaptic learning in the two main types of neural networks, namely the deep neural network and the spiking neural network (SNN). Bio-inspired learning, such as the spike-timing dependent plasticity scheme, is shown to enable unsupervised learning processes which are typical of the human brain. Hardware implementations of SNNs for the recognition of spatial and spatio-temporal patterns are also shown to support the cognitive computation in silico. Finally, we explore the recent advances in reproducing bio-neural processes via device physics, such as insulating-metal transitions, nanoionics drift/diffusion, and magnetization flipping in spintronic devices. By harnessing the device physics in emerging materials, neuromorphic engineering with advanced functionality, higher density and better energy efficiency can be developed.
Vibroacoustic treatment to improve functioning and ability to work: a multidisciplinary approach to chronic pain rehabilitation

Abstract Purpose To study the use of Vibroacoustic treatment and an added self-care intervention for improving the functioning and ability to work of patients with chronic pain and potential comorbid depressive and anxious symptoms. Materials and methods A mixed methods study with four single cases. Participants received bi-weekly Vibroacoustic practitioner-led treatment sessions for five weeks, followed by a one-month washout period without treatments. Then, participants conducted four self-care vibroacoustic sessions per week for five weeks, followed by another month-long washout period. Participants kept diaries of their experiences during this time. Quantitative scales included the World Health Organization Disability Assessment Schedule 2.0, Visual Analogue Scales (pain, mood, relaxation, anxiety, and ability to work), Beck’s Depression Inventory-II, and Hospital Anxiety and Depression Scale (Anxiety only). The use of physiological markers was also explored. Results The greatest improvement was from the practitioner-led sessions, but self-care was beneficial for pain relief and relaxation. Participants became more aware of sensations in their own bodies, and during washout periods noticed more clearly the treatment effects when symptoms returned. An added self-care phase to standard Vibroacoustic treatment could be beneficial for maintaining the effects from the more intensive Vibroacoustic treatment as part of multidisciplinary rehabilitation. Implications for rehabilitation Chronic pain and comorbid mood disorders negatively impact functioning and ability to work. Vibroacoustic treatment with a self-care phase could be beneficial for managing the symptoms of chronic pain if implemented within a naturalistic multidisciplinary rehabilitation context. In four single cases, this study shows functioning, pain, and depression improved after Vibroacoustic treatment with self-care.
The cyclin B2/CDK1 complex inhibits separase activity in mouse oocyte meiosis I

ABSTRACT Chromosome segregation is driven by separase, activity of which is inhibited by binding to securin and cyclin B1/CDK1. In meiosis, premature separase activity will induce aneuploidy or abolish chromosome segregation owing to the untimely destruction of cohesin. Recently, we have proved that cyclin B2 can compensate for cyclin B1 in CDK1 activation for the oocyte meiosis G2/M transition. In the present study, we identify an interaction between cyclin B2/CDK1 and separase in mouse oocytes. We find that cyclin B2 degradation is required for separase activation during the metaphase I-anaphase I transition because the presence of stable cyclin B2 leads to failure of homologous chromosome separation and to metaphase I arrest, especially in the simultaneous absence of securin and cyclin B1. Moreover, non-phosphorylatable separase rescues the separation of homologous chromosomes in stable cyclin B2-arrested cyclin B1-null oocytes. Our results indicate that cyclin B2/CDK1 is also responsible for separase inhibition via inhibitory phosphorylation to regulate chromosome separation in oocyte meiosis, which may not occur in other cell types. Summary: Cyclin B2 regulates separase activity through inhibition of phosphorylation, especially in the absence of securin and cyclin B1, during the first meiotic division of mouse oocytes.
Geohelminth transmission among slum-dwelling children in Durban, South Africa.

Geohelminthiasis is a serious problem in city slums and despite being easily treatable in the short term, its elimination enjoys a low priority by parents, teachers and public health authorities. This is partly due to the greater emphasis given to the AIDS and TB programmes. This study of the prevalence, intensity, and reinfection rates of single and multiple geohelminth (AscariS lumbricoides, Trichuris trichiura and Necator americanus) infections in young children living in slums (informal settlements) in the Durban Unicity is a first for an African city and one of few similar studies anywhere in the world. The geohelminth status was assessed by means of a baseline survey of ten different slums, followed by two further surveys, one after 4Y:z 6 months and another after 12 months. Infections were measured by microscopic examination of faeces before and after chemotherapy, and risk factors within and between slums were identified by means of a quantifiable questionnaire. The study showed that: 1. The slums have a high endemicity and transmission rate of geohelminth infections. 2. The sub-tropical climate and environment ensured a high survival rate of infective stages . 3. A. lumbricoides had a high prevalence and intensity, followed by T. trichiura with a moderately high prevalence and light intensity. A small proportion of children had intensities of these helminths an order of magnitude higher than previously recorded from rural areas of South Africa. N americanus had a very low prevalence and a very light intensity. 4. Egg output from follow-up 1 to follow-up 2 increased 4.6 fold for A. lumbricoides and 9.4 fold for T. trichiura. 5. Albendazole proved to be a very effective drug against A. lumbricoides and N americanus but not as effective against T. trichiura. 6. The infection and reinfection rates of A. lumbricoides and T. trichiura proved to be influenced by different risk factors . 7. The most important risk factors included topographical position of the slum, quality of the dwelling, number of inhabitants, geophagy and source of fruit and vegetables .
The Endophytic Fungus Chaetomium cupreum Regulates Expression of Genes Involved in the Tolerance to Metals and Plant Growth Promotion in Eucalyptus globulus Roots

The endophytic strain Chaetomium cupreum isolated from metal-contaminated soil was inoculated in Eucalyptus globulus roots to identify genes involved in metal stress response and plant growth promotion. We analyzed the transcriptome of E. globulus roots inoculated with C. cupreum. De novo sequencing, assembly, and analysis were performed to identify molecular mechanisms involved in metal stress tolerance and plant growth promotion. A total of 393,371,743 paired-end reads were assembled into 135,155 putative transcripts. It was found that 663 genes significantly changed their expression in the presence of treatment, of which 369 were up-regulated and 294 were down-regulated. We found differentially expressed genes (DEGs) encoding metal transporters, transcription factors, stress and defense response proteins, as well as DEGs involved in auxin biosynthesis and metabolism. Our results showed that the inoculation of C. cupreum enhanced tolerance to metals and growth promotion on E. globulus. This study provides new information to understand molecular mechanisms involved in plant–microbe interactions under metals stress.