Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurological Outcome After Traumatic Transverse Sacral Fractures: A Systematic Review of 521 Patients Reported in the Literature

Background: The purpose of this study was to determine the neurological outcome after transverse sacral fractures in patients with neurological impairment. Methods: A systematic review of the English, French, German, and Dutch literature was conducted. All study designs, including retrospective cohort studies and case reports, describing transverse sacral fractures were included. Two authors independently extracted the predefined data and scored the neurological impairment according to the Gibbons classification after the trauma and at the time of follow-up. The neurological outcomes were pooled according to the Gibbons classification. Results: No randomized controlled trials or prospective case series were found. A total of 139 articles were included, consisting of 81 case reports and 58 retrospective case series involving 521 patients. Regardless of the type of management, neurological recovery of at least 1 Gibbons category was reported in 62% of these patients. A comparison of the neurological outcome of nonoperatively treated patients and surgically treated patients showed similar neurological recovery rates. For the surgically treated patients, fixation of the fracture resulted in a better neurological improvement compared with an isolated decompression. Conclusions: This review could not provide evidence of improved neurological recovery after surgical treatment compared with nonoperative treatment. When surgical treatment was considered, there was a low level of evidence that fixation of the fracture results in better neurological improvement compared with isolated decompression. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
External validation of change formulae in neuropsychology with neuroimaging biomarkers: A methodological recommendation and preliminary clinical data

Abstract Objective: Within neuropsychology, a number of mathematical formulae (e.g. reliable change index, standardized regression based) have been used to determine if change across time has reliably occurred. When these formulae have been compared, they often produce different results, but ‘different’ results do not necessarily indicate which formulae are ‘best. ’ The current study sought to further our understanding of change formulae by comparing them to clinically relevant external criteria (amyloid deposition and hippocampal volume). Method: In a sample of 25 older adults with varying levels of cognitive intactness, participants were tested twice across one week with a brief cognitive battery. Seven different change scores were calculated for each participant. An amyloid PET scan (to get a composite of amyloid deposition) and an MRI (to get hippocampal volume) were also obtained. Results: Deviation-based change formulae (e.g. simple discrepancy score, reliable change index with or without correction for practice effects) were all identical in their relationship to the two neuroimaging biomarkers, and all were non-significant. Conversely, regression-based change formulae (e.g. simple and complex indices) showed stronger relationships to amyloid deposition and hippocampal volume. Conclusions: These results highlight the need for external validation of the various change formulae used by neuropsychologists in clinical settings and research projects. The findings also preliminarily suggest that regression-based change formulae may be more relevant than deviation-based change formulae in this context.
Ability of disease-modifying antirheumatic drugs to prevent or delay rheumatoid arthritis onset: a systematic literature review and meta-analysis

Background Recent advances in knowledge of the pathogenesis of rheumatoid arthritis (RA) has led to promoting very early intervention. Objectives To assess the efficacy of therapeutic interventions in preventing or delaying RA onset with a systematic literature review (SLR) and meta-analysis (MA). Methods The SLR aimed to include all reports of randomised controlled trials of disease-modifying antirheumatic drugs or glucocorticoids used in patients presenting genetic and/or environmental risk factors for RA and/or systemic autoimmunity associated with RA, and/or symptoms without clinical arthritis and/or unclassified arthritis and in patients with RA. We searched PubMed, EMBASE and Cochrane databases for English articles published from 2006 to 2016 using the keywords ‘undifferentiated arthritis’ or ‘very early rheumatoid arthritis’ with ‘therapy’ or ‘treatment’. Main outcome was RA occurrence, defined as fulfilment of the 1987 ACR criteria. The MA was performed with RevMan with the Mantel-Haenszel method. Results Among 595 abstracts screened, 10 reports of trials were selected. The studies included 1156 patients, with mean symptom duration 16.2±12.6 weeks. The occurrence of RA was available for nine studies, assessing methylprednisolone, methotrexate, a tumour necrosis factor blocker, abatacept or rituximab. In the group arthralgia without arthritis (people at risk of RA), the MA of the two available studies did not show significant reduction in RA occurrence at week 52 or more (pooled OR 0.74, 95% CI 0.37 to 1.49). For people with undifferentiated arthritis, the MA of the seven available studies revealed significant risk reduction with OR 0.73(95% CI 0.56 to 0.97). Conclusions This MA demonstrates that early therapeutic intervention may significantly reduce the risk of RA onset in this very first phase of the disease.
P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: implications for EEG models of working memory function

Abstract Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTIs) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct (‘match’) or incorrect (‘non-match’ or ‘oddball’) stimuli. Moreover, the recall series included either a brief (500 ms) or extended (2000 ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in TTI. These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.
Macrophages protect Talaromyces marneffei conidia from myeloperoxidase-dependent neutrophil fungicidal activity during infection establishment in vivo

Neutrophils and macrophages provide the first line of cellular defence against pathogens once physical barriers are breached, but can play very different roles for each specific pathogen. This is particularly so for fungal pathogens, which can occupy several niches in the host. We developed an infection model of talaromycosis in zebrafish embryos with the thermally-dimorphic intracellular fungal pathogen Talaromyces marneffei and used it to define different roles of neutrophils and macrophages in infection establishment. This system models opportunistic human infection prevalent in HIV-infected patients, as zebrafish embryos have intact innate immunity but, like HIV-infected talaromycosis patients, lack a functional adaptive immune system. Importantly, this new talaromycosis model permits thermal shifts not possible in mammalian models, which we show does not significantly impact on leukocyte migration, phagocytosis and function in an established Aspergillus fumigatus model. Furthermore, the optical transparency of zebrafish embryos facilitates imaging of leukocyte/pathogen interactions in vivo. Following parenteral inoculation, T. marneffei conidia were phagocytosed by both neutrophils and macrophages. Within these different leukocytes, intracellular fungal form varied, indicating that triggers in the intracellular milieu can override thermal morphological determinants. As in human talaromycosis, conidia were predominantly phagocytosed by macrophages rather than neutrophils. Macrophages provided an intracellular niche that supported yeast morphology. Despite their minor role in T. marneffei conidial phagocytosis, neutrophil numbers increased during infection from a protective CSF3-dependent granulopoietic response. By perturbing the relative abundance of neutrophils and macrophages during conidial inoculation, we demonstrate that the macrophage intracellular niche favours infection establishment by protecting conidia from a myeloperoxidase-dependent neutrophil fungicidal activity. These studies provide a new in vivo model of talaromycosis with several advantages over previous models. Our findings demonstrate that limiting T. marneffei’s opportunity for macrophage parasitism and thereby enhancing this pathogen’s exposure to effective neutrophil fungicidal mechanisms may represent a novel host-directed therapeutic opportunity.
Median nerve stimulation induced motor learning in healthy adults: A study of timing of stimulation and type of learning

Median nerve stimulation (MNS) has been shown to change brain metaplasticity over the somatosensory networks, based on a bottom‐up mechanism and may improve motor learning. This exploratory study aimed to test the effects of MNS on implicit and explicit motor learning as measured by the serial reaction time task (SRTT) using a double‐blind, sham‐controlled, randomized trial, in which participants were allocated to one of three groups: (a) online active MNS during acquisition, (b) offline active MNS during early consolidation and (c) sham MNS. SRTT was performed at baseline, during the training phase (acquisition period), and 30 min after training. We assessed the effects of MNS on explicit and implicit motor learning at the end of the training/acquisition period and at retest. The group receiving online MNS (during acquisition) showed a significantly higher learning index for the explicit sequences compared to the offline group (MNS during early consolidation) and the sham group. The offline group also showed a higher learning index as compared to sham. Additionally, participants receiving online MNS recalled the explicit sentence significantly more than the offline MNS and sham groups. MNS effects on motor learning have a specific effect on type of learning (explicit vs. implicit) and are dependent on timing of stimulation (during acquisition vs. early consolidation). More research is needed to understand and optimize the effects of peripheral electrical stimulation on motor learning. Taken together, our results show that MNS, especially when applied during the acquisition phase, is a promising tool to modulate motor leaning.
Clinical and Hematological Profiles of Malaysian Ponies Experimentally Infected with a Field Strain of Trypanosoma evansi

No outbreak has been reported on Trypanosoma evansi infection in Malaysia ponies since 1983, and little is known about the interaction between T. evansi and ponies in the country. Therefore, an experimental study was designed to evaluate the pathogenicity of a local strain of T. evansi in the local ponies. For this purpose, four healthy local ponies were inoculated with 102 live trypanosomes/kg body weight, whereas two ponies served as negative control. Blood samples and rectal temperature were collected on alternate days from both groups for 54 days. Physical examination comprised visible mucous membrane and any appearance of clinical signs were observed daily. The number of trypanosomes was estimated using the Neubauer haemocytometer method. Complete haemogram measurements were performed immediately using an automated blood cell counter and the data obtained was evaluated using the general linear model as linear regression. All infected ponies were salvaged treated with 7 mg/kg of diminazene diaceturate. The four infected ponies developed parasitaemia on the 4th day post-infection (DPI), whereas the first high mean of parasites count was recorded on the 8th DPI. Parasitaemia was detected at a level that fluctuated throughout the infection period (30 days) in all infected ponies with a mean of 13.5x106 trypanosomes/ml blood on the 30th DPI. Successive peaks of pyrexia were accompanied by the peaks of parasitaemia and the highest temperature (39.4°C) was observed on the 20th DPI. Excessive weakness and a reduction of appetite fluctuated in the infected ponies during the infection and one animal died unexpectedly on the 23rd DPI. The mean values for RBC, PCV, Hb and thrombocyte count were significantly lower in the infected ponies than the control groups. Neutrophil and eosinophil were significantly declined after the onset of parasitaemia, whereas monocyte increased significantly in the infected group. The appearance of clinical signs and changes in haematological parameters suggests that Malaysian local ponies are susceptible to T. evansi infection. Treatment of the infected ponies with the recommended dosage of diminazene diaceturate was successful in the surviving ponies.
Discriminative value of CA-125, HE4, Risk of Malignancy Index II (RMI-II) and Risk of Malignancy Algorithm (ROMA) in the differential diagnosis of pelvic masses: conclusions from a referral Centre in Portugal

Abstract The major purpose of this article was to compare the discriminative value of different algorithms and serum biomarkers in the differential diagnosis of adnexal masses. We performed a retrospective study with 247 women with adnexal neoplasia, submitted to surgical treatment and with a histological diagnosis. The evaluation of the area under the curve (AUC) for isolated CA-125 and HE4, and for ROMA and RMI-II, showed a better specificity of HE4 and RMI-II in premenopausal women. In the postmenopausal group, ROMA and RMI-II were the algorithms with a better performance. Impact Statement What is already known on this subject? CA-125 remains the most commonly used biomarker used to predict the behaviour of an adnexal mass, but it has a low sensitivity for stage I tumours. Other isolated serum markers have emerged more recently, such as HE4, as well as more complex algorithms, such as RMI or ROMA. It remains unclear which is the best marker/algorithm to predict the behaviour of an adnexal mass. What do the results of this study add? Our findings showed that ROMA is a suitable marker for postmenopausal women, with no advantage found in the premenopausal women when compared with an isolated HE4. What are the implications of these findings for clinical practice and/or further research? The different algorithms of the preoperative discrimination of ovarian neoplasia appear to have different AUC, SN and SP in the pre- or the postmenopausal patients. For the premenopausal women, the use of ROMA does not seem to have any advantage over the isolated use of HE4, which does not lose specificity even when the borderline tumours are considered for discrimination. In the postmenopausal women, ROMA is a valid algorithm with a good sensitivity. The RMI-II showed a good performance in both groups, although it depends on the ultrasound findings and has an important interobserver variability. This information allows a more targeted selection of markers and algorithms to be requested prior to surgery of ovarian neoplasms regarding the menopausal status of each patient.
Social interaction recruits mentalizing and reward systems in middle childhood

Social cognition develops in the context of reciprocal social interaction. However, most neuroimaging studies of mentalizing have used noninteractive tasks that may fail to capture important aspects of real‐world mentalizing. In adults, social‐interactive context modulates activity in regions linked to social cognition and reward, but few interactive studies have been done with children. The current fMRI study examines children aged 8–12 using a novel paradigm in which children believed they were interacting online with a peer. We compared mental and non‐mental state reasoning about a live partner (Peer) versus a story character (Character), testing the effects of mentalizing and social interaction in a 2 × 2 design. Mental versus Non‐Mental reasoning engaged regions identified in prior mentalizing studies, including the temporoparietal junction, superior temporal sulcus, and dorsomedial prefrontal cortex. Moreover, peer interaction, even in conditions without explicit mentalizing demands, activated many of the same mentalizing regions. Peer interaction also activated areas outside the traditional mentalizing network, including the reward system. Our results demonstrate that social interaction engages multiple neural systems during middle childhood and contribute further evidence that social‐interactive paradigms are needed to fully capture how the brain supports social processing in the real world.
Stem cell transplantation in sickle cell disease: therapeutic potential and challenges faced

ABSTRACT Introduction: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide, and is a life-limiting disease with limited therapeutic options to reduce disease severity. Despite being a monogenic disorder, the clinical phenotypes of SCD are variable, with few reliable predictors of disease severity easily identifying patients where the benefits of curative therapy outweigh the risks. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option, though significant advances in gene therapy raise the promise for additional curative methods. Areas covered: Allogeneic transplantation in SCD has evolved and improved over the last two decades, now offering a standard of care curative option using a human leukocyte antigen (HLA)-matched sibling donor. Many of the seminal transplantation studies are reviewed here, demonstrating how initial failures and successes have influenced and led to current HSCT strategies. Such strategies aim to overcome setbacks and limitations, and focus on conditioning regimens, immune suppression methods, the use alternative donor sources, and gene therapy approaches. Expert commentary: SCD is a curable disease. Each dedicated effort to refine transplantation methods, expand the donor pool, and bring gene therapy models to fruition will make enormous impacts reducing disease burden and improving outcomes and quality of life for patients with SCD.
Prevalence of diarrhoea and its associated factors in children under five years of age in Baghdad, Iraq

Introduction: Diarrhoeal disease is one of the principal causes of morbidity and mortality among children in developing countries. Poor nutrition leads to ill health and it contributes to further deterioration in nutritional status. Methodology: A cross-sectional study was conducted in Baghdad, Iraq. The study was conducted in three paediatric hospitals and from paediatric departments in other three general hospitals in Baghdad, Iraq. Sample was drawn conveniently, three paediatric hospitals from Baghdad hospital list. 150 respondents were chosen from these paediatric hospitals and 50 respondents were chosen from the paediatric departments in three general hospitals. Results: males had twice the risk of diarrhoea (OR 1.9, 95% CI 1.1; 3.5). The risk of diarrhoea was 3 times higher among children with mothers who had lower level of education (OR 3.5 95% CI 1.3; 10.1), 5 times higher with unemployed mothers (OR 4.7 95% CI 2.1; 10.4) and 2 times higher with mothers who had poor nutritional knowledge (OR 2.5 95% CI 1.4; 4.9). The risk of diarrhoea was three times higher among children with fathers who had lower level of education (OR 3.3 95% CI 1.7; 6.6). The binomial logistics regression, Mothers’ level of education and employment status, fathers’ level of education, mothers’ nutritional knowledge were used as possible independent associated factors. Conclusion: Children in Baghdad remain at risk of frequent diarrhoea episodes and other complications which might affect their development status. It is becoming increasingly important to focus on improving the underlying factors by increasing the mother nutritional knowledge through special antenatal classes, and improving family economic status.
Lightweight Stochastic Optimization for Minimizing Finite Sums with Infinite Data

Variance reduction has been commonly used in stochastic optimization. It relies crucially on the assumption that the data set is finite. However, when the data are imputed with random noise as in data augmentation, the perturbed data set be- comes essentially infinite. Recently, the stochastic MISO (S-MISO) algorithm is introduced to address this expected risk minimization problem. Though it converges faster than SGD, a significant amount of memory is required. In this pa- per, we propose two SGD-like algorithms for expected risk minimization with random perturbation, namely, stochastic sample average gradient (SSAG) and stochastic SAGA (S-SAGA). The memory cost of SSAG does not depend on the sample size, while that of S-SAGA is the same as those of variance reduction methods on un- perturbed data. Theoretical analysis and experimental results on logistic regression and AUC maximization show that SSAG has faster convergence rate than SGD with comparable space requirement, while S-SAGA outperforms S-MISO in terms of both iteration complexity and storage.
Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone

Corticosteroids are highly prescribed and effective anti-inflammatory drugs but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models. miRNAs are increasingly recognized as key regulators of inflammatory responses. To define effects of prednisolone and vamorolone on the muscle miRNAome, we performed a preclinical discovery study in the mdx mouse model of DMD. miRNAs associated with inflammation were highly elevated in mdx muscle. Both vamorolone and prednisolone returned these toward wild-type levels (miR-142-5p, miR-142-3p, miR-146a, miR-301a, miR-324-3p, miR-455-5p, miR-455-3p, miR-497, miR-652). Effects of vamorolone were largely limited to reduction of proinflammatory miRNAs. In contrast, prednisolone activated a separate group of miRNAs associated with steroid side effects and a noncoding RNA cluster homologous to human chromosome 14q32. Effects were validated for inflammatory miRNAs in a second, independent preclinical study. For the anti-inflammatory miRNA signature, bioinformatic analyses showed all of these miRNAs are directly regulated by, or in turn activate, the inflammatory transcription factor NF-κB. Moving forward miR-146a and miR-142 are of particular interest as biomarkers or novel drug targets. These data validate NF-κB signaling as a target of dissociative GR-ligand efficacy in vivo and provide new insight into miRNA signaling in chronic inflammation.