Miracle-dz/UniFAR-FTUs huggingface dataset:
High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome

Abstract Down syndrome is the phenotypic consequence of trisomy 21, with clinical presentation including both neurodevelopmental and neurodegenerative components. Although the intellectual disability typically displayed by individuals with Down syndrome is generally global, it also involves disproportionate deficits in hippocampally-mediated cognitive processes. Hippocampal dysfunction may also relate to Alzheimer’s disease-type pathology, which can appear in as early as the first decade of life and becomes universal by age 40. Using 7-tesla MRI of the brain, we present an assessment of the structure and function of the hippocampus in 34 individuals with Down syndrome (mean age 24.5 years ± 6.5) and 27 age- and sex-matched typically developing healthy controls. In addition to increased whole-brain mean cortical thickness and lateral ventricle volumes (P < 1.0 × 10−4), individuals with Down syndrome showed selective volume reductions in bilateral hippocampal subfields cornu Ammonis field 1, dentate gyrus, and tail (P < 0.005). In the group with Down syndrome, bilateral hippocampi showed widespread reductions in the strength of functional connectivity, predominately to frontal regions (P < 0.02). Age was not related to hippocampal volumes or functional connectivity measures in either group, but both groups showed similar relationships of age to whole-brain volume measures (P < 0.05). Finally, we performed an exploratory analysis of a subgroup of individuals with Down syndrome with both imaging and neuropsychological assessments. This analysis indicated that measures of spatial memory were related to mean cortical thickness, total grey matter volume and right hemisphere hippocampal subfield volumes (P < 0.02). This work provides a first demonstration of the usefulness of high-field MRI to detect subtle differences in structure and function of the hippocampus in individuals with Down syndrome, and suggests the potential for development of MRI-derived measures as surrogate markers of drug efficacy in pharmacological studies designed to investigate enhancement of cognitive function.
Association between body mass index and blood pressure levels across socio-demographic groups and geographical settings: analysis of pooled data in Peru

Background Understanding the relationship between BMI and blood pressure requires assessing whether this association is similar or differs across population groups. This study aimed to assess the association between body mass index (BMI) and blood pressure levels, and how these associations vary between socioeconomic groups and geographical settings. Methods Data from the National Demographic Health Survey of Peru from 2014 to 2019 was analyzed considering the complex survey design. The outcomes were levels of systolic (SBP) and diastolic blood pressure (DBP), and the exposure was BMI. Exposure and outcomes were fitted as continuous variables in a non-linear quadratic regression model. We explored effect modification by six socioeconomic and geographical variables (sex, age, education level, socioeconomic position, study area, and altitude), fitting an interaction term between each of these variables and BMI. Results Data from 159, 940 subjects, mean age 44.4 (SD: 17.1), 54.6% females, was analyzed. A third (34.0%) of individuals had ≥12 years of education, 24.7% were from rural areas, and 23.7% lived in areas located over 2,500 m above sea level. In the overall sample mean BMI was 27.1 (SD: 4.6) kg/m2, and mean SBP and DBP were 122.5 (SD: 17.2) and 72.3 (SD: 9.8) mmHg, respectively. In the multivariable models, greater BMI levels were associated with higher SBP (p-value < 0.001) and DBP (p-value < 0.001). There was strong evidence that sex, age, education level, and altitude were effect modifiers of the association between BMI and both SBP and DBP. In addition to these socio-demographic variables, socioeconomic position and study area were also effect modifiers of the association between BMI and DBP, but not SBP. Conclusions The association between BMI and levels of blood pressure is not uniform on a range of socio-demographic and geographical population groups. This characterization can inform the understanding of the epidemiology and rise of blood pressure in a diversity of low-resource settings.
Diabetic kidney disease in type 2 diabetes: a review of pathogenic mechanisms, patient-related factors and therapeutic options

The global prevalence of diabetic kidney disease is rapidly accelerating due to an increasing number of people living with type 2 diabetes. It has become a significant global problem, increasing human and financial pressures on already overburdened healthcare systems. Interest in diabetic kidney disease has increased over the last decade and progress has been made in determining the pathogenic mechanisms and patient-related factors involved in the development and pathogenesis of this disease. A greater understanding of these factors will catalyse the development of novel treatments and influence current practice. This review summarises the latest evidence for the factors involved in the development and progression of diabetic kidney disease, which will inform better management strategies targeting such factors to improve therapeutic outcomes in patients living with diabetes.
Engineering a mobile platform to promote sleep in the pediatric primary care setting

Abstract Study Objectives Pediatricians lack tools to support families at home for the promotion of childhood sleep. We are using the Multiphase Optimization Strategy (MOST) framework to guide the development of a mobile health platform for childhood sleep promotion. The objective of this study is to demonstrate feasibility of a mobile health platform towards treating children with insufficient sleep. Methods Children aged 10–12 years were enrolled (Study #1: N = 30; Study #2: N = 43). Participants wore a sleep tracker to measure sleep duration. Data were retrieved by a mobile health platform, programmed to send introductory messages during run-in (2 weeks) and goal achievement messages during intervention (7 weeks) periods. In study #1, participants were randomized to control, gain-framed incentive or loss-framed incentive arms. In study #2, participants were randomized to control, loss-framed incentive, normative feedback or loss-framed incentive plus normative feedback arms. Results In study #1, 1514 nights of data were captured (69%) and sleep duration during the intervention was higher by an average of 21 (95% CI: −8, 51) and 34 (95% CI: 7, 61) minutes per night for the gain-framed and loss-framed arms, respectively, compared to controls. In study #2, 2,689 nights of data were captured (81%), with no major differences in average sleep duration between the control and the loss-framed or normative feedback arms. Conclusions We have developed and deployed a mobile health platform that can capture sleep data and remotely communicate with families. Promising candidate intervention components will be further investigated under the optimization phase of the MOST framework. Clinical Trials Both studies included in this manuscript were registered at clinicaltrials.gov: -Study #1: NCT03263338 -Study #2: NCT03426644
“Peanut saves the day”: an innovative solution to massive, cryptogenic haemoptysis—a case study

Massive (or life‐threatening) haemoptysis is a time‐sensitive emergency encountered by a physician that requires an interdisciplinary, collaborative effort to arrest the bleeding in a prompt and timely manner. Placement of an endobronchial Watanabe spigot (EWS) to halt haemoptysis is a relatively recent technique finding its wide application in airway pathology, with the current extension of its use to bronchial bleeding. However, the lack of immediate access to EWS gives rise to the need to innovate with day‐to‐day materials used in routine surgical practice and available in resource‐limited settings, which may serve the purpose of a spigot. In this report, we bring to light a case of life‐threatening, cryptogenic haemoptysis that was managed by a novel technique of using peanut gauze as a spigot resulting in a successful endobronchial tamponade.
Active triggering control of pneumatic rehabilitation gloves based on surface electromyography sensors

The portable and inexpensive hand rehabilitation robot has become a practical rehabilitation device for patients with hand dysfunction. A pneumatic rehabilitation glove with an active trigger control system is proposed, which is based on surface electromyography (sEMG) signals. It can trigger the hand movement based on the patient’s hand movement trend, which may improve the enthusiasm and efficiency of patient training. Firstly, analysis of sEMG sensor installation position on human’s arm and signal acquisition process were carried out. Then, according to the statistical law, three optimal eigenvalues of sEMG signals were selected as the follow-up neural network classification input. Using the back propagation (BP) neural network, the classifier of hand movement is established. Moreover, the mapping relationship between hand sEMG signals and hand actions is built by training and testing. Different patients choose the same optimal eigenvalues, and the calculation formula of eigenvalues’ amplitude is unique. Due to the differences among individuals, the weights and thresholds of each node in the BP neural network model corresponding to different patients are not the same. Therefore, the BP neural network model library is established, and the corresponding network is called for operation when different patients are trained. Finally, based on sEMG signal trigger, the pneumatic glove training control algorithm was proposed. The combination of the trigger signal waveform and the motion signal waveform indicates that the pneumatic rehabilitation glove is triggered to drive the patient’s hand movement. Preliminary tests have confirmed that the accuracy rate of trend recognition for hand movement is about 90%. In the future, clinical trials of patients will be conducted to prove the effectiveness of this system.
AI-driven deep CNN approach for multi-label pathology classification using chest X-Rays

Artificial intelligence (AI) has played a significant role in image analysis and feature extraction, applied to detect and diagnose a wide range of chest-related diseases. Although several researchers have used current state-of-the-art approaches and have produced impressive chest-related clinical outcomes, specific techniques may not contribute many advantages if one type of disease is detected without the rest being identified. Those who tried to identify multiple chest-related diseases were ineffective due to insufficient data and the available data not being balanced. This research provides a significant contribution to the healthcare industry and the research community by proposing a synthetic data augmentation in three deep Convolutional Neural Networks (CNNs) architectures for the detection of 14 chest-related diseases. The employed models are DenseNet121, InceptionResNetV2, and ResNet152V2; after training and validation, an average ROC-AUC score of 0.80 was obtained competitive as compared to the previous models that were trained for multi-class classification to detect anomalies in x-ray images. This research illustrates how the proposed model practices state-of-the-art deep neural networks to classify 14 chest-related diseases with better accuracy.
Development of Porcine Somatic Cell Nuclear Transfer Embryos Following Treatment Time of Endoplasmic Reticulum Stress Inhibitor

Abstract We examine the effect of endoplasmic reticulum (ER) stress inhibitor treatment time on the in vitro development of porcine somatic cell nuclear transfer (SCNT) embryos. Porcine SCNT embryos were classified by four groups following treatment time of ER stress inhibitor, tauroursodeoxycholic acid (TUDCA; 100 μM); 1) non-treatment group (control), 2) treatment during micromanipulation process and for 3 h after fusion (NT+3 h group), 3) treatment only during in vitro culture after fusion (IVC group), and 4) treatment during micromanipulation process and in vitro culture (NT+IVC group). SCNT embryos were cultured for six days to examine the X-box binding protein 1 (Xbp1) splicing levels, the expression levels of ER stress-associated genes, oxidative stress-related genes, and apoptosis-related genes in blastocysts, and in vitro development. There was no significant difference in Xbp1 splicing level among all groups. Reduced expression of some ER stress-associated genes was observed in the treatment groups. The oxidative stress and apoptosis-related genes were significantly lower in all treatment groups than control (p<0.05). Although blastocyst development rates were not different among all groups (17.5% to 21.7%), the average cell number in blastocysts increased significantly in NT+3 h (48.5±2.3) and NT+IVC (47.7±2.4) groups compared to those of control and IVC groups (p<0.05). The result of this study suggests that the treatment of ER stress inhibitor on SCNT embryos from the micromanipulation process can improve the reprogramming efficiency of SCNT embryos by inhibiting the ER and oxidative stresses that may occur early in the SCNT process.
Defective cyclophilin A induces TDP-43 proteinopathy: implications for amyotrophic lateral sclerosis and frontotemporal dementia

Aggregation and cytoplasmic mislocalization of TDP-43 are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum. However, the molecular mechanism by which TDP-43 aggregates form and cause neurodegeneration remains poorly understood. Cyclophilin A, also known as peptidyl-prolyl cis-trans isomerase A (PPIA), is a foldase and molecular chaperone. We previously found that PPIA interacts with TDP-43 and governs some of its functions, and its deficiency accelerates disease in a mouse model of ALS. Here we characterized PPIA knock-out mice throughout their lifespan and found that they develop a neurodegenerative disease with key behavioural features of FTD, marked TDP-43 pathology and late-onset motor dysfunction. In the mouse brain, deficient PPIA induces aggregation of the GTP-binding nuclear protein Ran, a PPIA substrate required for TDP-43 nucleocytoplasmic trafficking. Moreover, in absence of PPIA, TDP-43 autoregulation is perturbed and TDP-43 and proteins involved in synaptic function are downregulated, leading to impairment of synaptic plasticity. Finally, we found that PPIA was downregulated in several ALS and ALS-FTD patients and identified a PPIA loss-of-function mutation in a sporadic ALS patient. The mutant PPIA has low stability, altered structure and impaired interaction with TDP-43. These findings strongly implicate that defective PPIA function causes TDP-43 mislocalization and dysfunction and should be considered in future therapeutic approaches.
Heterogeneity of monocyte subsets and susceptibility to influenza virus contribute to inter-population variability of protective immunity

There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use an ex vivo model to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. Using single-cell RNA-sequencing, we show widespread inter-individual variability in the percentage of IAV-infected monocytes. We show that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. While this host defense strategy is shared between CD16+/CD16- monocytes, we also uncover CD16+-specific mRNA expression of IL6 and TNF in response to IAV, and a stronger resistance of CD16+ monocytes to IAV infection. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3, MX1, and OAS3. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16+ monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Collectively, our results reveal the effects of IAV infection on the transcriptional landscape of human monocytes and highlight previously unappreciated differences in cellular susceptibility to IAV infection between individuals of African and European ancestry, which may account for the greater susceptibility of Africans to severe influenza. Significance Statement Monocytes may play a critical role during severe viral infections. Our study tackles how heterogeneity in monocyte subsets and activation contributes to shape individual differences in the transcriptional response to viral infections. Using single-cell RNA-sequencing, we reveal heterogeneity in monocyte susceptibility to IAV infection, both between CD16+/CD16- monocytes and across individuals, driven by differences in basal activation of an IRF/STAT-induced antiviral program. Furthermore, we show a decreased ability of IAV to infect and replicate in monocytes from African-ancestry individuals, with possible implications for antigen presentation and lymphocyte activation. These results highlight the importance of early cellular activation in determining an individuals’ innate immune response to viral infection.
Cas9-mediated gene disruption in tetraploid Giardia intestinalis

CRISPR/Cas9 system is an extremely powerful technique that is extensively used for various genome modifications in different organisms including parasitic protists. Giardia intestinalis, a protist parasite infecting about 280 million people around the world each year, has been eluding the routine use of CRISPR/Cas9 for generating knock-out cell lines due to the presence of four copies of each gene in its two nuclei. Apart from single exception employing rather laborious Cre/loxP system, no full knock-out cell line has been established yet. In this work, we show the ability of in-vitro assembled CRISPR/Cas9 components to successfully edit the genome of G. intestinalis. We further established a cell line stably expressing Cas9 in both G. intestinalis nuclei. Subsequent introduction of a template for homologous recombination containing the transcription units for the resistance marker and gRNA resulted in the removal of all gene copies at once for three independent experimental genes, mem, cwp1 and mlf1. The method was also applicable for the incomplete disruption of an essential gene, as documented by markedly decreased expression of tom40. Finally, testing the efficiency of Cas9-induced recombination revealed that homologous arms as short as 150 bp can be sufficient to establish a full knock-out cell line in G. intestinalis.
A Murine Model for Enhancement of Streptococcus pneumoniae Pathogenicity upon Viral Infection and Advanced Age

Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx (NP) but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human coinfection. ABSTRACT Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx (NP) but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human coinfection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2-month-old) mice, coinfection triggered bacterial dispersal from the nasopharynx into the lungs, pulmonary inflammation, disease, and mortality in a fraction of mice. In aged mice (18 to 24 months), coinfection resulted in earlier and more severe disease. Aging was not associated with greater bacterial burdens but rather with more rapid pulmonary inflammation and damage. Both aging and IAV infection led to inefficient bacterial killing by neutrophils ex vivo. Conversely, aging and pneumococcal colonization also blunted alpha interferon (IFN-α) production and increased pulmonary IAV burden. Thus, in this multistep model, IAV promotes pneumococcal pathogenicity by modifying bacterial behavior in the nasopharynx, diminishing neutrophil function, and enhancing bacterial growth in the lung, while pneumococci increase IAV burden, likely by compromising a key antiviral response. Thus, this model provides a means to elucidate factors, such as age and coinfection, that promote the evolution of S. pneumoniae from asymptomatic colonizer to invasive pathogen, as well as to investigate consequences of this transition on antiviral defense.
Alternatives to mental health admissions for children and adolescents experiencing mental health crises: A systematic review of the literature

Background: Many children and young people (CYP) presenting with mental health crises are admitted to hospital due to concerns around illness severity and risk. Whilst inpatient admissions have an important role for such children, there are a number of burdens associated with them, and safe avoidance of admissions is favourable. We systematically reviewed the literature for studies of interventions reported as alternatives to a hospital admission in CYP presenting with mental health crises, in any inpatient setting. Methods: Three databases (PsychInfo, PubMed and Web of Science) were searched for peer-reviewed papers in October 2020, with an updated search in May 2021. Results: We identified 19 papers of interventions delivered in the emergency department, the home, outside of home but outside of clinics and in hospital clinics. The quality of most included studies was low, with less than half being randomised controlled trials and only half of these at low risk of bias. The best quality studies and greatest evidence for efficacy came from in-home interventions, in particular multisystemic therapy, which improved psychological outcomes, and though a large number of CYP still ended up being admitted, there appeared to be decreased length of stay. Conclusions: Overall, we could not recommend a particular intervention as an alternative to inpatient admission; however, our review describes benefits across a range of types of interventions that might be considered in multi-modal treatments. We also provide recommendations for future research, in particular the evaluation of new interventions as they emerge.