Miracle-dz/UniFAR-FTUs huggingface dataset:
Dilemma of Reporting Incidental Findings in Newborn Screening Programs for SCID: Parents’ Perspective on Ataxia Telangiectasia

Background: Ataxia Telangiectasia (A-T) is a severe DNA repair disorder that leads to a broad range of symptoms including neurodegeneration and a variable immunodeficiency. A-T is one of the incidental findings that accompanies newborn screening (NBS) for severe combined immunodeficiency (SCID), leading to an early diagnosis of A-T at birth in a pre-symptomatic stage. While some countries embrace all incidental findings, the current policy in the Netherlands on reporting untreatable incidental findings is more conservative. We present parents' perspectives and considerations on the various advantages vs. disadvantages of early and late diagnosis of A-T. Methods: A questionnaire was developed and sent to 4,000 parents of healthy newborns who participated in the Dutch SONNET-study (implementation pilot for newborn screening for SCID). The questionnaire consisted of open-ended and scale questions on advantages and disadvantages of early and late diagnosis of A-T. To address potential bias, demographic characteristics of the study sample were compared to a reference population. Results: A total of 664 of 4,000 parents sent back the questionnaire (response rate 16.6%). The vast majority of parents (81.9%) favored early diagnosis of A-T over late diagnosis. Main arguments were to avoid a long period of uncertainty prior to diagnosis and to ensure the most optimal clinical care and guidance from the onset of symptoms. Parents who favored late diagnosis of A-T stated that early diagnosis would not lead to improved quality of life and preferred to enjoy the asymptomatic “golden years” with their child. The majority of parents (81.1%) stated that they would participate in newborn screening for A-T if a test was available. Conclusions: Reporting untreatable incidental findings remains a disputed topic worldwide. Although the current policy in the Netherlands is not to report untreatable incidental findings, unless the health advantage is clear, the majority of parents of healthy newborns are in favor of an early A-T diagnosis in the pre-symptomatic phase of the disorder. Our results as well as other studies that showed support for the screening of untreatable disorders may serve as valuable tools to inform policymakers in their considerations about NBS for untreatable disorders.
Region-Specific Reduction of BDNF Protein and Transcripts in the Hippocampus of Juvenile Rats Prenatally Treated With Sodium Valproate

Autism is a neurodevelopmental disorder characterized by a deep deficit in language and social interaction, accompanied by restricted, stereotyped and repetitive behaviors. The use of genetic autism animal models has revealed that the alteration of the mechanisms controlling the formation and maturation of neural circuits are points of convergence for the physiopathological pathways in several types of autism. Brain Derived Neurotrophic Factor (BDNF), a key multifunctional regulator of brain development, has been related to autism in several ways. However, its precise role is still elusive, in part, due to its extremely complex posttranscriptional regulation. In order to contribute to this topic, we treated prenatal rats with Valproate, a well-validated model of autism, to analyze BDNF levels in the hippocampus of juvenile rats. Valproate-treated rats exhibited an autism-like behavioral profile, characterized by a deficit in social interaction, anxiety-like behavior and repetitive behavior. In situ hybridization (ISH) experiments revealed that Valproate reduced BDNF mRNA, especially long-3′UTR-containing transcripts, in specific areas of the dentate gyrus (DG) and CA3 regions. At the same time, Valproate reduced BDNF immunoreactivity in the suprapyramidal and lucidum layers of CA3, but improved hippocampus-dependent spatial learning. The molecular changes reported here may help to explain the cognitive and behavioral signs of autism and reinforce BDNF as a potential molecular target for this neurodevelopmental disorder.
Evaluating scale and roughness effects in urban flood modelling using terrestrial LIDAR data

Abstract. This paper evaluates the results of benchmark testing a new inertial formulation of the St. Venant equations, implemented within the LISFLOOD-FP hydraulic model, using different high resolution terrestrial LiDAR data (10 cm, 50 cm and 1 m) and roughness conditions (distributed and composite) in an urban area. To examine these effects, the model is applied to a hypothetical flooding scenario in Alcester, UK, which experienced surface water flooding during summer 2007. The sensitivities of simulated water depth, extent, arrival time and velocity to grid resolutions and different roughness conditions are analysed. The results indicate that increasing the terrain resolution from 1 m to 10 cm significantly affects modelled water depth, extent, arrival time and velocity. This is because hydraulically relevant small scale topography that is accurately captured by the terrestrial LIDAR system, such as road cambers and street kerbs, is better represented on the higher resolution DEM. It is shown that altering surface friction values within a wide range has only a limited effect and is not sufficient to recover the results of the 10 cm simulation at 1 m resolution. Alternating between a uniform composite surface friction value (n = 0.013) or a variable distributed value based on land use has a greater effect on flow velocities and arrival times than on water depths and inundation extent. We conclude that the use of extra detail inherent in terrestrial laser scanning data compared to airborne sensors will be advantageous for urban flood modelling related to surface water, risk analysis and planning for Sustainable Urban Drainage Systems (SUDS) to attenuate flow.
Linear Ballistic Accumulator Modeling of Attentional Bias Modification Revealed Disturbed Evidence Accumulation of Negative Information by Explicit Instruction

In recent years, several attentional bias modification (ABM) studies have been conducted. Previous studies have suggested that explicit instruction (i.e., informing participants of the contingency of stimuli) enhances the effect of ABM. However, the specific working mechanism has not been identified. This is partly because reaction time (RT) data are typically reduced to an attention bias score, which is a mere difference of RT between experimental and control conditions. This data reduction causes a loss of information, as RT reflects various cognitive processes at play while making a response or decision. To overcome this issue, the present study applied linear ballistic accumulator (LBA) modeling to the outcomes (RT measures) of explicitly guided (compared to standard) ABM. This computational modeling approach allowed us to dissociate RTs into distinct components that can be relevant for attentional bias, such as efficiency of information processing or prior knowledge of the task; this provides an understanding of the mechanism of action underlying explicitly guided ABM. The analyzed data were RT-observed in the dot-probe task, which was administered before and after 3-days of ABM training. Our main focus was on the changes in LBA components that would be induced by the training. Additionally, we analyzed in-session performances over the 3 days of training. The LBA analysis revealed a significant reduction in processing efficiency (i.e., drift rate) in the congruent condition, where the target probe is presented in the same location as a negative stimulus. This explains the reduction in the overall attentional bias score, suggesting that explicit ABM suppresses processing of negative stimuli. Moreover, the results suggest that explicitly guided ABM may influence prior knowledge of the target location in the training task and make participants prepared to respond to the task. These findings highlight the usefulness of LBA-based analysis to explore the underlying cognitive mechanisms in ABM, and indeed our analyses revealed the differences between the explicit and the standard ABM that could not be identified by traditional RT analysis or attentional bias scores.
Part II. Comparison of Neurodevelopmental Outcomes Between Normothermic and Hypothermic Pediatric Cardiopulmonary Bypass

Objectives: In the previous study we demonstrated that normothermic cardiopulmonary bypass (N-CPB, ≥35°C) provided better early clinical outcomes compared to mild/moderate hypothermic cardiopulmonary bypass (H-CPB, 28–34°C) for congenital heart surgery. In this follow-up study we compare early neurodevelopmental outcomes 2–3 years post-surgery. Methods: In this retrospective, non-randomized observational study, the medical notes of children from our previous cohort were reviewed after 2–3 years. Demographic and neurodevelopmental outcomes were tabulated to enable blinded statistical analysis comparing outcomes between N-CPB and H-CPB surgery for congenital heart defects. Multivariate logistic regression models were developed to identify any differences in outcomes after adjustment for confounders. Results: Ninety-five children who underwent H-CPB (n = 50) or N-CPB (n = 45) were included. The proportions of patients with one or more adverse neurodevelopmental outcomes 2–3 years later were 14/50 (28.0%) in the H-CPB group and 11/45 (24.4%) in N-CPB, which was not significantly different between groups (p = 0.47). The two CPB groups were balanced for demographic and surgical risk factors, with the exception of genetic conditions. A higher incidence of H-CPB patients acquired learning difficulties [23.1% compared to 2.56% for N-CPB (p = 0.014)] and neurological deficits [30.8% compared to 7.69% for N-CPB (p = 0.019)], but these differences were not robust to adjustment for genetic syndromes. Conclusions: Our study did not reveal any significant differences in early neurodevelopmental outcomes between H-CPB or N-CPB surgery for congenital heart defects. The most important factor in predicting outcomes was, as expected, the presence of a genetic syndrome. We found no evidence that CPB temperature affects early neurodevelopmental outcomes.
Clinical Utility of Intraoperative Parathyroid Hormone Measurement in Children and Adolescents Undergoing Total Thyroidectomy

Background: Hypoparathyroidism is one of the most common complications for patients undergoing total thyroidectomy. Our study's primary objective was to assess if intraoperative PTH levels correlate with parathyroid gland function recovery time in pediatric patients following total thyroidectomy. Methods: Retrospective review of pediatric patients who underwent thyroid surgery at CHOP for demographics and laboratory test values (calcium, phosphorus, and parathyroid hormone). We defined Time of Recovery (TOR) as the time difference from first intra-operative parathyroid hormone level (ioPTH) timepoint until normalization of PTH (> 10 pg/mL) post-thyroidectomy. Calcium and vitamin D supplements were weaned following normalization of calcium and phosphorous levels postoperatively. Patients were excluded if they lacked three intraoperative PTH timepoints or were missing postoperative follow-up PTH data. Results: 65 patients (54 female), median age 15 (range 5–23 years), underwent thyroid surgery and met study inclusion criteria. The correlations of 2nd and 3rd ioPTHs with TOR were statistically significant (p < 0.05): the lower the ioPTH, the greater the recovery time. Stratifying patients into high-risk (2nd ioPTH ≤ 10 pg/mL), moderate-risk (2nd ioPTH between 10 and 20 pg/mL), and low-risk (2nd ioPTH ≥ 20 pg/mL) tertiles, the TOR decreased by orders of magnitudes from an average of 43.13 ± 76.00 to 6.10 ± 17.44 to 1.85 ± 6.20 days. These differences were statistically significant (p < 0.05). Conclusions: Our study results confirm the usefulness of intraoperative PTH levels to predict pediatric patient recovery post-surgery and provides useful anticipatory guidance to optimize timing and frequency of postoperative laboratory surveillance.
Thermal alteration of soil physico-chemical properties : a systematic study to infer response of Sierra Nevada climosequence soils to forest fires

Fire is a common ecosystem perturbation that affects many soil properties. As global fire regimes continue to change with climate change, we investigated thermal alteration of soils’ physical and chemical properties after they are exposed to a range of temperatures that are expected during prescribed and wildland fires. For this study, we used topsoils collected from a climosequence transect along the western slope of the Sierra Nevada that spans from 210 to 2865 m a.s. l. All the soils we studied were formed on a granitic parent material and had significant differences in soil organic matter (SOM) concentration and mineralogy owing to the effects of climate on soil development. Topsoils (0–5 cm depth) from the Sierra Nevada climosequence were heated in a muffle furnace at six set temperatures that cover the range of major fire intensity classes (150, 250, 350, 450, 550 and 650 C). We determined the effects of heating temperature on soil aggregate strength, aggregate size distribution, specific surface area (SSA), mineralogy, pH, cation exchange capacity (CEC), and carbon (C) and nitrogen (N) concentrations. With increasing temperature, we found significant reduction of total C, N and CEC. Aggregate strength also decreased with further implications for loss of C protected inside aggregates. Soil pH and SSA increased with temperature. Most of the statistically significant changes (p< 0.05) occurred between 350 and 450 C. We observed relatively smaller changes at temperature ranges below 250 C. This study identifies critical temperature thresholds for significant physico-chemical changes in soils that developed under different climate regimes. Our findings will be of interest to studies of inferences for how soils are likely to respond to different fire intensities under anticipated climate change scenarios.
Exposure to Cigarette Smoke Augments Post-ischemic Brain Injury and Inflammation via Mobilization of Neutrophils and Monocytes

Cigarette smoke is a major preventable risk factor of ischemic stroke. Cigarette smoke induces a significant increase in circulating leukocytes. However, it remains unclear to what extent and by what mechanisms smoke priming influences stroke severity. Here we report that exposure to cigarette smoke exacerbated ischemic brain injury in mice subjected to transient middle cerebral artery occlusion (MCAO). The augmentation of neurodeficits and brain infarction was accompanied by increased production of pro-inflammatory factors and brain infiltration of neutrophils and monocytes. Prior to brain ischemia, exposure to cigarette smoke induced mobilization of peripheral neutrophils, and monocytes. Furthermore, the detrimental effects of smoke priming on ischemic brain injury were abolished either by pharmacological inhibition of the recruitment of neutrophils and monocytes or by blockade of the NLRP3 inflammasome, an effector protein of neutrophils and monocytes. Our findings suggest that cigarette smoke-induced mobilization of peripheral neutrophils and monocytes augments ischemic brain injury.
Urocortin 3 Levels Are Impaired in Overweight Humans With and Without Type 2 Diabetes and Modulated by Exercise

Urocortin3 (UCN3) regulates metabolic functions and is involved in cellular stress response. Although UCN3 is expressed in human adipose tissue, the association of UCN3 with obesity and diabetes remains unclear. This study investigated the effects of Type 2 diabetes (T2D) and increased body weight on the circulatory and subcutaneous adipose tissue (SAT) levels of UCN3 and assessed UCN3 modulation by a regular physical exercise. Normal-weight (n = 37) and overweight adults with and without T2D (n = 98 and n = 107, respectively) were enrolled in the study. A subset of the overweight subjects (n = 39 for each group) underwent a supervised 3-month exercise program combining both moderate intensity aerobic exercise and resistance training with treadmill. UCN3 levels in SAT were measured by immunofluorescence and RT-PCR. Circulatory UCN3 in plasma was assessed by ELISA and was correlated with various clinical and metabolic markers. Our data revealed that plasma UCN3 levels decreased in overweight subjects without T2D compared with normal-weight controls [median; 11.99 (0.78–86.07) and 6.27 (0.64–77.04), respectively; p < 0.001], whereas plasma UCN3 levels increased with concomitant T2D [median; 9.03 (0.77–104.92) p < 0.001]. UCN3 plasma levels were independently associated with glycemic index; fasting plasma glucose and hemoglobin A1c (r = 0.16 and r = 0.20, p < 0.05, respectively) and were significantly different between both overweight, with and without T2D, and normal-weight individuals (OR = 2.11 [1.84–4.11, 95% CI] and OR = 2.12 [1.59–3.10, 95% CI], p < 0.01, respectively). Conversely, the UCN3 patterns observed in SAT were opposite to those in circulation; UCN3 levels were significantly increased with body weight and decreased with T2D. After a 3-month supervised exercise protocol, UCN3 expression showed a significant reduction in SAT of both overweight groups (2.3 and 1.6-fold change; p < 0.01, respectively). In conclusion, UCN levels are differentially dysregulated in obesity in a tissue-dependent manner and can be mitigated by regular moderate physical exercise.
The Influence of Pedagogy on Problem-based Learning Students’ Perceptions of Knowledge

Problem-based learning requires students to work in small groups and apply knowledge they see as relevant to a given problem or learning task. Previous research has explored students’ experiences of problem-based learning in relation to learning styles, however, differences in how students perceive knowledge has received little attention in the literature. Drawing on the theories of Basil Bernstein, this study explored occupational therapy students’ perceptions of knowledge. Twenty students were sampled on the basis of their having followed two, different, educational pathways into a problem based occupational therapy undergraduate course. Qualitative interviews were used to gather students’ perceptions of occupational therapy knowledge and the findings show that in the first year of the problem-based course the students’ views on knowledge could be contrasted according to their respective educational pathway. Different interpretations of knowledge have consequences in how students engage with problem-based learning and how they approach assessment tasks.
A Novel Large Animal Model of Thrombogenic Coronary Microembolization

Coronary microembolization is one of the main causes of the “no-reflow” phenomenon, which commonly occurs after reperfusion of an occluded coronary artery. Given its high incidence and the fact that it has been proven to be an independent predictor of cardiac morbidity and mortality, there is an imperative need to study its underlying mechanisms and pathophysiology. Large animal models are essential to perform translational studies. Currently there is no animal model that recapitulates a clinical scenario of thrombogenic microembolism with preceding myocardial ischemia. Therefore, the goal of this study was to develop and characterize a novel pig model of coronary microembolization using autologous thrombus injection (CMET). Twenty-three pigs underwent myocardial infarction through percutaneous balloon occlusion of the left anterior descending artery (LAD). Each animal was enrolled in one of two groups: (1) the CMET group, in which the LAD occlusion was followed by delivery of autologous clotted blood in the LAD (distal to the balloon occlusion) and reperfusion; (2) the ischemic reperfusion (I/R) group, in which the LAD ischemia was followed by reperfusion. Surviving animals underwent functional and morphological characterization at 1-week post-procedure. Three sham operated animals were used as a control. CMET resulted in impaired left ventricular function compared to I/R pigs at 1 week. Three-dimensional echocardiography demonstrated reduced ejection fraction in the CMET group (CMET vs. I/R: 35.6 ± 4.2% vs. 47.6 ± 2.4%, p = 0.028). Invasive hemodynamic measurements by Swan-Ganz and left ventricular pressure-volume catheters revealed that CMET impaired left ventricular contractility and diastolic function. This was confirmed by both load-dependent indices including cardiac output (CMET vs. I/R: 2.7 ± 0.2 l/min, vs. 4.0 ± 0.1 l/min, p = 0.002) and load independent indices including preload-recruitable stroke work (CMET vs. I/R: 25.8 ± 4.0 vs. 47.5 ± 6.5 mmHg, p = 0.05) and end-diastolic pressure-volume relationship (slope, 0.68 ± 0.07 vs. 0.40 ± 0.11 mmHg/ml, p = 0.01). Our unique closed-chest model of coronary microembolization using autologous thrombus injection resembles the clinical condition of thrombogenic coronary microembolization in I/R injury. This model offers opportunities to conduct translational studies for understanding and treating coronary microembolization in myocardial infarction.
Pou2f2 Regulates the Distribution of Dorsal Interneurons in the Mouse Developing Spinal Cord

Spinal dorsal interneurons, which are generated during embryonic development, relay and process sensory inputs from the periphery to the central nervous system. Proper integration of these cells into neuronal circuitry depends on their correct positioning within the spinal parenchyma. Molecular cues that control neuronal migration have been extensively characterized but the genetic programs that regulate their production remain poorly investigated. Onecut (OC) transcription factors have been shown to control the migration of the dorsal interneurons (dINs) during spinal cord development. Here, we report that the OC factors moderate the expression of Pou2f2, a transcription factor essential for B-cell differentiation, in spinal dINs. Overexpression or inactivation of Pou2f2 leads to alterations in the differentiation of dI2, dI3 and Phox2a-positive dI5 populations and to defects in the distribution of dI2-dI6 interneurons. Thus, an OC-Pou2f2 genetic cascade regulates adequate diversification and distribution of dINs during embryonic development.
Natural Killer Cells Prevent the Formation of Teratomas Derived From Human Induced Pluripotent Stem Cells

The safe utilization of induced pluripotent stem cell (iPSC) derivatives in clinical use is attributed to the complete elimination of the risk of forming teratomas after transplantation. The extent by which such a risk exists in immune-competent hosts is mostly unknown. Here, using humanized mice reconstituted with fetal hematopoietic stem cells and autologous thymus tissue (bone–liver–thymus humanized mice [Hu-BLT]) or following the adoptive transfer of peripheral blood mononuclear cells(PBMCs) (Hu-AT), we evaluated the capacity of immune cells to prevent or eliminate teratomas derived from human iPSCs (hiPSCs). Our results showed that the injection of hiPSCs failed to form teratomas in Hu-AT mice reconstituted with allogeneic or autologous PBMCs or purified natural killer (NK) cells alone. However, teratomas were observed in Hu-AT mice reconstituted with autologous PBMCs depleted from NK cells. In line with these results, Hu-BLT, which do not have functional NK cells, could not prevent the growth of teratomas. Finally, we found that established teratomas were not targeted by NK cells and instead were efficiently rejected by allogeneic but not autologous T cells in Hu-AT mice. Overall, our findings suggest that autologous hiPSC-derived therapies are unlikely to form teratomas in the presence of NK cells.
A multi-wavelength analysis of the diffuse H II region G25.8700+0.1350

Fil: Cichowolski, Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Astronomia y Fisica del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomia y Fisica del Espacio; Argentina