Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered relaxation times in MRI indicate bronchopulmonary dysplasia

We developed a MRI protocol using transverse (T2) and longitudinal (T1) mapping sequences to characterise lung structural changes in preterm infants with bronchopulmonary dysplasia (BPD). We prospectively enrolled 61 infants to perform 3-Tesla MRI of the lung in quiet sleep. Statistical analysis was performed using logistic Group Lasso regression and logistic regression. Increased lung T2 relaxation time and decreased lung T1 relaxation time indicated BPD yielding an area under the curve (AUC) of 0.80. Results were confirmed in an independent study cohort (AUC 0.75) and mirrored by lung function testing, indicating the high potential for MRI in future BPD diagnostics. Trial registration DRKS00004600.
Novel Bypass Surgery for Moyamoya Disease Using Pericranial Flap: Its Impacts on Cerebral Hemodynamics and Long‐term Outcome

OBJECTIVEWe reviewed our 11-year experience with a novel bypass procedure, superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-arterio-pericranio-synangiosis (EDMAPS), for moyamoya disease regarding cerebral hemodynamics and long-term outcome. METHODSThis prospective study included 75 patients with moyamoya disease, including 28 children and 47 adults. We performed STA-MCA anastomosis and EDMAPS on 123 hemispheres of 75 patients. In addition to conventional STA-MCA anastomosis and indirect bypass for the MCA territory, the medial frontal lobe was revascularized using the frontal pericranial flap through medial frontal craniotomy. Surgical results were analyzed with magnetic resonance imaging, cerebral angiography, and single-photon emission computed tomography/positron emission tomography. RESULTSOverall incidences of mortality and morbidity were 0% and 5.7%, respectively. The annual risk of cerebrovascular events during the follow-up periods was very low: 0% in pediatric patients and 0.4% in adults over approximately 67 months. Postoperative cerebral angiography showed that the pericranial flap functioned well as donor tissue for indirect bypass, especially in pediatric patients. Follow-up single-photon emission computed tomography/positron emission tomography studies revealed that cerebral blood flow and its reactivity to acetazolamide markedly improved in both the MCA and anterior cerebral artery territories. CONCLUSIONThese findings strongly suggest that STA-MCA anastomosis and EDMAPS using a frontal pericranial flap is a safe and effective surgical procedure to further improve the long-term prognosis in moyamoya disease by improving cerebral hemodynamics in both the MCA and anterior cerebral artery territories.
Neighbor-Sensitive Hashing

Approximate kNN (k-nearest neighbor) techniques using binary hash functions are among the most commonly used approaches for overcoming the prohibitive cost of performing exact kNN queries. However, the success of these techniques largely depends on their hash functions' ability to distinguish kNN items; that is, the kNN items retrieved based on data items' hashcodes, should include as many true kNN items as possible. A widely-adopted principle for this process is to ensure that similar items are assigned to the same hashcode so that the items with the hashcodes similar to a query's hashcode are likely to be true neighbors. In this work, we abandon this heavily-utilized principle and pursue the opposite direction for generating more effective hash functions for kNN tasks. That is, we aim to increase the distance between similar items in the hashcode space, instead of reducing it. Our contribution begins by providing theoretical analysis on why this revolutionary and seemingly counter-intuitive approach leads to a more accurate identification of kNN items. Our analysis is followed by a proposal for a hashing algorithm that embeds this novel principle. Our empirical studies confirm that a hashing algorithm based on this counter-intuitive idea significantly improves the efficiency and accuracy of state-of-the-art techniques.
Thrombin signaling promotes pancreatic adenocarcinoma through PAR-1-dependent immune evasion.

Pancreatic ductal adenocarcinoma (PDAC) is associated with robust activity of the coagulation system. To determine mechanisms by which clotting factors influence PDAC tumor progression, we generated and characterized C57Bl/6-derived KPC (KRasG12D, TRP53R172H) cell lines. Tissue factor (TF) and protease-activated receptor-1 (PAR-1) were highly expressed in primary KPC pancreatic lesions and KPC cell lines similar to expression profiles observed in PDAC patient biopsies. In allograft studies, tumor growth and metastatic potential were significantly diminished by depletion of TF or Par-1 in cancer cells or by genetic or pharmacological reduction of the coagulation zymogen prothrombin in mice. Notably, PAR-1-deleted KPC cells (KPC-Par-1KO) failed to generate sizable tumors, a phenotype completely rescued by restoration of Par-1 expression. Expression profiling of KPC and KPC-Par-1KO cells indicated that thrombin-PAR-1 signaling significantly altered immune regulation pathways. Accordingly, KPC-Par-1KO cells failed to form tumors in immune-competent mice but displayed robust tumor growth comparable to that observed with control KPC cells in immune-compromised NSG mice. Immune cell depletion studies indicated that CD8 T cells, but not CD4 cells or NK cells, mediated elimination of KPC-Par-1KO tumor cells in C57Bl/6 mice. These results demonstrate that PDAC is driven by activation of the coagulation system through tumor cell-derived TF, circulating prothrombin, and tumor cell-derived PAR-1 and further indicate that one key mechanism of thrombin/PAR-1-mediated tumor growth is suppression of anti-tumor immunity in the tumor microenvironment.
Self-regulation as a mediator of the effects of childhood traumatic brain injury on social and behavioral functioning

This study builds on our earlier investigation (see Ganesalingam et al., 2006). We showed previously that children with moderate to severe traumatic brain injuries (TBI) had poorer self-regulation and social and behavioral functioning than their uninjured peers and that self-regulation predicted significant variance in parent- and teacher-rated social and behavioral outcomes, regardless of the presence or absence of TBI. In this study, we examine self-regulation as a mediator of the relationship between TBI and the outcomes. Participants included 65 children with moderate to severe TBI and 65 children without TBI matched for age and gender. Participants were between 6 and 11 years of age. Children completed an assessment of cognitive, emotional, and behavioral self-regulation, and social and behavioral functioning. Mediation was assessed using a bootstrapping approach (a relatively novel statistical method for assessing specific indirect effects in models with multiple mediators). Analyses indicated that, after controlling for socioeconomic status (SES), aspects of self-regulation accounted for individual variation in the outcomes, and acted as a significant mediator of the effects of TBI on the outcomes. Self-regulatory deficits may reflect the relative vulnerability of the prefrontal cortex to TBI and may help account for post-injury difficulties in social and behavioral functioning. (JINS, 2007, 13, 298–311.)
Association of measures of fetal and childhood growth with non-clinical psychotic symptoms in 12-year-olds: the ALSPAC cohort

Background Previous studies have suggested that impaired fetal and childhood growth are associated with an increased risk of schizophrenia, but the association of pre-adult growth with non-clinical psychotic symptoms (psychosis-like symptoms) in children is not known. Aims To explore the associations of body size at birth and age 7.5 years with childhood psychosis-like symptoms. Method Prospective cohort of children followed up from birth to age 12: the ALSPAC cohort. Results Data on 6000 singleton infants born after 37 weeks of gestation. A one standard deviation increase in birth weight was associated with an 18% reduction in the risk of definite psychosis-like symptoms after adjusting for age and gestation (Odds ratio (OR) = 0.82, 95% CI = 0.73–0.92, P = 0.001). This association was partly confounded by maternal anthropometry, smoking during pregnancy, socioeconomic status and IQ. A similar association was seen for birth length and psychosis-like symptoms, which disappeared after controlling for birth weight. There was little evidence for an association of 7-year height or adiposity with psychosis-like symptoms. Conclusions Measures of impaired fetal, but not childhood, growth are associated with an increased risk of psychosis-like symptoms in 12-year-olds.
Declining incidence of keratinocyte carcinoma in organ transplant recipients

All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population‐based studies on post‐transplant rates of basal cell carcinoma (BCC).
Multidisciplinary home-based rehabilitation in inoperable lung cancer: a randomised controlled trial

Background Lung cancer is associated with poor health-related quality of life (HRQoL) and high symptom burden. This trial aimed to assess the efficacy of home-based rehabilitation versus usual care in inoperable lung cancer. Methods A parallel-group, assessor-blinded, allocation-concealed, randomised controlled trial. Eligible participants were allocated (1:1) to usual care (UC) plus 8 weeks of aerobic and resistance exercise with behaviour change strategies and symptom support (intervention group (IG)) or UC alone. Assessments occurred at baseline, 9 weeks and 6 months. The primary outcome, change in between-group 6 min walk distance (6MWD), was analysed using intention-to-treat (ITT). Subsequent analyses involved modified ITT (mITT) and included participants with at least one follow-up outcome measure. Secondary outcomes included HRQoL and symptoms. Results Ninety-two participants were recruited. Characteristics of participants (UC=47, IG=45): mean (SD) age 64 (12) years; men 55%; disease stage n (%) III=35 (38) and IV=48 (52); radical treatment 46%. There were no significant between-group differences for the 6MWD (n=92) at 9 weeks (p=0.308) or 6 months (p=0.979). The mITT analyses of 6MWD between-group differences were again non-significant (mean difference (95% CI): 9 weeks: −25.4 m (−64.0 to 13.3), p=0.198 and 6 months: 41.3 m (−26.7 to 109.4), p=0.232). Significant 6-month differences, favouring the IG, were found for HRQoL (Functional Assessment of Cancer Therapy–Lung: 13.0 (3.9 to 22.1), p=0.005) and symptom severity (MD Anderson Symptom Inventory–Lung Cancer: −2.2 (−3.6 to –0.9), p=0.001). Conclusions Home-based rehabilitation did not improve functional exercise capacity but there were improvements in patient-reported exploratory secondary outcomes measures observed at 6 months. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12614001268639).
Alternate splicing of transcripts shape macrophage response to Mycobacterium tuberculosis infection

Transcriptional reprogramming of macrophages upon Mycobacterium tuberculosis (Mtb) infection is widely studied; however, the significance of alternate splicing (AS) in shaping cellular responses to mycobacterial infections is not yet appreciated. Alternate splicing can influence transcript stability or structure, function and localization of corresponding proteins thereby altering protein stoichiometry and physiological consequences. Using comprehensive analysis of a time-series RNA-seq data obtained from human macrophages infected with virulent or avirulent strains of Mtb, we show extensive remodeling of alternate splicing in macrophage transcriptome. The global nature of this regulation was evident since genes belonging to functional classes like trafficking, immune response, autophagy, redox and metabolism showed marked departure in the pattern of splicing in the infected macrophages. The systemic perturbation of splicing machinery in the infected macrophages was apparent as genes involved at different stages of spliceosome assembly were also regulated at the splicing level. Curiously there was a considerable increase in the expression of truncated/non-translatable variants of several genes, specifically upon virulent infections. Increased expression of truncated transcripts correlated with a decline in the corresponding protein levels. We verified the physiological relevance for one such candidate gene RAB8B; whose truncated variant gets enriched in H37Rv infected cells. Upon tweaking relative abundance of longer or shorter variants of RAB8B transcripts by specialized transduction, mycobacterial targeting to lysosomes could be promoted or blocked respectively, which also resulted in corresponding changes in the bacterial survival. Our results show RAB8B recruitment to the mycobacterial phagosomes is required for phagosome maturation. Thus the abundance of truncated RAB8B variant helps virulent Mtb survival by limiting the RAB8B levels in the cells, a mechanism which we subsequently verified in human primary macrophages. Taken together we demonstrate alternate splicing as a new locus of intervention by Mtb and provide attractive alternative to exploit for novel drug targets against Mtb.
Regularization Methods for High-Dimensional Instrumental Variables Regression With an Application to Genetical Genomics

In genetical genomics studies, it is important to jointly analyze gene expression data and genetic variants in exploring their associations with complex traits, where the dimensionality of gene expressions and genetic variants can both be much larger than the sample size. Motivated by such modern applications, we consider the problem of variable selection and estimation in high-dimensional sparse instrumental variables models. To overcome the difficulty of high dimensionality and unknown optimal instruments, we propose a two-stage regularization framework for identifying and estimating important covariate effects while selecting and estimating optimal instruments. The methodology extends the classical two-stage least squares estimator to high dimensions by exploiting sparsity using sparsity-inducing penalty functions in both stages. The resulting procedure is efficiently implemented by coordinate descent optimization. For the representative L1 regularization and a class of concave regularization methods, we establish estimation, prediction, and model selection properties of the two-stage regularized estimators in the high-dimensional setting where the dimensionality of covariates and instruments are both allowed to grow exponentially with the sample size. The practical performance of the proposed method is evaluated by simulation studies and its usefulness is illustrated by an analysis of mouse obesity data. Supplementary materials for this article are available online.
Heme Oxygenase 1 in Schwann Cells Regulates Peripheral Nerve Degeneration Against Oxidative Stress

During Wallerian degeneration, Schwann cells lose their characteristic of myelinating axons and shift into the state of developmental promyelinating cells. This recharacterized Schwann cell guides newly regrowing axons to their destination and remyelinates reinnervated axons. This Schwann cell dynamics during Wallerian degeneration is associated with oxidative events. Heme oxygenases (HOs) are involved in the oxidative degradation of heme into biliverdin/bilirubin, ferrous iron, and carbon monoxide. Overproduction of ferrous iron by HOs increases reactive oxygen species, which have deleterious effects on living cells. Thus, the key molecule for understanding the exact mechanism of Wallerian degeneration in the peripheral nervous system is likely related to oxidative stress-mediated HOs in Schwann cells. In this study, we demonstrate that demyelinating Schwann cells during Wallerian degeneration highly express HO1, not HO2, and remyelinating Schwann cells during nerve regeneration decrease HO1 activation to levels similar to those in normal myelinating Schwann cells. In addition, HO1 activation during Wallerian degeneration regulates several critical phenotypes of recharacterized repair Schwann cells, such as demyelination, transdedifferentiation, and proliferation. Thus, these results suggest that oxidative stress in Schwann cells after peripheral nerve injury may be regulated by HO1 activation during Wallerian degeneration and oxidative-stress-related HO1 activation in Schwann cells may be helpful to study deeply molecular mechanism of Wallerian degeneration.
The Effect of the Cool Dialysate on the Restless Leg Syndrome in Hemodialysis Patients: Randomized Triple-Blind Clinical Trial

Background: Restless leg syndrome (RLS) is a common symptom of some diseases specially observed during hemodialysis. Cooling the dialysate is a safe and nonpharmacological method. The aim of this study was to assess the effect of cool dialysate on RLS in hemodialysis patients. Materials and Methods: A total of 79 patients were selected for screening based on the four main criteria set by the RLS International Association. Finally, in line with the inclusion and exclusion criteria, 63 hemodialysis patients were recruited and participated in this clinical trial. The patients were randomly assigned to the intervention group (n = 32) and the control group (n = 31). The intervention group received 35.5°C dialysate and the control group received 37°C dialysate three times a week for a period of 1 month. The severity of RLS was measured in both groups using a standardized RLS questionnaire. Using R software version 3.3. 1, the data were analyzed using the Student's t-test, and Wilcoxon test, at 95% confidence interval. Results: In terms of RLS severity, there was no significant difference between intervention and control groups before the intervention (t = -2.11, p > 0.05). After the intervention, the mean (SD) of RLS severity in the control group was 28.77 (5.45) and in the intervention group was 11.66 (4.69), in which t test showed a significant difference between two groups (t = 14.03, p= 0.001). Conclusions: Using cool dialysate as a nonpharmacological treatment may reduce the severity of RLS in patients on hemodialysis. Therefore, using this method to improve RLS in hemodialysis patients is recommended.
The Impact of Sibling Behavior on Oral Health: A Narrative Review

Objective: The repetition of any behavior until it becomes a learned behavior begins in childhood. Oral health practices being no exception to this, are also acquired at this tender age, and have the potential of greatly affecting one in their lives. Oral health behaviors are learned through a multifactorial interplay, of which the family is a crucial and relatively unexplored area and will be highlighted in this review. This review discusses gender differences among siblings in relation to oral health, familial influence on acquisition and maintenance of oral hygiene habits, media influence on oral health attitudes and more. Methods: A thorough literature search between 1972 and 2017 was done using Scopus, PubMed, and Google Scholar databases, results reviewed, prioritized, and findings compiled. The keywords of the search strategy was as below: Siblings, sibling behavior, sibling oral health, siblings in dentistry, maternal oral health, family influence on oral health. 35 studies were evaluated for the review. The keywords were limited to activities of siblings and their behavior patterns in relation to dentistry and oral health. Results: Results showed that sibling dynamics have been involved in influencing the learning of oral health behaviors in children. Other factors include peer pressure and maternal influences. Conclusion: Sibling relationships play a vital role in shaping behavior characteristics including tooth brushing, oral hygiene, dental perceptions, and snacking behaviors which are pertinent to dentistry.
Accumulation of saturated intramyocellular lipid is associated with insulin resistance[S]

Intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and insulin-sensitive (athletes) states. Biochemical analysis of intramuscular triglyceride composition is confounded by extramyocellular triglycerides in biopsy samples, and hence the specific composition of IMCLs is unknown in these states. 1H magnetic resonance spectroscopy (MRS) can be used to overcome this problem. Thus, we used a recently validated 1H MRS method to compare the compositional saturation index (CH2:CH3) and concentration independent of the composition (CH3) of IMCLs in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic subjects with that of age- and gender-matched athletes (n = 14) and healthy controls (n = 41). The IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic subjects compared with controls but was similar in athletes and controls. IMCL CH2:CH3 was dependent on the IMCL concentration in the controls and, after adjusting the compositional index for quantity (CH2:CH3adj), could distinguish lipodystrophics from athletes. This CH2:CH3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO2max. The association of insulin resistance with the accumulation of saturated IMCLs is consistent with a potential pathogenic role for saturated fat and the reported benefits of exercise and diet in insulin-resistant states.
EMOTIONAL LEARNING: A COMPUTATIONAL MODEL OF THE AMYGDALA

We describe work in progress with the aim of constructing a computational model of emotional learning and processing inspired by neurophysiological findings. The main brain areas modeled are the amygdala and the orbitofrontal cortex and the interaction between them. We want to show that (1) there exists enough physiological data to suggest the overall architecture of a computational model, (2) emotion plays a clear role in learning the behavior. We review neurophysiological data and present a computational model that is subsequently tested in simulation.
Low voltage performance of a microwave CMOS Gilbert cell mixer

This paper demonstrates the low voltage operation of a doubly balanced Gilbert mixer fabricated in a 0.8-/spl mu/m CMOS process and operating as both a down-converter and an up-converter. As a down-converter with an RF input of 1.9 GHz, the mixer has a single sideband noise figure as low as 7.8 dB and achieved down-conversion gain for supply voltages as low as 1.8 V. As an up-converter, the mixer demonstrates 10 dB of conversion gain at an RF frequency of 2.4 GHz with an applied local oscillator (LO) power of -7 dBm and LO-RF/LO-IF isolation of at least 30 dB. Up-conversion gain was achieved over a 5-GHz bandwidth and at supply voltages as low as 1.5 V. The mixer presented demonstrates the lowest single side band noise figure for a CMOS doubly balanced down-converting mixer and the highest frequency of operation for a mixer fabricated in CMOS technology to date.