Miracle-dz/UniFAR-FTUs huggingface dataset:
Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders

Individuals with a family history of substance use disorder (FH+) show impaired frontal white matter as indicated by diffusion tensor imaging (DTI). This impairment may be due to impaired or delayed development of myelin in frontal regions, potentially contributing to this population's increased risk for developing substance use disorders. In this study, we examined high angular resolution DTI and proton magnetic resonance spectroscopy data from the anterior corona radiata were collected in 80 FH+ and 34 FH− youths (12.9 ± 1.0 years old). White matter integrity indices included fractional anisotropy (FA), N‐acetylaspartate (NAA), and total choline (tCho). Lower FA suggests decreased myelination. Decreased NAA coupled with higher tCho suggests impaired build‐up and maintenance of cerebral myelin and consequently greater breakdown of cellular membranes. We found FH+ youths had lower FA (P < 0.0001) and NAA (P = 0.017) and higher tCho (P = 0.04). FH density (number of parents and grandparents with substance use disorders) was negatively correlated with FA (P < 0.0001) and NAA (P = 0.011) and positively correlated with tCho (P = 0.001). FA was independently predicted by both FH density (P =0.006) and NAA (P= 0.002), and NAA and tCho were both independent predictors of FH density (P < 0.001). Our finding of lower frontal FA in FH+ youths corresponding to lower NAA and increased tCho is consistent with delayed or impaired development of frontal white matter in FH+ youths. Longitudinal studies are needed to determine how these differences relate to substance use outcomes. Hum Brain Mapp 35:5877–5887, 2014. © 2014 Wiley Periodicals, Inc.
Effects of adding luteinizing hormone activity to gonadotropin releasing hormone antagonist protocols may differ according to age

Objective. In spite of previous reports on the beneficial effects of adding exogenous luteinizing hormone (LH) activity to gonadotropin releasing hormone (GnRH) antagonist protocols for conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), these effects in various age groups are still controversial. This study was performed to evaluate the clinical efficacy of adding LH activity to GnRH antagonist protocols according to patient's age. Methods. In this medical record review, responses to controlled ovarian hyperstimulation (COH) and IVF/ICSI outcomes were compared between follicle stimulating hormone (FSH) alone and FSH supplemented with LH activity groups in women ≤35 years (n = 135) and those >35 years (n = 97), respectively. Results. Estradiol level on hCG day in LH-added group was higher (2.150.6 ± 1.345.1 pg/ml vs. 1.606.2 ± 994.6 pg/ml, P = 0.011) in women ≤35 years, while it did not differ in those >35 years. Less oocytes were retrieved in LH-added group of women >35 years (8.1 ± 6.5 vs. 5.7 ± 3.0, P = 0.013), however, this figure did not differ in those ≤35 years. Regardless of age, the clinical pregnancy rates were not different between the two groups. Conclusions. Supplementation of exogenous LH activity to GnRH antagonist protocols affects the COH outcomes. These LH-adding effects may vary according to patient's age.
Irinotecan and Capecitabine (CAPIRI) Plus Bevacizumab in First-Line Treatment of Metastatic Colorectal Cancer

The purpose of this prospective study was to assess the efficacy and safety of bevacizumab in combination with reduced doses of irinotecan plus capecitabine (CAPIRI regimen), in patients with metastatic colorectal cancer (mCRC), as first-line chemotherapy. A cohort of 120 mCRC consecutive patients was included. The overall response rate was 63.3% (76 patients; 95% confidence interval [CI], 53.97%-71.77%). Median time to progression and overall survival were 15 months (range: 2-49 months; 95% CI: 13.00, 17.00 months) and 22.5 months (range: 4-54 months; 95% CI: 21.00, 27.00 months), respectively. The one year survival rate was 81.5%. CAPIRI-related grade 3/4 adverse events included alopecia (29.2%) and diarrhoea (16.7%), which were manageable. Bevacizumab-related grade 3 hypertension was reported in 2 patients. One patient died due to treatment related adverse event, which was no bevacizumab-related. In conclusion, combination of bevacizumab plus CAPIRI is a feasible treatment which provides a clinical benefit as first-line treatment in chemonaive patients with mCRC.
Fates of CD4+ T Cells in a Tolerant Environment Depend on Timing and Place of Antigen Exposure

In experimental organ transplantation, tolerance is induced by administration of anti‐CD40L mAb in conjunction with donor‐specific splenocyte transfusion. Multiple, sometimes conflicting mechanisms of action resulting from this treatment have been reported. To resolve these issues, this study assessed the fates of graft reactive cells at different times and locations in the tolerant environment. Alloantigen‐specific CD4+ T cells transferred at time of tolerance induction (7 days before transplantation) became activated, expressed CD69 and CD44, and proliferated. Importantly, a large subset of this population became Foxp3+, more so in the lymph nodes than spleen, indicative of differentiation to a regulatory phenotype. In contrast, graft reactive CD4+ T cells transferred to tolerogen‐treated recipients at the time of transplantation failed either to proliferate or to differentiate, and instead were deleted via apoptosis. In untreated rejecting recipients graft reactive CD4+ T cells became activated, proliferated and differentiated mainly in the spleen, and many of these cells were eventually deleted. These data resolve many apparent contradictions in the literature by showing that the timing of antigen exposure, the immunologic status of the recipients and secondary lymphoid organ location act together as key factors to determine the fate of graft reactive CD4+ T cells.
Shared and nonshared neural networks of cognitive and affective theory‐of‐mind: A neuroimaging study using cartoon picture stories

Theory of mind (ToM) refers to the ability to represent one's own and others' cognitive and affective mental states. Recent imaging studies have aimed to disentangle the neural networks involved in cognitive as opposed to affective ToM, based on clinical observations that the two can functionally dissociate. Due to large differences in stimulus material and task complexity findings are, however, inconclusive. Here, we investigated the neural correlates of cognitive and affective ToM in psychologically healthy male participants (n = 39) using functional brain imaging, whereby the same set of stimuli was presented for all conditions (affective, cognitive and control), but associated with different questions prompting either a cognitive or affective ToM inference. Direct contrasts of cognitive versus affective ToM showed that cognitive ToM recruited the precuneus and cuneus, as well as regions in the temporal lobes bilaterally. Affective ToM, in contrast, involved a neural network comprising prefrontal cortical structures, as well as smaller regions in the posterior cingulate cortex and the basal ganglia. Notably, these results were complemented by a multivariate pattern analysis (leave one study subject out), yielding a classifier with an accuracy rate of more than 85% in distinguishing between the two ToM‐conditions. The regions contributing most to successful classification corresponded to those found in the univariate analyses. The study contributes to the differentiation of neural patterns involved in the representation of cognitive and affective mental states of others. Hum Brain Mapp, 36:29–39, 2015. © 2014 Wiley Periodicals, Inc.
Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy

Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task‐related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel‐based morphometry (VBM) on T1‐weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp. Hum Brain Mapp 36:1165–1179, 2015. © 2014 Wiley Periodicals, Inc.
Sex differences in normal age trajectories of functional brain networks

Resting‐state functional magnetic resonance image (rs‐fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting‐state networks (RSNs) using a novel voxel‐wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large‐scale RSNs during normal aging from early adulthood to late middle‐age. In some networks, such as the default‐mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto‐parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex‐related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. Hum Brain Mapp 36:1524–1535, 2015. © 2014 Wiley Periodicals, Inc.
ABCs of Natriuretic Peptides: Cardiac Aspects

Background: The natriuretic peptides are a family of structurally similar peptides. Atrial natriuretic peptide and B-type natriuretic peptide (BNP) are cardiac hormones secreted from the heart in response to cardiac chamber distention. Their biological actions include diuresis, natriuresis and vasodilatation, as well as suppression of the renin-angiotensin-aldosterone and endothelin systems. The hemodynamic actions of the secreted natriuretic peptide unload the heart in response to increased intravascular volume. Knowledge regarding the biological actions of the natriuretic peptides continues to evolve into clinical use. A synthetic BNP analogue has shown a beneficial short-term effect in acute decompensated heart failure, while plasma levels of natriuretic peptides have been shown to be elevated in patients with heart disease. Conclusions: BNP and the N-terminal segment of its prohormone, NT-pro-BNP, are very sensitive markers for many forms of heart disease. Future research will likely allow greater use of these peptides in the diagnosis and treatment of heart diseases in adults and children.
Intrinsic brain activity as a diagnostic biomarker in children with benign epilepsy with centrotemporal spikes

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting‐state functional magnetic resonance imaging (RS‐fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age‐matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS‐fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878–3889, 2015. © 2015 Wiley Periodicals, Inc.
Genetic influences on resting‐state functional networks: A twin study

Alterations in resting‐state networks (RSNs) are often associated with psychiatric and neurologic disorders. Given this critical linkage, it has been hypothesized that RSNs can potentially be used as endophenotypes for brain diseases. To validate this notion, a critical step is to show that RSNs exhibit heritability. However, the investigation of the genetic basis of RSNs has only been attempted in the default‐mode network at the region‐of‐interest level, while the genetic control on other RSNs has not been determined yet. Here, we examined the genetic and environmental influences on eight well‐characterized RSNs using a twin design. Resting‐state functional magnetic resonance imaging data in 56 pairs of twins were collected. The genetic and environmental effects on each RSN were estimated by fitting the functional connectivity covariance of each voxel in the RSN to the classic ACE twin model. The data showed that although environmental effects accounted for the majority of variance in wide‐spread areas, there were specific brain sites that showed significant genetic control for individual RSNs. These results suggest that part of the human brain functional connectome is shaped by genomic constraints. Importantly, this information can be useful for bridging genetic analysis and network‐level assessment of brain disorders. Hum Brain Mapp 36:3959–3972, 2015. © 2015 Wiley Periodicals, Inc.
Processing of false belief passages during natural story comprehension: An fMRI study

The neural correlates of theory of mind (ToM) are typically studied using paradigms which require participants to draw explicit, task‐related inferences (e.g., in the false belief task). In a natural setup, such as listening to stories, false belief mentalizing occurs incidentally as part of narrative processing. In our experiment, participants listened to auditorily presented stories with false belief passages (implicit false belief processing) and immediately after each story answered comprehension questions (explicit false belief processing), while neural responses were measured with functional magnetic resonance imaging (fMRI). All stories included (among other situations) one false belief condition and one closely matched control condition. For the implicit ToM processing, we modeled the hemodynamic response during the false belief passages in the story and compared it to the hemodynamic response during the closely matched control passages. For implicit mentalizing, we found activation in typical ToM processing regions, that is the angular gyrus (AG), superior medial frontal gyrus (SmFG), precuneus (PCUN), middle temporal gyrus (MTG) as well as in the inferior frontal gyrus (IFG) billaterally. For explicit ToM, we only found AG activation. The conjunction analysis highlighted the left AG and MTG as well as the bilateral IFG as overlapping ToM processing regions for both implicit and explicit modes. Implicit ToM processing during listening to false belief passages, recruits the left SmFG and billateral PCUN in addition to the “mentalizing network” known form explicit processing tasks. Hum Brain Mapp 36:4231–4246, 2015. © 2015 Wiley Periodicals, Inc.
Intermittent Bolus or Semicontinuous Feeding for Preterm Infants?

Objectives: The aim of the present study was to assess the clinical benefits and risks of semicontinuous (CON) versus intermittent nasogastric tube feeding in low-birth-weight infants. Methods: Infants with a birth weight <1750 g and gestational age <32 weeks were stratified according to birth weight and assigned to either CON or intermittent bolus (BOL) feeding. The primary endpoint was days to full enteral feeding (defined as 120 mL · kg−1 · day−1). We also collected data on feeding tolerance, weight gain, respiratory support, and complications (sepsis, necrotising enterocolitis, and death). Results: There was no difference between the 2 groups (CON n = 121, BOL n = 125) in days to reach full enteral feeding—7 (5–10) versus 6 (5–8) days, respectively, with a difference 1 (−0.05 to 2.1). Mean daily gastric residual volumes, however, were significantly lower in the BOL group (4.8 vs 3.9 mL/day, difference 0.9 mL/day [0.1–1.7]), as was the total number of patients with feeding interruptions (76 vs 59, difference 16% [3%–28%]). Conclusions: Bolus and continuous feeding are equally suitable feeding strategies for preterm neonates. BOL feeding, however, may be preferable.
A 16‐Year Multi‐Institutional Study of the Role of Age and EBV Status on PTLD Incidence Among Pediatric Heart Transplant Recipients

The objective was to determine the incidence and hazard for posttransplant lymphoproliferative disease (PTLD) in a study of 3170 pediatric primary heart transplants between 1993 and 2009 at 35 institutions in the Pediatric Heart Transplant Study. 147 of 151 reported malignancy events were classified as PTLD. Overall freedom from PTLD was 98.5% at 1 year, 94% at 5 years and 90% at 10 years. Freedom from PTLD was lowest in children (ages 1 to < 10 years) versus infants (<1 year) and adolescents (10 to < 18 years) with children at highest risk for PTLD with a relative risk of 2.4 compared to infants and 1.7 compared to adolescents. Positive donor EBV status was a strong risk factor for PTLD in the seronegative recipient, but risk magnitude was dependent on recipient age at the time of transplantation. Nearly 25% of EBV seronegative recipients of EBV+ donors at ages 4–7 at transplantation developed some form of PTLD. The overall risk for PTLD declined in the most recent transplant era (2001–2009, p = 0.003). These findings indicate that EBV status and the age of the recipient at the time of transplantation are important variables in the development of PTLD in the pediatric heart transplant recipient.
Mother's but not father's education predicts general fluid intelligence in emerging adulthood: Behavioral and neuroanatomical evidence

Lower parental education impairs cognitive abilities of their offspring such as general fluid intelligence dependent on the prefrontal cortex (PFC), but the independent contribution of mother's and father's education is unknown. We used an individual difference approach to test whether mother's and father's education independently affected general fluid intelligence in emerging adulthood at both the behavioral and neural level. Behaviorally, mother's but not father's education accounted for unique variance in general fluid intelligence in emerging adulthood (assessed by the Raven's advanced progressive matrices). Neurally, the whole‐brain correlation analysis revealed that the regional gray matter volume (rGMV) in the medial PFC was related to both mother's education and general fluid intelligence but not father's education. Furthermore, after controlling for mother's education, the association between general fluid intelligence and the rGMV in medial PFC was no longer significant, indicating that mother's education plays an important role in influencing the structure of the medial PFC associated with general fluid intelligence. Taken together, our study provides the first behavioral and neural evidence that mother's education is a more important determinant of general cognitive ability in emerging adulthood than father's education. Hum Brain Mapp 36:4582–4591, 2015. © 2015 Wiley Periodicals, Inc.
Human Herpesvirus 8 (HHV8) Transmission and Related Morbidity in Organ Recipients

The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2‐year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow‐up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8‐related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.