Miracle-dz/UniFAR-FTUs huggingface dataset:
Model‐based estimation of microscopic anisotropy using diffusion MRI: a simulation study

Non‐invasive estimation of cell size and shape is a key challenge in diffusion MRI. This article presents a model‐based approach that provides independent estimates of pore size and eccentricity from diffusion MRI data. The technique uses a geometric model of finite cylinders with gamma‐distributed radii to represent pores of various sizes and elongations. We consider both macroscopically isotropic substrates and substrates of semi‐coherently oriented anisotropic pores and we use Monte Carlo simulations to generate synthetic data. We compare the sensitivity of single and double diffusion encoding (SDE and DDE) sequences to the size distribution and eccentricity, and further analyse different protocols of DDE sequences with parallel and/or perpendicular pairs of gradients. We show that explicitly accounting for size distribution is necessary for accurate microstructural parameter estimates, and a model that assumes a single size yields biased eccentricity values. We also find that SDE sequences support estimates, although DDE sequences with mixed parallel and perpendicular gradients enhance accuracy. In the case of macroscopically anisotropic substrates, this model‐based approach can be extended to a rotationally invariant framework to provide features of pore shape (specifically eccentricity) in the presence of size distribution and orientation dispersion. Copyright © 2016 John Wiley & Sons, Ltd.
Human γδ T-Cell Control of Mucosal Immunity and Inflammation

Human γδ T-cells include some of the most common “antigen-specific” cell types in peripheral blood and are enriched yet further at mucosal barrier sites where microbial infection and tumors often originate. While the γδ T-cell compartment includes multiple subsets with highly flexible effector functions, human mucosal tissues are dominated by host stress-responsive Vδ1+ T-cells and microbe-responsive Vδ2+ T-cells. Widely recognized for their potent cytotoxicity, emerging data suggest that γδ T-cells also exert strong influences on downstream adaptive immunity to pathogens and tumors, in particular via activation of antigen-presenting cells and/or direct stimulation of other mucosal leukocytes. These unique functional attributes and lack of MHC restriction have prompted considerable interest in therapeutic targeting of γδ T-cells. Indeed, several drugs already in clinical use, including vedolizumab, infliximab, and azathioprine, likely owe their efficacy in part to modulation of γδ T-cell function. Recent clinical trials of Vδ2+ T-cell-selective treatments indicate a good safety profile in human patients, and efficacy is set to increase as more potent/targeted drugs continue to be developed. Key advances will include identifying methods of directing γδ T-cell recruitment to specific tissues to enhance host protection against invading pathogens, or alternatively, retaining these cells in the circulation to limit peripheral inflammation and/or improve responses to blood malignancies. Human γδ T-cell control of mucosal immunity is likely exerted via multiple mechanisms that induce diverse responses in other types of tissue-resident leukocytes. Understanding the microenvironmental signals that regulate these functions will be critical to the development of new γδ T-cell-based therapies.
Engaging MSW Students in Faculty Research: Students' Perspectives of Involvement in a Program Evaluation.

ABSTRACTEngaging social work students in research is challenging, in part, because of the way research is taught in the classroom and the need for learners to effectively develop connections between the “abstract world” of research concepts with the “real world” of professional experiences. This article describes the experiences of graduate social work students involved in a process and outcome evaluation of a community-based program. Analysis of student learning outcomes and the team-based model used to engage students in the evaluation are provided to put forth a paradigm of teaching social work research through direct, supervised, and collaborative engagement.
Liposomes as Gene Delivery Vectors for Human Placental Cells

Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations carrying rhodamine-labelled siRNAs were evaluated on an in vitro model, i.e., human primary villous cytotrophoblasts. siRNA internalization rate from lipoplexes were compared to the one in the presence of the lipofectamine reagent and assessed by confocal microscopy. Results showed cellular internalization of nucleic acid with all three formulations, based on two cationic lipids, either DMAPAP or CSL-3. Moreover, incubation with DMAPAP+AA provided a rate of labelled cells as high as with lipofectamine (53 ± 15% and 44 ± 12%, respectively) while being more biocompatible. The proportion of cells which internalized siRNA were similar when using DMAPAP/DDSTU (16 ± 5%) and CSL-3 (22 ± 5%). This work highlights that liposomes could be a promising approach for gene therapy dedicated to pregnant patients.
CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy

Abstract Aims Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity to model, and add clarity to, HCM. Methods and results CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated to hPSC-CMs for high-throughput, non-subjective molecular and functional assessment using 12 approaches in 2D monolayers and/or 3D engineered heart tissues. Although immature, edited hPSC-CMs exhibited the main hallmarks of HCM (hypertrophy, multi-nucleation, hypertrophic marker expression, sarcomeric disarray). Functional evaluation supported the energy depletion model due to higher metabolic respiration activity, accompanied by abnormalities in calcium handling, arrhythmias, and contraction force. Partial phenotypic rescue was achieved with ranolazine but not omecamtiv mecarbil, while RNAseq highlighted potentially novel molecular targets. Conclusion Our holistic and comprehensive approach showed that energy depletion affected core cardiomyocyte functionality. The engineered R453C-βMHC-mutation triggered compensatory responses in hPSC-CMs, causing increased ATP production and αMHC to energy-efficient βMHC switching. We showed that pharmacological rescue of arrhythmias was possible, while MHY7: MYH6 and mutant: wild-type MYH7 ratios may be diagnostic, and previously undescribed lncRNAs and gene modifiers are suggestive of new mechanisms.
Smith–Magenis syndrome and moyamoya disease in a patient with del(17)(p11.2p13.1)

Chromosomal rearrangements causing microdeletions and microduplications are a major cause of congenital malformation and mental retardation. Because they are not visible by routine chromosome analysis, high resolution whole‐genome technologies are required for the detection and diagnosis of small chromosomal abnormalities. Recently, array‐comparative genomic hybridization (aCGH) and multiplex ligation‐dependent probe amplification (MLPA) have been useful tools for the identification and mapping of deletions and duplications at higher resolution and throughput. Smith–Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome caused by deletion or mutation of the retinoic acid induced 1 (RAI1) gene and is often associated with a chromosome 17p11.2 deletion. We report here on the clinical and molecular analysis of a 10‐year‐old girl with SMS and moyamoya disease (occlusion of the circle of Willis). We have employed a combination of aCGH, FISH, and MLPA to characterize an ∼6.3 Mb deletion spanning chromosome region 17p11.2–p13.1 in this patient, with the proximal breakpoint within the RAI1 gene. Further, investigation of the genomic architecture at the breakpoint intervals of this large deletion documented the presence of palindromic repeat elements that could potentially form recombination substrates leading to unequal crossover. © 2007 Wiley‐Liss, Inc.
A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review

Background Functional cognitive disorder (FCD) describes cognitive dysfunction in the absence of an organic cause. It is increasingly prevalent in healthcare settings yet its key neuropsychological features have not been reported in large patient cohorts. We hypothesised that cognitive profiles in fibromyalgia (FM), chronic fatigue syndrome (CFS) and functional neurological disorders (FNDs) would provide a template for characterising FCD. Methods We conducted a systematic review of studies with cognition-related outcomes in FM, CFS and FND. Results We selected 52 studies on FM, 95 on CFS and 39 on FND. We found a general discordance between high rates of subjective cognitive symptoms, including forgetfulness, distractibility and word-finding difficulties, and inconsistent objective neuropsychological deficits. Objective deficits were reported, including poor selective and divided attention, slow information processing and vulnerability to distraction. In some studies, cognitive performance was inversely correlated with pain, exertion and fatigue. Performance validity testing demonstrated poor effort in only a minority of subjects, and patients with CFS showed a heightened perception of effort. Discussion The cognitive profiles of FM, CFS and non-cognitive FND are similar to the proposed features of FCD, suggesting common mechanistic underpinnings. Similar findings have been reported in patients with mild traumatic brain injury and whiplash. We hypothesise that pain, fatigue and excessive interoceptive monitoring produce a decrease in externally directed attention. This increases susceptibility to distraction and slows information processing, interfering with cognitive function, in particular multitasking. Routine cognitive processes are experienced as unduly effortful. This may reflect a switch from an automatic to a less efficient controlled or explicit cognitive mode, a mechanism that has also been proposed for impaired motor control in FND. These experiences might then be overinterpreted due to memory perfectionism and heightened self-monitoring of cognitive performance.
Population Wide Decline in Somatic Growth in Harbor Seals—Early Signs of Density Dependence

The harbour seal populations of Danish and Swedish waters have had turbulent population dynamics during the last century. They were severely depleted by hunting in the beginning of the 20th century, followed by rapid recovery due to protective measures. They were victims to two mass mortalities caused by Phocine Distemper Virus (PDV) epidemics. Long term monitoring and intensive sampling during the last decades now allow analysis of population level phenomena in response to shifting population size. We compare somatic growth curves from several seal populations including 2 041 specimens with known age, length and population size at birth. Asymptotic body lengths of female harbour seals were 148 cm in all four regions in 1988, when seal abundances had been kept low by hunting for decades. Males were 158 cm, being 10 cm longer. However, in 2002 the asymptotic lengths of seals differed among regions. While seals in the Kattegat showed similar asymptotic lengths as in 1988, seals in the Skagerrak were significantly shorter, where both male and female asymptotic lengths declined by 7 cm. We estimate the area of available feeding grounds in the two sea regions and find the density of seals per square kilometre feeding ground to be three times greater in the Skagerrak compared to the Kattegat. Thus, the shorter body length of seals in the Skagerrak can be an early signal of density dependence. Hampered body growth is known to trigger a suite of changes in life history traits, including delayed age at sexual maturity, higher juvenile mortality and lowered fecundity. These mechanisms all point at a possible ‘’smooth route towards carrying capacity’’ with gradually reduced population growth rate as the main response to high population density. Recent aerial surveys confirm declining rates of population increase in the Skagerrak.
Metamorphic records of multiple seismic cycles during subduction

Garnets record subduction earthquakes. Large earthquakes occur in rocks undergoing high-pressure/low-temperature metamorphism during subduction. Rhythmic major-element zoning in garnet is a common product of such metamorphism, and one that must record a fundamental subduction process. We argue that rhythmic major-element zoning in subduction zone garnets from the Franciscan Complex, California, developed in response to growth-dissolution cycles driven by pressure pulses. Using electron probe microanalysis and novel techniques in Raman and synchrotron Fourier transform infrared microspectroscopy, we demonstrate that at least four such pressure pulses, of magnitude 100–350 MPa, occurred over less than 300,000 years. These pressure magnitude and time scale constraints are most consistent with the garnet zoning having resulted from periodic overpressure development-dissipation cycles, related to pore-fluid pressure fluctuations linked to earthquake cycles. This study demonstrates that some metamorphic reactions can track individual earthquake cycles and thereby opens new avenues to the study of seismicity.
Deep Neural Networks for Optimal Team Composition

Cooperation is a fundamental social mechanism, whose effects on human performance have been investigated in several environments. Online games are modern-days natural settings in which cooperation strongly affects human behavior. Every day, millions of players connect and play together in team-based games: the patterns of cooperation can either foster or hinder individual skill learning and performance. This work has three goals: (i) identifying teammates' influence on players' performance in the short and long term, (ii) designing a computational framework to recommend teammates to improve players' performance, and (iii) setting to demonstrate that such improvements can be predicted via deep learning. We leverage a large dataset from Dota 2, a popular Multiplayer Online Battle Arena game. We generate a directed co-play network, whose links' weights depict the effect of teammates on players' performance. Specifically, we propose a measure of network influence that captures skill transfer from player to player over time. We then use such framing to design a recommendation system to suggest new teammates based on a modified deep neural autoencoder and we demonstrate its state-of-the-art recommendation performance. We finally provide insights into skill transfer effects: our experimental results demonstrate that such dynamics can be predicted using deep neural networks.
Human neural stem cells dispersed in artificial ECM form cerebral organoids when grafted in vivo

Human neural stem cells (hNSC) derived from induced pluripotent stem cells can be differentiated into neurons that could be used for transplantation to repair brain injury. In this study we dispersed such hNSC in a three‐dimensional artificial extracellular matrix (aECM) and compared their differentiation in vitro and following grafting into the sensorimotor cortex (SMC) of postnatal day (P)14 rat pups lesioned by localised injection of endothelin‐1 at P12. After 10–43 days of in vitro differentiation, a few cells remained as PAX6+ neuroprogenitors but many more resembled post‐mitotic neurons expressing doublecortin, β‐tubulin and MAP2. These cells remained dispersed throughout the ECM, but with extended long processes for over 50 μm. In vivo, by 1 month post grafting, cells expressing human specific markers instead organised into cerebral organoids: columns of tightly packed PAX6 co‐expressing progenitor cells arranged around small tubular lumen in rosettes, with a looser network of cells with processes around the outside co‐expressing markers of immature neurons including doublecortin, and CTIP2 characteristic of corticofugal neurons. Host cells also invaded the graft including microglia, astrocytes and endothelial cells forming blood vessels. By 10 weeks post‐grafting, the organoids had disappeared and the aECM had started to break down with fewer transplanted cells remaining. In vitro, cerebral organoids form in rotating incubators that force oxygen and nutrients to the centre of the structures. We have shown that cerebral organoids can form in vivo; intrinsic factors may direct their organisation including infiltration by host blood vessels.
Epidemiology of Robin sequence with cleft palate in the East of Scotland between 2004 and 2013

Robin sequence (RS) is a congenital disorder characterized by cleft palate, micrognathia, and glossoptosis which can result in clinically significant upper airway obstruction (UAO). Historically, incidence of RS in the UK has been estimated as 1 in 8500 live births. Our study describes birth prevalence, clinical characteristics, and management of RS in the East of Scotland (EoS) region.
Towards Augmented Human Memory: Retrieval-Induced Forgetting and Retrieval Practice in an Interactive, End-of-Day Review

The authors report 6 experiments that examined the contention that an end-of-day review could lead to augmentation in human memory. In Experiment 1, participants in the study phase were presented with a campus tour of different to-be-remembered objects in different university locations. Each to-be-remembered object was presented with an associated specific comment. Participants were then shown the location name and photographs of half of the objects from half of the locations, and they were asked to try to name the object and recall the associated comment specific to each item. Following a filled delay, participants were presented with the name of each campus location and were asked to free recall the to-be-remembered objects. Relative to the recall from the unpracticed location categories, participants recalled the names of significantly more objects that they practiced (retrieval practice) and significantly fewer unpracticed objects from the practiced locations (retrieval-induced forgetting, RIF). These findings were replicated in Experiment 2 using a campus scavenger hunt in which participants selected their own stimuli from experimenter’s categories. Following an examination of factors that maximized the effects of RIF and retrieval practice in the laboratory (Experiment 3), the authors applied these findings to the campus scavenger hunt task to create different retrieval practice schedules to maximize and minimize recall of items based on experimenter-selected (Experiment 4) and participant-selected items using both category-cued free recall (Experiment 5) and item-specific cues (Experiment 6). Their findings support the claim that an interactive, end-of-day review could lead to augmentation in human memory.
Bacterial community analysis in three types of the fermented seafood, jeotgal, produced in South Korea

ABSTRACT Jeotgal is a traditional Korean seafood fermented by indigenous microbes. The bacterial community in five myeolchi-jeot (Engraulis japonica), five meongge-jeot (Halocynthia roretzi), and six saeu-jeot (Acetes japonicas) produced in South Korea was analyzed by barcoded pyrosequencing targeting the V1/V2 hyper-variable regions of the 16S rRNA gene. All samples were dominated by the phyla Firmicutes, which represented 67.7% (SD = 27.2%) of the population. Tetragenococcus halophilus and Tetragenococcus muriaticus were the predominant species in myeolchi-jeot. The LABs, Lactobacillus sakei, Lactobacillus curvatus, and Weissella koreensis were the predominant species in meongge-jeot. In myeolchi-jeot and meongge-jeot, the bacterial communities within samples were consistent in their predominance, however each of saeu-jeot samples had inter-individual variety in the bacterial community leading to the difficulties of standardization for the commercial production of saeu-jeot. The results of this study will conclusively help to expand our basic knowledge of jeotgal and the related microorganisms involved in food fermentation. Bacterial community analysis in three types of the Korean traditional fermented seafood, jeotgal.
Immunosuppressive treatments for immunoglobulin A nephropathy: A meta‐analysis of randomized controlled trials

SUMMARY: Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end‐stage kidney disease (ESRD) in up to 15–20% of affected patients within 10 years from the apparent onset of disease and in up to 30–40% of individuals within 20 years from diagnosis. No specific treatment has been established and there is wide variation in current practice. This systematic review evaluates the use of immunosuppressive agents to treat patients with IgA nephropathy. The Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE and article reference lists were searched for randomized or quasi randomized trials. Two independent reviewers assessed studies for inclusion criteria (biopsy proven IgA nephropathy, randomized trial, use of immunosuppressive agents) and extracted data regarding the effects of immunosuppressive agents on ESRD, doubling of serum creatinine, glomerular filtration rate, urinary protein excretion and side‐effects. Data were analysed with a random effects model. The published trials were few (13 trials, 623 patients) and were generally of poor quality. Compared with placebo, steroids were associated with a lower risk of progression to ESRD (six trials, 341 patients, RR 0.44, 95% CI 0.25–0.80) and lower end‐of‐trial proteinuria (six trials, 263 patients, weighted mean difference (WMD) −0.49 g/day, 95% CI −0.25 to −0.72). Treatment with alkylating agents significantly reduced end of treatment proteinuria (two trials, 122 patients, WMD −0.94, 95% CI −0.46 to −1.43). Although the optimal management of patients with IgA nephropathy remains uncertain because of limitations with the existing published data, immunosuppressive agents are a promising strategy and should be investigated further.