Miracle-dz/UniFAR-FTUs huggingface dataset:
New Similarity Metric for Registration of MRI to Histology: Golden Retriever Muscular Dystrophy Imaging

Objective: Histology is often used as a gold standard to evaluate noninvasive imaging modalities such as a magnetic resonance imaging (MRI). Spatial correspondence between histology and MRI is a critical step in quantitative evaluation of skeletal muscle in golden retriever muscular dystrophy (GRMD). Registration becomes technically challenging due to nonorthogonal histology section orientation, section distortion, and the different image contrast and resolution. Methods: This study describes a three-step procedure to register histology images with multiparametric MRI, i.e., interactive slice localization controlled by a three-dimensional mouse, followed by an affine transformation refinement, and a B-spline deformable registration using a new similarity metric. This metric combines mutual information and gradient information. Results: The methodology was verified using ex vivo high-resolution multiparametric MRI with a resolution of 117.19 μm (i.e., T1-weighted and T2-weighted MRI images) and trichrome stained histology images acquired from the pectineus muscles of ten dogs (nine GRMD and one healthy control). The proposed registration method yielded a root mean squares (RMS) error of 148.83 ± 34.96 μm averaged for ten muscle samples based on landmark points validated by five observers. The best RMS error averaged for ten muscles, was 128.48 ± 25.39 μm. Conclusion: The established correspondence between histology and in vivo MRI enables accurate extraction of MRI characteristics for histologically confirmed regions (e.g., muscle, fibrosis, and fat). Significance: The proposed methodology allows creation of a database of spatially registered multiparametric MRI and histology. This database will facilitate accurate monitoring of disease progression and assess treatment effects noninvasively.
Neighborhood Characteristics, Maternal Parenting, and Health and Development of Children from Socioeconomically Disadvantaged Families

The present study examined the direct and indirect effects of neighborhood conditions on the health and development of children from socioeconomically disadvantaged families. Two waves of data were analyzed from the Fragile Families and Child Wellbeing study and its subsample of 3,656 mothers and their young children at ages 3 and 5. The results show that social cohesion was directly and indirectly associated with children's behavioral problems and health status. Social control was found to have an indirect effect on children's behavioral problems and cognitive development transmitted through maternal parenting quality and parenting stress. There were significant direct effects of neighborhood physical disorder on children's behavioral problems and cognitive development. In terms of effect size, mothers' parenting stress and parenting quality, economic hardship, education level, and health care coverage were also prominent factors in determining the health and development of children. Implications for interventions and future research are discussed.
Increased autumn productivity permits temperate trees to compensate for spring frost damage.

Climate warming is leading to earlier budburst and therefore an increased risk of spring frost injury to young leaves. But to what extent are second-cohort leaves, which trees put out after leaf-killing frosts, able to compensate incurred losses? To investigate whether second-cohort leaves behave differently from first-cohort leaves, we exposed saplings of beech (Fagus sylvatica), oak (Quercus robur), and honeysuckle (Lonicera xylosteum) to experimental treatments mimicking either a warm spring or a warm spring with a leaf-killing frost. Refoliation took 48, 43, and 36 d for beech, oak and honeysuckle, respectively. In beech and oak, autumn Chl content and photosynthesis rates were higher in second- than in first-cohort leaves, senescence in second-cohort leaves occurred c. 2-wk-later, and autumn bud growth in beech was elevated 66% in frost-damaged plants compared with the warm spring treatment. No differences in autumn phenology and growth were observed for honeysuckle. Overall, in beech and oak, delayed Chl breakdown in second-cohort leaves mitigated 31% and 25%, respectively, of the deficit in growing-season length incurred by spring frost damage. These results reveal an unexpected ability of second-cohort leaves of beech and oak to compensate for spring frost damage, and demonstrate that long-lived trees vary their autumnal phenology depending on preceding productivity.
Attenuation of human hypoxic pulmonary vasoconstriction by acetazolamide and methazolamide.

RATIONALE Acetazolamide, a carbonic anhydrase inhibitor used for preventing altitude illness attenuates hypoxic pulmonary vasoconstriction (HPV) while improving oxygenation. Methazolamide, an analog of acetazolamide, is more lipophilic, has a longer half-life, and activates a major antioxidant transcription factor. However, its influence on the hypoxic pulmonary response in humans is unknown. OBJECTIVE To determine if a clinically relevant dosing of methazolamide improves oxygenation, attenuates HPV and augments plasma antioxidant capacity in men exposed to hypoxia when compared to an established dosing of acetazolamide known to suppress HPV. METHODS In this double-blind, placebo-controlled, cross-over trial, eleven participants were randomized to treatments with methazolamide (100mg b.i.d.) and acetazolamide (250mg t.i.d.) for two days prior to 60 minutes of hypoxia (FIO2≈0.12). MEASUREMENTS Pulmonary artery systolic pressure (PASP), alveolar ventilation (V̇A), blood gases and markers of redox status were measured. Pulmonary vascular sensitivity to hypoxia was determined by indexing PASP to alveolar PO2. RESULTS Acetazolamide caused greater metabolic acidosis compared with methazolamide, but the augmented V̇A and improved oxygenation with hypoxia were similar. The rise in PASP with hypoxia was lower with methazolamide (9.0 ± 0.9 mmHg) and acetazolamide (8.0 ± 0.7 mmHg) compared with placebo (14.1 ± 1.3 mmHg; P < 0.05). The pulmonary vascular sensitivity to hypoxia (ΔPASP/ΔPAO2) was reduced equally by both drugs. Only acetazolamide improved the non-enzymatic plasma antioxidant capacity. CONCLUSIONS Although acetazolamide only had plasma antioxidant properties, methazolamide led to similar improvements in oxygenation and reduction in HPV at a dose causing less metabolic acidosis than acetazolamide in humans.
Multispectroscopic studies of the interaction of folic acid with glycated human serum albumin

Abstract The interaction between glycated human serum albumin (gHSA) and folic acid (FA) was investigated by various spectroscopic techniques, such as fluorescence, circular dichroism, UV–vis absorption spectroscopy and electrophoretic light scattering technique. These methods characterize the binding properties of an albumin–folic acid system. The binding constants values (Ka) at 300 and 310 K are about 104 M−1. The standard enthalpy change (ΔH) and the standard entropy change (ΔS) were calculated to be ∼−20 kJ mol−1 and ∼16 J mol−1 K−1, respectively, which indicate characteristic electrostatic interactions between gHSA and folic acid. The CD studies showed that there are no significant conformational changes in the secondary structure of the protein. Moreover, the zeta potential measurements proved that under physiological conditions the gHSA–folic acid complex shows instability. No significant changes in the secondary structure of the protein and reversible drug binding are the desirable effect from pharmacological point of view. Communicated by Ramaswamy H. Sarma
Influenza vaccination and the ‘diversity paradox’

ABSTRACT The antigenic evolution of influenza is widely assumed to occur by antigenic drift, in which strains incrementally acquire mutations in highly variable epitopes under strong immune selective pressure, such as those in the major influenza antigen haemagglutinin. However, this is not easy to reconcile with epidemiological observations, which show that each influenza season is dominated by a limited number of strains. Here, we discuss this paradox in light of recent influenza epidemics that have been characterised by low vaccine effectiveness and dominated by strains of limited antigenic and genetic diversity.
Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity

Abstract The purpose of our study was to better understand the effects of mitochondrial-division inhibitor 1 (Mdivi-1) on mitochondrial fission, mitochondrial biogenesis, electron transport activities and cellular protection. In recent years, researchers have found excessive mitochondrial fragmentation and reduced fusion in a large number of diseases with mitochondrial dysfunction. Therefore, several groups have developed mitochondrial division inhibitors. Among these, Mdivi-1 was extensively studied and was found to reduce dynamin-related protein 1 (Drp1) levels and excessive mitochondrial fission, enhance mitochondrial fusion activity and protect cells. However, a recent study by Bordt et al. (1) questioned earlier findings of the beneficial, inhibiting effects of Mdivi-1. In the current study, we studied the protective effects of Mdivi-1 by studying the following: mRNA and protein levels of electron transport chain (ETC) genes; mitochondrial dynamics and biogenesis genes; enzymatic activities of ETC complexes I, II, III and IV; the mitochondrial network; mitochondrial size & number; Drp1 GTPase enzymatic activity and mitochondrial respiration (1) in N2a cells treated with Mdivi-1, (2) overexpressed with full-length Drp1 + Mdivi-1-treated N2a cells and (3) Drp1 RNA silenced+Mdivi-1-treated N2a cells. We found reduced levels of the fission genes Drp1 and Fis1 levels; increased levels of the fusion genes Mfn1, Mfn2 and Opa1; and the biogenesis genes PGC1α, nuclear respiration factor 1, nuclear respiratory factor 2 and transcription factor A, mitochondrial. Increased levels mRNA and protein levels were found in ETC genes of complexes I, II and IV genes. Immunoblotting data agreed with mRNA changes. Transmission electron microscopy analysis revealed reduced numbers of mitochondria and increased length of mitochondria (1) in N2a cells treated with Mdivi-1, (2) cells overexpressed with full-length Drp1 + Mdivi-1-treated N2a cells and (3) Drp1 RNA silenced+Mdivi-1-treated N2a cells. Immunofluorescence analysis revealed that mitochondrial network was increased. Increased levels of complex I, II and IV enzymatic activities were found in all three groups of cells treated with low concentration of Mdivi-1. Mitochondrial function was increased and GTPase Drp1 activity was decreased in all three groups of N2a cells. These observations strongly suggest that Mdivi-1 is a Drp1 inhibitor and directly reduces mitochondrial fragmentation and further, Mdivi-1 is a promising molecule to treat human diseases with ETC complexes, I, II and IV.
The truth squad.

Tilburg University in the Netherlands made headlines in 2011 when Diederik Stapel, a prominent psychologist and a dean, confessed to faking data for dozens of papers over 15 years. Since then, Tilburg has seen the birth of a metaresearch group that studies how scientists operate, and what can go wrong. Led by Marcel van Assen and Jelte Wicherts, they focus on questionable research practices, such as selective reporting of statistical tests, that help explain why many findings in psychology cannot be replicated. By scrutinizing the problems, metaresearchers aim to make science more rigorous and efficient. The Tilburg group became briefly notorious when it posted the results of an automated check for statistical mistakes on PubPeer, upsetting some scientists. They advocate for better practices, such as preregistering studies—declaring a plan for the research in advance, which can lessen the chance of dodgy analyses—and making the data behind research papers immediately available so others can check the findings. Ultimately, they and others say, the perverse incentives of careerist academia, to hoard data and sacrifice rigor for headline-generating findings, must be fixed.
Feature Extraction for Classification of Hyperspectral and LiDAR Data Using Patch-to-Patch CNN

Multisensor fusion is of great importance in Earth observation related applications. For instance, hyperspectral images (HSIs) provide wealthy spectral information while light detection and ranging (LiDAR) data provide elevation information, and using HSI and LiDAR data together can achieve better classification performance. In this paper, an unsupervised feature extraction framework, named as patch-to-patch convolutional neural network (PToP CNN), is proposed for collaborative classification of hyperspectral and LiDAR data. More specific, a three-tower PToP mapping is first developed to seek an accurate representation from HSI to LiDAR data, aiming at merging multiscale features between two different sources. Then, by integrating hidden layers of the designed PToP CNN, extracted features are expected to possess deeply fused characteristics. Accordingly, features from different hidden layers are concatenated into a stacked vector and fed into three fully connected layers. To verify the effectiveness of the proposed classification framework, experiments are executed on two benchmark remote sensing data sets. The experimental results demonstrate that the proposed method provides superior performance when compared with some state-of-the-art classifiers, such as two-branch CNN and context CNN.
Physical responses of professional soccer players during 4 vs. 4 small-sided games with mini-goals according to rule changes

The aim of this study was to investigate the influence of the number of ball touches authorised per game (one touch [T1], two touches [T2], and free touches [FT]) on the players’ physical responses throughout the bouts in 4 vs 4 soccer small-sided games (SSGs) with mini-goals (without a goalkeeper). Fourteen professional Polish players (age 23.2±2.7 years, height 177.9±6.1 cm, weight: 73.2±6.9 kg, body fat 12.6±2%, playing experience: 14±5 years) completed nine series of 4 vs 4 SSGs. Each trial included three series of SSGs with a game duration of 4 minutes on an equal sized pitch (30x24 m; 720 m2; individual occupied area per player=90 m2). Differences in physical responses and time-motion characteristics of players were measured with the Global Positioning System (GPS) and assessed using a repeated measures ANOVA to compare the three game conditions and the magnitude-based inference to evaluate the pairwise comparison effects. The results showed that only the variables distance covered at low speed, time walking, time at low speed, and accelerations of >4 m/s² were statistically significantly different among game conditions. The pairwise comparisons only identified significant effects for distance covered at low speed (between FT and T2), for time walking (between FT and T1), for time at moderate and low speed (between FT and T2), and for accelerations of >4 m/s² (between FT and T1). The players’ performances are affected by the ball touch constraint during SSGs with mini-goals. The results provide useful information for training and task design that replicate specific physical demands (i.e., accelerations of >4 m/s², time walking or running at a lower speed).
Is Postexercise Blood Flow Restriction a Viable Alternative to Other Resistance Exercise Protocols?

ABSTRACT Purpose: The purpose of this study was to identify whether post-resistance exercise (REx) blood flow restriction (BFR) can elicit a similar acute training stimulus to that offered by either heavy REx or traditional low-load BFR REx. Method: Ten men completed trials with 30% one-repetition maximum (1RM) for 5 sets of 15 repetitions without BFR (30%), with BFR during exercise (30% RD), and with postexercise BFR (30% RP) and at 75% 1RM for 3 sets of 10 repetitions. Lactate and cortisol were measured before and up to 60 min after exercise. Thigh circumference, ratings of perceived exertion (RPE), and pain were measured before and after exercise. Surface electromyography was measured during exercise. Results: All conditions had a large effect (effect size [ES] > 0.8) on lactate, with the largest effects observed with the 75% condition; no differences were observed between the 30% conditions. All conditions had a moderate effect (ES > 0.25 ≤ 0.4) on increasing thigh circumference. This effect was maintained (ES = 0.35) with the application of BFR after REx (30% RP). Change in RPE, from the first to last set, was significantly greater with 30% RD compared with other conditions (all p < .05). Electromyography amplitude was higher and percentage change was greater for the 75% condition compared with the other conditions (both p < .05). Conclusions: The application of BFR immediately post-REx altered several of the responses associated with REx that is aimed at inducing muscular hypertrophy. Additionally, these changes occurred with less pain and perceived exertion suggesting that this form of REx may offer an alternative, tolerable method of REx.
Enhancing Behavior Change Technique Coding Methods: Identifying Behavioral Targets and Delivery Styles in Smoking Cessation Trials.

BACKGROUND The behavior change technique (BCT) taxonomy v1 is often used in systematic reviews for identifying active components of interventions. Its utility could be enhanced by linking BCTs to specific target behaviors and qualifying BCT delivery style. PURPOSE To determine whether behavioral targets and delivery styles of BCTs can be coded reliably and to determine the utility of coding these characteristics. METHODS As part of a large systematic review of 142 smoking cessation trials, two researchers independently coded publicly and privately held intervention and comparator group materials, specifying the behavioral target (quitting, abstinence, medication adherence, or treatment engagement) and delivery style (tailored vs. not tailored; active participation vs. passive receipt) of each BCT. RESULTS Researchers coded 3,843 BCTs, which were reliably attributed to behavioral targets (AC1 = 0.92, PABAK = 0.91). Tailoring (AC1 = 0.80, PABAK = 0.74) and participation (AC1 = 0.71, PABAK = 0.64) were also coded reliably. There was considerable variability between groups in quitting and abstinence BCTs (ranges: 0-41; 0-18) and in tailoring and participation (ranges: 0-20; 0-32), but less variability for medication adherence and treatment engagement (ranges: 0-6; 0-7). CONCLUSIONS Behavioral targets and delivery styles of BCTs can be reliably identified and occur with sufficient frequency in smoking cessation trials for inclusion in quantitative syntheses (e.g., meta-regression analyses). Systematic reviewers could consider adopting these methods to evaluate the impact of intervention components targeting different behaviors, as well as the benefits of different BCT delivery styles.
Increased Expression of Maturation Promoting Factor Components Speeds Up Meiosis in Oocytes from Aged Females

The rate of chromosome segregation errors that emerge during meiosis I in the mammalian female germ line are known to increase with maternal age; however, little is known about the underlying molecular mechanism. The objective of this study was to analyze meiotic progression of mouse oocytes in relation to maternal age. Using the mouse as a model system, we analyzed the timing of nuclear envelope breakdown and the morphology of the nuclear lamina of oocytes obtained from young (2 months old) and aged females (12 months old). Oocytes obtained from older females display a significantly faster progression through meiosis I compared to the ones obtained from younger females. Furthermore, in oocytes from aged females, lamin A/C structures exhibit rapid phosphorylation and dissociation. Additionally, we also found an increased abundance of MPF components and increased translation of factors controlling translational activity in the oocytes of aged females. In conclusion, the elevated MPF activity observed in aged female oocytes affects precocious meiotic processes that can multifactorially contribute to chromosomal errors in meiosis I.
Uterine stem cells: from basic research to advanced cell therapies

BACKGROUND Stem cell research in the endometrium and myometrium from animal models and humans has led to the identification of endometrial/myometrial stem cells and their niches. This basic knowledge is beginning to be translated to clinical use for incurable uterine pathologies. Additionally, the implication of bone marrow-derived stem cells (BMDSCs) in uterine physiology has opened the field for the exploration of an exogenous and autologous source of stem cells. OBJECTIVE AND RATIONALE In this review, we outline the progress of endometrial and myometrial stem/progenitor cells in both human and mouse models from their characterization to their clinical application, indicating roles in Asherman syndrome, atrophic endometrium and tissue engineering, among others. SEARCH METHODS A comprehensive search of PubMed and Google Scholar up to December 2017 was conducted to identify peer-reviewed literature related to the contribution of bone marrow, endometrial and myometrial stem cells to potential physiological regeneration as well as their implications in pathologies of the human uterus. OUTCOMES The discovery and main characteristics of stem cells in the murine and human endometrium and myometrium are presented together with the relevance of their niches and cross-regulation. The current state of advanced stem cell therapy using BMDSCs in the treatment of Asherman syndrome and atrophic endometrium is analyzed. In the myometrium, the understanding of genetic and epigenetic defects that result in the development of tumor-initiating cells in the myometrial stem niche and thus contribute to the growth of uterine leiomyoma is also presented. Finally, recent advances in tissue engineering based on the creation of novel three-dimensional scaffolds or decellularisation open up new perspectives for the field of uterine transplantation. WIDER IMPLICATIONS More than a decade after their discovery, the knowledge of uterine stem cells and their niches is crystalising into novel therapeutic approaches aiming to treat with cells those conditions that cannot be cured with drugs, particularly the currently incurable uterine pathologies. Additional work and improvements are needed, but the basis has been formed for this therapeutic application of uterine cells.