deepPGSegNet: MRI-based pituitary gland segmentation using deep learning.

Introduction: In clinical research on pituitary disorders, pituitary gland (PG) segmentation plays a pivotal role, which impacts the diagnosis and treatment of conditions such as endocrine dysfunctions and visual impairments. Manual segmentation, which is the traditional method, is tedious and susceptible to inter-observer differences. Thus, this study introduces an automated solution, utilizing deep learning, for PG segmentation from magnetic resonance imaging (MRI). Methods: A total of 153 university students were enrolled, and their MRI images were used to build a training dataset and ground truth data through manual segmentation of the PGs. A model was trained employing data augmentation and a three-dimensional U-Net architecture with a five-fold cross-validation. A predefined field of view was applied to highlight the PG region to optimize memory usage. The model's performance was tested on an independent dataset. The model's performance was tested on an independent dataset for evaluating accuracy, precision, recall, and an F1 score. Results and discussion: The model achieved a training accuracy, precision, recall, and an F1 score of 92.7%, 0.87, 0.91, and 0.89, respectively. Moreover, the study explored the relationship between PG morphology and age using the model. The results indicated a significant association between PG volume and midsagittal area with age. These findings suggest that a precise volumetric PG analysis through an automated segmentation can greatly enhance diagnostic accuracy and surveillance of pituitary disorders.

Impact of Homocysteine as a Preconceptional Screening Factor for In Vitro Fertilization and Prevention of Miscarriage with Folic Acid Supplementation Following Frozen-Thawed Embryo Transfer: A Hospital-Based Retrospective Cohort Study.

Homocysteine is an amino acid naturally produced in the body and metabolized via the methionine cycle. High homocysteine levels can increase the risk of infertility and pregnancy complications, such as preeclampsia, preterm delivery, miscarriage, and low birth weight. Preconceptional homocysteine levels may be reduced by taking folic acid supplements to reduce the risk of such complications. This cross-sectional, hospital-based study was conducted to examine the role of homocysteine in 1060 infertile women with a history of IVF/intracytoplasmic sperm injection (ICSI) failure. We analyzed whether folic acid intervention altered homocysteine levels and influenced reproductive outcome. We found that a higher homocysteine level was statistically associated with a lower fertilization rate in patients with a history of IVF/ICSI failure. There was an inverse relationship between homocysteine levels and serum 25(OH)VD, and a trend towards lower anti mullerian hormone in the group with higher homocysteine levels. This is the first interventional study to identify that folic acid supplementation improved pregnancy outcomes following freeze embryo transfer (FET) in women with a history of FET failure by monitoring the reduction in homocysteine levels. Therefore, folic acid supplementation and homocysteine level monitoring may constitute a novel intervention for improving IVF/ICSI pregnancy outcomes.

DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians.

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer's and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer's disease.

Involvement of the intrinsic functional network of the red nucleus in complex behavioral processing.

Previous studies suggested the possibility that the red nucleus (RN) is involved in other cognitive functions than motion per se, even though such functions have yet to be clarified. We investigated the activation of RN during several tasks and its intrinsic functional network associated with social cognition and musical practice. The tasks included finger tapping, n-back, and memory recall tasks. Region of interest for RN was identified through those tasks, anatomical information of RN, and a brain atlas. The intrinsic functional network was identified for RN by an analysis of connectivity between RN and other regions typically involved in seven known resting state functional networks with RN used as the seed region. Association of the RN network with a psychological trait of the interpersonal reactivity index and musical training years revealed subnetworks that included empathy related regions or music practice related regions. These social or highly coordinated motor activity represent the most complex functions ever known to involve the RN, adding further evidence for the multifunctional roles of RN. These discoveries may lead to a new direction of investigations to clarify probable novel roles for RN in high-level human behavior.

MicroRNAs secreted by human preimplantation embryos and IVF outcome.

OBJECTIVE: To generate an effective embryo prediction model and identify a non-invasive evaluation method by analyzing microRNAs (miRNAs) in embryo culture medium. DESIGN: Analysis of microRNA profiles from spent culture medium of blastocysts with good morphology that did or did not result in pregnancy. SETTING: Clinical and experimental research. PATIENTS: Sixty patients who underwent thawed embryo transfer of blastocysts after intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association of miRNA abundance levels secreted by blastocysts in culture medium and implantation success. RESULTS: Our RNA sequencing analysis found a total of 53 differentially expressed miRNAs in the culture media of pregnancy and non-pregnancy groups. Twenty-one miRNAs were analyzed for their potential to predict implantation success. Eight miRNAs (hsa-miR-191-5p, hsa-miR-320a, hsa-miR-92a-3p, hsa-miR-509-3p, hsa-miR-378a-3p, hsa-miR-28-3p, hsa-miR-512-5p, and hsa-miR-181a-5p) were further extracted from the results of a logistic regression analysis of qPCR Ct values. A prediction model for high-quality blastocysts was generated using the eight miRNAs, with an average accuracy of 0.82 by 5-fold cross validation. CONCLUSION: We isolated blastocyst miRNAs that may predict implantation success and created a model to predict viable embryos. Increasing the number of investigated cases and further studying the effect of each miRNA on embryonic development is needed to refine the miRNA-based predictive model.

Effects of Physiological Signal Removal on Resting-State Functional MRI Metrics.

Resting-state fMRIs (rs-fMRIs) have been widely used for investigation of diverse brain functions, including brain cognition. The rs-fMRI has easily elucidated rs-fMRI metrics, such as the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity (VMHC), and degree centrality (DC). To increase the applicability of these metrics, higher reliability is required by reducing confounders that are not related to the functional connectivity signal. Many previous studies already demonstrated the effects of physiological artifact removal from rs-fMRI data, but few have evaluated the effect on rs-fMRI metrics. In this study, we examined the effect of physiological noise correction on the most common rs-fMRI metrics. We calculated the intraclass correlation coefficient of repeated measurements on parcellated brain areas by applying physiological noise correction based on the RETROICOR method. Then, we evaluated the correction effect for five rs-fMRI metrics for the whole brain: FC, fALFF, ReHo, VMHC, and DC. The correction effect depended not only on the brain region, but also on the metric. Among the five metrics, the reliability in terms of the mean value of all ROIs was significantly improved for FC, but it deteriorated for fALFF, with no significant differences for ReHo, VMHC, and DC. Therefore, the decision on whether to perform the physiological correction should be based on the type of metric used.

Brain Plasticity Reflects Specialized Cognitive Development Induced by Musical Training.

Learning a musical instrument requires a long period of training and might induce structural and functional changes in the brain. Previous studies have shown brain plasticity resulting from training with a musical instrument. However, these studies did not distinguish the effects on brain plasticity of specific musical instruments as they examined the brain of musicians who had learned a single musical instrument/genre and did not control for confounding factors, such as common or interactive effects involved in music training. To address this research gap, the present work investigated musicians who had experience with both a piano and a wind instrument, for example, flute, trumpet, clarinet etc. By examining the difference between the 2 musical instruments in the same subject, we avoided the effects common to all musical instruments and the confounding factors. Therefore, we identified several high-tier brain areas displaying a brain plasticity specific to each musical instrument. Our findings show that learning a musical instrument might result in the development of high cognitive functions reflecting the skills/abilities unique to the instrument played.

Measurement of ultra-fast signal progression related to face processing by 7T fMRI.

Given that the brain is a dynamic system, the temporal characteristics of brain function are important. Previous functional magnetic resonance imaging (fMRI) studies have attempted to overcome the limitations of temporal resolution to investigate dynamic states of brain activity. However, finding an fMRI method with sufficient temporal resolution to keep up with the progress of neuronal signals in the brain is challenging. This study aimed to detect between-hemisphere signal progression, occurring on a timescale of tens of milliseconds, in the ventral brain regions involved in face processing. To this end, we devised an inter-stimulus interval (ISI) stimulation scheme and used a 7T MRI system to obtain fMRI signals with a high signal-to-noise ratio. We conducted two experiments: one to measure signal suppression depending on the ISI and another to measure the relationship between the amount of suppression and the ISI. These two experiments enabled us to measure the signal transfer time from a brain region in the ventral visual stream to its counterpart in the opposite hemisphere through the corpus callosum. These findings demonstrate the feasibility of using fMRI to measure ultra-fast signals (tens of milliseconds) and could facilitate the elucidation of further aspects of dynamic brain function.

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence.

Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies in older women result in higher rates of miscarriage with aneuploidy. Age-related decline in fertility is strongly attributed to ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes. In this review, we discuss the underlying mechanisms of age-related decline in oocyte quality, focusing on oxidative stress (OS) in oocytes. The primary cause is the accumulation of spontaneous damage to the mitochondria arising from increased reactive oxygen species (ROS) in oocytes, generated by the mitochondria themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis and influences the meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a decline in the fidelity of the protective mechanisms against ROS, namely the ROS-scavenging metabolism, repair of ROS-damaged DNA, and the proteasome and autophagy system for ROS-damaged proteins. Accordingly, increased ROS and increased vulnerability of oocytes to ROS lead to spindle instability, chromosomal abnormalities, telomere shortening, and reduced developmental competence of aged oocytes.

Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.

Zygotic genome activation (ZGA) begins after fertilization and is essential for establishing pluripotency and genome stability. However, it is unclear how ZGA genes prevent mitotic errors. Here we show that knockout of the ZGA gene Zscan5b, which encodes a SCAN domain with C2H2 zinc fingers, causes a high incidence of chromosomal abnormalities in embryonic stem cells (ESCs), and leads to the development of early-stage cancers. After irradiation, Zscan5b-deficient ESCs displayed significantly increased levels of γ-H2AX despite increased expression of the DNA repair genes Rad51l3 and Bard. Re-expression of Zscan5b reduced γ-H2AX content, implying a role for Zscan5b in DNA damage repair processes. A co-immunoprecipitation analysis showed that Zscan5b bound to the linker histone H1, suggesting that Zscan5b may protect chromosomal architecture. Our report demonstrates that the ZGA gene Zscan5b is involved in genomic integrity and acts to promote DNA damage repair and regulate chromatin dynamics during mitosis.

Selected Topics Relating to Functional MRI Study of the Brain.

The authors selected some interesting current topics among many in the field of functional MRI (fMRI) of the brain. The selection was based on authours' immediate interests in exploring these aspects further; the topics are presented and discussed along with their perspectives. If progress can be made in these areas, it would be very advantageous to the field of brain research. The topics are (I) Detectable MRI signals in response to functional activity of the brain, including the current status of neurocurrent MRI; (II) Vascular-dependent and vascular-independent MRI signals, leading to the distinction of functional and structural MRI; (III) Functional specificity and functional connectivity of local sites, including differences between task-fMRI and resting state fMRI; (IV) Functional networks: an example of application to assessing the vocational aptitude test by fMRI; (V) Neural oscillation relevant to the formation of fMRI signals and of networks; (VI) Upgrading fMRI to "information-content-reflecting" fMRI, discussed as one of the prospects of near-future fMRI.

Identification of biologically active δ-lactone eicosanoids as paraoxonase substrates.

The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities. However, their physiological function(s) and native substrates are uncertain. Previous structure-activity relationship studies demonstrate that PONs have a high specificity for lipophilic lactones, suggesting that such compounds may be representative of native substrates. This report describes the ability of PONs to hydrolyze two bioactive δ-lactones derived from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and cyclo-epoxycyclopentenone (cyclo-EC). Both lactones were very efficiently hydrolyzed by purified PON3. PON1 efficiently hydrolyzed 5,6-DHTL, but with a specific activity about 15-fold lower than PON3. 5,6-DHTL was a poor substrate for PON2. Cyclo-EC was a poor substrate for PON1 and not hydrolyzed by PON2. Studies with the PON inhibitor EDTA and a serine esterase inhibitor indicated that the PONs are the main contributors to hydrolysis of the lactones in human and mouse liver homogenates. Studies with homogenates from PON3 knockout mouse livers indicated that >80% of the 5,6-DHTL and cyclo-EC lactonase activities were attributed to PON3. The findings provide further insight into the structural requirements for PONs substrates and support the hypothesis that PONs, particularly PON1 and PON3, evolved to hydrolyze and regulate a class of lactone lipid mediators derived from polyunsaturated fatty acids.

Synthesis and Structure-Activity Relationship Studies of Anti-Inflammatory Epoxyisoprostane Analogues.

The lactone derivative of the epoxyisoprostane EC is a highly effective inhibitor of the secretion of the proinflammatory cytokine IL-6. Herein, a modular synthesis of analogues is described, allowing flexible variations of the cyclic side chain of the parent lactone. A structure-activity relationship study identified a lactam analogue that retains the high activity. Furthermore, the exocyclic allylic alcohol was shown to be crucial for the observed effect.

Estimation of vocational aptitudes using functional brain networks.

The success of human life in modern society is highly dependent on occupation. Therefore, it is very important for people to identify and develop a career plan that best suits their aptitude. Traditional test batteries for vocational aptitudes are not oriented to measure developmental changes in job suitability because repeated measurements can introduce bias as the content of the test batteries is learned. In this study, we attempted to objectively assess vocational aptitudes by measuring functional brain networks and identified functional brain networks that intrinsically represented vocational aptitudes for 19 job divisions in a General Aptitude Test Battery. In addition, we derived classifiers based on these networks to predict the aptitudes of our test participants for each job division. Our results suggest that the measurement of brain function can indeed yield an objective evaluation of vocational aptitudes; this technique will enable a person to follow changes in one's job suitability with additional training or learning, paving a new way to advise people on career development.

Benzyl isothiocyanate attenuates the hydrogen peroxide-induced interleukin-13 expression through glutathione S-transferase P induction in T lymphocytic leukemia cells.

We investigated the effect of benzyl isothiocyanate (BITC) on the hydrogen peroxide-induced gene expression of a T-helper-2 cytokine, interleukin (IL)-13, in T lymphocytic leukemia Jurkat cells. The 24-h pretreatment of BITC significantly inhibited the IL-13 expression enhanced by hydrogen peroxide. Although the BITC pretreatment did not change the enhanced level of the phosphorylated c-Jun N-terminal kinase (JNK), it significantly inhibited the nuclear translocation of c-Jun induced by hydrogen peroxide. BITC also increased the protein expression of glutathione S-transferase (GST) isozymes, GSTP1/2, as well as the total GST activity. A GSTP1/2-specific inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly counteracted the inhibitory effect of BITC on the hydrogen peroxide-enhanced IL-13 upregulation as well as the c-Jun nuclear translocation. Taken together, these results suggested that BITC inhibits the oxidative stress-mediated IL-13 mRNA expression, possibly through interference of the c-Jun phosphorylation by GSTP.

A Set of Functional Brain Networks for the Comprehensive Evaluation of Human Characteristics.

Many human characteristics must be evaluated to comprehensively understand an individual, and measurements of the corresponding cognition/behavior are required. Brain imaging by functional MRI (fMRI) has been widely used to examine brain function related to human cognition/behavior. However, few aspects of cognition/behavior of individuals or experimental groups can be examined through task-based fMRI. Recently, resting state fMRI (rs-fMRI) signals have been shown to represent functional infrastructure in the brain that is highly involved in processing information related to cognition/behavior. Using rs-fMRI may allow diverse information about the brain through a single MRI scan to be obtained, as rs-fMRI does not require stimulus tasks. In this study, we attempted to identify a set of functional networks representing cognition/behavior that are related to a wide variety of human characteristics and to evaluate these characteristics using rs-fMRI data. If possible, these findings would support the potential of rs-fMRI to provide diverse information about the brain. We used resting-state fMRI and a set of 130 psychometric parameters that cover most human characteristics, including those related to intelligence and emotional quotients and social ability/skill. We identified 163 brain regions by VBM analysis using regression analysis with 130 psychometric parameters. Next, using a 163 × 163 correlation matrix, we identified functional networks related to 111 of the 130 psychometric parameters. Finally, we made an 8-class support vector machine classifiers corresponding to these 111 functional networks. Our results demonstrate that rs-fMRI signals contain intrinsic information about brain function related to cognition/behaviors and that this set of 111 networks/classifiers can be used to comprehensively evaluate human characteristics.

Attitude and practice of physical activity and social problem-solving ability among university students.

BACKGROUND: Effective social problem-solving abilities can contribute to decreased risk of poor mental health. In addition, physical activity has a favorable effect on mental health. These previous studies suggest that physical activity and social problem-solving ability can interact by helping to sustain mental health. The present study aimed to determine the association between attitude and practice of physical activity and social problem-solving ability among university students. METHODS: Information on physical activity and social problem-solving was collected using a self-administered questionnaire. We analyzed data from 185 students who participated in the questionnaire surveys and psychological tests. Social problem-solving as measured by the Social Problem-Solving Inventory-Revised (SPSI-R) (median score 10.85) was the dependent variable. Multiple logistic regression analysis was employed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for higher SPSI-R according to physical activity categories. RESULTS: The multiple logistic regression analysis indicated that the ORs (95% CI) in reference to participants who said they never considered exercising were 2.08 (0.69-6.93), 1.62 (0.55-5.26), 2.78 (0.86-9.77), and 6.23 (1.81-23.97) for participants who did not exercise but intended to start, tried to exercise but did not, exercised but not regularly, and exercised regularly, respectively. This finding suggested that positive linear association between physical activity and social problem-solving ability (p value for linear trend < 0.01). CONCLUSIONS: The present findings suggest that regular physical activity or intention to start physical activity may be an effective strategy to improve social problem-solving ability.

Steady-state and dynamic network modes for perceptual expectation.

Perceptual expectation can attenuate repetition suppression, the stimulus-induced neuronal response generated by repeated stimulation, suggesting that repetition suppression is a top-down modulatory phenomenon. However, it is still unclear which high-level brain areas are involved and how they interact with low-level brain areas. Further, the temporal range over which perceptual expectation can effectively attenuate repetition suppression effects remains unclear. To elucidate the details of this top-down modulatory process, we used two short and long inter-stimulus intervals for a perceptual expectation paradigm of paired stimulation. We found that top-down modulation enhanced the response to the unexpected stimulus when repetition suppression was weak and that the effect disappeared at 1,000 ms prior to stimulus exposure. The high-level areas involved in this process included the left inferior frontal gyrus (IFG_L) and left parietal lobule (IPL_L). We also found two systems providing modulatory input to the right fusiform face area (FFA_R): one from IFG_L and the other from IPL_L. Most importantly, we identified two states of networks through which perceptual expectation modulates sensory responses: one is a dynamic state and the other is a steady state. Our results provide the first functional magnetic resonance imaging (fMRI) evidence of temporally nested networks in brain processing.

Structural optimization and structure-functional selectivity relationship studies of G protein-biased EP2 receptor agonists.

The modification of the novel G protein-biased EP2 agonist 1 has been investigated to improve its G protein activity and develop a better understanding of its structure-functional selectivity relationship (SFSR). The optimization of the substituents on the phenyl ring of 1, followed by the inversion of the hydroxyl group on the cyclopentane moiety led to compound 9, which showed a 100-fold increase in its G protein activity compared with 1 without any increase in ß-arrestin recruitment. Furthermore, SFSR studies revealed that the combination of meta and para substituents on the phenyl moiety was crucial to the functional selectivity.

Discovery of G Protein-Biased EP2 Receptor Agonists.

To identify G protein-biased and highly subtype-selective EP2 receptor agonists, a series of bicyclic prostaglandin analogues were designed and synthesized. Structural hybridization of EP2/4 dual agonist 5 and prostacyclin analogue 6, followed by simplification of the ω chain enabled us to discover novel EP2 agonists with a unique prostacyclin-like scaffold. Further optimization of the ω chain was performed to improve EP2 agonist activity and subtype selectivity. Phenoxy derivative 18a showed potent agonist activity and excellent subtype selectivity. Furthermore, a series of compounds were identified as G protein-biased EP2 receptor agonists. These are the first examples of biased ligands of prostanoid receptors.