Complementary Approaches Research Articles

TARGETING RESIDUAL CANCER FROM THE INVASIVE MARGIN OF GLIOBLASTOMA USING COMPUTATIONAL TOOLKITS

Abstract AIMS Infiltrative margin GBM, as a proxy for residual disease post-surgery, can be identified by 5-aminolevulininc acid (5ALA) to facilitate the discovery of uniquely expressed or upregulated molecular pathways. Complementary bioinformatics approaches offer reproducible ways to enable interoperability of heterogenous data sources towards identification of therapeutic targets associated with GBM infiltration. METHOD RNA-seq primary tumour data was first categorised as: 5ALA+ (infiltrative margin) vs tumour core and 5ALA+ vs 5ALA- (reactive brain). Two levels of filtration (genes with adjusted p-value <0.05; degree of fold change with log2>1.5) were applied to genes, creating two separate gene lists. Cross-referencing gene lists identified transcripts upregulated in both 5ALA+ vs core and 5ALA+ vs 5ALA-. This candidate gene list was inputted into STRING to generate an uncurated protein-protein interaction (PPI) network, which returned a significant PPI enrichment p-value to confirm network connectivity, and next inputted into Metascape to elucidate biological processes associated with tumour infiltration. RESULTS Of 141 upregulated 5ALA+ genes TCP10L3, HELT, MGAM, ALOX5 and FOXI1 exhibited the greatest fold change. The most prevalent 5ALA+ biological processes were primitive streak formation, disaccharide metabolic process and sodium ion transmembrane transport. LOC157273, LINC00200, LINC00656, LOC285626 and LINC01568 were identified as long non-coding RNAs (lncRNA) most abundant in the infiltrative margin of GBM relative to tumour core and reactive brain. Regulatory associations between candidate 5ALA+ lncRNA and genes, and in silico drug repurposing via molecular docking, are being investigated. CONCLUSION The plasticity of GBM warrants analysis of the GBM infiltrative margin via computational toolkits to enhance understanding of upregulated molecular pathways, functionally associated with an invasive phenotype.

How can ethology inform the neuroscience of fear, aggression and dominance?

The study of behaviour is dominated by two approaches. On the one hand, ethologists aim to understand how behaviour promotes adaptation to natural contexts. On the other, neuroscientists aim to understand the molecular, cellular, circuit and psychological origins of behaviour. These two complementary approaches must be combined to arrive at a full understanding of behaviour in its natural setting. However, methodological limitations have restricted most neuroscientific research to the study of how discrete sensory stimuli elicit simple behavioural responses under controlled laboratory conditions that are only distantly related to those encountered in real life. Fortunately, the recent advent of neural monitoring and manipulation tools adapted for use in freely behaving animals has enabled neuroscientists to incorporate naturalistic behaviours into their studies and to begin to consider ethological questions. Here, we examine the promises and pitfalls of this trend by describing how investigations of rodent fear, aggression and dominance behaviours are changing to take advantage of an ethological appreciation of behaviour. We lay out current impediments to this approach and propose a framework for the evolution of the field that will allow us to take maximal advantage of an ethological approach to neuroscience and to increase its relevance for understanding human behaviour.

HOW SHOULD HISTORIANS EMPATHIZE?

ABSTRACTReflecting on the ethical and unethical ways of empathizing is a necessary task for historians interested in the ethics of history. Research on empathy often classifies its various parts into affective, cognitive, and prosocial dimensions. However, in historical scholarship, the cognitive‐intellectual dimension of empathy is overemphasized to the detriment of its affective and prosocial dimensions, whose roles in determining the ways historians should practice history are often disregarded. In this article, I will discuss the relations between empathy and ethics and how historians should empathize. Doing so, I argue that empathy's ethical potential for historical scholarship needs to be de‐intellectualized by historical scholarship, a task that requires a complementary and supplementary approach to empathy that is in dialogue with moral philosophy, psychology, neurosciences, and animal studies. Only by recognizing empathy as a socially developed evolutionary capacity shared among humans and other species can historians fully develop its possibilities as a tool to guide human morality and ethical decision‐making. Finally, I will claim that empathy as an ethical imperative for an ethics of care and vulnerability should guide historians' ethics toward more responsive and responsible ways of relating with others across time, space, cultures, generations, species, and so on.

Surface-Modified Iron Oxide Nanoparticles with Natural Biopolymers for Magnetic Hyperthermia: Effect of Reducing Agents and Type of Biopolymers

Magnetic fluid hyperthermia, a minimally invasive localized therapy that uses heat generated by magnetic nanoparticles under an AC magnetic field, is a complementary approach for cancer treatment that is excellent due to its advantages of being noninvasive and addressing only the affected region. Still, its use as a stand-alone therapy is hindered by the simultaneous requirement of nanoparticle biocompatibility, good heating efficiency, and physiological safe dose. To overcome these limits, the biocompatible magnetic nanoparticles’ heating efficiency must be optimized. Iron oxide nanoparticles are accepted as the more biocompatible magnetic nanoparticles available. Therefore, in this work, superparamagnetic iron oxide nanoparticles were synthesized by a low-cost coprecipitation method and modified with starch and gum to increase their heating efficiency and compatibility with living tissues. Two different reducing agents, sodium hydroxide (NaOH) and ammonium hydroxide (NH4OH), were used to compare their influence. The X-ray diffraction results indicate the formation of a single magnetite/maghemite phase in all cases, with the particle size distribution depending on the coating and reducing agent. Citric acid functionalized water-based ferrofluids were also prepared to study the heating efficiency of the nanoparticles under a magnetic field with a 274 kHz frequency and a 14 kAm−1 amplitude. The samples prepared with NaOH display a higher specific loss power (SLP) compared to the ones prepared with NH4OH. The SLP value of 72 Wg−1 for the magnetic nanoparticles coated with a combination of starch and gum arabic, corresponding to an intrinsic loss power (ILP) of 2.60 nWg−1, indicates that they are potential materials for magnetic hyperthermia therapy.

Prezygotic barriers effectively limit hybridization in a rapid evolutionary radiation.

Hybridization is increasingly recognized as an important evolutionary process across the tree of life. In many clades, phylogenomic approaches have permitted unparalleled insight into the extent and frequency of hybridization. However, we continue to lack a deep understanding of the factors that limit and shape patterns of hybridization, especially in evolutionary radiations. In this study, we characterized patterns of introgression across Costus (Costaceae), a young evolutionary radiation of tropical understory plants that maintain widespread interfertility despite exhibiting strong prezygotic reproductive isolation. We analyzed a phylogenomic dataset of 756 genes from 54 Costus species using multiple complementary approaches - D-statistics, gene-tree-based tests, and phylogenetic network analyses - to detect and characterize introgression events throughout the evolutionary history of the radiation. Our results identified a moderate number of introgression events, including a particularly ancient, well-supported event spanning one of the deepest divergences in the clade. Most introgression events occurred between taxa or ancestral lineages that shared the same pollination syndrome (bee-pollinated or hummingbird-pollinated). These findings suggest that prezygotic barriers, including pollinator specialization, have been key to the balance between introgression and reproductive isolation in Costus.

A comprehensive review of natural compounds and their structure-activity relationship in Parkinson's disease: exploring potential mechanisms.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in the Substantia nigra region of the brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing the symptoms and progression of PD. Naturalcompounds have gained attention for their potential neuroprotective effects and ability to target various pathways involved in the pathogenesis of PD. This comprehensive review aims to provide an in-depth analysis of the molecular targets and mechanisms of natural compounds in various experimental models of PD. This review will also explore the structure-activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD.

Efficacy and safety of traditional Chinese medicine in managing bone loss post-endocrine therapy in hormone receptor-positive breast cancer patients.

This study aims to evaluate the efficacy and safety of traditional Chinese medicine (TCM) kidney-tonifying methods in treating bone loss and osteoporosis following endocrine therapy in patients with hormone receptor-positive breast cancer. This research systematically searched 6 major medical electronic databases, initially identifying 986 articles, ultimately including 22 randomized controlled trials. These studies encompassed a total of 1579 patients and investigated the impact of TCM kidney-tonifying methods on lumbar spine bone density, lumbar spine bone density T-values, femoral neck bone density, clinical efficacy, and drug safety. The Cochrane quality scoring system was utilized to assess the quality of the literature, and data were synthesized using meta-analysis techniques. TCM kidney-tonifying methods significantly improved lumbar spine bone density (standardized mean difference [SMD] = 0.70, 95% confidence interval [CI]: 0.43-0.97) and lumbar spine bone density T-values (SMD = 1.012, 95% CI: 0.506-1.517). There was also a positive trend in enhancing femoral neck bone density (SMD = 0.645, 95% CI: 0.321-0.970). Although improvements in clinical efficacy did not reach statistical significance (relative risk [RR] = 1.122, 95% CI: 0.933-1.348), the studies indicated good safety of the treatment, with most studies reporting no significant adverse reactions. TCM kidney-tonifying methods may have a positive therapeutic effect on bone loss and osteoporosis following endocrine therapy in patients with hormone receptor-positive breast cancer, demonstrating good tolerability and safety. Given the current evidence, it is recommended to include TCM kidney-tonifying methods as a complementary therapeutic approach in treatment protocols. Future research should further validate these findings and explore their application in different patient subgroups.

Isolation and purification of DNA double-strand break repair intermediates for understanding complex molecular mechanisms.

Branched DNA molecules are key intermediates in the molecular pathways of DNA replication, repair and recombination. Understanding their structural details, therefore, helps to envisage the mechanisms underlying these processes. While the configurations of DNA molecules can be effectively analysed in bulk using gel electrophoresis techniques, direct visualization provides a complementary single-molecule approach to investigating branched DNA structures. However, for microscopic examination, the sample needs to be free from impurities that could obscure the molecules of interest, and free from the bulk of unwanted non-specific DNA molecules that would otherwise dominate the field of view. Additionally, in the case of recombination intermediates, the length of the DNA molecules becomes an important factor to consider since the structures can be spread over a large distance on the chromosome in vivo. As a result, apart from sample purity, efficient isolation of large-sized DNA fragments without damaging their branched structures is crucial for further analysis. These factors are illustrated by the example of DNA double-strand break repair in the bacterium E. coli. In E. coli recombination intermediates may be spread over a distance of 40 kb which constitutes less than 1% of the 4.6 Mb genome. This study reveals ways to overcome some of the technical challenges that are associated with the isolation and purification of large and complex branched DNA structures using E. coli DNA double-strand break repair intermediates. High-molecular weight and branched DNA molecules do not run into agarose gels subjected to electrophoresis. However, they can be extracted from the wells of the gels if they are agarose embedded, by using β-agarase digestion, filtration, and concentration. Furthermore, a second round of gel electrophoresis followed by purification is recommended to enhance the purity of the specific DNA samples. These preliminary findings may prove to be pioneering for various single-molecule analyses of large and complex DNA molecules of DNA replication, repair and recombination.

Gene regulatory network inference from CRISPR perturbations in primary CD4+ T cells elucidates the genomic basis of immune disease

The effects of genetic variation on complex traits act mainly through changes in gene regulation. Although many genetic variants have been linked to target genes in cis, the trans-regulatory cascade mediating their effects remains largely uncharacterized. Mapping trans-regulators based on natural genetic variation has been challenging due to small effects, but experimental perturbations offer a complementary approach. Using CRISPR, we knocked out 84 genes in primary CD4+ Tcells, targeting inborn error of immunity (IEI) disease transcription factors (TFs) and TFs without immune disease association. We developed a novel gene network inference method called linear latent causal Bayes (LLCB) to estimate the network from perturbation data and observed 211 regulatory connections between genes. We characterized programs affected by the TFs, which we associated with immune genome-wide association study (GWAS) genes, finding that JAK-STAT family members are regulated by KMT2A, an epigenetic regulator. These analyses reveal the trans-regulatory cascades linking GWAS genes to signaling pathways.

Obesity Control and Supplementary Nutraceuticals as Cofactors of Brain Plasticity in Multiple Sclerosis Populations.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in the MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS can provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for the MS population.

Age-based scoring as a complementary approach to sustainable trophy hunting

Age-based scoring as a complementary approach to sustainable trophy hunting

Impact of complementary health approaches on opioid prescriptions among veterans with musculoskeletal disorders – A retrospective cohort study

To examine whether complementary and integrative health approaches mitigate opioid prescriptions for pain and whether the relationship differs by post-dramatic stress disorder (PTSD) diagnosis, we followed 1,993,455 Veterans with musculoskeletal disorders during 2005–2017 using Veterans Healthcare Administration electronic health records. Complementary and integrative health (CIH) approaches were defined as ≥ 1 primary care visits for meditation, Yoga, and acupuncture etc using natural language processing. Opioid prescriptions were ascertained from pharmacy dispensing records. A propensity score was estimated and used to match one control Veteran to each CIH recipient. Over the 2-year follow-up period after the index diagnosis, 140,902 (7.1 %) Veterans received ≥ 1 modalities. Among the matched analytic sample (272,296 Veterans), the likelihood of dispensing opioid prescriptions was significantly lower for Veterans in the CIH group than their controls [adjusted hazard ratio (aHR), 0.45 (95 % Confidence Intervals (CI): 0.44–0.46)]. The association did not differ between Veterans with [aHR: 0.46 (95 % CI: 0.45–0.47)] and without [aHR: 0.44 (95 % CI: 0.43–0.45)] PTSD. In sensitivity analyses, the exposure group had 3.82 (95 % CI: 3.76–3.87) months longer restricted mean survival time to opioid initiation, 2 % (95 % CI: 4 %–1 %) lower morphine equivalent and 17 % lower total days’ supply (95 % CI: 18 %–16 %). The relationship remains significant but was attenuated after eliminating waiting time for the exposure group (aHR, 0.63 (95 % CI: 0.62–0.64)). These observations suggest that CIH approaches may help reduce opioid prescriptions for Veterans with musculoskeletal disorders and related pain. The impact of the timing of receiving such approaches warrants further investigation. PerspectiveThis article presents a quasi-experimental investigation into potential benefit of complementary and integrative health approaches (CIH) on de-prescribing opioids. The findings may potentially help clinicians who are seeking non-pharmacological alternative options to manage patient pain and opioid dependence”.

Parent-reported offering of allergen foods to infants during complementary feeding: An observational study of New Zealand infants

The prevalence of food allergies in New Zealand infants is uncertain but is believed to be similar to Australia, exceeding 10%. Current recommendations for reducing food allergy risk are to offer all major food allergens to infants from as early as six months of age (start of complementary feeding), and before 12 months of age. However, little is known regarding parental practices around introducing major food allergens. This study aimed to explore parental offering of major food allergens to infants during complementary feeding, and parent-reported food allergies. The cross-sectional study is a secondary analysis of the multi-centre (Auckland and Dunedin) First Foods New Zealand study of 625 parent-infant dyads. Participants were recruited in 2020–2022 when infants were 7–10 months of age. Questionnaires assessed sociodemographic characteristics, complementary feeding approach, infant pouch use and parental responses to five food allergy questions. All major food allergens had been offered to only 17% of infants by 9–10 months of age. Having offered egg, peanut, tree nuts, sesame, soy and seafood was more commonly associated with using a baby-led complementary feeding approach than a parent-led approach (p < 0.001). Frequent baby food pouch use was associated with a lower likelihood of offering egg and peanut (both p < 0.001). Overall, 12.6% of infants had a reported food allergy, with symptomatic response after exposure being the most common diagnostic tool. Most infants are not offered all major food allergens during early complementary feeding, with some parents actively avoiding major food allergens in the first year of life. These results provide up-to-date knowledge of parental practices, highlighting the need for more targeted advice and strategies to improve parental engagement with allergy prevention and diagnosis.

Training of Awareness in ADHD: Leveraging Metacognition.

Attention deficit hyperactivity disorder (ADHD) is a disorder that is prevalent in children and adults, with significant impact on life outcomes. Common treatment strategies include a combination of pharmacological and psychosocial interventions which have recognized limits to their effectiveness. Consequently, there exists interest in additional non-pharmacological interventions. In the current minireview we aim to complement existing surveys by focusing on a complementary approach, namely rooted in metacognition or the training of awareness. We review programs that incorporate metacognitive training of awareness in skill-training, psychosocial interventions, and mindfulness, and discuss existing assessments of metacognitive ability in ADHD. Existing data suggest that metacognitive approaches have potential in supporting symptom management in ADHD, with gains in objective assessments in near and far transfer tasks in educational research and high satisfaction from parents. Further research is warranted in assessment of the relative contribution of metacognitive elements relative to other treatment components, objective assessments of outcomes in psychosocial interventions, and efficacy in adult interventions.

Impaired 11β-hydroxysteroid dehydrogenase type 2 activity in kidney disease disrupts 11-oxygenated androgen biosynthesis.

11-oxygenated androgens are a group of adrenal-derived steroids that require peripheral activation. In vitro data highlight a putative role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione (11OHA4) to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone (11KT). As the kidney is the major site of HSD11B2 expression, we hypothesized that patients with chronic kidney disease (CKD) would have reduced 11-oxygenated androgen biosynthesis due to impaired HSD11B2 activity. To determine the role of HSD11B2 in 11-oxygenated androgen biosynthesis using a human CKD cohort alongside complementary cell culture and computational modeling approaches. Cross-sectional observational study of patients with CKD (n=85) and healthy controls (n=46) measuring serum and urinary concentrations of glucocorticoids, classic and 11-oxygenated androgens by liquid chromatography-tandem mass spectrometry. A computational model of peripheral 11-oxygenated androgen biosynthesis was fitted to the serum data to calculate relative HSD11B2 expression levels for each participant. HSD11B2 activity declined with eGFR, evidenced by higher cortisol (F)/cortisone (E) ratios in CKD patients compared to controls (p<0.0001). Serum concentrations of E, 11KA4, 11KT and 11β-hydroxytestosterone were lower in patients with CKD compared to controls (p<0.0001 for each). A computational model based on enzyme kinetic parameters of HSD11B2, 11β-hydroxysteroid dehydrogenase type 1, 17β-hydroxysteroid dehydrogenase type 2 and aldo-keto reductase 1C3 confirmed HSD11B2 as the key enzyme responsible for reduced 11-oxygenated androgen biosynthesis in CKD. Predicted HSD11B2 expression correlated with eGFR. This is the first in vivo study to confirm a central role for renal HSD11B2 in 11-oxygenated androgen biosynthesis. Determining the clinical implications of this observation for patients with CKD requires further research.

Association between loneliness, social isolation, and frailty: A two-sample Mendelian randomization

Abstract Objective: This study aimed to examine the causal relationship between loneliness, social isolation, and frailty using Mendelian Randomization (MR) analysis. Methods: Data were obtained from a large-scale genome-wide association study (GWAS) of a European-descent population. Variables included frailty index (FI), two loneliness variables (Feeling lonely, able to confide), and three social isolation variables (Frequency of friend/family visits, number in household, no leisure/social activities).The inverse variance weighting (IVW) method was set as the primary MR analysis, with MR-Egger and weighted median methods employed as complementary approaches. Cochran’s Q test, the MR-Egger intercept test, and MR-PRESSO methods were used to evaluate the robustness of MR results. Bonferroni corrected P values &lt;0.01 were considered statistically significant. Results: Genetic predisposition to feeling lonely (IVW: odds ratio [OR]=1.47; 95% confidence interval [CI]=1.34 to 1.60; P&lt;0.001) and no leisure or social activities (IVW: OR=1.78; 95% CI=1.50 to 2.11; P&lt;0.001) were significantly associated with increased FI. In addition, the genetically predicted ability to confide was positively associated with decreased FI (IVW: OR=0.91; 95% CI=0.87 to 0.95; P&lt;0.001). There was no statistically significant causal association between the number in the household, frequency of friend/family visits, and the risk of frailty. Conclusion: This MR study provides evidence of the causal relationship between loneliness, social isolation, and frailty from a genetic perspective and highlights the importance of decreasing social isolation in the development of frailty prevention and intervention programs.

Clonality Determination by Detecting Unmodified Monoclonal Serum Free Light Chains Using On-Probe Extraction Coupled with Liquid Chromatography-High-Resolution Mass Spectrometry.

Serum free light chains (FLCs) are an essential clinical biomarker for the diagnosis and monitoring of patients with plasma cell neoplasms. The current widely used immunoassay methods quantify total serum FLCs, which include monoclonal FLCs as well as FLCs in the polyclonal background. Patients with chronic diseases, inflammatory disorders, or renal dysfunction can have elevated total FLCs that lead to ambiguous results. These patients may benefit from a direct measurement of monoclonal FLCs. The purpose of this study was to develop a method that couples on-probe extraction (OPEX) with liquid chromatography-high-resolution mass spectrometry (LC-HR-MS), abbreviated to OPEX-MS, to directly determine the clonality of FLCs. OPEX immunocapture was performed using microprobes loaded with anti-kappa or anti-lambda light chain antibodies. Captured proteins were separated by reversed-phase LC and analyzed by HR-MS. Four cohorts of samples from unique patients were tested based on immunoassay FLC results. The LC-HR-MS analysis in the OPEX-MS method provides both a unique retention time along with deconvoluted masses of FLC monomers and dimers for each clone. The study found that 16 out of 49 (33%) kappa FLC elevated samples as well as 83 out of 100 (83%) dual kappa and lambda FLC elevated samples did not have monoclonal FLCs, which is consistent with the knowledge that there is often no clonal population in samples with mildly elevated FLC immunoassay results. The OPEX-MS method can serve as a complementary approach to directly determine clonality in patients with difficult-to-interpret FLC immunoassay results.

Complementary and integrative medicine in cancer-related fatigue

The majority of cancer patients experience fatigue during the course of their illness. Fatigue should not be seen as an inevitable consequence of cancer and its treatment. Cancer-related fatigue (CRF) is amultidimensional symptom complex that is influenced by avariety of factors. Complementary medicine approaches offer potentially promising strategies to address this fatigue and can therefore be avaluable addition to conventional therapies.In this narrative review, complementary medicine treatment approaches for tumor-associated fatigue are presented according to the historical development and current scientific evidence. The focus is on methods with the highest current evidence based on the recommendations of national and international guidelines. Therapeutic approaches from mind-body medicine, such as mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), yoga, tai chi, and qigong, as well as acupuncture, acupressure, moxibustion, and phytotherapeutic treatment approaches are presented.In Germany, the complementary therapies listed here are not generally covered by health insurances. However, afew clinics have developed comprehensive programs in mind-body medicine, for which cost coverage has already been obtained. As aresult, complementary medical treatments for cancer-related fatigue that adhere to national and international guidelines are typically available only as private services or within the framework of study participation.

Role of Membrane Estrogen Receptor Alpha on the Positive Feedback of Estrogens on Kisspeptin and GnRH Neurons.

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling to the central regulation of reproduction is unclear. To address this question, two complementary approaches were used: estetrol (E4) a natural estrogen acting as an agonist of nuclear ERs, but as an antagonist of their membrane fraction, and the C451A-ERα mouse lacking mERα. E4 dose- dependently blocks ovulation in female rats, but the central mechanism underlying this effect is unknown. To determine whether E4 acts centrally to control ovulation, its effect was tested on the positive feedback of estradiol (E2) on neural circuits underlying luteinizing hormone (LH) secretion. In ovariectomized females chronically exposed to a low dose of E2, estradiol benzoate (EB) alone or combined with progesterone (P) induced an increase in the number of kisspeptin (Kp) and gonadotropin-releasing hormone (GnRH) neurons coexpressing Fos, a marker of neuronal activation. E4 blocked these effects of EB, but not when combined to P. These results indicate that E4 blocked the central induction of the positive feedback in the absence of P, suggesting an antagonistic effect of E4 on mERα in the brain as shown in peripheral tissues. In parallel, as opposed to wild-type females, C451A-ERα females did not show the activation of Kp and GnRH neurons in response to EB unless they are treated with P. Together these effects support a role for membrane-initiated estrogen signaling in the activation of the circuit mediating the LH surge.

MRI at low field: A review of software solutions for improving SNR.

Low magnetic field magnetic resonance imaging (MRI) ( <1T) is regaining interest in the magnetic resonance (MR) community as a complementary, more flexible, and cost-effective approach to MRI diagnosis. Yet, the impaired signal-to-noise ratio (SNR) per square root of time, or SNR efficiency, leading in turn to prolonged acquisition times, still challenges its relevance at the clinical level. To address this, researchers investigate various hardware and software solutions to improve SNR efficiency at low field, including the leveraging of latest advances in computing hardware. However, there may not be a single recipe for improving SNR at low field, and it is key to embrace the challenges and limitations of each proposed solution. In other words, suitable solutions depend on the final objective or application envisioned for a low-field scanner and, more importantly, on the characteristics of a specific low field. In this review, we aim to provide an overview on software solutions to improve SNR efficiency at low field. First, we cover techniques for efficient k-space sampling and reconstruction. Then, we present post-acquisition techniques that enhance MR images such as denoising and super-resolution. In addition, we summarize recently introduced electromagnetic interference cancellation approaches showing great promises when operating in shielding-free environments. Finally, we discuss the advantages and limitations of these approaches that could provide directions for future applications.