Imaging/Microscopy

Oncotarget

Oncotarget published this trending research paper in Volume 12, Issue 25, entitled, "Radiomics in predicting recurrence for patients with locally advanced breast cancer using quantitative ultrasound" by researchers from the Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Physical Sciences, Sunnybrook Research Institute, Toronto, Canada; Department of Medical Oncology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada; Department of Surgical Oncology, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Department of Electrical Engineering and Computer Sciences, Lassonde School of Engineering, York University, Toronto, Canada; Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Medical Imaging, University of Toronto, Toronto, Canada; Department of Physics, Ryerson University, Toronto, Canada.

Abstract:
Background: The purpose of the study was to investigate the role of pre-treatment quantitative ultrasound (QUS)-radiomics in predicting recurrence for patients with locally advanced breast cancer (LABC).

Materials and Methods: A prospective study was conducted in patients with LABC (n = 83). Primary tumours were scanned using a clinical ultrasound device before starting treatment. Ninety-five imaging features were extracted-spectral features, texture, and texture-derivatives. Patients were determined to have recurrence or no recurrence based on clinical outcomes. Machine learning classifiers with k-nearest neighbour (KNN) and support vector machine (SVM) were evaluated for model development using a maximum of 3 features and leave-one-out cross-validation.

Results: With a median follow up of 69 months (range 7–118 months), 28 patients had disease recurrence (local or distant). The best classification results were obtained using an SVM classifier with a sensitivity, specificity, accuracy and area under curve of 71%, 87%, 82%, and 0.76, respectively. Using the SVM model for the predicted non-recurrence and recurrence groups, the estimated 5-year recurrence-free survival was 83% and 54% (p = 0.003), and the predicted 5-year overall survival was 85% and 74% (p = 0.083), respectively.

Conclusions: A QUS-radiomics model using higher-order texture derivatives can identify patients with LABC at higher risk of disease recurrence before starting treatment.

Press release - https://www.oncotarget.com/news/pr/radiomics-for-patients-with-breast-cancer-using-ultrasound/

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DOI - https://doi.org/10.18632/oncotarget.28139

Full text - https://www.oncotarget.com/article/28139/text/

Correspondence to - Gregory J. Czarnota - gregory.czarnota@sunnybrook.ca

Keywords - radiomics, breast cancer, quantitative ultrasound, recurrence, machine learning

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Trending With Impact: Pre-Treatment Ultrasound Used to Predict Breast Cancer Recurrence

Aging (Aging-US)

The researchers recruited healthy older participants to two groups according to their history of tea drinking frequency and investigated both functional and structural networks to reveal the role of tea drinking on brain organization.

The suppression of hemispheric asymmetry in the structural connectivity network was observed as a result of tea drinking.

The authors did not observe any significant effects of tea drinking on the hemispheric asymmetry of the functional connectivity network.

Dr. Junhua Li and Dr. Lei Feng said, "Tea has been a popular beverage since antiquity, with records referring to consumption dating back to the dynasty of Shen Nong (approximately 2700 BC) in China."

Tea is consumed in diverse ways, with brewed tea and products with a tea ingredient extremely prevalent in Asia, especially in China and Japan.

Although individual constituents of tea have been related to the roles of maintaining cognitive abilities and preventing cognitive decline, a study with behavioural and neurophysiological measures showed that there was a degraded effect or no effect when a constituent was administered alone and a significant effect was observed only when constituents were combined.

The superior effect of the constituent combination was also demonstrated in a comparative experiment that suggested that tea itself should be administered instead of tea extracts; a review of tea effects on the prevention of Alzheimers disease, found that the neuroprotective role of herbal tea was apparent in eight out of nine studies.

It is worth noting that the majority of studies thus far have evaluated tea effects from the perspective of neurocognitive and neuropsychological measures, with direct measurement of brain structure or function less-well represented in the extant literature.

These studies focusing on brain regional alterations did not ascertain tea effects on interregional interactions at the level of the entire brain.

The Li/Feng Research team concluded, "In summary, our study comprehensively investigated the effects of tea drinking on brain connectivity at both global and regional scales using multi-modal imaging data and provided the first compelling evidence that tea drinking positively contributes to brain structure making network organization more efficient."

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DOI - https://doi.org/10.18632/aging.102023

Full Text - https://www.aging-us.com/article/1020...

Correspondence to: Junhua Li email: junhua.li@essex.ac.uk and Lei Feng email: pcmfl@nus.edu.sg

Keywords: tea drinking, brain efficiency, fMRI, DTI, default mode network, hemispheric asymmetry

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com or connect with us on:

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Author Insight: Evidence From Brain Connectivity Evaluation: Brain Efficiency Modulated by Tea Drinking

Author Testimonial: Dr. Junhua Li - University of Essex

For Aging’s Volume 11, Issue 18, the Journal devoted the Cover to a research paper by Dr. Alejandro Martin-Montalvo from the Department of Regeneration and Cell Therapy, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Sevilla, Spain

Herein, the authors show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan.

Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan.

Dr. Martin-Montalvo said, "The increasing burden of age-related diseases highlights the importance of uncovering the mechanisms underlying the aging process."

TSH stimulates the production of T4 and T3 in the thyroid gland, which in turn inhibit both TRH and TSH synthesis when THs reach the hypothalamus and hypophysis, respectively.

Greater life expectancy has been associated with reduced circulating levels of T4, T3, and/or high TSH levels in both animal models and humans.

In this line, the Laron, Ames and Snell dwarf mice, which have reduced GH signalling and reduced circulating TH levels, exhibit a consistent exceptional lifespan as well as other metabolic alterations such as enhanced hepatic insulin sensitivity.

Both rodents and humans under calorie restriction, which comprises a variety of nutritional interventions with several beneficial effects including extended longevity, exhibit reduced circulating T3 levels and/or high TSH levels.

Likewise, nonagenarians from families with exceptional long lifespans, as well as their descendants, have been reported to exhibit increased TSH levels and/or decreased circulating T3 levels.

The Martin-Montalvo research team concluded, "In 1908 Dr. Max Rubner proposed the rate of living theory of aging and longevity, postulating that species with a low metabolic rate would have increased life expectancy when compared to species with a higher metabolic rate.

In this line, restricted levels of THs, which control the metabolic rate, have been associated with increased longevity as well as metabolic fitness."

Full Text - https://www.aging-us.com/article/102285/text

Correspondence to: Alejandro Martin-Montalvo; email: alejandro.martinmontalvo@cabimer.es and Benoit Raymond Gauthier; email: benoit.gauthier@cabimer.es

Keywords: lifespan, healthspan, thyroid hormones, hyperthyroidism, hypothyroidism, glucose metabolism

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

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Author Insight: Imbalanced Thyroid Hormones Sensitize to Hepatocarcinogenesis, Unhealthy Aging

The researchers recruited healthy older participants to two groups according to their history of tea drinking frequency and investigated both functional and structural networks to reveal the role of tea drinking on brain organization.

The suppression of hemispheric asymmetry in the structural connectivity network was observed as a result of tea drinking.

The authors did not observe any significant effects of tea drinking on the hemispheric asymmetry of the functional connectivity network.

Dr. Junhua Li and Dr. Lei Feng said, "Tea has been a popular beverage since antiquity, with records referring to consumption dating back to the dynasty of Shen Nong (approximately 2700 BC) in China."

Tea is consumed in diverse ways, with brewed tea and products with a tea ingredient extremely prevalent in Asia, especially in China and Japan.

Although individual constituents of tea have been related to the roles of maintaining cognitive abilities and preventing cognitive decline, a study with behavioural and neurophysiological measures showed that there was a degraded effect or no effect when a constituent was administered alone and a significant effect was observed only when constituents were combined.

The superior effect of the constituent combination was also demonstrated in a comparative experiment that suggested that tea itself should be administered instead of tea extracts; a review of tea effects on the prevention of Alzheimers disease, found that the neuroprotective role of herbal tea was apparent in eight out of nine studies.

It is worth noting that the majority of studies thus far have evaluated tea effects from the perspective of neurocognitive and neuropsychological measures, with direct measurement of brain structure or function less-well represented in the extant literature.

These studies focusing on brain regional alterations did not ascertain tea effects on interregional interactions at the level of the entire brain.

The Li/Feng Research team concluded, "In summary, our study comprehensively investigated the effects of tea drinking on brain connectivity at both global and regional scales using multi-modal imaging data and provided the first compelling evidence that tea drinking positively contributes to brain structure making network organization more efficient."

Full Text - https://www.aging-us.com/article/102023/text

Correspondence to: Junhua Li email: junhua.li@essex.ac.uk and Lei Feng email: pcmfl@nus.edu.sg

Keywords: tea drinking, brain efficiency, fMRI, DTI, default mode network, hemispheric asymmetry

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com or connect with us on:

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Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
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Author Insight: Habitual Tea Drinking Modulates Brain Efficiency

Oncotarget published "Host targeted antiviral (HTA): functional inhibitor compounds of scaffold protein RACK1 inhibit herpes simplex virus proliferation" which reported that due to the small number of molecular targets in viruses and the rapid evolution of viral genes, it is very challenging to develop specific antiviral drugs.

In addition, HIV-1 and Herpes Simplex virus are known to use IRES as well. By utilizing the crystal structure of the RACK1A protein from the model plant Arabidopsis and using a structure based drug design method, dozens of small compounds were identified that could potentially bind to the experimentally determined functional site of the RACK1A protein.

Dr. Sivanesan Dakshanamurthy from The Georgetown University Medical Center, Dr. Qiyi Tang from The Howard University College of Medicine and Dr. Hemayet Ullah from Howard University said, "With the small number of molecular targets in viruses and the rapid evolution of viral genes, it is very challenging to develop specific antiviral drugs."

Unlike other infectious agents, viruses offer few intrinsic targets for inhibition by antiviral molecules [1]. With their simple structural form and their ability to hijack molecular machinery from host cells to complete their replication cycle, viruses evade most efforts to contain them [2]. However, as viruses require host factors to translate their transcripts, targeting the host factor offers a unique opportunity to develop novel antiviral drugs.

In this regard, identification of the ribosome localized host protein Receptor for Activated C Kinase 1 for viral Internal Ribosomal Entry Site -mediated translation of non-capped mRNAs has been established as a target for developing antiviral drugs [3, 4]. Indeed, many of the animal and human viruses containing IRESs are RNA viruses, and most of them belong only to three families of + ssRNA viruses.

To date, although IRES elements have been widely reported in RNA viruses, only a very limited number of IRES elements have been reported in a few DNA viruses, including Kaposi's sarcoma-associated herpesvirus [7–9], Epstein-Barr virus [10], herpes simplex virus [11], murine gammaherpesvirus 68 [12], Marek's disease virus [13], and simian vacuolating virus 40 [14]. In addition, presence of the IRES in double stranded DNA containing White Spot Syndrome virus, which is in the family Nimaviradae, is also reported [15]. WSSV is widely known as the causative pathogen of a serious disease in shrimp [15].

One of the characteristics of HSV infection is its ability to latently infect neurons so that it can be reactivated, thereby causing recurrent infections [21]. Although the clinical symptoms of HSV-caused diseases can be controlled with antiviral drugs, these drugs are not strong enough to stop subclinical transmission [20, 22].

The Dakshanamurthy/Tang/Ullah Research Team concluded in their Oncotarget Research Output that this work will usher a new avenue to develop effective and durable drugs that can potentially circumvent the selection pressure induced drug-resistance scenarios. Future endeavors to generate next generation drugs targeting the host RACK1 protein with enhanced efficacy will advance this approach to a significantly new level where direct targeting anti-viral drugs are slowly being rendered as non-effective in term of their effective durability

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DOI - https://doi.org/10.18632/oncotarget.26907

Full text - https://www.oncotarget.com/article/26907/text/

Correspondence to - Sivanesan Dakshanamurthy - sd233@georgetown.edu, Qiyi Tang - qiyi.tang@howard.edu, and Hemayet Ullah - hullah@howard.edu

Keywords - host targeted antiviral (HTA), herpes simplex virus (HSV), receptor for activated C kinase 1 (RACK1), RACK1 inhibitor, internal ribosomal entry site (IRES)

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. 

To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:

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Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls

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Author Insight: Functional Inhibitor Compounds Inhibit Herpes Simplex Virus Proliferation

Aging-US published a Special Collection on Eye Disease which included "Age-related changes in eye lens biomechanics, morphology, refractive index and transparency" which reported that life-long eye lens function requires an appropriate gradient refractive index, biomechanical integrity and transparency.

The authors conducted an extensive study of wild-type mouse lenses 1-30 months of age to define common age-related changes. Biomechanical testing and morphometrics revealed an increase in lens volume and stiffness with age. Their results suggest similarities between murine and primate lenses and provide a baseline for future lens aging studies.

Dr. Velia M. Fowler and Dr. Catherine Cheng said, "The eye lens is required for fine focusing of light onto the retina to form a clear image, and the function of the lens is intimately tied to its shape, biomechanical properties, transparency and refractive index."

The eye lens is required for fine focusing of light onto the retina to form a clear image. It has long been known that age-related changes in these lens properties lead to two major lens pathologies, cataracts and presbyopia. Presbyopia is caused by a reduction in the lens' ability to change shape during focusing (accommodation), and, by extension, the need for reading glasses. Mice offer an opportunity to investigate changes in lens morphometrics, stiffness, transparency and refractive properties with age in a relatively shortened period of time. Little is known about the morphological, mechanical, refractive and cellular changes that occur with advanced age in the lens. The authors demonstrate that age-related changes in mouse lenses mimic some aspects of aging in human lenses.

The Fowler/Cheng Research Team concluded in their Aging-US Research Output, "the increases in lens size and nucleus size are correlated with increase stiffness with age. The addition of new fiber cells at the lens periphery becomes disordered with age, but this does not appear to impact lens biomechanical properties. Cataracts in aged lenses can be due to cell structural abnormalities, including incomplete suture closure, collapse of the lens epithelial cell layer into the suture gap and loss of epithelial-fiber cell attachments and compaction of the cortical lens fiber cells forming a circumferential light scattering ring. GRIN is present in the lens from 2 weeks of age and continues to increase until about 6 months of age, after which the maximum refractive index remains stable. The increase in the area of highest refractive index at the center of the lens is directly correlated with the increase in lens nucleus size, suggesting nuclear compaction drives the maximum GRIN. Whether there is a common molecular mechanism that drives changes in all the measured parameters remains unknown, but further biochemical and cell morphology studies will be needed to determine how subcellular aging affects the whole tissue. Thus, our study provides a baseline for future studies of lens aging by providing quantitative measurements of key parameters and identifying common age-related changes in the overall tissue and in individual cells"

Full Text - https://www.aging-us.com/article/102584/text

Correspondence to: Velia M. Fowler email: vfowler@udel.edu and Catherine Cheng email: ckcheng@iu.edu

Keywords: fiber cell, strain, epithelial cell, cataract, stiffness

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us on:

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Author Insight: Age-related Changes in Eye Lens Biomechanics

Teach Me in 10

Despite the growing relevance of 3D cell culture as a research model, imaging techniques used to characterize these models are highly limited. Due to the thickness and opacity of 3D cellular structures, most current imaging technologies cannot penetrate to the center of the tissues, resulting in only the outer two to three layers of cells being detected. This causes the dark centers that are often seen in images of 3D cell culture models. This proves highly problematic for accurate analysis as these outer cells are most exposed to compounds, nutrients and oxygen and thus do not reflect the entire cell population. 

In this Teach Me in 10 we speak with Dr. Ann Rossi Bilodeau about the best practices for 3D cell imaging, whether tissue clearing reagent can be used to clear spheroids expressing fluorescent proteins and we learn more about the new 3D Clear Tissue Clearing reagent from Corning.

Best Practices for 3D Cell Imaging

Aging-US published this trending high-scoring research paper back on June 12, 2016, entitled, “Reversal of cognitive decline in Alzheimer's disease,” by researchers from the University of California, Los Angeles, CA; Buck Institute for Research on Aging, Novato, CA; California Pacific Medical Center, San Francisco, CA; Private Practice of Psychiatry, Tucson, AZ; Brainreader, Horsens, Denmark.


Abstract:
Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.

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DOI - https://doi.org/10.18632/aging.100981
Full text - https://www.aging-us.com/article/100981/text

Correspondence to: Dale E. Bredesen, MD email: dbredesen@buckinstitute.org

Keywords: neurodegeneration, cognition, biomarkers, dementia, neuropsychology, imaging, Alzheimer's disease, Apolipoprotein E

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us on:

Twitter - https://twitter.com/AgingJrnl​
Facebook - https://www.facebook.com/AgingUS/​
SoundCloud - https://soundcloud.com/aging-us​
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LinkedIn -  https://www.linkedin.com/company/aging​

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

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Imaging/Microscopy

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