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"Chung, B"
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Isostructural metal-insulator transition in VO2
Separating structure and electrons in VO2Above 341 kelvin—not far from room temperature—bulk vanadium dioxide (VO2) is a metal. But as soon as the material is cooled below 341 kelvin, VO2 turns into an insulator and, at the same time, changes its crystal structure from rutile to monoclinic. Lee et al. studied the peculiar behavior of a heterostructure consisting of a layer of VO2 placed underneath a layer of the same material that has a bit less oxygen. In the VO2 layer, the structural transition occurred at a higher temperature than the metal-insulator transition. In between those two temperatures, VO2 was a metal with a monoclinic structure—a combination that does not occur in the absence of the adjoining oxygen-poor layer.Science, this issue p. 1037The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.
Journal Article
Clinical application of ultrashort echo time (UTE) and zero echo time (ZTE) magnetic resonance (MR) imaging in the evaluation of osteoarthritis
Novel compositional magnetic resonance (MR) imaging techniques have allowed for both the qualitative and quantitative assessments of tissue changes in osteoarthritis, many of which are difficult to characterize on conventional MR imaging. Ultrashort echo time (UTE) and zero echo time (ZTE) MR imaging have not been broadly implemented clinically but have several applications that leverage contrast mechanisms for morphologic evaluation of bone and soft tissue, as well as biochemical assessment in various stages of osteoarthritis progression. Many of the musculoskeletal tissues implicated in the initiation and progression of osteoarthritis are short T2 in nature, appearing dark as signal has already decayed to its minimum when image sampling starts. UTE and ZTE MR imaging allow for the qualitative and quantitative assessments of these short T2 tissues (bone, tendon, calcified cartilage, meniscus, and ligament) with both structural and functional reference standards described in the literature [1–3]. This review will describe applications of UTE and ZTE MR imaging in musculoskeletal tissues focusing on its role in knee osteoarthritis. While the review will address tissue-specific applications of these sequences, it is understood that osteoarthritis is a whole joint process with involvement and interdependence of all tissues.Key points• UTE MR imaging allows for the qualitative and quantitative evaluation of short T2 tissues (bone, calcified cartilage, and meniscus), enabling identification of both early degenerative changes and subclinical injuries that may predispose to osteoarthritis.• ZTE MR imaging allows for the detection of signal from bone, which has some of the shortest T2 values, and generates tissue contrast similar to CT, potentially obviating the need for CT in the assessment of osseous features of osteoarthritis.
Journal Article
NSD1 mutations generate a genome-wide DNA methylation signature
Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase,
NSD1
. As layered epigenetic modifications are often interdependent, we propose that pathogenic
NSD1
mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant
NSD1
+/−
-specific signature that differentiates pathogenic
NSD1
mutations from controls, benign
NSD1
variants and the clinically overlapping Weaver syndrome. Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly. This highly specific and sensitive
NSD1
+/−
signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing.
Sotos syndrome is an growth syndrome characterized by advanced growth in childhood, characteristic facial appearance and intellectual disability. Here the authors identify a genome-wide DNA methylation signature that accurately diagnoses Sotos Syndrome and distinguishes it from similar conditions.
Journal Article
Overcoming existential loneliness: a cross-cultural study
Background
Moving into a long-term care facility (LTCF) can reduce the ability for older adults to engage in meaningful roles and activities and the size of their social network. These changes and losses can lead them to experience existential loneliness (EL)—the intolerable emptiness and lack of meaningful existence resulted from the losses they have experienced. While EL has often been understood as a universal human experience, it has primarily been studied in people from Western cultures; little is known about how EL may be experienced by and manifested in people from Eastern cultures. Hence, this qualitative study aimed to describe the experience and coping of EL in Hong Kong Chinese and Swedish older adults living in LTCFs.
Methods
A qualitative study using Thorne’s (2004) interpretive description was conducted. Thirteen Chinese and 9 Swedes living in LTCFs in Hong Kong, China and Malmo, Sweden, respectively were interviewed about their experience of EL in two series of semi-structured interviews. Data were analyzed using thematic analysis.
Results
The core theme of “overcoming EL” described the participants’ experience of EL, which came about through the combined process of “Feeling EL” and “Self-Regulating”. Both Chinese and Swedish participants had similar experience with EL. Realizing that they did not want to living with EL anymore, they coped by reframing their experience and identifying new meaning in their life.
Conclusions
The study findings suggested that early and clear counselling support that help older adults to define new meaning in life may help them cope. In addition, more opportunities should be available at the LTCFs to promote quality relationships, enable older adults to reflect on their lives with pride, and support their ability to do the things they enjoy.
Journal Article
Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial
Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren–Lawrence II–IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (
n
= 120), CSI (
n
= 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (
n
= 120), CSI (
n
= 40); arm 3: stromal vascular fraction (
n
= 120), CSI (
n
= 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier:
NCT03818737
The multicenter phase 3 trial of stem cell therapy for osteoarthritis (MILES) for knee pain revealed that cell therapies showed no significant difference in knee pain outcomes, compared to corticosteroid injections, 1 year following treatment.
Journal Article
Beyond death and dying: how Chinese spouses navigate the final days with their loved ones suffering from terminal cancer
While advances in biomedicine exist for cancer, its diagnosis and treatment still bring the threat of mortality to the forefront of spouses’ lives. Family conflict is largely due to unmet expectations that generate a lot of physical and emotional distress for spouses, as the primary surrogates. Moreover, older individuals in Hong Kong tend to lack control of where they die and who is present at the end of their lives. Deeper understanding of Chinese spouses’ perspectives is needed to generate new insights, particularly in how spouses cope with caregiving. The aim of the study was to explore the Chinese spousal experience with their dying loved ones suffering from terminal cancer. A qualitative study using interpretive description was conducted. Spousal caregivers were purposively recruited through a hospice unit of two regional hospitals in Hong Kong, China. Documentary sources were used as secondary data. Fifteen individuals, consisting of seven men and eight women, participated in individual interviews. The overarching theme was a socially constructed “we” experience of confronting mortality, characterized by five subthemes: (a) balancing end-of-life tension between cure and comfort, (b) prioritizing the family goals and concerns, (c) de-medicalizing caregiving, (d) working for mutuality, and (e) creating a legacy of love. The study suggests that clinicians might consider harnessing the capacity of spouses to help work through confronting experiences of mortality and transforming events for goals that go beyond death. This places a major emphasis on salutary strategies surrounding transitions from curative to palliative care.
Journal Article
DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress
The antineoplastic drug hydroxyurea (HU), when used at subtoxic doses, induces prolonged replication stress and centrosome amplification. This causes genomic instability and increases the malignancy of the recurring tumor. The mechanism of centrosome amplification induced by prolonged replication stress, however, is still unclear. Here, we examined the involvement of ataxia telangiectasia, mutated (ATM), ataxia telangiectasia, mutated and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) and found that HU-induced centrosome amplification was inhibited by the depletion of DNA-PKcs, but not ATM and ATR. Inactivation of ATM/ATR in U2OS cells instead caused aneuploidy and cell death. We found DNA-PKcs depletion also abrogated ATM phosphorylation, indicating that ATM activation during prolonged replication stress depends on DNA-PK. Depletion of DNA-PK abrogated checkpoint kinase (Chk)2 activation and partially reduced Chk1 activation. Chk2 depletion blocked HU-induced centrosome amplification, indicating a function of Chk2 in centrosome amplification. We further found that Chk2 was phosphorylated at Thr68 on the mother centriole at late G2 and mitosis when unstressed and on all amplified centrioles induced by HU. In summary, we have elucidated that DNA-PK/Chk2 signaling induces centrosome amplification upon long-term HU treatment, therefore increasing our insight into tumor recurrence after initial chemotherapy.
Journal Article
Endothelial dysfunction in diabetes mellitus: Molecular mechanisms and clinical implications
Cardiovascular disease is a major complication of diabetes mellitus, and improved strategies for prevention and treatment are needed. Endothelial dysfunction contributes to the pathogenesis and clinical expression of atherosclerosis in diabetes mellitus. This article reviews the evidence linking endothelial dysfunction to human diabetes mellitus and experimental studies that investigated the responsible mechanisms. We then discuss the implications of these studies for current management and for new approaches for the prevention and treatment of cardiovascular disease in patients with diabetes mellitus.
Journal Article
Observation of Half-Height Magnetization Steps in Sr2RuO4
Spin-triplet superfluids can support exotic objects, such as half-quantum vortices characterized by the nontrivial winding of the spin structure. We present cantilever magnetometry measurements performed on mesoscopic samples of Sr(2)RuO(4), a spin-triplet superconductor. With micrometer-sized annular-shaped samples, we observed transitions between integer fluxoid states as well as a regime characterized by \"half-integer transitions\"--steps in the magnetization with half the height of the ones we observed between integer fluxoid states. These half-height steps are consistent with the existence of half-quantum vortices in superconducting Sr(2)RuO(4).
Journal Article