Publications by authors named "Takashi Kato"

508 Publications

A modified surgical technique for the Jarvik 2000 using a postauricular approach.

Surg Today 2021 Sep 4. Epub 2021 Sep 4.

Department of Cardiac and Vascular Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi, 321-0293, Japan.

The Jarvik 2000, with a postauricular cable, is a left ventricular assistance device with a driveline that is passed to the postauricular region subcutaneously. A titanium pedestal base that holds a 3-pin connector is fixed to the parietal bone, posterior to the auricle. Essentially, the device is fixed in the same position as a cochlear implant; however, the disadvantages include continuous mechanical stress on the cable by neck rotations, and the visibility of the apparatus. To improve such concerns, we adjusted the location of the pedestal of the lower parietal bone to just above the transverse sinus and closer to the mastoid process. To reach this point, the internal cable was passed through the retromastoid pathway commonly used in ventriculoperitoneal shunting. The thickness of the skull at this location is sufficient for safe fixation; however, preoperative evaluation by a neurosurgeon using CT is necessary.
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http://dx.doi.org/10.1007/s00595-021-02368-5DOI Listing
September 2021

Preoperative neutrophil-to-lymphocyte ratio predicts the prognosis of esophageal squamous cell cancer patients undergoing minimally invasive esophagectomy after neoadjuvant chemotherapy.

J Surg Oncol 2021 Aug 30. Epub 2021 Aug 30.

Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.

Background: One of the primary treatment for resectable advanced esophageal squamous cell cancer (ESCC) is neoadjuvant chemotherapy (NAC) followed by minimally invasive esophagectomy (MIE). Because the neutrophil-to-lymphocyte ratio (NLR) is a widely reported prognostic factor in several cancers, we investigated whether the preoperative NLR is a biomarker in ESCC patients treated with NAC and MIE.

Methods: In this study, we investigated 174 ESCC patients who underwent MIE from January 2010 to December 2015, including 121 patients who received NAC. The cutoff value of the NLR was analyzed using the receiver operating characteristic curve. Multivariate analyses were performed to clarify independent prognostic factors for overall survival (OS).

Results: The cutoff value of the NLR for OS in 121 patients who received NAC was 2.5 ng/ml, and the area under the curve was 0.63026 (p = 0.0127). The 5-year OS rate was 64% in those with an NLR <2.5 and 39% in those with an NLR ≥2.5. According to multivariate analysis, NLR ≥2.5, pathological T, pathological N, and intraoperative blood loss of >415 ml were independent poor prognostic factors.

Conclusions: NLR is a biomarker of prognosis in ESCC patients who undergo MIE after NAC.
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http://dx.doi.org/10.1002/jso.26611DOI Listing
August 2021

Can Medial Temporal Impairment Be an Imaging Red Flag for Neurodegeneration in Disproportionately Enlarged Subarachnoid Space Hydrocephalus?

J Alzheimers Dis 2021 Aug 17. Epub 2021 Aug 17.

Choju Medical Institute, Fukushimura Hospital, Aichi, Japan.

Background: The differentiation of idiopathic normal pressure hydrocephalus (iNPH) from neurodegenerative diseases such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is often challenging because of their non-specific symptoms. Therefore, various neuroradiological markers other than ventriculomegaly have been proposed. Despite the utility of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) for the appropriate selection of shunt surgery candidates, the specificity and neuropathology of this finding have not been sufficiently evaluated.

Objective: Investigation of the clinicopathological features and comparison of the neuroradiological findings between DESH with postmortem neuropathological diagnoses (pDESH) and clinically-diagnosed iNPH (ciNPH) patients are the main purposes of this study.

Method: In addition to the retrospective evaluation of clinicopathological information, quantitative, semiquantitative, and qualitative magnetic resonance imaging (MRI) indices were compared between pathologically-investigated 10 patients with pDESH and 10 patients with ciNPHResults:Excluding one patient with multiple cerebral infarctions, the postmortem neuropathological diagnoses of the pathologically-investigated patients were mainly neurodegenerative diseases (five AD, one DLB with AD pathologies, one DLB, one argyrophilic grain disease, and one Huntington's disease). In addition to the common neuroradiological featuresConclusion:Hippocampal atrophy and deformation with temporal horn enlargement seem to be characteristic neuroradiological findings of long-standing severely demented patients with DESH and neurodegenerative diseases, mainly advanced-stage AD.
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http://dx.doi.org/10.3233/JAD-210535DOI Listing
August 2021

Depth of vertebral screw insertion using a cortical bone trajectory technique in lumbar spinal fusion: radiological significance of a long cortical bone trajectory.

J Neurosurg Spine 2021 Aug 13:1-6. Epub 2021 Aug 13.

Objective: Contrary to original cortical bone trajectory (CBT), "long CBT" directed more anteriorly in the vertebral body has recently been recommended because of improved screw fixation and load sharing within the vertebra. However, to the authors' knowledge there has been no report on the clinical significance of the screw length and screw insertion depth used with the long CBT technique. The aim of the present study was to investigate the influence of the screw insertion depth in the vertebra on lumbar spinal fusion using the CBT technique.

Methods: A total of 101 consecutive patients with L4 degenerative spondylolisthesis who underwent single-level posterior lumbar interbody fusion at L4-5 using the CBT technique were included (mean follow-up 32.9 months). Screw loosening and bone fusion were radiologically assessed to clarify the factors contributing to these outcomes. Investigated factors were as follows: 1) age, 2) sex, 3) body mass index, 4) bone mineral density, 5) intervertebral mobility, 6) screw diameter, 7) screw length, 8) depth of the screw in the vertebral body (%depth), 9) facetectomy, 10) crosslink connector, and 11) cage material.

Results: The incidence of screw loosening was 3.1% and bone fusion was achieved in 91.7% of patients. There was no significant factor affecting screw loosening. The %depth in the group with bone fusion [fusion (+)] was significantly higher than that in the group without bone fusion [fusion (-)] (50.3% ± 8.2% vs 37.0% ± 9.5%, respectively; p = 0.001), and multivariate logistic regression analysis revealed that %depth was a significant independent predictor of bone fusion. Receiver operating characteristic curve analysis identified %depth > 39.2% as a predictor of bone fusion (sensitivity 90.9%, specificity 75.0%).

Conclusions: This study is, to the authors' knowledge, the first to investigate the significance of the screw insertion depth using the CBT technique. The cutoff value of the screw insertion depth in the vertebral body for achieving bone fusion was 39.2%.
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http://dx.doi.org/10.3171/2021.2.SPINE202229DOI Listing
August 2021

Recent trends in the prevalence and distribution of colonic diverticula in Japan evaluated using computed tomography colonography.

World J Gastroenterol 2021 Jul;27(27):4441-4452

Department of Coloproctology, Fukushima Medical University, Aizu Medical Center, Aizuwakamatsu 969-3492, Fukushima, Japan.

Background: Computed tomography colonography (CTC) may be superior to colonoscopy and barium enema for detecting diverticula. However, few studies have used CTC to diagnose diverticula.

Aim: To evaluate the current prevalence and distribution of colonic diverticula in Japan using CTC.

Methods: This study was conducted as part of the Japanese National Computed Tomographic Colonography Trial, which included 1181 participants from 14 hospitals in Japan. We analyzed the prevalence and distribution of colonic diverticula and their relationships with age and sex. The relationship between the diverticula and the length of the large intestine was also analyzed.

Results: Diverticulosis was present in 48.1% of the participants. The prevalence of diverticulosis was higher in the older participants ( < 0.001 for trend). The diverticula seen in younger participants were predominantly located in the right-sided colon. Older participants had a higher frequency of bilateral type (located in the right- and left-sided colon) diverticulosis ( < 0.001 for trend). The length of the large intestine with multiple diverticula in the sigmoid colon was significantly shorter in those without diverticula ( < 0.001).

Conclusion: The prevalence of colonic diverticulosis in Japan is higher than that previously reported. The prevalence was higher, and the distribution tended to be bilateral in older participants.
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http://dx.doi.org/10.3748/wjg.v27.i27.4441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316905PMC
July 2021

Molecular insights on confined water in the nanochannels of self-assembled ionic liquid crystal.

Sci Adv 2021 Jul 28;7(31). Epub 2021 Jul 28.

Graduate School of Information Science, University of Hyogo, 7-1-28 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.

Self-assembled ionic liquid crystals can transport water and ions via the periodic nanochannels, and these materials are promising candidates as water treatment membranes. Molecular insights on the water transport process are, however, less investigated because of computational difficulties of ionic soft matters and the self-assembly. Here we report specific behavior of water molecules in the nanochannels by using the self-consistent modeling combining density functional theory and molecular dynamics and the large-scale molecular dynamics calculation. The simulations clearly provide the one-dimensional (1D) and 3D-interconnected nanochannels of self-assembled columnar and bicontinuous structures, respectively, with the precise mesoscale order observed by x-ray diffraction measurement. Water molecules are then confined inside the nanochannels with the formation of hydrogen bonding network. The quantitative analyses of free energetics and anisotropic diffusivity reveal that, the mesoscale geometry of 1D nanodomain profits the nature of water transport via advantages of dissolution and diffusion mechanisms inside the ionic nanochannels.
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http://dx.doi.org/10.1126/sciadv.abf0669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318373PMC
July 2021

Structural basis of ethnic-specific variants of PAX4 associated with type 2 diabetes.

Hum Genome Var 2021 Jul 5;8(1):25. Epub 2021 Jul 5.

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Recently, we conducted genome-wide association studies of type 2 diabetes (T2D) in a Japanese population, which identified 20 novel T2D loci that were not associated with T2D in Europeans. Moreover, nine novel missense risk variants, such as those of PAX4, were not rare in the Japanese population, but rare in Europeans. We report in silico structural analysis of ethnic-specific variants of PAX4, which suggests the pathogenic effect of these variants.
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http://dx.doi.org/10.1038/s41439-021-00156-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257626PMC
July 2021

[Right Coronary Ostial Aneurysm after Modified Bentall Procedure with Carrel Patch Technique in a Patient with Marfan Syndrome:Report of a Case].

Kyobu Geka 2021 Jul;74(7):554-557

Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi, Japan.

A 58-year-old man with Marfan syndrome visited our clinic for a routine examination. He had undergone a modified Bentall procedure with Carrel patch technique for annuloaortic ectasia 15 years previously. Computed tomography revealed an aneurysm of 43×57 mm in diameter at the right coronary ostium. He underwent resection of the aneurysm and coronary reconstruction using Piehler technique. He was discharged on the 37th postoperative day when his renal function recovered. Although the modified Bentall procedure may improve the surgical outcome, long-term follow-up is important because of various postoperative anastomotic complications in patients with Marfan syndrome.
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July 2021

Green tea consumption is associated with annual changes in hippocampal volumes: A longitudinal study in community-dwelling middle-aged and older Japanese individuals.

Arch Gerontol Geriatr 2021 Sep-Oct;96:104454. Epub 2021 Jun 1.

National Center for Geriatrics and Gerontology, Aichi, Japan.

Background: To investigate the association between green tea consumption and the annual rate of change of gray matter (GM), white matter (WM), and hippocampal volumes in community-dwelling middle-aged and older Japanese individuals.

Methods: A prospective cohort study with two years of follow-up was conducted as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project. A total of 1693 participants (862 men and 831 women, aged 40-89 years) were included. Green tea consumption (mL/day) data were collected with a 3-day dietary record. Volumes of GM, WM, and the hippocampus were estimated by T1-weighted brain magnetic resonance imaging and FreeSurfer software. The GM ratio, WM ratio, and hippocampal ratio (HR) were calculated as the percentages of total intracranial volume, respectively.

Results: The mean (SD) annual rate of change of hippocampal volume [(HR at baseline - HR at follow-up)/HR at baseline/follow-up years×100%] was 0.499 (1.128) (%). In the multivariable-adjusted general linear model, green tea consumption was negatively associated only with the annual rate of change of hippocampal volume (%) [β (95% CI) for each 1 mL/day increase in green tea consumption = -20.2E-5 (-35.0E-5 to -5.3E-5); P-value = 0.008]. No associations were observed for the annual rate of change of GM or WM volumes. The results remained significant when the analysis was limited to those with stable green tea consumption and were especially evident among individuals aged 65 years and older and among women.

Conclusions: In this study, higher green tea consumption was associated with less annual hippocampal atrophy, and each additional 100 mL/day of green tea intake was related to a reduction of approximately 5% in annual hippocampal atrophy. This association was especially evident among older individuals and among women. Further study in different settings is needed to confirm this association.
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http://dx.doi.org/10.1016/j.archger.2021.104454DOI Listing
September 2021

Nanostructured liquid-crystalline Li-ion conductors with high oxidation resistance: molecular design strategy towards safe and high-voltage-operation Li-ion batteries.

Chem Sci 2020 Jun 23;11(39):10631-10637. Epub 2020 Jun 23.

Department Chemistry and Biotechnology, School of Engineering, The University of Tokyo Hongo, Bunkyo-ku Tokyo 113-8656 Japan

Nanostructured, uncharged liquid-crystalline (LC) electrolyte molecules having bicyclohexyl and cyclic carbonate moieties have been developed for application in Li-ion batteries as quasi-solid electrolytes, which suppress leakage and combustion. Towards the development of safe and high performance Li-ion batteries, we have designed Li-ion conductive LC materials with high oxidation resistance using density functional theory (DFT) calculation. The DFT calculation suggests that a mesogen with a bicyclohexyl moiety is suitable for the high-oxidation-resistance LC electrolytes compared to a mesogen containing phenylene moieties. A tri(oxyethylene) chain introduced between the cyclic carbonate and the bicyclohexyl moiety in the core part tunes the viscosity and the miscibility with Li salts. The designed Li-ion conductive LC molecules exhibit smectic LC phases over a wide temperature range, and they are miscible with added lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt up to 5 : 5 in molar ratio in their smectic phases. The resulting LC mixtures with LiTFSI show oxidation resistance above 4.0 V Li/Li in cyclic voltammetry measurements. The enhanced oxidation resistance improves the performance of Li half-cells containing LC electrolytes.
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http://dx.doi.org/10.1039/d0sc01646bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162368PMC
June 2020

A case of -negative early gastric adenocarcinoma with gastrointestinal phenotype.

Endosc Int Open 2021 Jun 27;9(6):E863-E866. Epub 2021 May 27.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

A 40-year-old man with slightly depressed (0-IIc) type gastric cancer of the pyloric anterior gastric area underwent pre-operative screening for tetralogy of Fallot and endoscopic submucosal dissection (ESD) and was tested for antigens and antibodies. Both tests were negative. He did not have a history of eradication. Pathological diagnosis of ESD showed a well-differentiated adenocarcinoma. The tumor was CD10-positive, MUC5AC-negative, and MUC6-confocal positive; it showed differentiation with gastrointestinal phenotype. Moreover, the tumor cells were lysozyme-positive, resembling Paneth cells. Mucosal glands exhibited intestinal metaplasia on the anal side of the tumor lesion. On the oral side of the tumor, metaplasia was non-existent, with normal pyloric glands present in the mucosal layer. The patient was not infected with ; however, intestinal metaplasia existed around the early gastric cancer. This suggested that the intestinal metaplasia occurred due to bile reflux, and the gastric neoplasia arose with the metaplasia without an infection. This case may potentially help explain gastric cancer development in the absence of infection.
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http://dx.doi.org/10.1055/a-1396-3854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159579PMC
June 2021

Genotype-Structure-Phenotype Correlations of Disease-Associated IGF1R Variants and Similarities to Those of INSR Variants.

Diabetes 2021 08 1;70(8):1874-1884. Epub 2021 Jun 1.

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

We previously reported genotype-phenotype correlations in 12 missense variants causing severe insulin resistance, located in the second and third fibronectin type III (FnIII) domains of the insulin receptor (INSR), containing the α-β cleavage and part of insulin-binding sites. This study aimed to identify genotype-phenotype correlations in FnIII domain variants of IGF1R, a structurally related homolog of INSR, which may be associated with growth retardation, using the recently reported crystal structures of IGF1R. A structural bioinformatics analysis of five previously reported disease-associated heterozygous missense variants and a likely benign variant in the FnIII domains of IGF1R predicted that the disease-associated variants would severely impair the hydrophobic core formation and stability of the FnIII domains or affect the α-β cleavage site, while the likely benign variant would not affect the folding of the domains. A functional analysis of these variants in CHO cells showed impaired receptor processing and autophosphorylation in cells expressing the disease-associated variants but not in those expressing the wild-type form or the likely benign variant. These results demonstrated genotype-phenotype correlations in the FnIII domain variants of , which are presumably consistent with those of and would help in the early diagnosis of patients with disease-associated variants.
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http://dx.doi.org/10.2337/db20-1145DOI Listing
August 2021

Preoperative Serum GDF-15, Endothelin-1 Levels, and Intraoperative Factors as Short-Term Operative Risks for Patients Undergoing Cardiovascular Surgery.

J Clin Med 2021 May 2;10(9). Epub 2021 May 2.

Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan.

Objectives: The Society of Thoracic Surgeons (STS) risk score is widely used for the risk assessment of cardiac surgery. Serum biomarkers such as growth differentiation factor-15 (GDF-15) and endothelin-1 (ET-1) are also used to evaluate risk. We investigated the relationships between preoperative serum GDF-15, ET-1 levels, and intraoperative factors and short-term operative risks including acute kidney injury (AKI) for patients undergoing cardiovascular surgery.

Methods: In total, 145 patients were included in this study (92 males and 53 females, age 68.4 ± 13.2 years). The preoperative STS score was determined, and the serum GDF-15 and ET-1 levels were measured by ELISA. These were related to postoperative risks, including AKI, defined according to the Acute Kidney Injury Network (AKIN) classification criteria.

Results: AKI developed in 23% of patients. The GDF-15 and ET-1 levels correlated with the STS score. The STS score and GDF-15 and ET-1 levels all correlated with preoperative eGFR, Alb, Hb, and BNP levels; perioperative data (urine output); ICU stay period; and postoperative admission days. Patients with AKI had longer circulatory pulmonary bypass (CPB) time, and male patients with AKI had higher ET-1 levels than those without AKI. In multivariable logistic regression analysis, the preoperative ET-1 level and CPB time were the independent determinants of AKI, even adjusted by age, sex, and BMI. The preoperative GDF-15 level, CPB time, and RCC transfusion were independent determinants of 30-day mortality plus morbidity.

Conclusion: Preoperative GDF-15 and ET-1 levels as well as intraoperative factors such as CPB time may be helpful to identify short-term operative risks for patients undergoing cardiovascular surgery.
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http://dx.doi.org/10.3390/jcm10091960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125127PMC
May 2021

Self-healing and shape memory functions exhibited by supramolecular liquid-crystalline networks formed by combination of hydrogen bonding interactions and coordination bonding.

Chem Sci 2021 Mar 22;12(17):6091-6098. Epub 2021 Mar 22.

Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo Hongo Bunkyo-ku Tokyo 113-8656 Japan

We here report a new approach to develop self-healing shape memory supramolecular liquid-crystalline (LC) networks through self-assembly of molecular building blocks combination of hydrogen bonding and coordination bonding. We have designed and synthesized supramolecular LC polymers and networks based on the complexation of a forklike mesogenic ligand with Ag ions and carboxylic acids. Unidirectionally aligned fibers and free-standing films forming layered LC nanostructures have been obtained for the supramolecular LC networks. We have found that hybrid supramolecular LC networks formed through metal-ligand interactions and hydrogen bonding exhibit both self-healing properties and shape memory functions, while hydrogen-bonded LC networks only show self-healing properties. The combination of hydrogen bonds and metal-ligand interactions allows the tuning of intermolecular interactions and self-assembled structures, leading to the formation of the dynamic supramolecular LC materials. The new material design presented here has potential for the development of smart LC materials and functional LC membranes with tunable responsiveness.
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http://dx.doi.org/10.1039/d0sc06676aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098694PMC
March 2021

Augmentation of STING-induced type I interferon production in COPA syndrome.

Arthritis Rheumatol 2021 May 13. Epub 2021 May 13.

Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.

Objectives: COPA syndrome, also known as an autoinflammatory interstitial lung, joint, and kidney (AILJK) disease, is caused by heterozygous mutations in the coatomer subunit alpha (COPA) gene. We found a novel COPA variant in four patients in one family. We aimed to elucidate whether and how the variant causes manifestations of COPA syndrome by studying these four patients and in a gene-targeted mouse model.

Method: We performed whole exome sequencing in seven family members and measured type I interferon (IFN) signature of the peripheral blood cells. We analyzed the effects of COPA variants in in vitro experiments and Copa mutant mice we generated.

Results: We identified a heterozygous variant of COPA gene in the four affected members of the family (c.725T>G, p.Val242Gly). IFN score was high in the members carrying the variant. In vitro analysis revealed that COPA V242G as well as the previously reported disease-causing variants augmented the stimulator of interferon genes (STING)-induced type I IFN promoter activities. Copa mice manifested interstitial lung disease and STING-dependent elevation of IFN-stimulated genes (ISGs) expression. In Copa dendritic cells, the STING pathway was not constitutively activated, but hyperactivated upon stimulation and led to increased type I IFN production.

Conclusion: V242G, a novel COPA variant, was found in four patients from one family. The gene-targeted mice with V242G variant recapitulated the interstitial lung disease and showed augmented responses of the STING pathway leading to increase of type I IFN production.
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http://dx.doi.org/10.1002/art.41790DOI Listing
May 2021

Giant coronary sinus aneurysm misdiagnosed as an extracardiac mediastinal tumor.

Gen Thorac Cardiovasc Surg 2021 Aug 27;69(8):1236-1239. Epub 2021 Apr 27.

Department of Cardiovascular Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi, 321-0293, Japan.

Coronary sinus aneurysm is a rare heart anomaly. Herein, we report a rare case with giant coronary sinus aneurysm misdiagnosed as an extracardiac mediastinal tumor. The preoperative diagnostic imaging failed to diagnose the correct location of the tumor and a simple resection was planned. It turned out to be coronary sinus aneurysm intraoperatively and required cardiopulmonary bypass support for the resection.
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http://dx.doi.org/10.1007/s11748-021-01636-yDOI Listing
August 2021

Simple Quantitative Indices for the Differentiation of Advanced-Stage Alzheimer's Disease and Other Limbic Tauopathies.

J Alzheimers Dis 2021 ;81(3):1093-1102

Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan.

Background: The differentiation of Alzheimer's disease (AD) from age-related limbic tauopathies (LT), including argyrophilic grain disease (AGD) and senile dementia of the neurofibrillary tangle type (SD-NFT), is often challenging because specific clinical diagnostic criteria have not yet been established. Despite the utility of specific biomarkers evaluating amyloid and tau to detect the AD-related pathophysiological changes, the expense and associated invasiveness preclude their use as first-line diagnostic tools for all demented patients. Therefore, less invasive and costly biomarkers would be valuable in routine clinical practice for the differentiation of AD and LT.

Objective: The purpose of this study is to develop a simple reproducible method on magnetic resonance imaging (MRI) that could be adopted in daily clinical practice for the differentiation of AD and other forms of LT.

Methods: Our newly proposed three quantitative indices and well-known medial temporal atrophy (MTA) score were evaluated using MRI of pathologically-proven advanced-stage 21 AD, 10 AGD, and 2 SD-NFT patients.

Results: Contrary to MTA score, hippocampal angle (HPA), inferior horn area (IHA), and ratio between HPA and IHA (i.e., IHPA index) demonstrated higher diagnostic performance and reproducibility, especially to differentiate advanced-stage AD patients with Braak neurofibrillary tangle stage V/VI from LT patients (the area under the receiver-operating-characteristic curve of 0.83, 089, and 0.91; intraclass correlation coefficients of 0.930, 0.998, and 0.995, respectively).

Conclusion: Quantitative indices reflecting hippocampal deformation with ventricular enlargement are useful to differentiate advanced-stage AD from LT. This simple and convenient method could be useful in daily clinical practice.
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http://dx.doi.org/10.3233/JAD-210043DOI Listing
September 2021

Gemini Thermotropic Smectic Liquid Crystals for Two-Dimensional Nanostructured Water-Treatment Membranes.

ACS Appl Mater Interfaces 2021 May 9;13(17):20598-20605. Epub 2021 Apr 9.

Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

We have developed a two-dimensional (2D) liquid-crystalline (LC) nanostructured water-treatment membrane showing high virus rejection ability (over 99.99997% for bacteriophage Qβ) and improved water permeation. Polymerizable gemini amphiphiles have been designed and synthesized. They have H-shaped gemini-type structures of thermotropic smectic liquid crystals composed of cationic imidazolium moieties. One of the gemini amphiphiles shows a smectic A phase with an interdigitated bilayer structure. A cross-linked self-standing 2D nanostructured polymer film has been obtained by in situ photopolymerization of the gemini amphiphile in the smectic phase. The length of linkers in gemini amphiphiles affects the formation of LC phases. The 2D nanostructured membrane also showed selective salt rejection.
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http://dx.doi.org/10.1021/acsami.0c20524DOI Listing
May 2021

Nuclear PTEN deficiency and heterozygous PTEN loss have distinct impacts on brain and lymph node size.

Biochem Biophys Res Commun 2021 05 1;555:81-88. Epub 2021 Apr 1.

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Defects in PTEN, a critical tumor suppressor, are associated with tumorigenesis and aberrant organ sizes. It has been shown that heterozygous PTEN loss increases brains and neuron size, while the specific loss of nuclear PTEN has the opposite effect. Here, we investigate the impact of a combination of heterozygous PTEN loss and nuclear PTEN loss on the size of various organs, including the brain, liver, thymus, spleen, and inguinal lymph node. We found that the effect of the combination varies among organs. Notably, the combination of heterozygous PTEN loss and nuclear PTEN loss restored the normal size of brains and neurons. In contrast, the liver's size was unaffected by either single PTEN defects or their combination. Strikingly, the size of the inguinal lymph node was greatly increased due to lymphoma by the combination of the two PTEN defects. These data suggest that nuclear PTEN and non-nuclear PTEN function in an antagonistic manner in the brain while acting synergistically in the inguinal lymph node.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085137PMC
May 2021

Computationally image-corrected dual-comb microscopy with a free-running single-cavity dual-comb fiber laser.

Opt Express 2021 Feb;29(4):5018-5032

Dual-comb microscopy (DCM), an interesting imaging modality based on the optical-frequency-comb (OFC) mode and image pixel one-to-one correspondence, benefits from scan-less full-field imaging and simultaneous confocal amplitude and phase imaging. However, the two fully frequency-stabilized OFC sources requirement hampers DCM practicality due to the complexity and costs. Here, a bidirectional single-cavity dual-comb fiber laser (SCDCFL) is adopted as a DCM low-complexity OFC source. Although the residual timing jitter in the SCDCFL blurs the image of a static object acquired by DCM, computational image correction significantly suppresses the image blur. Nanometer-order step surface profilometry with a 14.0 nm uncertainty highlights the computationally image-corrected DCM effectiveness. We further discuss a possibility to expand the computational image correction to a dynamic object and demonstrate its preliminary experiment. The proposed method enhances the DCM generality and practicality due to low-complexity OFC source.
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http://dx.doi.org/10.1364/OE.415242DOI Listing
February 2021

Central airway obstruction treated with initial support by venovenous extracorporeal membrane oxygenation.

BMJ Case Rep 2021 Mar 10;14(3). Epub 2021 Mar 10.

Department of emergency and critical care medicine, St Luke's International University, Chuo-ku, Tokyo, Japan.

A 24-year-old man with Down syndrome and congenital tracheal stenosis, who had undergone cartilage patch tracheoplasty twice in infancy, was transferred from a local hospital to manage an airway emergency. On arrival, the patient was in severe respiratory distress. Increased airway pressure following endotracheal intubation complicated the administration of mechanical ventilation. CT of the chest showed widespread consolidation and tracheal stenosis 3 cm above the carina distal to the tip of the endotracheal tube. The diagnosis was tracheal stenosis with type A influenza infection. The patient was transferred to another hospital for initiating venovenous extracorporeal membrane oxygenation (VV-ECMO). Intubation with a 6.0 mm spiral tube was successful after intraluminal balloon dilatation of the tracheal stenosis. The patient was admitted to the intensive care unit and was weaned off VV-ECMO on day 3 due to improvement in respiratory status. A tracheotomy was performed on day 28 and the tracheal tube was removed on day 41.
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http://dx.doi.org/10.1136/bcr-2020-237282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949422PMC
March 2021

Nuclear PTEN and p53 suppress stress-induced liver cancer through distinct mechanisms.

Biochem Biophys Res Commun 2021 04 2;549:83-90. Epub 2021 Mar 2.

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Electronic address:

PTEN and p53 are highly mutated in many cancers. These two tumor suppressors have critical functions in the nucleus, such as DNA repair, cell cycle progression, and genome maintenance. However, the in vivo functional relationship of nuclear PTEN and p53 is unknown. Here, we analyzed the liver of mice in which nuclear PTEN and p53 are individually or simultaneously depleted. We found that nuclear PTEN loss greatly upregulates p53 expression upon oxidative stress, while the loss of p53 potentiates stress-induced accumulation of PTEN in the nucleus. Next, we examined oxidative stress-induced DNA damage in hepatocytes, and found that nuclear PTEN loss aggravated the damage while p53 loss did not. Notably, mice lacking nuclear PTEN had increased hepatocellular carcinoma under oxidative stress, while mice lacking p53 in hepatocytes had accelerated hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The formation of cholangiocarcinoma appears to involve the transformation of hepatocytes into cholangiocarcinoma. Simultaneous loss of nuclear PTEN and p53 exacerbated both types of liver cancers. These data suggest that nuclear PTEN and p53 suppress liver cancers through distinct mechanisms.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995232PMC
April 2021

Quantitative Evaluation of F-Flutemetamol PET in Patients With Cognitive Impairment and Suspected Alzheimer's Disease: A Multicenter Study.

Front Neurol 2020 13;11:578753. Epub 2021 Jan 13.

Department of Radiology, National Center of Neurology and Psychiatry, Kodaira, Japan.

In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development. We aimed to determine cutoffs for positivity in quantitative analysis of F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321). Ninety-three patients suspected of having AD underwent F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area. Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ = 51.3, < 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%. Quantitative analysis of amyloid PET using F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.
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http://dx.doi.org/10.3389/fneur.2020.578753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838486PMC
January 2021

Factors important in bone union after posterior lumbar interbody fusion using the cortical bone trajectory technique.

J Spine Surg 2020 Dec;6(4):713-720

Department of Orthopaedic Surgery, National Hospital Organization, Murayama Medical Center, Musashimurayama, Tokyo, Japan.

Background: The cortical bone trajectory (CBT) technique has developed as an alternative to the traditional pedicle screw fixation technique due to its minimum invasiveness for screw insertion and rigid fixation for posterior lumbar interbody fusion (PLIF). However, the factors contributing to bone union after CBT-PLIF is a controversial subject. The aim of this study was to investigate factors important to bone union after CBT-PLIF.

Methods: We analyzed 69 consecutive patients who underwent single-level CBT-PLIF from October 2011 to December 2016 and were followed for over two years. Bone union was evaluated using computed tomography (CT) and dynamic assessment in the radiograph within two years after CBT-PLIF. The following factors that may influence bone union were investigated: age, gender, bone mineral density (BMD), cage materials [polyether-ether-ketone (PEEK) or titanium (Ti)], vertebral-slip (neutral), translational motion (flexion/extension), angular motion (flexion/extension), screw depth into the vertebral body (% depth), interval of bilateral screw heads, and cage position.

Results: The bone union rate at the two-year follow-up was 88.4% (61/69). A univariate analysis revealed that variables with values of P<0.20 were age (P<0.01), gender (P=0.07), cage material (P=0.18), vertebral slip (neutral) (P=0.14), % depth (P=0.086), and cage position (P<0.01). Multiple logistic regression analyses revealed that factors related to bone union were young age (P<0.01), Ti cage (P<0.01), small vertebral slip (neutral) (P<0.01), high % depth (P<0.01), and anterior cage position (P<0.01).

Conclusions: For CBT-PLIF, deeper screw insertion into the vertebral body, anterior cage placement, and Ti cage usage may be important surgical techniques to achieve a successful bone union.
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http://dx.doi.org/10.21037/jss-20-608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797788PMC
December 2020

Association of drugs with special caution in the guidelines with falls: A case-control and case-crossover study in Japan.

Geriatr Gerontol Int 2021 Mar 13;21(3):285-290. Epub 2021 Jan 13.

Department of Internal Medicine, Kudanzaka Hospital, Company Overview of Federation of National Public Service Personnel Mutual Aid Associations, Tokyo, Japan.

Aim: To determine the relationship between multiple medications and falls.

Methods: This case-control and case-crossover study was carried out at Kudanzaka Hospital in Chiyoda, Tokyo, Japan. A total of 325 patients who experienced their first falls when hospitalized between January 2016 and November 2018, and 1285 controls matched by sex, age and clinical departments were included in this study. Hospitalization duration and fall risk score were adjusted for in the analyses.

Results: In the case-control study, multivariable logistic regression showed that increasing the intake of oral medications was not significantly associated with the incidence of falls (odds ratio 1.02, 95% confidence interval 0.998-1.049). In contrast, drugs prescribed with special caution in accordance with the Elderly Oral Medication Guidelines were significantly associated with falls (odds ratio 1.17, 95% confidence interval 1.09-1.26). A similar pattern was observed in the case-crossover analysis. Among the drugs to be prescribed with special caution according to the guidelines, atypical antipsychotics, non-benzodiazepine hypnotics and magnesium oxide were significantly associated with the risk of falls.

Conclusion: The drugs to be prescribed with special caution according to the guidelines were associated with an increased fall risk. The risk of falls in hospitalized older people due to multiple medications varies among medications. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.
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http://dx.doi.org/10.1111/ggi.14127DOI Listing
March 2021

Methoxy-Functionalized Glycerol-Based Aliphatic Polycarbonate: Organocatalytic Synthesis, Blood Compatibility, and Hydrolytic Property.

ACS Biomater Sci Eng 2021 02 5;7(2):472-481. Epub 2021 Jan 5.

Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.

Polymers that are biocompatible and degradable are desired for tissue engineering approaches in the treatment of vascular diseases, especially for those involving small-diameter blood vessels. Herein, we report the compatibility of a newly developed glycerol-based aliphatic polycarbonate possessing simple methoxy side groups, named poly(5-methoxy-1,3-dioxan-2-one) (PMDO), with blood cells and plasma proteins as well as its susceptibility to hydrolysis. As a consequence of the organocatalytic ring-opening polymerization (ROP) of a methoxy-functionalized cyclic carbonate derived from glycerol, PMDO with a sufficiently high molecular weight ( 14 kg/mol) and a narrow distribution ( 1.12) was obtained for evaluation as a bulk biomaterial. This study demonstrates for the first time the organocatalytic ROP of a glycerol-based cyclic carbonate in a controlled manner. Compared with the clinically applied aliphatic polycarbonate poly(trimethylene carbonate) (PTMC), PMDO inhibits platelet adhesion by 33% and denaturation of fibrinogen by 23%. Although the wettability of PMDO based on water contact angle was almost comparable to those of PTMC and poly(ethylene terephthalate), the reason for the inhibited platelet adhesion and protein denaturation appeared to be related to the presence of specific hydrated water formed in the hydrated polymer. The improved hydration of PMDO also enhanced the susceptibility to hydrolysis, with PMDO demonstrating a slightly higher hydrolytic property than PTMC. This simple glycerol-based aliphatic polycarbonate has the following benefits: bio-based characteristics of glycerol and improved blood compatibility and hydrolytic biodegradability stemming from moderate hydration of the methoxy side groups.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01460DOI Listing
February 2021

Exploring Structures and Dynamics of Molecular Assemblies: Ultrafast Time-Resolved Electron Diffraction Measurements.

Acc Chem Res 2021 Feb 15;54(3):731-743. Epub 2020 Dec 15.

Department of Chemistry & Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

ConspectusMolecular assemblies have been widely applied to functional soft materials in a variety of fields. Liquid crystal is one of the representative molecular soft materials in which weak intermolecular interactions induce its dynamic molecular behavior under external stimuli, such as electric and magnetic fields, photoirradiation, and thermal treatment. It is important to understand molecular behavior and motion in the liquid-crystalline (LC) states at the picosecond level for further functionalization of liquid crystals and molecular assembled materials. For investigation of assembled structures of the materials on the nanometer scale, X-ray diffraction (XRD) measurements have been a powerful tool. Despite the dynamic nature of the assembled materials, however, time resolution of XRD is limited to millisecond due to the response speed of the detector, which hampered real-time observation of the dynamics of the molecular assembly. For further understanding of the dynamic behavior of functional molecules and improvement of performance for their applications, the insights of faster dynamics on the micro-, nano-, pico-, and even femtosecond time scales are required. In this context, the interdisciplinary approaches of the emerging fields of materials chemistry and ultrafast science will open up new aspects of molecular science and technology. These approaches may lead to more effective design of new functional materials, which enables us to control molecular behaviors and motions.The development of ultrashort pulsed X-ray and electron sources has resulted in the visualization of the key structural dynamics on the femto- to picosecond time scale not only in isolated molecules but also in assembled molecules, such as in the LC, crystal, and amorphous phases. We focus on ultrafast phenomena in molecular assemblies induced by photoexcitation. Ultrafast time-resolved electron diffraction measurements are sensitive to the molecular periodicity under photoexcitation, and thus the methodologies directly provide the ultrafast photoinduced molecular dynamic arrangements.In this Account, we describe ultrafast structural dynamics of molecules in the LC phases observed by time-resolved electron diffraction measurements. Photoinduced conformational changes of LC molecules is shown as the example, which is the first observation of LC molecule using time-resolved electron diffraction. It is important to understand the correlation between the conformational or configurational changes induced in a photoirradiated single molecule and the oriented collective motions of molecular assemblies induced by intermolecular interaction. We also show observation of collective motions of azobenzene LC molecules. The collective motions are initiated from photoreaction in a single molecule and are subsequently amplified by the steric interaction with its neighboring molecules.One remaining challenge is to create the platform of materials and sample preparations for time-resolved electron diffraction experiments, which can only be achieved by the interdisciplinary fusion of the fields of materials chemistry and ultrafast science. Time-resolved electron diffraction is a powerful tool for structural investigation of molecular materials with a dynamic nature, whose adaptability goes beyond that of more complex assemblies of carbon nanomaterials. This methodology will extend the possibility to investigate motions of a variety of molecular self-assemblies on a larger scale, for example, to understand responses of biomolecular assemblies and intermolecular chemical reactions.
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http://dx.doi.org/10.1021/acs.accounts.0c00576DOI Listing
February 2021

Low-grade myofibroblastic sarcoma of the levator scapulae muscle: a case report and literature review.

BMC Musculoskelet Disord 2020 Dec 10;21(1):836. Epub 2020 Dec 10.

Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.

Background: Low-grade myofibroblastic sarcoma (LGMS) is described as a distinct atypical myofibroblastic tumor often with fibromatosis-like features and predilection for the head and neck, especially the oral cavity and larynx. LGMS arising in the levator scapulae muscle is extremely rare.

Case Presentation: A 69-year-old woman was admitted to our hospital because she noticed a hard mass in her left neck six months prior. Magnetic resonance images (MRI) showed a soft tissue tumor of the left levator scapulae muscle. A core needle biopsy showed cellular fascicles or a storiform growth pattern of spindle-shaped tumor cells with minimally atypia. Immunohistochemistry revealed focally positive for α-smooth muscle actin (α-SMA), negative for S-100, and a low-grade spindle cell sarcoma was suspected. Following a biopsy, the tumor was resected with a wide surgical margin. Immunohistochemical staining was a positive for vimentin and α-SMA and negative for desmin, CD34, nuclear β-catenin, and h-caldesmon. LGMS diagnosis was determined based on the histopathological findings. The patient was alive with no evidence of disease eight years after the surgery.

Conclusions: To the best of our knowledge, this is the first case report of LGMS arising in the levator scapulae muscle. In addition to the case report, 48 reports with 103 LGMS cases are reviewed and discussed. In previous reports of LGMS, there were 43 females and 60 males, with a mean age of 43.0 years (range, 2-75). There were 13 (12.6%) patients aged < 18 years, 67 (65.1%) patients aged 18 to 59 years, and 23 (22.3%) patients aged ≥60 years. The average tumor size was 4.4 cm (range: 0.4-22.0). The commonest sites of LGMS was the tongue. Tumor growth patterns were evaluated in 52 cases, and 44 cases (84.6%) showed infiltrative growth patterns. Local recurrence was 26.7%, and distant metastasis was 4.4%. Because of the locally aggressive feature, it is important to diagnose LGMS with biopsy and to excise the tumor with an adequately wide margin.
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http://dx.doi.org/10.1186/s12891-020-03857-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731512PMC
December 2020

Mesh exposure after transvaginal mesh prolapse surgery: Out of permissible range?

Int J Urol 2021 02 10;28(2):202-207. Epub 2020 Nov 10.

Department of, Urology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.

Objectives: To investigate the prevalence of postoperative complications after transvaginal mesh prolapse surgery, and whether modified transvaginal mesh prolapse surgery (without transobturator arms or posterior mesh) has less prevalence of mesh exposure compared with conventional transvaginal mesh prolapse surgery.

Methods: Medical charts were retrospectively examined for 2648 patients who underwent transvaginal mesh prolapse surgery in a general hospital (2006-2017). Conventional transvaginal mesh prolapse surgery (Prolift-type, n = 2258) was used, with a shift from 2015 to modified transvaginal mesh prolapse surgery (Uphold-type, n = 330). Patients were instructed to have >2 years of follow up and to report if they had problems regarding the operation.

Results: The prevalence of mesh exposure was 34 out of 2648 (1.28%); 18 vagina (0.68%), 10 bladder (0.38%), two ureter (0.08%) and four rectum (0.15%). The modified transvaginal mesh prolapse surgery group had only one case with vaginal exposure. Vaginal exposure was managed transvaginally or followed by observation. Rectal exposure was managed transvaginally without colostomy. Bladder exposure was managed by transurethral resection with saline. Open ureterocystostomy was carried out to treat ureteral exposure. In the conventional transvaginal mesh prolapse surgery group, three cases of ureteral stenosis and one case with vaginal evisceration of the small intestine were managed transvaginally. The prevalence of postoperative chronic pain was 13 out of 2648 (0.49%; with one patient in the modified transvaginal mesh prolapse surgery group). The patients underwent pharmacotherapy, and one patient underwent additional surgical treatment.

Conclusions: The reoperation rate as a result of complications after transvaginal mesh prolapse surgery seems to be low. The reoperation rate as a result of prolapse recurrence is also low. A shift from conventional transvaginal mesh prolapse surgery to modified transvaginal mesh prolapse surgery might contribute to a further decrease in the risk of complications.
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http://dx.doi.org/10.1111/iju.14425DOI Listing
February 2021

Drp1 Tubulates the ER in a GTPase-Independent Manner.

Mol Cell 2020 11 4;80(4):621-632.e6. Epub 2020 Nov 4.

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

Mitochondria are highly dynamic organelles that continuously grow, divide, and fuse. The division of mitochondria is crucial for human health. During mitochondrial division, the mechano-guanosine triphosphatase (GTPase) dynamin-related protein (Drp1) severs mitochondria at endoplasmic reticulum (ER)-mitochondria contact sites, where peripheral ER tubules interact with mitochondria. Here, we report that Drp1 directly shapes peripheral ER tubules in human and mouse cells. This ER-shaping activity is independent of GTP hydrolysis and located in a highly conserved peptide of 18 amino acids (termed D-octadecapeptide), which is predicted to form an amphipathic α helix. Synthetic D-octadecapeptide tubulates liposomes in vitro and the ER in cells. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.
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http://dx.doi.org/10.1016/j.molcel.2020.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680448PMC
November 2020
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