Publications by authors named "Hiroki Takahashi"

730 Publications

Monitoring Intramural Hematoma on Vessel Wall Imaging to Evaluate the Healing of Intracranial Vertebral Artery Dissection.

J Stroke Cerebrovasc Dis 2021 Jul 19;30(9):105992. Epub 2021 Jul 19.

Department of Neurosurgery Graduate School of Biomedical and Health Sciences Hiroshima University, Hiroshima, Japan.

Objective: Unruptured intracranial vertebral artery dissection (VAD) generally heals spontaneously. A chronological evaluation of intramural hematoma (IMH) using T1-weighted vessel wall imaging (VWI) may provide a more detailed understanding of the pathophysiology of VAD. We herein investigated the relationship between chronological signal changes in IMH on VWI and the spontaneous healing of VAD.

Materials And Methods: We retrospectively investigated 26 patients with 27 unruptured VADs who underwent magnetic resonance (MR) imaging more than three times during the follow-up period. Morphological changes were evaluated using MR angiography (MRA). The relative signal intensity (RSI) of IMH against the posterior cervical muscle on T1-weighted VWI was calculated. The ratio of chronological RSI changes was defined as follows: maximum RSI/minimum RSI (RSI ). Based on the median value of RSI , 27 VADs were divided into VADs with and without chronological RSI changes. Statistical analyses were performed to compare clinical and radiological findings between the two groups.

Results: Spontaneous healing occurred in 17 out of 27 VADs (63%). The median value of RSI was 1.48. The RSI of VADs with chronological RSI changes (RSI ≥ 1.48) increased until three weeks after their onset and decreased over time, while that of VADs without chronological RSI changes (RSI < 1.48) showed no change. The frequency of healing was significantly higher in VADs with than without chronological RSI changes (100% vs 23%, p < 0.0001).

Conclusions: Chronological signal changes in IMH on T1-weighted VWI have potential as a diagnostic imaging marker of the spontaneous healing of VAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105992DOI Listing
July 2021

Serum IgG level is a predicting factor for the response to neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma.

World J Surg Oncol 2021 Jul 19;19(1):217. Epub 2021 Jul 19.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya City, Aichi, 467-8602, Japan.

Background: Despite the established oncological benefits of neoadjuvant chemotherapy for esophageal squamous cell cancer, not all cases demonstrate benefit. Hence, predicting the response to chemotherapy before treatment is desirable. Some reports have shown that immune factors are related to the chemotherapy response. This study aimed to investigate the utility of serum IgG levels for predicting chemotherapy response.

Methods: Among the patients who underwent esophagectomy after neoadjuvant chemotherapy at Nagoya City University Hospital between December 2012 and June 2019, 130 cases were included in this study. Response to chemotherapy and pretreatment serum IgG levels were examined in 77 cases. FP (5-fluorouracil and cisplatin) therapy or DCF (docetaxel, cisplatin, and 5-FU) therapy was performed as neoadjuvant chemotherapy. DCF therapy was selected for patients aged <75 years, who could be safely administered chemotherapy based on their medical history.

Results: This study divided cases into two groups: the effective response group (PR) and ineffective response group (SD and PD). We classified 1, 37, and 39 cases as PD, PR, and SD, respectively. None of the cases were classified as CR. The effective response group had significantly lower serum IgG levels than the ineffective response group (p < 0.001). The cutoff serum IgG value was determined to be 1087 mg/dL. The low IgG group had significantly more cases who had effective response to chemotherapy compared with the high IgG group (odds ratio [OR] = 9.009; 95% confidence interval [CI] = 2.974-30.157; p < 0.001). Univariate and multivariate analyses revealed serum IgG level to be an independent predictor for response to chemotherapy (p = 0.001). Furthermore, cases with effective pathological response had significantly lower pretreatment serum IgG levels than those who did not (p = 0.006).

Conclusions: Our finding showed that serum IgG levels can be an independent predictor of the response to neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

Trial Registration: This retrospective study was approved by the review board of Nagoya City University Graduate School of Medical Sciences (reception number: 60-18-0008 ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-021-02290-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290605PMC
July 2021

Association between thrombolysis in myocardial infarction grade and clinical outcome after emergent percutaneous coronary intervention in patients with acute myocardial infarction who have suffered out-of-hospital cardiac arrest: the Yamagata AMI registry.

Heart Vessels 2021 Jul 6. Epub 2021 Jul 6.

Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.

Despite improvements in the survival rate of acute myocardial infarction (AMI), out-of-hospital cardiac arrest (OHCA) due to AMI is still a devastating condition. Thrombolysis in myocardial infarction (TIMI) grade is used to classify coronary reperfusion after percutaneous coronary intervention (PCI), but it remains unclear whether TIMI grade after emergent PCI is associated with short-term mortality in patients with AMI who have suffered OHCA. We analyzed data collected from 2012 to 2017 and recorded in the Yamagata AMI registry, which is a multicenter surveillance conducted in all institutions in Yamagata prefecture. Among 3332 patients with AMI, 254 had suffered OHCA. There were 564 deaths during the 30 days after the onset of AMI. The survival rate was lower in patients who had suffered OHCA than in those who had not (40% vs. 87%; P < 0.0001). Patients with AMI who had suffered OHCA were divided into three groups based on TIMI grade (TIMI III group, n = 70; TIMI ≤ II group, n = 21; and no coronary angiography [non-CAG] group, n = 163). The survival rates in the TIMI III, TIMI ≤ II, and non-CAG groups were 87%, 38%, and 5%, respectively. Kaplan-Meier analysis demonstrated that the survival rate was highest in the TIMI III group. Multivariate Cox proportional hazard regression analysis demonstrated that TIMI III was closely associated with survival after adjustment for confounding factors. Achieving TIMI grade III during emergent PCI is crucial to improve survival in patients with AMI who have suffered OHCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00380-021-01903-1DOI Listing
July 2021

Crystal structure and photoreactive behaviour of ,-diisoprop-yl(-phenyl-phen-yl)glyoxyl-amide.

Acta Crystallogr E Crystallogr Commun 2021 Jun 28;77(Pt 6):653-657. Epub 2021 May 28.

Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.

The title compound [systematic name: 2-([1,1'-biphen-yl]-4-yl)-2-oxo-,-bis(propan-2-yl)acetamide], CHNO was synthesized and its photoreactive properties in the crystalline state and in aceto-nitrile solution were investigated. The compound crystallizes in the chiral space group 222. The crystal does not react under UV light irradiation, perhaps due to the presence of the biphenyl group. However, the compound is photoreactive in aceto-nitrile solution to give racemic 3-(-phenyl-phen-yl)-3-hy-droxy--isopropyl-4,4-di-methyl-azetidin-2-one.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2056989021005387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183449PMC
June 2021

The clinical impact of robot-assisted laparoscopic rectal cancer surgery associated with robot-assisted radical prostatectomy.

Asian J Endosc Surg 2021 Jun 19. Epub 2021 Jun 19.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Introduction: Robot-assisted laparoscopic surgery has been performed in various fields, especially in the pelvic cavity. However, little is known about the utility of robot-assisted laparoscopic rectal cancer surgery associated with robot-assisted radical prostatectomy (RARP). We herein report the clinical impact of robot-assisted laparoscopic rectal cancer surgery associated with RARP.

Methods: We experienced five cases of robot-assisted laparoscopic rectal cancer surgery associated with RARP. One involved robot-assisted laparoscopic abdominoperineal resection with en bloc prostatectomy for T4b rectal cancer, and one involved robot-assisted laparoscopic intersphincteric resection combined with RARP for synchronous rectal and prostate cancer. The remaining three involved robot-assisted laparoscopic low anterior resection (RaLAR) after RARP. For robot-assisted laparoscopic rectal cancer surgery, the da Vinci Xi surgical system was used.

Results: We could perform planned robotic rectal cancer surgery in all cases. The median operation time was 529 min (373-793 min), and the median blood loss was 307 ml (32-1191 ml). No patients required any transfusion in the intra-operative or immediate peri-operative period. The circumferential resection margin was negative in all cases. There were no complications of grade ≥III according to the Clavien-Dindo classification and no conversions to conventional laparoscopic or open surgery.

Conclusion: Robot-assisted laparoscopic surgery associated with RARP is feasible in patients with rectal cancer. The long-term surgical outcomes remain to be further evaluated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ases.12961DOI Listing
June 2021

Identification of novel mutations contributing to azole tolerance of through exposure to tebuconazole.

Antimicrob Agents Chemother 2021 Jun 14:AAC0265720. Epub 2021 Jun 14.

Medical Mycology Research Center, Chiba University, Chiba, Chiba, Japan.

Azole resistance of is a global problem. The major resistant mechanism is a cytochrome P 14-α sterol demethylase Cyp51A alteration such as mutation(s) in the gene and the acquisition of a tandem repeat in the promoter. Although other azole tolerances and resistant mechanisms such as (a 3-hydroxy-3-methylglutaryl-coenzyme-A reductase gene) mutation are known, few reports have described studies elucidating non-Cyp51A resistance mechanisms. This study explored genes contributing to azole tolerance in by mutant selection with tebuconazole, an azole fungicide. After three-round selection, we obtained four isolates with low susceptibility to tebuconazole. These isolates also showed low susceptibility to itraconazole and voriconazole. Comparison of the genome sequences of the obtained isolates and the parental strain revealed a non-synonymous mutation in MfsD for a major facilitator superfamily protein (Afu1g11820, R337L mutation) in all isolates. Furthermore, non-synonymous mutations in AgcA for a mitochondrial inner membrane aspartate/glutamate transporter (Afu7g05220, E535Stop mutation), UbcD for a ubiquitin-conjugating enzyme E2 (Afu3g06030, T98K mutation), AbcJ for an ABC transporter (Afu3g12220, G297E mutation), and RttA for a putative protein esponsible for ebuconazole olerance (Afu7g04740, A83T mutation), were found in at least one isolate. Disruption of the gene led to decreased susceptibility to azoles. Reconstruction of the A83T point mutation in RttA led to decreased susceptibility to azoles. Reversion of T98K mutation to wild type in UbcD led to decreased susceptibility to azoles. These results suggest that these mutations contribute to lowered susceptibility to medical azoles and agricultural azole fungicides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02657-20DOI Listing
June 2021

Prognostic value of 6-min walk stress echocardiography in patients with interstitial lung disease.

J Echocardiogr 2021 Jun 5. Epub 2021 Jun 5.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan.

Background: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD.

Methods: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected.

Results: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD.

Conclusions: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12574-021-00532-xDOI Listing
June 2021

Suitable Diagnosis and Treatment of Esophageal Ruptures in Cases of Non-Boerhaave Syndrome: A Comparison With Boerhaave Syndrome.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211014683

Nagoya City University, Nagoya City, Japan.

Boerhaave syndrome (BS) is frequently reported in cases of esophageal perforation; however, there are relatively few studies on non-Boerhaave syndrome (nBS). This study clarifies the appropriate diagnosis and treatment for patients with nBS among those with esophageal ruptures. Twelve patients with esophageal ruptures who underwent surgery at our department over 14 years were classified into 2 groups: 4 in the nBS group and 8 in the BS group. Patient characteristics, surgical methods, surgical outcomes, and complications were compared between the groups. The chief complaints varied between the groups. The nBS group had significantly higher preoperative C-reactive protein ( = .007) and required 5 days (median) from onset to surgery. Moreover, the perforation diameter was significantly smaller in the nBS group than in the BS group ( = .013). Suturing of the perforation site was performed during the initial surgery in 8 BS group patients (100%) and 1 nBS group patient (25%; = .018). Only drainage was performed during the initial surgery for 3 nBS group patients (75%). The complications did not significantly differ between the groups ( = 1.000), and no deaths were reported. The chief complaints of patients with nBS are diverse, and esophageal perforation should be cited as a differential diagnosis even in the absence of vomiting or chest pain symptoms. In the initial surgery for patients with nBS, the perforation site does not necessarily need to be closed. It is treatable by second-stage surgery or by natural closing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/23247096211014683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127747PMC
May 2021

Motobamide, an Antitrypanosomal Cyclic Peptide from a sp. Marine Cyanobacterium.

J Nat Prod 2021 05 13;84(5):1649-1655. Epub 2021 May 13.

Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.

Motobamide (), a new cyclic peptide containing a -prenylated cyclotryptophan residue, was isolated from a marine sp. cyanobacterium. Its planar structure was established by spectroscopic and MS/MS analyses. The absolute configuration was elucidated based on a combination of chemical degradations, chiral-phase HPLC analyses, spectroscopic analyses, and computational chemistry. Motobamide () moderately inhibited the growth of bloodstream forms of (IC 2.3 μM). However, it exhibited a weaker cytotoxicity against normal human cells (IC 55 μM).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.1c00234DOI Listing
May 2021

Diagnosis of recurrent laryngeal nerve paralysis following esophagectomy by evaluating movement of the vocal cords and arytenoid cartilages using ultrasonography.

Esophagus 2021 Jul 5;18(3):704-709. Epub 2021 May 5.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, 1 Kawasumi, Mizuho-ku, Nagoya, Aichi, Japan.

Advancements in thoracoscopic surgery have provided us with a deeper anatomical understanding of recurrent laryngeal nerve paralysis (RLNP), which is likely to occur after lymph node dissection. Taking a novel approach to researching the diagnosis of RLNP, we evaluated movement of the vocal cords and arytenoid cartilages using ultrasonography in patients who underwent thoracoscopic esophagectomy. RLNP occurred in six of the 24 patient cohort. The rate of hoarseness and difficulty in discharging sputum was significantly higher in the paralyzed group than in the non-paralyzed group. The diagnostic accuracy of RLNP by ultrasonography had a sensitivity of 83.3% (5/6), a specificity of 88.8% (16/18), a false positive rate of 5.6% (1/18), and a false negative rate of 0% (0/6). Although it is not completely accurate, our findings indicate that ultrasonography is quite effective for diagnosing RLNP, more so in combination with clinical symptoms. Ultrasonography may also be effective for identifying patients who are amenable to laryngoscopy for diagnosing RLNP, or for evaluating the recovery status of nerve paralysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10388-021-00830-4DOI Listing
July 2021

Peptidylarginine Deiminase 4 as a Possible Biomarker of Plaque Instability in Carotid Artery Stenosis.

J Stroke Cerebrovasc Dis 2021 Jul 24;30(7):105816. Epub 2021 Apr 24.

Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address:

Background And Purpose: Neutrophil extracellular traps (NETs) exhibit pro-inflammatory and pro-thrombotic properties. However, they have only been reported as important regulators in atherosclerosis, especially in atherothrombosis. We investigated the presence of NETs and plaque instability in patients with carotid artery stenosis.

Material And Methods: A total of 39 consecutive patients with carotid artery stenosis were evaluated. All patients underwent carotid artery stenting (CAS) with dual protection (simultaneous flow reversal + distal filter) and blood aspiration as a method of distal embolism prevention. Local arterial blood was aspirated at the stent site and peptidylarginine deiminase 4 (PAD4), which is essential for the formation of NETs, was measured. The relationships between PAD4 and the patient profile, blood examination and plaque data were investigated.

Results: The mean value of PAD4 in local arterial blood in CAS was 0.5 ng/ml. Bivariate analysis demonstrated that PAD4 was associated with the neutrophil to lymphocyte ratio (p = 0.007), high-density lipoprotein (p = 0.02), triglycerides to high-density lipoprotein ratio (p = 0.007), ulceration (p = 0.02) and plaque contrast enhancement on T1 black blood imaging (p = 0.03). In multiple linear regression analyses, PAD4 was correlated with the neutrophil to lymphocyte ratio (p = 0.01) and ulceration (p = 0.01, cut-off value: 0.49 odds ratio: 19.3).

Conclusions: PAD4, representative of the presence of NETs, was high in carotid plaques with unstable features. The neutrophil to lymphocyte ratio in peripheral blood was suggested to be a biomarker of vulnerable plaques. Elucidating the role of NETs may aid in clarifying factors that promote the instability of carotid plaques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105816DOI Listing
July 2021

T-staging of rectal cancer: Utility of single-shot turbo spin-echo diffusion-weighted imaging with T2-weighted images and fusion images.

PLoS One 2021 21;16(4):e0249433. Epub 2021 Apr 21.

Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Purpose: The purpose of this study was to evaluate the usefulness of turbo spin-echo (TSE) DWI with fusion images in the T-staging compared with T2-weighted imaging (T2WI) alone and conventional echo-planner imaging (EPI) DWI.

Methods: In this prospective study, 4-mm-thick axial EPI-DWI, TSE-DWI, and T2WI were performed with the same slice locations for 20 patients with rectal cancer. Fusion images of DWI and T2WI were created for both EPI-DWI and TSE-DWI. Ten readers independently diagnosed the T-stages and scored the degree of confidence referring to T2WI alone and then to DWI, T2WI, and fusion images (DWI+T2WI) for each EPI-DWI and TSE-DWI. Visual score assessments of image quality were performed for each DWI.

Results: Inter-observer agreement of T-staging for 10 readers was slight on T2WI alone but fair on EPI-DWI+T2WI and excellent on TSE-DWI+T2WI images. No readers gave higher confidence scores for T2WI compared to EPI/TSE-DWI+T2WI and for EPI-DWI+T2WI compared to TSE-DWI+T2WI. In seven pathologically-proven cases, poor, poor to slight, and fair to perfect agreements with the pathological T-stage were observed with T2WI alone, EPI-DWI+T2WI, and TSE-DWI+T2WI, respectively. All readers gave higher scores regarding image distortion and lower scores regarding image noise for TSE-DWI compared to EPI-DWI. For DWI utility, higher scores were assigned for TSE-DWI compared to EPI-DWI in 7 readers and there were no significant differences in the other 3 readers.

Conclusion: TSE-DWI images might be more appropriate for image fusion with T2WI and rectal cancer T-staging compared with EPI-DWI and T2WI alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249433PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059798PMC
April 2021

Sarcoidosis development during ulcerative colitis remission in a patient with a susceptible human leukocyte antigen serotype.

Sarcoidosis Vasc Diffuse Lung Dis 2021 31;38(1):e2021010. Epub 2021 Mar 31.

Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.

The combination of sarcoidosis and ulcerative colitis (UC) is very rare, and its pathogenesis remains unknown. Hereditary factors as well as environmental factors have been speculated, including an association with the human leucocyte antigen (HLA) genotype. A 62-year-old Japanese woman with UC presented with complaint of a cough. Abnormal shadows were evident on the chest X-ray during mesalazine therapy. Multiple indolent subcutaneous nodules were also detected. Transbronchial lung and skin biopsies showed non-caseous epithelioid granulomas, which were pathologically compatible with sarcoidosis. After steroid therapy, she became asymptomatic and the abnormal shadows and subcutaneous nodules disappeared. HLA serological typing revealed that she harbored the sarcoidosis-related HLA-DR14 allele, as well as UC-related HLA-B52 and HLA-DR15 alleles. This case suggests that a susceptible HLA genotype may influence the onset of the combination of sarcoidosis and UC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.36141/svdld.v38i1.6722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050618PMC
March 2021

The complete chloroplast genome of medic (Malvaceae).

Mitochondrial DNA B Resour 2021 Mar 16;6(3):912-913. Epub 2021 Mar 16.

Medical Mycology Research Center, Chiba University, Chiba, Japan.

Medic is a traditional Chinese medicine, which can be seen nearly everywhere in China. In order to study its complete chloroplast genome, we collected leaves and obtained chloroplast genome information through next-generation sequencing. It showed that the genome whole length is 160,331 bp, resulted from 24,578,194 raw reads with 3,669,530,829 bases in total, and the GC contents ratio is 36.90%. Besides, the large single-copy region (LSC) is 89,006 bp, the small single-copy region (SSC) 20,149 bp, and inverted repeat (IR) 25,588 bp. The chloroplast genome encodes 76 genes, which contains 38 protein genes, five rRNA genes, and 33 tRNA. By conducting phylogenetic analysis for , plants from genus demonstrated close relationship with it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2021.1886886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971203PMC
March 2021

Outcomes of patients with OHCA of presumed cardiac etiology that did not achieve prehospital restoration of spontaneous circulation: The All-Japan Utstein Registry experience.

Resuscitation 2021 05 22;162:245-250. Epub 2021 Mar 22.

Department of Emergency and Critical Care Medicine, Kansai Medical University, Hirakata, Osaka, Japan.

Background: Correct identification of futile prehospital resuscitation for out-of-hospital cardiac arrest (OHCA) may reduce unnecessary transports. Prehospital return of spontaneous circulation (ROSC) is considered by many to be an important predictor of outcome. The purpose of this study was to evaluate OHCA victims without prehospital ROSC characteristics and their outcomes in relation to the universal Termination of Resuscitation (TOR) rule.

Methods: A retrospective, population-based review of OHCA victims without prehospital ROSC from January 1, 2010 to December 31, 2017 in the All-Japan Utstein Registry. We compared those that met the universal TOR rule and those that did not for the primary outcome: one-month survival with neurologically favorable Cerebral Performance Category (CPC) 1 or 2.

Results: 989,929 OHCA cases, 18 years of age or older, were registered in the All-Japan Utstein Registry and 525,801 cases were of presumed cardiac origin and had no prehospital ROSC. Of these, the one-month CPC was 1 or 2 for 3957 cases (0.8%). In the 'no ROSC' group who also met the TOR rule, the number of cases was 433,571 with a one-month survival of 0.9% (3799 cases), and the proportion with a CPC 1or 2 was 0.2% (699 cases).

Conclusions: Continued resuscitation and transport of cases with no field ROSC who fulfill the TOR rule is futile and could be considered for adoption in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resuscitation.2021.03.003DOI Listing
May 2021

Escin inhibits angiogenesis by suppressing interleukin‑8 and vascular endothelial growth factor production by blocking nuclear factor‑κB activation in pancreatic cancer cell lines.

Oncol Rep 2021 05 24;45(5). Epub 2021 Mar 24.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.

Pancreatic cancer (PaCa) is one of the most aggressive types of cancer. Thus, the development of new and more effective therapies is urgently required. Escin, a pentacyclic triterpenoid from the horse chestnut, has been reported to exhibit antitumor potential by reducing cell proliferation and blocking the nuclear factor‑κB (NF‑κB) signaling pathway in several types of cancer. Our previous study reported that NF‑κB enhanced the secretion of interleukin (IL)‑8 and vascular endothelial growth factor (VEGF), thereby inducing angiogenesis in PaCa cell lines. In the present study, it was examined whether escin inhibited angiogenesis by blocking NF‑κB activation in PaCa. It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NF‑κB. Furthermore, ELISA confirmed that NF‑κB activity in the escin‑treated PaCa cells was significantly inhibited and reverse transcription‑quantitative PCR showed that the mRNA expression levels of tumor necrosis factor‑α‑induced and were significantly suppressed following escin treatment in the PaCa cell lines. ELISA also showed that escin decreased the secretion of IL‑8 and VEGF from the PaCa cells. Furthermore, tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin‑treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the secretion of IL‑8 and VEGF by blocking NF‑κB activity in PaCa. In conclusion, escin could be used as a novel molecular therapy for PaCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2021.8006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962110PMC
May 2021

Differential effect of malnutrition between patients hospitalized with new-onset heart failure and worsening of chronic heart failure.

ESC Heart Fail 2021 06 2;8(3):1819-1826. Epub 2021 Mar 2.

Department of Cardiology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, 5708507, Japan.

Aims: We aimed to investigate the differences in the prevalence, severity, and prognostic impact of malnutrition between patients with new-onset heart failure (HF) and worsening of chronic HF.

Methods And Results: In older (≥60 years) hospitalized patients with acute HF, malnutrition was assessed according to the Geriatric Nutritional Risk Index (GNRI). A score <92 was defined as malnutrition. The primary endpoint was a composite endpoint, including cardiac death or rehospitalization for HF. Among 210 patients, 37% (52/142) of patients with new-onset HF and 31% (21/68) of patients with worsening of chronic HF had malnutrition (P = 0.41). The GNRI classification was comparable between the two groups. Kaplan-Meier analysis revealed a significant difference in the incidence of the composite endpoint in patients with new-onset HF (GNRI < 92 vs. GNRI ≥ 92: 50% vs. 32%, P = 0.007), but not in patients with worsening of chronic HF (GNRI < 92 vs. GNRI ≥ 92: 67% vs. 68%, P = 0.91). The adjusted Cox proportional hazards model demonstrated that a GNRI of <92 was an independent prognostic factor for the composite endpoint in patients with new-onset HF only.

Conclusions: Among older hospitalized patients with acute HF, the prevalence and severity of malnutrition were comparable between the two categories of patients. Malnutrition was an independent prognostic factor in patients with new-onset HF, while clinical prognosis was poor in patients with worsening of HF, irrespective of malnutrition. The prognostic impact of malnutrition differs between new-onset HF and worsening of chronic HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120416PMC
June 2021

A novel balloon-attached endoscopy-assisted reduction technique for an acute strangulated stoma prolapse.

Endoscopy 2021 Feb 19. Epub 2021 Feb 19.

Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1346-8427DOI Listing
February 2021

A hybrid approach for chronic pancreatitis: combination of laparoscopic assisted distal pancreatectomy and open Frey procedure.

BMC Surg 2021 Feb 18;21(1):91. Epub 2021 Feb 18.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 4678601, Japan.

Background: The treatment of chronic pancreatitis requires a surgical approach in patients who are refractory to medical therapy. During surgical treatment, ductal decompression is required, but a pancreatectomy is necessary for some patients, such as those with severe stenosis of the pancreatic duct. Indeed, suboptimal procedures lead to recurrent pancreatitis. We used a laparoscopic hybrid approach for patients with severe stenosis of the pancreatic duct. In this report, we present the feasibility and outcomes of our approach.

Methods: We selected a laparoscopic approach for the distal pancreatectomy, which is relatively safe and the effect of reducing the length of the wound is substantial. We selected an open approach for the Frey procedure because complete ductal compression has a high risk for injury to the vessels posterior to the pancreas. We recorded the operative outcomes, postoperative complications, and recurrence of pancreatitis.

Results: We performed the laparoscopic hybrid approach on 3patients between January and December 2018. There were no major intraoperative complications (Clavien-Dindo classification IIIa or more) and the postoperative course was uneventful in all patients. There were no recurrences of pancreatitis and no postoperative pain in all patients in > 2 years of follow-up.

Conclusion: Our hybrid method with a focus on complete ductal compression with safety and minimal invasiveness might be the optimal approach for the surgical treatment of chronic pancreatitis that requires a pancreatectomy with the Frey procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12893-021-01096-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891013PMC
February 2021

Prognostic significance of the controlling nutritional (CONUT) score in patients with acute coronary syndrome.

Heart Vessels 2021 Aug 4;36(8):1109-1116. Epub 2021 Feb 4.

The Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.

Background: Malnutrition is an independent predictor of adverse outcomes in patients with acute coronary syndrome. The controlling nutritional (CONUT) score has been applied to assess nutritional status, and has been reported to be associated with poor prognosis in patients with heart failure. However, the prognostic impact of the CONUT score in patients with acute coronary syndrome (ACS) remains to be elucidated.

Methods: We evaluated the CONUT score in 196 patients with ACS who underwent percutaneous coronary intervention. We divided the patients into four groups according to CONUT score (undernutrition degree: normal, CONUT 0-1 (reference); mild, CONUT 2-4; moderate, CONUT 5-8; severe, CONUT 9-12). The endpoint of the present study was composite events including all-cause death, acute coronary syndrome, target vessel revascularization, and stroke.

Results: The median CONUT score was significantly higher in patients with composite events than in those without events (P = 0.0058). Kaplan-Meier analysis revealed that a significantly higher event rate in patients with severe malnutrition (log-rank test, P = 0.0222). In the multivariate Cox proportional hazards analysis, CONUT score was independently associated with composite events after adjustment for confounding factors (adjusted hazard ratio 1.284, 95% confidence interval 1.126-1.457, P = 0.0003).

Conclusion: Higher CONUT scores were associated with unfavorable outcomes in patients with ACS. Malnutrition assessed by the CONUT score may provide valuable prognostic information in patients with ACS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00380-021-01792-4DOI Listing
August 2021

Efficacy of intraoperative ICG fluorescence imaging evaluation for preventing anastomotic leakage after left-sided colon or rectal cancer surgery: a propensity score-matched analysis.

Surg Endosc 2021 05 25;35(5):2373-2385. Epub 2021 Jan 25.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi-cho, Mizuho-ku, Nagoya, Aichi, 467-8602, Japan.

Background: Intestinal perfusion at the anastomotic site is thought to be one of the most influential risk factors for postoperative anastomotic leakage (AL). We evaluated the efficacy of indocyanine green (ICG) fluorescence imaging at the stump of the proximal colon in left-sided colectomy or rectal resection in terms of decreasing the incidence of AL.

Methods: Prospectively collected data were retrospectively evaluated. Patients who underwent left-sided colectomy or rectal resection were enrolled (ICG group; n = 197), and patients who had undergone a similar procedure before the ICG group were enrolled from the charts as historical controls (HC group; n = 187). After ICG evaluation, anastomosis was performed where fluorescence was sufficient. The incidence of AL was compared between the ICG and HC groups. Propensity score (PS)-matched data were analyzed to clarify the risk of AL.

Results: AL occurred in 6 patients (3.3%) in the ICG group and 17 (10.7%) in the HC group. ICG evaluation revealed 179 patients with good fluorescence and 18 with poor/none perfusion (9.1%). The transection line was changed in all patients with poor/none fluorescence. Three of these 18 patients developed AL (16.7%), though transection line was changed at which is thought to be good. We hope AL in poor/none fluorescence can be prevented at the same rate of cases with good fluorescence. Actually, the rate of that was significantly higher compared with good fluorescence patients (P = 0.038). 93 patients in each group were compared by PS-matched data analysis, which showed the AL rate in the ICG group was significantly lower than that in the HC group (3.2% vs 10.8%, respectively; P = 0.046).

Conclusions: Even though this study has limitations of comparison of data prospectively collected and retrospectively analyzed, intraoperative ICG fluorescence imaging evaluation could significantly decrease the incidence of AL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-020-08230-yDOI Listing
May 2021

Idiopathic retroperitoneal fibrosis diagnosed by endoscopic ultrasonography-guided fine-needle biopsy.

JGH Open 2021 Jan 14;5(1):151-152. Epub 2020 Oct 14.

Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan.

We demonstrate a case, in which endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) was useful for determining the diagnosis of lesions of retroperitoneal fibrosis. In our case, accessing the retroperitoneal lesions by conventional percutaneous biopsy procedures was not feasible due to the difficulty of avoiding the inferior vena cava and ureter. We believe that our case demonstrates a unique approach for performing histological analysis in a challenging case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812448PMC
January 2021

[A Case of Gallbladder Cancer with Para-Aortic Lymph Node Metastasis Successfully Treated by Gemcitabine plus Cisplatin Combination Chemotherapy and Conversion Surgery].

Gan To Kagaku Ryoho 2020 Dec;47(13):2204-2206

Dept. of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences.

The case is a 59-year-old woman. A medical examination revealed a high CA19-9, she visited a nearby hospital. Abdominal echo showed thickening of the gallbladder wall, and she was referred to our hospital for further examination. EUS-FNA was performed and a biopsy of #12 lymph node revealed undifferentiated cancer, which was diagnosed as gallbladder cancer. FDG-PET showed accumulation of FDG in the gallbladder lumen and swollen lymph nodes around the aorta. Therefore, the cancer was considered unresectable and chemotherapy was performed. FDG-PET was re-examined after 4 courses of gemcitabine plus cisplatin combination chemotherapy. As a result, the lymph node swelling contracted, the accumulation of FDG disappeared, and surgery was scheduled. Extended cholecystectomy and extrahepatic bile duct resection were performed. She was discharged 22 days after the surgery without complications. Histopathological examination showed fibrotic tissue at the gallbladder and lymph nodes, but no residual tumor cells. There are no recurrences 11 months after surgery. Although the prognosis of gallbladder cancer with para-aortic lymph node metastasis is generally poor, it is suggested that conversion surgery with multimodality treatment including preoperative chemotherapy may be a useful therapeutic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2020

Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis.

Nat Commun 2021 01 15;12(1):405. Epub 2021 Jan 15.

Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.

Plant genomes remain highly fragmented and are often characterized by hundreds to thousands of assembly gaps. Here, we report chromosome-level reference and phased genome assembly of Ophiorrhiza pumila, a camptothecin-producing medicinal plant, through an ordered multi-scaffolding and experimental validation approach. With 21 assembly gaps and a contig N50 of 18.49 Mb, Ophiorrhiza genome is one of the most complete plant genomes assembled to date. We also report 273 nitrogen-containing metabolites, including diverse monoterpene indole alkaloids (MIAs). A comparative genomics approach identifies strictosidine biogenesis as the origin of MIA evolution. The emergence of strictosidine biosynthesis-catalyzing enzymes precede downstream enzymes' evolution post γ whole-genome triplication, which occurred approximately 110 Mya in O. pumila, and before the whole-genome duplication in Camptotheca acuminata identified here. Combining comparative genome analysis, multi-omics analysis, and metabolic gene-cluster analysis, we propose a working model for MIA evolution, and a pangenome for MIA biosynthesis, which will help in establishing a sustainable supply of camptothecin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20508-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810986PMC
January 2021

The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.

Mod Rheumatol 2021 May 28;31(3):529-533. Epub 2021 Jan 28.

Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14397595.2020.1859710DOI Listing
May 2021

Unmet needs for emergency care and prevention of prehospital death in acute myocardial infarction.

J Cardiol 2021 Jun 30;77(6):605-612. Epub 2020 Nov 30.

Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

Introduction: Percutaneous coronary intervention (PCI) has successfully reduced the mortality of patients with acute myocardial infarction (AMI). However, patients with out-of-hospital cardiac arrest have high mortality, which is difficult to control by hospital staff. In this study, we investigated the prevalence of prehospital death (PHD) in patients with AMI. Furthermore, we investigated the risk factors associated with 30-day mortality in patients with AMI who survived PHD.

Methods: We investigated the prevalence of PHD using data from the Yamagata AMI registry and from death certification of the entire Yamagata Prefecture in Japan between 2010 and 2015. Furthermore, we investigated the risk factors for 30-day mortality in patients who survived PHD, using data from the Yamagata AMI registry from 1993 to 2015. AMI was identified by the International Classification of Diseases, 10th revision code I21.

Results: Out of the 6984 patients with AMI, 3771 patients had PHD. Patients with PHD were older and more likely to be women than those without PHD. More PHD occurred in winter and spring than in summer or autumn. Multivariate regression analysis showed that age, female sex, and winter onset were independently associated with PHD. We also investigated the risk factors associated with 30-day mortality in 9675 patients who survived PHD. The rate of PCI was remarkably lower in patients with acute death than in those without acute death. Multivariate regression analysis showed that age, anterior infarction, estimated glomerular filtration rate, Killip class, and PCI were independently associated with 30-day mortality after adjusting for confounding factors.

Conclusion: Approximately half of the patients with AMI died before they could reach the destination hospital. Although emergency PCI is the most important factor in reducing 30-day mortality in patients with AMI, attempts to reduce patient delay and system delay are possibly needed to further reduce PHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2020.11.013DOI Listing
June 2021

Simple Synthesis of a Heterocyclophane Exhibiting Anti-c-Met Activity by Acting as a Hatch Blocking Access to the Active Site*.

Chemistry 2021 Jan 15;27(5):1648-1654. Epub 2020 Dec 15.

SilcsBio LLC, 20 Penn Street, Baltimore, Maryland, 21201, USA.

A simple approach to the synthesis of heterocyclophane consisting of two 4,4'-bithiazoles has been developed in mild conditions. The heterocyclophane with two short chains was conveniently prepared by Hantzsch thiazoles synthesis using the reaction of 3-tert-butoxycarbonyl-3-azapentanethiocarboxamide with 1,4-dibromobutane-2,3-dione in methanol under reflux for only 15 min. Amino groups at the linkers of this heterocyclophane can be functionalized to give acylated and carbamate derivatives. Their properties as protein kinase inhibitors were investigated, and one of the heterocyclophanes exhibited specific anti-activity for c-mesenchymal epithelial transition factor (IC =603 nm), among seven types of protein kinases investigated. The computational site identification by ligand competitive saturation method was used to determine why the one heterocyclophane exhibited strong anti-activity for c-mesenchymal epithelial transition factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202001382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887132PMC
January 2021

Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan.

Respir Res 2020 Nov 30;21(1):316. Epub 2020 Nov 30.

Department of Respiratory Medicine and Allergology, School of Medicine, Sapporo Medical University, South 1, West 16, Sapporo, 060-8543, Japan.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone.

Methods: We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated.

Results: In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group.

Conclusions: Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-020-01582-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706186PMC
November 2020

Correction to: G:U‑Independent RNA Minihelix Aminoacylation by Nanoarchaeum equitans Alanyl‑tRNA Synthetase: An Insight into the Evolution of Aminoacyl‑tRNA Synthetases.

J Mol Evol 2020 Dec;88(10):759-760

Department of Biological Science and Technology, Tokyo University of Science, 6‑3‑1 Niijuku, Katsushika‑ku, Tokyo, 125‑8585, Japan.

In the original version of this article, "A73" in Fig 6b was inadvertently labeled as "G73". The corrected Fig. 6 is given here.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00239-020-09975-9DOI Listing
December 2020
-->