Publications by authors named "Simon Lee"

652 Publications

Electronic Health Records-Based Cardio-Oncology Registry for Care Gap Identification and Pragmatic Research: Procedure and Observational Study.

JMIR Cardio 2021 Mar 12. Epub 2021 Mar 12.

Cardiology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, US.

Background: Professional society guidelines are emerging for cardiovascular care in cancer patients. How effectively the cancer survivor population is screened and treated for cardiomyopathy in contemporary clinical practice remains unclear. As EHRs are now widely used in clinical practice, we tested the hypothesis whether an EHR-based cardio-oncology registry can address these questions.

Objective: To develop an electronic health records (EHR)-based pragmatic cardio-oncology registry and, as proof of principle, to investigate care gaps in cardiovascular care of cancer patients.

Methods: We generated programmatically a de-identified, real-time, EHR-based cardio-oncology registry from all patients in our institutional Cancer Population Registry (n=8275, 2011-2017). We investigated: 1) left ventricular ejection fraction (LVEF) assessment before and after treatment with potentially cardiotoxic agents, and 2) guideline-directed medical therapy (GDMT) for left ventricular dysfunction (LVD), defined as LVEF<50%, and symptomatic heart failure with reduced LVEF (HFrEF), defined as LVEF<50% and problem list documentation of systolic congestive heart failure or dilated cardiomyopathy.

Results: Rapid development of an EHR-based cardio-oncology registry was feasible. Identification of tests and outcomes was similar by EHR-based cardio-oncology registry and manual chart abstraction (100% sensitivity and 83% specificity for LVD). LVEF was documented prior to initiation of cancer therapy in 19.8% of patients. Prevalence of post-chemotherapy LVD and HFrEF was relatively low (9.4% and 2.5%, respectively). Among patients with post-chemotherapy LVD or HFrEF, those referred to cardiology had significantly higher prescription of GDMT.

Conclusions: EHR data can efficiently populate a real-time, pragmatic cardio-oncology registry as a byproduct of clinical care for healthcare delivery investigation.

Clinicaltrial:
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http://dx.doi.org/10.2196/22296DOI Listing
March 2021

A comparative investigation of the interaction and pharmacokinetics of hemoglobin with berberine and its oxymetabolite.

J Pharm Biomed Anal 2021 Mar 20;199:114032. Epub 2021 Mar 20.

The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China. Electronic address:

Berberine (BBR), isolated from Coptis chinensis, is one type of isoquinoline alkaloids. BBR exerts numerous of bioactivities but the plasma concentration is really low. In our previous study, a new oxymetabolite (OBB) has been discovered and showed superior anti-inflammatory effect comparing with BBR. The aim of this study is to investigate the interaction, metabolite and pharmacokinetics of BBR with hemoglobin. Sprague-Dawley rats were used to carry out the interaction, metabolite and pharmacokinetics of BBR and OBB in vivo. Fluorescence spectra were used to analyse the interaction in vitro. Results showed that OBB could be generated after intravenous injection or incubating with BBR in vitro and in vivo; Both BBR and OBB exerted much stronger binding interaction with hemoglobin than plasma and affect the conformation of bovine hemoglobin and change the fluorescence spectral properties; BBR and OBB were mainly presented and transported in the proteins-bound form. These results provide a new insight to understand the dynamic equilibrium of BBR and OBB within body from the perspective of new metabolic pathways.
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http://dx.doi.org/10.1016/j.jpba.2021.114032DOI Listing
March 2021

Hepatoprotective effect of Qushihuayu formula on non-alcoholic steatohepatitis induced by MCD diet in rat.

Chin Med 2021 Mar 16;16(1):27. Epub 2021 Mar 16.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.

Background: Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD) for which there is yet any standard pharmacotherapy. Traditional Chinese medicine formula such as Qushihuayu (QSHY) composing of multiple bioactive compounds has been used to treat NAFLD and NASH and shows beneficial effects over single compound treatment. This study aimed to investigate the mechanism of hepatoprotective effect of QSHY formula using a rat model.

Methods: Six-weeks old male Wistar rats were given methionine/choline supplemented (MCS) diet for 8 weeks and used as the blank control. Another 7 rats, which received methionine/choline deficient (MCD) diet in the first 6 weeks and a MCS&MCD (1:1) mixture diet in the last 2 weeks, were used as the model group. The groups of QSHY pre-treatment, low dosage, medium dosage and high dosage were given the same diet as the model group. Except for pre-treatment group (1 week in advanced of other groups), all QSHY treatment groups received QSHY formula by gavage every day since the MCD diet started.

Results: In the MCD diet group, the QSHY formula decreased the serum ALT and AST levels, lipid droplets, inflammation foci, FAS and α-SMA protein expression than MCD diet group. MAPK pathways phospharylation were markedly depressed by the QSHY formula. Moreover, QSHY formula enhanced PPAR-γ and p-p65 translocating into nucleus. The administration of QSHY increased hepatic mRNA levels of Transcription Factor 1 alpha (HNF1A), Hepatocyte Nuclear Factor 4 alpha (HNF4A) and Forkhead box protein A3 (FOXA3) which play a pivotal role in Hepatic stellate cell (HSCs) reprogramming.

Conclusion: These findings suggest that QSHY formula exerts a hepatoprotective effect against steatosis and fibrosis presumably via depressed MAPK pathways phosphorylation, reinforcement of PPAR-γ and p-p65 translocating into nucleus and enhanced HSCs reprogramming.
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http://dx.doi.org/10.1186/s13020-021-00434-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962269PMC
March 2021

The role of imaging in characterizing the cardiac natural history of Duchenne muscular dystrophy.

Pediatr Pulmonol 2021 Apr 2;56(4):766-781. Epub 2021 Mar 2.

Department of Pediatrics, The Heart Center, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio, USA.

Duchene muscular dystrophy (DMD) is a rare but devastating disease resulting in progressive loss of ambulation, respiratory failure, DMD-associated cardiomyopathy (DMD-CM), and premature death. The use of corticosteroids and supportive respiratory care has improved outcomes, such that DMD-CM is now the leading cause of death. Historically, most programs have focused on skeletal myopathy with less attention to the cardiac phenotype. This omission is rather astonishing since patients with DMD possess an absolute genetic risk of developing cardiomyopathy. Unfortunately, heart failure signs and symptoms are vague due to skeletal muscle myopathy leading to limited ambulation. Traditional assessment of cardiac symptoms by the New York Heart Association American College of Cardiology/American Heart Association Staging (ACC/AHA) classification is of limited utility, even in advanced stages. Echocardiographic assessment can detect cardiac dysfunction late in the disease course, but this has proven to be a poor surrogate marker of early cardiovascular disease and an inadequate predictor of DMD-CM. Indeed, one explanation for the paucity of cardiac therapeutic trials for DMD-CM has been the lack of a suitable end-point. Improved outcomes require a better proactive treatment strategy; however, the barrier to treatment is the lack of a sensitive and specific tool to assess the efficacy of treatment. The use of cardiac imaging has evolved from echocardiography to cardiac magnetic resonance imaging to assess cardiac performance. The purpose of this article is to review the role of cardiac imaging in characterizing the cardiac natural history of DMD-CM, highlighting the prognostic implications and an outlook on how this field might evolve in the future.
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http://dx.doi.org/10.1002/ppul.25227DOI Listing
April 2021

Protects PC12 Cells against 6-OHDA-Induced Neurotoxicity through Antioxidant and Antiapoptotic Effects.

Oxid Med Cell Longev 2021 3;2021:6683270. Epub 2021 Feb 3.

Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.

(AR) is a dietary mushroom in the family whose pharmacological activity and medicinal value have rarely been reported. In this study, the antioxidant capacity and neuroprotective effects of AR were investigated. The aqueous extract of AR was confirmed to contain phenolic compounds, polysaccharides, and triterpenes. The results of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and total antioxidant capacity assays revealed that AR extract scavenged reactive oxygen species. Moreover, AR extract decreased the cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis of PC12 cells induced by 6-hydroxydopamine (6-OHDA). In addition, 6-OHDA upregulated the expressions of proapoptotic proteins and downregulated the Akt (protein kinase B)/mTOR- (mammalian target of rapamycin-) and MEK (mitogen-activated protein kinase kinase)/ERK- (extracellular signal-regulated kinases-) dependent signaling pathways. These effects of 6-OHDA were abolished or partially reversed by AR extract. Furthermore, the neuroprotective effects of AR in 6-OHDA-treated PC12 cells were significantly abolished by Akt and MEK inhibitor. Thus, AR extract possesses neuroprotective effects, probably through its antioxidant and antiapoptotic effects. These findings suggest the potential application of AR in the prevention or treatment of oxidative stress-related neurodegenerative diseases such as Parkinson's disease.
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http://dx.doi.org/10.1155/2021/6683270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889343PMC
February 2021

Using local rather than general anesthesia for inguinal hernia repair may significantly reduce complications for frail Veterans.

Am J Surg 2021 Jan 22. Epub 2021 Jan 22.

Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA; North Texas VA Healthcare System, Dallas, TX, USA.

Background: Frailty predisposes patients to poor postoperative outcomes. We evaluated whether using local rather than general anesthesia for hernia repair could mitigate effects of frailty.

Methods: We used the Risk Analysis Index (RAI) to identify 8,038 frail patients in the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database who underwent elective, open unilateral inguinal hernia repair under local or general anesthesia. Our outcome of interest was the incidence of postoperative complications.

Results: In total, 5,188 (65%) patients received general anesthesia and 2,850 (35%) received local. Local anesthesia was associated with a 48% reduction in complications (OR 0.52, 95%CI 0.38-0.72). Among the frailest patients (RAI≥70), predicted probability of a postoperative complication ranged from 22 to 33% with general anesthesia, compared to 13-21% with local.

Conclusions: Local anesthesia was associated with a ∼50% reduction in postoperative complications in frail Veterans. Given the paucity of interventions for frail patients, there is an urgent need for a randomized trial comparing effects of anesthesia modality on postoperative complications in this vulnerable population.
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http://dx.doi.org/10.1016/j.amjsurg.2021.01.026DOI Listing
January 2021

Reimbursement Matters: Overcoming Barriers to Clinical Trial Accrual.

Med Care 2021 May;59(5):461-466

Department of Population & Data Sciences, University of Texas Southwestern Medical Center.

Background: Accrual to cancer clinical trials is suboptimal. Few data exist regarding whether financial reimbursement might increase accruals.

Objective: The objective of this study was to assess perceptions about reimbursement to overcome barriers to trial accrual.

Research Design: This was a cross-sectional survey.

Subjects: Oncologists identified from the American Medical Association Physician Masterfile.

Measures: We report descriptive statistics, associations of physician characteristics with perceptions of reimbursement, domains, and subthemes of free-text comments.

Results: Respondents (n=1030) were mostly medical oncologists (59.4%), ages 35-54 (67%), and male (75%). Overall, 30% reported discussing trials with >25% of patients. Barriers perceived were administrative/regulatory, physician/staff time, and eligibility criteria. National Cancer Institute cooperative group participants and practice owners were more likely to endorse higher reimbursement. Respondents indicated targeted reimbursement would help improve infrastructure, but also noted potential ethical problems with reimbursement for discussion (40.7%) and accrual (85.9%). Free-text comments addressed reimbursement sources, recipients, and concerns about the real and apparent conflict of interest.

Conclusions: Though concerns about a potential conflict of interest remain paramount and must be addressed in any new system of reimbursement, oncologists believe reimbursement to enhance infrastructure could help overcome barriers to trial accrual.
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http://dx.doi.org/10.1097/MLR.0000000000001509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026490PMC
May 2021

Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group.

Semin Arthritis Rheum 2021 Jan 9. Epub 2021 Jan 9.

Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark. Electronic address:

Background: Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms.

Methods: We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting.

Results: The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review.

Conclusions: Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives.

Registration: PROSPERO: CRD42018108393.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.023DOI Listing
January 2021

Clinician Variation in Ordering and Completion of Low-Dose Computed Tomography for Lung Cancer Screening in a Safety-Net Medical System.

Clin Lung Cancer 2020 Dec 11. Epub 2020 Dec 11.

Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.

Background: Less than 5% of eligible individuals in the United States undergo lung cancer screening. Variation in clinicians' participation in lung cancer screening has not been determined.

Patients And Methods: We studied medical providers who ordered ≥ 1 low-dose computed tomography (LDCT) for lung cancer screening from February 2017 through February 2019 in an integrated safety-net healthcare system. We analyzed associations between provider characteristics and LDCT orders and completion using chi-square, Fisher exact, and Student t tests, as well as ANOVA and multinomial logistic regression.

Results: Among an estimated 194 adult primary care physicians, 144 (74%) ordered at least 1 LDCT, as did 39 specialists. These 183 medical providers ordered 1594 LDCT (median, 4; interquartile range, 2-9). In univariate and multivariate models, family practice providers (P < .001) and providers aged ≥ 50 years (P = .03) ordered more LDCT than did other clinicians. Across providers, the median proportion of ordered LDCT that were completed was 67%. The total or preceding number of LDCT ordered by a clinician was not associated with the likelihood of LDCT completion.

Conclusion: In an integrated safety-net healthcare system, most adult primary care providers order LDCT. The number of LDCT ordered varies widely among clinicians, and a substantial proportion of ordered LDCT are not completed.
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http://dx.doi.org/10.1016/j.cllc.2020.12.001DOI Listing
December 2020

Composite outcomes for pain trials: considerations for design and interpretation.

Pain 2021 Jan 8. Epub 2021 Jan 8.

Department of Anesthesiology and Perioperative Medicine, University of Rochester, Rochester, NY, USA Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA Department of Biostatistics and Bioinformatics, George Washington University, Rochville, MD, USA Analgesic Solutions, Natick, MA, and Tufts University, Boston, MA, USA Department of Neurosurgery, University of Rochester, Rochester, NY, USA SDG, LLC, Cambridge, MA, USA Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, USA.

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http://dx.doi.org/10.1097/j.pain.0000000000002188DOI Listing
January 2021

Pearls and Pitfalls in the Management of Cam-Type Femoroacetabular Impingement: Deformity and Approach.

Instr Course Lect 2021 ;70:209-234

The arthroscopic treatment of cam-type femoroacetabular impingement (FAI) is a technically demanding surgery, which has been shown to yield successful clinical outcomes, and improved hip biomechanics and range of motion and may also favorably alter the natural history of FAI-induced osteoarthritis. Assessing the presenting symptoms, clinical history, and physical examination findings can help to confirm the diagnosis of symptomatic cam-type FAI. Appropriate preoperative imaging studies are important in the characterization of cam-type deformities and often guide the decision between open and arthroscopic management. Although most cam-type FAI can be successfully managed using an arthroscopic approach, certain complex deformity patterns might best be addressed with surgical dislocation. Command of intraoperative techniques for exposure and instrumentation, as well as effective use of fluoroscopy, allows for consistent and reproducible cam deformity correction while minimizing complications.
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January 2021

Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial.

J Natl Cancer Inst 2021 Jan 12. Epub 2021 Jan 12.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Patients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy.

Methods: In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided.

Results: Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation-related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03).

Conclusions: Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.
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http://dx.doi.org/10.1093/jnci/djaa184DOI Listing
January 2021

Patterns and Results of Triage Advice Before Emergency Department Visits Made by Patients With Cancer.

JCO Oncol Pract 2021 Jan 8:OP2000617. Epub 2021 Jan 8.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.

Purpose: Patients with cancer undergoing treatment frequently visit the emergency department (ED) for commonly anticipated complaints (eg, pain, nausea, and vomiting). Nearly all Medicare Oncology Care Model (OCM) participants prioritized ED use reduction, and the OCM requires that patients have 24-hour telephone access to a clinician, but actual reductions in ED visits have been mixed. Little is known about the use of telephone triage for acute care.

Methods: We identified adults aged 18+ years newly diagnosed with cancer, linked to ED visits from a single institution within 6 months after diagnosis, and then analyzed the telephone and secure electronic messages in the preceding 24 hours. We coded interactions to classify the reason for the call, the main ED referrer, and other attempted management. We compared the acuity of patient self-referred versus clinician-referred ED visits by modeling hospitalization and ED visit severity.

Results: From 2011 to 2018, 3,247 adults made 5,371 ED visits to the university hospital and self-referred to the ED 58.5% of the time. Clinicians referred to outpatient or oncology urgent care for 10.3% of calls but referred to the ED for 61.3%. Patient self-referred ED visits were likely to be hospitalized (adjusted Odds Ratio [aOR], 0.89, 95% CI, 0.64 to 1.22) and were not more severe (aOR, 0.75, 95% CI, 0.55 to 1.02) than clinician referred.

Conclusion: Although patients self-referred for six of every 10 ED visits, self-referred visits were not more severe. When patients called for advice, clinicians regularly recommended the ED. More should be done to understand barriers that patients and clinicians experience when trying to access non-ED acute care.
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http://dx.doi.org/10.1200/OP.20.00617DOI Listing
January 2021

The Jak/STAT pathway: A focus on pain in rheumatoid arthritis.

Semin Arthritis Rheum 2021 Feb 18;51(1):278-284. Epub 2020 Dec 18.

Department of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85718, USA. Electronic address:

Pain is a manifestation of rheumatoid arthritis (RA) that is mediated by inflammatory and non-inflammatory mechanisms and negatively affects quality of life. Recent findings from a Phase 3 clinical trial showed that patients with RA who were treated with a Janus kinase 1 (Jak1) and Janus kinase 2 (Jak2) inhibitor achieved significantly greater improvements in pain than those treated with a tumor necrosis factor blocker; both treatments resulted in similar changes in standard clinical measures and markers of inflammation. These findings suggest that Jak1 and Jak2 inhibition may relieve pain in RA caused by inflammatory and non-inflammatory mechanisms and are consistent with the overarching involvement of the Jak-signal transducer and activator of transcription (Jak/STAT) pathway in mediating the action, expression, and regulation of a multitude of pro- and anti-inflammatory cytokines. In this review, we provide an overview of pain in RA, the underlying importance of cytokines regulated directly or indirectly by the Jak/STAT pathway, and therapeutic targeting of the Jak/STAT pathway in RA. As highlighted herein, multiple cytokines directly or indirectly regulated by the Jak/STAT pathway play important roles in mediating various mechanisms underlying pain in RA. Having a better understanding of these mechanisms may help clinicians make treatment decisions that optimize the control of inflammation and pain.
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http://dx.doi.org/10.1016/j.semarthrit.2020.10.008DOI Listing
February 2021

Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos.

Environ Pollut 2021 Feb 7;271:115791. Epub 2020 Oct 7.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau. Electronic address:

Forchlorfenuron (CPPU) has been used worldwide, to boost size and improve quality of various agricultural products. CPPU and its metabolites are persistent and have been detected frequently in fruits, water, sediments, and organisms in aquatic systems. Although the public became aware of CPPU through the exploding watermelon scandal of 2011 in Zhenjiang, China, little was known of its potential effects on the environment and wildlife. In this study, adverse effects of CPPU on developmental angiogenesis and vasculature, which is vulnerable to insults of persistent toxicants, were studied in vivo in zebrafish embryos (Danio rerio). Exposure to 10 mg CPPU/L impaired survival and hatching, while development was hindered by exposure to 2.5 mg CPPU/L. Developing vascular structure, including common cardinal veins (CCVs), intersegmental vessels (ISVs) and sub-intestinal vessels (SIVs), were significantly restrained by exposure to CPPU, in a dose-dependent manner. Also, CPPU caused disorganization of the cytoskeleton. In human umbilical vein endothelial cells (HUVECs), CPPU inhibited proliferation, migration and formation of tubular-like structures in vitro. Results of Western blot analyses revealed that exposure to CPPU increased phosphorylation of FLT-1, but inhibited phosphorylation of FAK and its downstream MAPK pathway in HUVECs. In summary, CPPU elicited developmental toxicity to the developing endothelial system of zebrafish and HUVECs. This was do, at least in part due to inhibition of the FAK/MAPK signaling pathway rather than direct interaction with the VEGF receptor (VEGFR).
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http://dx.doi.org/10.1016/j.envpol.2020.115791DOI Listing
February 2021

Current Practices for Screening and Addressing Financial Hardship within the NCI Community Oncology Research Program.

Cancer Epidemiol Biomarkers Prev 2021 Apr 21;30(4):669-675. Epub 2020 Dec 21.

Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Cancer-related financial hardship is associated with poor care outcomes and reduced quality of life for patients and families. Scalable intervention development to address financial hardship requires knowledge of current screening practices and services within community cancer care.

Methods: The NCI Community Oncology Research Program (NCORP) 2017 Landscape Assessment survey assessed financial screening and financial navigation practices within U.S. community oncology practices. Logistic models evaluated associations between financial hardship screening and availability of a cancer-specific financial navigator and practice group characteristics (e.g., safety-net designation, critical access hospital, proportion of racial and ethnic minority patients served).

Results: Of 221 participating NCORP practice groups, 72% reported a financial screening process and 50% had a cancer-specific financial navigator. Practice groups with more than 10% of new patients with cancer enrolled in Medicaid (OR = 2.81, = 0.02) and with less than 30% racial/ethnic minority cancer patient composition (OR = 3.91, < 0.01) were more likely to screen for financial concerns. Practice groups with less than 30% racial/ethnic minority cancer patient composition (OR = 2.37, < 0.01) were more likely to have a dedicated financial navigator or counselor for patients with cancer.

Conclusions: Most NCORP practice groups screen for financial concerns and half have a cancer-specific financial navigator. Practices serving more racial or ethnic minority patients are less likely to screen and have a designated financial navigator.

Impact: The effectiveness of financial screening and navigation for mitigating financial hardship could be tested within NCORP, along with specific interventions to address cancer care inequities..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026561PMC
April 2021

Pathogenesis, Evaluation, and Management of Osteolysis Following Total Ankle Arthroplasty.

Foot Ankle Int 2021 Feb 21;42(2):230-242. Epub 2020 Dec 21.

Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, USA.

Periprosthetic osteolysis is a common occurrence after total ankle arthroplasty (TAA) and poses many challenges for the foot and ankle surgeon. Osteolysis may be asymptomatic and remain benign, or it may lead to component instability and require revision or arthrodesis. In this article, we present a current and comprehensive review of osteolysis in TAA with illustrative cases. We examine the basic science principles behind the etiology of osteolysis, discuss the workup of a patient with suspected osteolysis, and present a review of the evidence of various management strategies, including grafting of cysts, revision TAA, and arthrodesis. Level V, expert opinion.
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http://dx.doi.org/10.1177/1071100720978426DOI Listing
February 2021

Screening of Xanthones from Identified Oliganthin H as a Novel Natural Inhibitor of Convulsions.

J Nat Prod 2020 12 9;83(12):3706-3716. Epub 2020 Dec 9.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China.

Epilepsy is a chronic neurological disorder, characterized by recurrent, spontaneous, and transient seizures, and affects more than 70 million people worldwide. Although two dozen antiepileptic drugs (AEDs) are approved and available in the market, seizures remain poorly controlled in one-third of epileptic patients who are suffering from drug resistance or various adverse effects. Recently, the xanthone skeleton has been regarded as an attractive scaffold for the discovery and development of emerging anticonvulsants. We had isolated several dihydroxanthone derivatives previously, including oliganthin H, oliganthin I, and oliganthin N, whose structures were similar and delicately elucidated by spectrum analysis or X-ray crystallographic data, from extracts of leaves of . These xanthone analogues were evaluated for anticonvulsant activity, and a novel xanthone, oliganthin H, has been identified as a sound and effective natural inhibitor of convulsions in zebrafish . A preliminary structure-activity relationship analysis on the relationship between structures of the xanthone analogues and their activities was also conducted. Oliganthin H significantly suppressed convulsant behavior and reduced to about 25% and 50% of PTZ-induced activity, in 12.5 and 25 μM treatment groups ( < 0.01 and 0.001), respectively. Meanwhile, it reduced seizure activity, velocity, seizure duration, and number of bursts in zebrafish larvae ( < 0.05). Pretreatment of oliganthin H significantly restored aberrant induction of gene expressions including , , , and , as well as , , , and , upon PTZ treatment. In addition, analysis revealed the stability of the oliganthin H-GABAA receptor complex and their detailed binding pattern. Therefore, direct interactions with the GABAA receptor and involvement of downstream GABA-glutamate pathways were possible mechanisms of the anticonvulsant action of oliganthin H. Our findings present the anticonvulsant activity of oliganthin H, provide a novel scaffold for further modifications, and highlight the xanthone skeleton as an attractive and reliable resource for the development of emerging AEDs.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00963DOI Listing
December 2020

Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine Project.

Clin J Am Soc Nephrol 2021 Apr 30;16(4):660-668. Epub 2020 Nov 30.

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

The Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP. Patients with CKD and AKI and clinicians from the study sites are members of the Community Engagement Committee, with representation on other KPMP committees. They participate in KPMP deliberations to address scientific, clinical, logistic, analytic, ethical, and community engagement issues. The Community Engagement Committee guides KPMP research priorities from perspectives of patients and clinicians. Patients led development of essential study components, including the informed consent process, no-fault harm insurance coverage, the ethics statement, return of results plan, a "Patient Primer" for scientists and the public, and Community Advisory Boards. As members across other KPMP committees, the Community Engagement Committee assures that the science is developed and conducted in a manner relevant to study participants and the clinical community. Patients have guided the KPMP to produce research aligned with their priorities. The Community Engagement Committee partnership has set new benchmarks for patient leadership in precision medicine research.
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http://dx.doi.org/10.2215/CJN.10270620DOI Listing
April 2021

Assessment of patient and provider attitudes towards therapeutic drug monitoring to improve medication adherence in low-income patients with hypertension: a qualitative study.

BMJ Open 2020 11 27;10(11):e039940. Epub 2020 Nov 27.

Hypertension Section, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Objectives: Previous studies have implicated therapeutic drug monitoring (TDM), by measuring serum or urine drug levels, as a highly reliable technique for detecting medication non-adherence but the attitudes of patients and physicians toward TDM have not been evaluated previously. Accordingly, we solicited input from patients with uncontrolled hypertension and their physicians about their views on TDM.

Design: Prospective analysis of responses to a set of questions during semistructured interviews.

Setting: Outpatient clinics in an integrated health system which provides care for a low-income, uninsured population.

Participants: Patients with uncontrolled hypertension with either systolic blood pressure of at least 130 mm Hg or diastolic blood pressure of at least 80 mm Hg despite antihypertensive drugs and providers in the general cardiology and internal medicine clinics.

Primary And Secondary Outcome Measures: Attitudes towards TDM and the potential impact on physician-patient relationship.

Results: We interviewed 11 patients and 10 providers and discussed the findings with 13 community advisory panel (CAP) members. Of the patients interviewed, 91% (10 of 11) and all 10 providers thought TDM was a good idea and should be used regularly to better understand the reasons for poorly controlled hypertension. However, 63% (7 of 11) of patients and 20% of providers expressed reservations that TDM could negatively impact the physician-patient relationship. Despite some concerns, the majority of patients, providers and CAP members believed that if test results are communicated without blaming patients, the potential benefits of TDM in identifying suboptimal adherence and eliciting barriers to adherence outweighed the risks.

Conclusion: The idea of TDM is well accepted by patients and their providers. TDM information if delivered in a non-judgmental manner, to encourage an honest conversation between patients and physicians, has the potential to reduce patient-physician communication obstacles and to identify barriers to adherence which, when overcome, can improve health outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-039940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703422PMC
November 2020

Technical Tip Kerfing for Lapidus Arthrodesis: Deformity Correction With Minimal Bone Resection.

J Foot Ankle Surg 2021 Mar-Apr;60(2):424-427. Epub 2020 Oct 7.

Associate Professor of Orthopaedic Surgery, Rush University Medical Center, Midwest Orthopedics at Rush, Chicago, IL.

The Lapidus arthrodesis can be a powerful but technically challenging procedure. Common pitfalls include gapping at the arthrodesis site, shortening, and residual malalignment. Herein is described a simple and reproducible technique to obtain a congruent arthrodesis site with excellent deformity correction and minimal bone loss by the use of joint kerfing.
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http://dx.doi.org/10.1053/j.jfas.2020.10.004DOI Listing
October 2020

Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.

J Clin Pathol 2020 Nov 4. Epub 2020 Nov 4.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA

Aims: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.

Methods: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).

Results: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.

Conclusions: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.
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http://dx.doi.org/10.1136/jclinpath-2020-207052DOI Listing
November 2020

Botanical Drug Puerarin Promotes Neuronal Survival and Neurite Outgrowth against MPTP/MPP-Induced Toxicity via Progesterone Receptor Signaling.

Oxid Med Cell Longev 2020 17;2020:7635291. Epub 2020 Oct 17.

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.

Background: Progesterone receptor (PR) modulates neuroprotective and regenerative responses in Parkinson's disease and related neurological diseases.

Objectives: The present study was designed to determine whether botanical drug puerarin could exhibit neuroprotective and neurorestorative activities via PR signaling.

Methods: The neuroprotective and neurotrophic activities of puerarin were investigated in MPTP-lesioned mice and MPP-challenged primary rat midbrain neurons. Rotarod performance test and tail suspension test were used to assess motor functions. Tyrosine hydroxylase (TH) and PR were determined by immunostaining, Western blotting, and luciferase reporter assays. Neurite outgrowth was assessed by fluorescence staining and immunostaining.

Results: Puerarin effectively ameliorated the MPTP-induced motor abnormalities in MPTP-lesioned mice and protected primary rat midbrain neurons against MPP-induced toxicity via PR signaling although progesterone exhibited the neuroprotection. PR antagonist mifepristone (RU486) diminished the neuroprotection of puerarin in MPTP-lesioned mice and MPP-induced primary rat midbrain neurons. Moreover, puerarin promoted the differentiation of primary rat midbrain neurons and potentiated NGF to induce neuritogenesis in PC12 cells. RU486 and PR-siRNA could inhibit the effect of puerarin. Puerarin and progesterone could enhance the PR promoter.

Conclusion: Puerarin attenuated MPTP- and MPP-induced toxicity and potentiated neurite outgrowth via PR. These results suggested that puerarin may become an alternative hormone for suppressing MPTP- and MPP-induced toxicity in neurodegenerative diseases.
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http://dx.doi.org/10.1155/2020/7635291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586160PMC
October 2020

Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis.

Front Pharmacol 2020 2;11:551745. Epub 2020 Oct 2.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.

Hemorrhage stroke is a severe vascular disease of the brain with a high mortality rate in humans. Bunge (Danshen) is a well-known Chinese Materia Medica for treating cerebral vascular and cardiovascular diseases in traditional Chinese medicine. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, which is the main active ingredient of Danshen. In our previous study, we established a zebrafish model of cerebral hemorrhage and found that STS dramatically decreased both the hemorrhage rate and hemorrhage area, although the underlying mechanism was not fully elucidated. We conducted a transcriptome analysis of the protective effect of STS against atorvastatin (Ator)-induced cerebral hemorrhage in zebrafish using RNA-seq technology. RNA-seq revealed 207 DEGs between the Ator-treated group and control group; the expression levels of 53 DEGs between the Ator-treated group and control group were reversed between the STS + Ator-treated group and Ator-treated group. GO enrichment analysis indicated that these 53 DEGs encode proteins with roles in hemoglobin complexes, oxygen carrier activity and oxygen binding, etc. KEGG analysis suggested that these 53 DEGs were most enriched in three items, namely, porphyrin and chlorophyll metabolism, ferroptosis, and the HIF-1 signaling pathway. The PPI network analysis identified 12 hub genes, and we further verified that Ator elevated the mRNA expression levels of hemoglobin (, , , and ), carbonic anhydrase (, HIF-1 () and Na+/H+ exchanger ( and ) genes, while STS significantly suppressed these genes. In addition, we found that pharmacological inhibition of PI3K/Akt, MAPKs, and mTOR signaling pathways by specific inhibitors partially attenuated the protective effect of STS against Ator-induced cerebral hemorrhage in zebrafish, regardless of mTOR inhibition. We concluded that hemoglobin, carbonic anhydrase, Na+/H+ exchanger and HIF-1 genes might be potential biomarkers of Ator-induced cerebral hemorrhage in zebrafish, as well as pharmacological targets of STS. Moreover, HIF-1 and its regulators, i.e., the PI3K/Akt and MAPK signaling pathways, were involved in the protective effect of STS against Ator-induced cerebral hemorrhage. This study also provided evidence of biomarkers involved in hemorrhage stroke and improved understanding of the effects of HMG-COA reductase inhibition on vascular permeability and cerebral hemorrhage.
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http://dx.doi.org/10.3389/fphar.2020.551745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567336PMC
October 2020

Outcomes after ST-elevation myocardial infarction presentation to hospitals with or without a routine primary percutaneous coronary intervention service (ANZACS-QI 46).

N Z Med J 2020 10 30;133(1524):64-81. Epub 2020 Oct 30.

Cardiologist, Department of Cardiology, Middlemore Hospital, Auckland; Adjunct Associate Professor, School of Medicine, University of Auckland, Auckland.

Aim: Primary percutaneous coronary intervention (PCI) is the optimal reperfusion strategy to manage ST-elevation myocardial infarction (STEMI). Where timely primary PCI cannot be achieved, an initial pharmacological reperfusion strategy is recommended with subsequent transfer to a PCI-capable hospital. The study aim was to assess STEMI outcomes according to the interventional capability of the New Zealand hospital to which patients initially present.

Methods: Nine thousand four hundred and eighty-eight New Zealand patients, aged 20-79 years, admitted with STEMI to a public hospital were identified. Patients were categorised into three groups-metropolitan hospitals with all-hours access to primary PCI (routine primary PCI cohort), metropolitan hospitals without routine access to PCI, and rural hospitals. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiac events (MACE) and major bleeding.

Results: Invasive coronary angiography was more frequent in the routine primary PCI cohort compared to metropolitan hospitals without routine access to PCI and rural hospitals (90.6 vs 83.0 vs 85.0% respectively; p<0.001) and occurred more commonly on the day of admission (78.9 vs 28.7 vs 25.7% respectively; p<0.001). There were no differences in multivariable adjusted all-cause mortality, MACE or major bleeding between patients admitted to any of the hospital groupings.

Conclusion: Outcomes after STEMI in New Zealand are similar regardless of the interventional capability of the hospital where they first present.
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October 2020

Neuroprotective Potency of Saffron Against Neuropsychiatric Diseases, Neurodegenerative Diseases, and Other Brain Disorders: From Bench to Bedside.

Front Pharmacol 2020 6;11:579052. Epub 2020 Oct 6.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China.

The increasing morbidity rates of brain disorders and conditions such as anxiety, depression, Alzheimer's disease, and Parkinson's disease have become a severe problem in recent years. Although researchers have spent considerable time studying these diseases and reported many positive outcomes, there still are limited drugs available for their treatment. As a common traditional Chinese medicine (TCM), saffron was employed to treat depression and some other inflammatory diseases in ancient China due to its antioxidant, anti-inflammatory, and antidepressant properties. In modern times, saffron and its constituents have been utilized, alone and in TCM formulas, to treat neuropsychiatric and neurodegenerative diseases. In this review, we mainly focus on recent clinical and preclinical trials of brain disorders in which saffron was applied, and summarize the neuroprotective properties of saffron and its constituents from chemical, pharmacokinetic, and pharmacological perspectives. We discuss the properties of saffron and its constituents, as well as their applications for treating brain disorders; we hope that this review will serve as a comprehensive reference for studies aimed at developing therapeutic drugs based on saffron.
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http://dx.doi.org/10.3389/fphar.2020.579052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573929PMC
October 2020

Deciphering the Microbial Taxonomy and Functionality of Two Diverse Mangrove Ecosystems and Their Potential Abilities To Produce Bioactive Compounds.

mSystems 2020 Oct 27;5(5). Epub 2020 Oct 27.

State Key Laboratory of Agricultural Genomics, BGI-Shenzhen, Shenzhen, China

Mangroves, as important and special ecosystems, create unique ecological environments for examining the microbial gene capacity and potential for producing bioactive compounds. However, little is known about the biogeochemical implications of microbiomes in mangrove ecosystems, especially the variations between pristine and anthropogenic mangroves. To elucidate this, we investigated the microbial taxonomic and functional shifts of the mangrove microbiomes and their potential for bioactive compounds in two different coastal mangrove ecosystems in southern China. A gene catalogue, including 87 million unique genes, was constructed, based on deep shotgun metagenomic sequencing. Differentially enriched bacterial and archaeal taxa between pristine mangroves (Guangxi) and anthropogenic mangroves (Shenzhen) were found. The and ammonia-oxidizing archaea, specifically, were more abundant in Shenzhen mangroves, while sulfate-reducing bacteria and methanogens were more abundant in Guangxi mangroves. The results of functional analysis were consistent with the taxonomic results, indicating that the Shenzhen mangrove microbiome has a higher abundance of genes involved in nitrogen metabolism while the Guangxi mangrove microbiome has a higher capacity for sulfur metabolism and methanogenesis. Biosynthetic gene clusters were identified in the metagenome data and in hundreds of reconstructed nonredundant microbial genomes, respectively. Notably, we found different biosynthetic potential in different taxa, and we identified three high quality and novel genomes with a large number of BGCs. In total, 67,278 unique genes were annotated with antibiotic resistance, indicating the prevalence and persistence in multidrug-resistant genes in the mangrove microbiome. This study comprehensively described the taxonomy and functionality of mangrove microbiomes, including their capacity for secondary metabolite biosynthesis and their ability to resist antibiotics. The microbial taxonomic and functional characteristics differed between geographical locations, corresponding to the environmental condition of two diverse mangrove regions. A large number of microbial biosynthetic gene clusters encoding novel bioactivities were found, and this can serve as a valuable resource to guide novel bioactive compound discovery for potential clinical uses.
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http://dx.doi.org/10.1128/mSystems.00851-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593590PMC
October 2020

An Indo-Pacific Humpback Dolphin Genome Reveals Insights into Chromosome Evolution and the Demography of a Vulnerable Species.

iScience 2020 Oct 3;23(10):101640. Epub 2020 Oct 3.

Marine Mammal and Marine Bioacoustics Laboratory, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya, Hainan 572000, China.

The Indo-Pacific humpback dolphin () is a small inshore species of odontocete cetacean listed as Vulnerable on the IUCN Red List. Here, we report on the evolution of . chromosomes from its cetruminant ancestor and elucidate the evolutionary history and population genetics of two neighboring . populations. We found that breakpoints in ancestral chromosomes leading to . could have affected the function of genes related to kidney filtration, body development, and immunity. Resequencing of individuals from two neighboring populations in the northwestern South China Sea, Leizhou Bay and Sanniang Bay, revealed genetic differentiation, low diversity, and small contemporary effective population sizes. Demographic analyses showed a marked decrease in the population size of the two investigated populations over the last ~4,000 years, possibly related to climatic oscillations. This study implies a high risk of extinction and strong conservation requirement for the Indo-Pacific humpback dolphin.
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http://dx.doi.org/10.1016/j.isci.2020.101640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569330PMC
October 2020

The Chromosome Level Genome and Genome-wide Association Study for the Agronomic Traits of .

iScience 2020 Sep 8;23(9):101538. Epub 2020 Sep 8.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.

The Chinese ginseng is a domesticated herb with significant medicinal and economic value. Here we report a chromosome-level genome assembly with a high (∼79%) repetitive sequence content. The juxtaposition with the widely distributed, closely related Korean ginseng () genome revealed contraction of plant defense genes (in particular -genes) in the genome. We also investigated the reasons for the larger genome size of species, revealing contributions from two -specific whole-genome duplication events and transposable element expansion. Transcriptome data and comparative genome analysis revealed the candidate genes involved in the ginsenoside synthesis pathway. We also performed a genome-wide association study on 240 cultivated individuals and identified the associated genes with dry root weight (63 genes) and stem thickness (168 genes). The genome represents a critical step toward harnessing the full potential of an economically important and enigmatic plant.
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http://dx.doi.org/10.1016/j.isci.2020.101538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509215PMC
September 2020