bluuebunny/crossref_metadata_2025 huggingface dataset:
Validamycin A Induces Broad-Spectrum Resistance Involving Salicylic Acid and Jasmonic Acid/Ethylene Signaling Pathways
Authors: Bian Chuanhong , Duan Yabing , Wang Jueyu , Xiu Qian , Wang Jianxin , Hou Yiping , Song Xiushi , Zhou Mingguo
Published: August 2020

Validamycin A (VMA) is an aminoglycoside antibiotic used to control rice sheath blight. Although it has been reported that VMA can induce the plant defense responses, the mechanism remains poorly understood. Here, we found that reactive oxygen species (ROS) bursts and callose deposition in Arabidopsis thaliana, rice (Oryza sativa L.), and wheat (Triticum aestivum L.) were induced by VMA and were most intense with 10 μg of VMA per milliliter at 24 h. Moreover, we showed that VMA induced resistance against Pseudomonas syringae, Botrytis cinerea, and Fusarium graminearum in Arabidopsis leaves, indicating that VMA induces broad-spectrum disease resistance in both dicots and monocots. In addition, VMA-mediated resistance against P. syringae was not induced in NahG transgenic plants, was partially decreased in npr1 mutants, and VMA-mediated resistance to B. cinerea was not induced in npr1, jar1, and ein2 mutants. These results strongly indicated that VMA triggers plant defense responses to both biotrophic and necrotrophic pathogens involved in salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) signaling pathways and is dependent on NPR1. In addition, transcriptome analysis further revealed that VMA regulated the expression of genes involved in SA, JA/ET, abscisic acid (ABA), and auxin signal pathways. Taken together, VMA induces systemic resistance involving in SA and JA/ET signaling pathways and also exerts a positive influence on ABA and auxin signaling pathways. Our study highlights the creative application of VMA in triggering plant defense responses against plant pathogens, providing a valuable insight into applying VMA to enhance plant resistance and reduce the use of chemical pesticides.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Position Paper on Critical Care Pharmacy Services: 2020 Update
Authors: Lat Ishaq , Paciullo Christopher , Daley Mitchell J. , MacLaren Robert , Bolesta Scott , McCann Jennifer , Stollings Joanna L. , Gross Kendall , Foos Sarah A. , Roberts Russel J. , Acquisto Nicole M. , Taylor Scott , Bentley Michael , Jacobi Judith , Meyer Tricia A.
Published: August 2020

Objectives:

To provide a multiorganizational statement to update recommendations for critical care pharmacy practice and make recommendations for future practice. A position paper outlining critical care pharmacist activities was last published in 2000. Since that time, significant changes in healthcare and critical care have occurred.

Design:

The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development.

Main Results:

There are 82 recommendation statements: 44 original recommendations and 38 new recommendation statements. Thirty-four recommendations represent the domain of patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations were made in the domain of training and education and eight recommendations regarding professional development.

Conclusions:

Critical care pharmacists are essential members of the multiprofessional critical care team. The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.
Long-term uveal and capsular biocompatibility of a new fluid-filled, modular accommodating intraocular lens
Authors: Bontu Sneha , Werner Liliana , Kennedy Sean , Kamae Kai , Jiang Bill , Ellis Nathan , Brady Daniel G. , Mamalis Nick
Published: August 2020

Purpose:

To evaluate long-term uveal and capsular biocompatibility of a new fluid-filled modular accommodating intraocular lens (IOL) consisting of base and fluid lenses.

Setting:

John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.

Design:

Experimental study.

Methods:

Bilateral phacoemulsification was performed on 8 rabbits; 1 eye received the test IOL (Juvene) and the other a hydrophobic acrylic control IOL (SA60AT). Slitlamp examinations were performed at postoperative weeks 1 and 4, and at months 2, 3, and 6. The rabbits were killed humanely at 6 months. After gross examination from the Miyake-Apple view, IOLs were removed for implant cytology. All globes were then processed for histopathologic examination.

Results:

Uveal biocompatibility was similar between test and control IOLs up to 6 months postoperatively. Anterior capsule opacification appeared absent in the test group, and posterior capsule opacification (PCO) was significantly less in comparison with the control group throughout the study. At 6 months, central PCO was scored as 0.12 ± 0.23 with test IOLs and as 4.0 ± 0 with control IOLs (P < .0001, 2-tailed t test: paired 2-sample for means). Histopathologic examination confirmed the relative lack of capsular opacification in test eyes in comparison to controls and the absence of toxicity in any eye.

Conclusions:

Six weeks in the rabbit model corresponds to approximately 2 years in the human eye for PCO. In this model, the Juvene IOL maintained an open and expanded capsular bag, preventing overall capsular bag opacification while retaining excellent uveal and capsular biocompatibility.
Timing of cataract surgery in patients with giant cell arteritis
Authors: Fong Joseph W. , Chacko Joseph G.
Published: August 2020

Purpose:

To determine a safe timeframe and parameters for performing cataract surgery after diagnosis and treatment of giant cell arteritis (GCA).

Setting:

Single institution in the United States.

Design:

Retrospective chart review.

Methods:

This retrospective study used ICD-9/10 and Current Procedural Terminology codes to identify all patients with biopsy-proven GCA who underwent cataract surgery from 2005 to 2019 at a single institution. Excluded from the study were patients whose date of biopsy diagnosis or dose of corticosteroids at the time of cataract surgery was unknown.

Results:

Chart review identified 15 eyes of 10 patients that met inclusion criteria; 80% of patients were women, and mean age was 74.4 years. Two patients had a history of arteritic ischemic optic neuropathy. There were no perioperative or postoperative complications in the 15 eyes that underwent cataract surgery with varying doses of prednisone at the time of surgery (1 to 25 mg daily prednisone ± 10 to 25 mg weekly methotrexate; median prednisone dose of 10.75 mg) and varying time from biopsy diagnosis of GCA to surgery of at least 7 months (median 13.75 months).

Conclusions:

Cataract surgery seemed safe for patients with GCA on varying doses of prednisone at the time of surgery at least 7 months from time of biopsy diagnosis. There is a need for a larger cohort of data from neuro-ophthalmologists and cataract surgeons nationally to establish guidelines for safe cataract surgery in patients with GCA.
Outcomes of cataract surgery in pseudoexfoliation syndrome in England: 10-year retrospective cohort study
Authors: Ong Ariel Y. , Shalchi Zaid
Published: August 2020

Purpose:

To investigate the outcomes of cataract surgery in eyes with pseudoexfoliation syndrome in a real-world National Health Service setting.

Setting:

Prince Charles Eye Unit, Windsor, United Kingdom.

Design:

Single-center retrospective cohort study.

Methods:

All eyes that underwent phacoemulsification cataract surgery from January 2010 to December 2019 were included. Eyes with combined intraocular surgery or with a history of ocular trauma were excluded. Eyes were classified as pseudoexfoliation (n = 280 [1.2%]) or no pseudoexfoliation (n = 23 049). The primary outcome was mean change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA). Secondary outcomes included intraoperative and postoperative complications.

Results:

The study comprised 23 329 eyes of 15 257 patients. Eyes in the pseudoexfoliation group were older and more likely to have multiple co-pathologies. Intraoperatively, they were more likely to experience zonular dialysis and dropped nucleus. Postoperatively, they had significantly higher rates of corneal edema, elevated intraocular pressure, postoperative uveitis, and intraocular lens subluxation and were more likely to require a second operation within 90 days. Although the pseudoexfoliation group had worse preoperative and postoperative logMAR VA, logistic regression analysis confirmed that mean VA improvement was comparable to reference group (mean ± standard deviation −0.49 ± 0.52 vs −0.55 ± 0.66, adjusted mean difference 0.02 [95% CI, −0.01 to 0.06]).

Conclusions:

Although patients with pseudoexfoliation had a significantly higher risk of some complications, they achieved similar VA improvements with cataract surgery compared to the nonpseudoexfoliation group. These findings will help inform the consent process and management of patient expectations.
Benchmarking Site of Death and Hospice Use
Authors: Intrator Orna , Li Jiejin , Gillespie Suzanne M. , Levy Cari , Davis Darlene , Edes Thomas , Kinosian Bruce , Karuza Jurgis
Published: August 2020

Objective:

The objective of this study was to examine site of death and hospice use, identifying potential disparities among veterans dying in Department of Veterans Affairs (VA) Home Based Primary Care (VA-HBPC).

Methods:

Administrative data (2008, 2012, and 2016) were compiled using the VA Residential-History-File which tracks health care service location, daily. Outcomes were site of death [home, nursing home (NH), hospital, inpatient hospice]; and hospice use on the day of death. We compared VA-HBPC rates to rates of 2 decedent benchmarks: VA patients and 5% Traditional Medicare non-veteran males. Potential age, race, urban/rural residence and living alone status disparities in rates among veterans dying in VA-HBPC in 2016 were examined by multinomial logistic regression.

Results:

In 2016, 7796 veterans died in VA-HBPC of whom 62.1% died at home, 11.8% in NHs, 14.7% in hospitals and 11.4% in inpatient hospice. Hospice was provided to 60.9% of veterans dying at home and 63.9% of veterans dying in NH. Over the 2008–2012–2016 period, rates of VA-HBPC veterans who died at home and rates of home death with hospice increased and were higher than both benchmarks. Among VA-HBPC decedents, younger/older veterans were more/less likely to die at home and less/more likely to die with hospice. Race/ethnicity and urban/rural residence were unrelated to death at home but veterans living alone were less likely to die at home.

Conclusions:

Results reflect VA-HBPC’s primary goal of supporting its veterans at home, including at the end-of-life, surpassing other population benchmarks with some potential disparities remaining.
Measurement Properties of the CAPACITY Instrument to Assess Perceived Communication With the Health Care Team Among Care Partners of Patients With Cognitive Impairment
Authors: Van Houtven Courtney H. , Lippmann Steven J. , Bélanger Emmanuelle , Smith Valerie A. , James Hailey J. , Shepherd-Banigan Megan , Jutkowitz Eric , O’Brien Emily , Wolff Jennifer L. , Burke James R. , Plassman Brenda L.
Published: August 2020

Background:

The CAregiver Perceptions About CommunIcaTion with Clinical Team members (CAPACITY) instrument measures how care partners perceive themselves to be supported by the patient’s health care team and their experiences communicating with the team.

Objectives:

The objective of this study was to assess the measurement properties (ie, structural validity of the construct and internal consistency) of the CAPACITY instrument in care partners of patients with cognitive impairment, and to examine whether care partner health literacy and patient cognitive impairment are associated with a higher or lower CAPACITY score.

Research Design:

This was a retrospective cohort study.

Subjects:

A total of 1746 dyads of community-dwelling care partners and older adults in the United States with cognitive impairment who obtained an amyloid positron emission tomography scan.

Measures:

The CAPACITY instrument comprises 12 items that can be combined as a total score or examined as subdomain scores about communication with the team and care partner capacity-assessment by the team. The 2 covariates of primary interest in the regression model are health literacy and level of cognitive impairment of the patient (Modified Telephone Interview Cognitive Status).

Results:

Confirmatory factor analysis showed the CAPACITY items fit the expected 2-factor structure (communication and capacity). Higher cognitive functioning of patients and higher health literacy among care partners was associated with lower communication domain scores, lower capacity domain scores, and lower overall CAPACITY scores.

Conclusions:

The strong psychometric validity of the CAPACITY measure indicates it could have utility in other family caregivers or care partner studies assessing the quality of interactions with clinical teams. Knowing that CAPACITY differs by care partner health literacy and patient impairment level may help health care teams employ tailored strategies to achieve high-quality care partner interactions.
Does Offering Battlefield Acupuncture Lead to Subsequent Use of Traditional Acupuncture?
Authors: Thomas Eva R. , Zeliadt Steven B. , Coggeshall Scott , Gelman Hannah , Resnick Adam , Giannitrapani Karleen , Olson Juli , Kligler Benjamin , Taylor Stephanie L.
Published: August 2020

Objectives:

Veterans Health Administration encourages auricular acupuncture (Battlefield Acupuncture/BFA) as a nonpharmacologic approach to pain management. Qualitative reports highlighted a “gateway hypothesis”: providing BFA can lead to additional nonpharmacologic treatments. This analysis examines subsequent use of traditional acupuncture.

Research Design:

Cohort study of Veterans treated with BFA and a propensity score matched comparison group with a 3-month follow-up period to identify subsequent use of traditional acupuncture. Matching variables included pain, comorbidity, and demographics, with further adjustment in multivariate regression analysis.

Subjects:

We identified 41,234 patients who used BFA across 130 Veterans Health Administration medical facilities between October 1, 2016 and March 31, 2019. These patients were matched 2:1 on Veterans who used VA care but not BFA during the same period resulting in a population of 24,037 BFA users and a comparison cohort of 40,358 non-BFA users. Patients with prior use of traditional acupuncture were excluded.

Results:

Among Veterans receiving BFA, 9.5% subsequently used traditional acupuncture compared with 0.9% of non-BFA users (P<0.001). In adjusted analysis, accounting for patient characteristics and regional availability of traditional acupuncture, patients who used BFA had 10.9 times greater odds (95% confidence interval, 8.67–12.24) of subsequent traditional acupuncture use.

Conclusions:

Providing BFA, which is easy to administer during a patient visit and does not require providers be formally certified, led to a substantial increase in use of traditional acupuncture. These findings suggest that the value of offering BFA may not only be its immediate potential for pain relief but also subsequent engagement in additional therapies.
T-Cell Immunity in Pancreatic Cancer
Authors: Ajina Reham , Weiner Louis M.
Published: August 2020

Worldwide, approximately half a million people are diagnosed with pancreatic cancer every year, with mortality rates of more than 90%. T cells within pancreatic tumors are generally infrequent and incapable of eliciting antitumor immunity. Thus, pancreatic cancer is considered an “immunologically cold” tumor. However, recent studies clearly show that when T-cell immunity in pancreatic cancer is sufficiently induced, T cells become effective weapons. This fact suggests that to improve pancreatic cancer patients' clinical outcomes, we need to unveil the complex immune biology of this disease. In this review, we discuss the elements of tumor immunogenicity in the specific context of pancreatic malignancy.
Currarino Syndrome
Authors: Liu Alex J. , Halfdanarson Thorvardur R. , Sonbol Mohamad B.
Published: August 2020

Objectives

Currarino syndrome (CS) is a congenital disorder that consists of a triad of anomalies: presacral mass, sacral dysgenesis, and anorectal malformations. Few cases of CS with neuroendocrine tumors (NETs) have been reported. In this study, we sought to determine the prevalence and characteristics of NET in patients with CS.

Methods

Mayo Clinic electronic medical records were searched for patients with CS. Data on demographics, CS diagnosis, family history, genetic testing, and NET diagnosis were extracted.

Results

A total of 26 patients with CS were identified with 3 (11.5%) of them having an additional diagnosis of NET. Three patients had a family history of NET (11.53%), and 7 patients had a family history of CS (26.9%). Of the 3 NET/CS patients, 2 had a confirmed primary NET from the presacral mass, with the third patient demonstrating focal uptake on the somatostatin receptor imaging within the presacral. Two patients received octreotide, followed by peptide receptor radionuclide therapy. The other patient was not treated because of complete resection of presacral mass and is currently undergoing surveillance scans.

Conclusions

In our patients with CS, the prevalence of NET is 11.53%. The coexistence of 2 rare conditions, CS and presacral NET, suggests that there may be an etiological connection.
Depression Before and After a Diagnosis of Pancreatic Cancer
Authors: Seoud Talal , Syed Aslam , Carleton Neil , Rossi Caitlan , Kenner Barbara , Quershi Hassan , Anand Mary , Thakkar Payal , Thakkar Shyam
Published: August 2020

Objectives

The aim of this study was to evaluate depression in pancreatic cancer (PC) patients before and after a cancer diagnosis using a US-based healthcare database. We also sought to study the impact of treatment of depression in PC patients on all-cause mortality.

Methods

Pancreatic cancer patients with comorbid depression in Explorys (1999–2019) were compared with controls using odds ratios with 95% confidence intervals. Rates of depression diagnosed within 6 months, 1 year, and 3 years before and after a PC diagnosis were recorded. Patients who developed depression after a PC diagnosis were further categorized into those treated for depression using mental health professionals (MHPs), pharmacologic treatment, or both (2015–2019).

Results

Of the 62,450 PC patients, 10,220 (16.4%) were diagnosed with depression before PC and 8130 (13%) were diagnosed with depression after PC. Patients diagnosed with depression after PC had a significantly higher all-cause mortality than patients with PC alone (P < 0.0001). Involvement of MHP significantly improved all-cause mortality (P = 0.0041).

Conclusions

Most post-PC depression is diagnosed in the first 6 months after a PC diagnosis. Although depression significantly increases PC mortality, integrating MHP in the care of PC patients with depression improves outcomes.
Pediatric Myelodysplastic Syndrome With Germline RRAS Mutation: Expanding the Phenotype of RASopathies
Authors: Catts Daniel S. , Mroske Cameron , Clark Rebecca O. , Hipp Sean J. , Berg Janet M. , Hunter Jesse M. , Whiteway Susan L.
Published: August 2020

The RAS/mitogen-activated protein kinase pathway plays a significant role in cell cycle regulation. Germline mutation of this pathway leads to overlapping genetic disorders, RASopathies, and is also an important component of tumorigenesis. Here we describe a rare case of myelodysplastic syndrome with monosomy 7 in a pediatric patient with a germline RRAS mutation. RRAS mutations have been implicated in the development of juvenile myelomonocytic leukemia, but our case suggests RRAS mutations display a broader malignant potential. Our case supports the recommendation that genetic testing should include RRAS in suspected RASopathy patients and if identified, these patients undergo surveillance for hematologic malignancy.
T-Cell Acute Lymphoblastic Leukemia in a Young Adult With Thrombocytopenia-absent Radius Syndrome: A Case Report and Review of the Literature
Authors: Beauvais David , Cabannes-Hamy Aurélie , Leblanc Thierry , Dhédin Nathalie , Magda Alexis , Cuccuini Wendy , Clappier Emmanuelle , Vial Yoann , Boissel Nicolas
Published: August 2020

Thrombocytopenia-absent radius (TAR) syndrome is a rare inherited bone marrow failure syndrome not generally associated with acute leukemia. The authors report a case of T-cell acute lymphoblastic leukemia in an adult female individual newly diagnosed with TAR syndrome. A 347-kb microdeletion of chromosome 1q21.1 involving the RBM8A gene was detected within a gain of whole chromosome 1. Next-generation sequencing on fibroblasts confirmed germline heterozygous deletion of RBM8A but on the other allele, noncoding low-frequency regulatory single-nucleotide polymorphism of RBM8A (rs139428292; rs201779890) were not found. The tolerance of the treatment was unusual and mostly marked by a slow hematopoietic recovery leading to a 6-month delay at the beginning of the maintenance phase. Only 5 cases of acute leukemia were reported in patients with TAR syndrome in the literature: 4 acute myeloid leukemia and one B-cell acute lymphoblastic leukemia. This is the first report of T-cell acute lymphoid leukemia occurring in the context of TAR syndrome.
Southeast Asian Ovalocytosis and Hemoglobinopathies in Newborns: Prevalence, Molecular, and Hematologic Analyses
Authors: Yamsri Supawadee , Kawon Watcharaphong , Duereh Amara , Fucharoen Goonnapa , Fucharoen Supan
Published: August 2020

Objectives:

Southeast Asian ovalocytosis (SAO) is an inherited red blood cell (RBC) membrane disorder, whereas hemoglobinopathies are inherited globin gene disorders. In an area where both diseases are prevalent, the interaction between them resulting in variable hematologic parameters can be encountered. However, little is known about the genetic interaction of SAO and thalassemia. We investigated the prevalence of SAO and hemoglobinopathy genotypes among newborns in southern Thailand.

Patients and Methods:

This study was carried out on 297 newborns recruited consecutively at Naradhiwas Rajanagarindra Hospital in the south of Thailand. The SAO was identified on blood smear examination and polymerase chain reaction analysis. Thalassemia genotypes were defined. Hematologic parameters and hemoglobin (Hb) profiles were recorded and analyzed.

Results:

Among 297 newborns, 15 (5.1%) carried SAO, whereas 70 (23.6%) had thalassemia with 15 different thalassemia genotypes. Abnormal Hb including Hb C, Hb Q-Thailand, and Hb D-Punjab were observed in 5 newborns. It was found in the nonthalassemic newborns that RBC count, Hb, and hematocrit of the nonthalassemic newborns with SAO were significantly lower than those without SAO. The same finding was also observed in the thalassemic newborns; RBC count, Hb, and hematocrit of the thalassemic newborns with SAO were significantly lower than those without SAO. However, the mean corpuscular volume, mean corpuscular Hb, and RBC distribution width of the SAO-newborns were significantly higher.

Conclusions:

Both SAO and hemoglobinopathy genotypes are common in southern Thailand. One should take this into consideration when evaluating neonatal anemia and other hematologic abnormalities. Identification of both genetic defects and long-term monitoring on the clinical outcome of this genetic interaction should be essential to understand the pathogenesis of these common genetic disorders in the region.
Sleep Disturbance Trajectories in Osteoarthritis
Authors: Song Jing , Lee Jungwha , Lee Yvonne C. , Chang Alison H. , Semanik Pamela A. , Chang Rowland W. , Ehrlich-Jones Linda , Dunlop Dorothy D.
Published: August 2020

Background/Objective

Sleep disturbance is common among adults with osteoarthritis (OA), but little is known about patterns over time. In this cohort study, we identified restless sleep trajectories and associated factors in adults with or at high risk for knee OA.

Methods

Longitudinal (2004–2014) restless sleep (≥3 nights/week) annual reports over 8 years from 4359 Osteoarthritis Initiative participants were analyzed. Group-based trajectory modeling identified heterogeneous temporal patterns. Logistic regression identified baseline health and behavioral predictors of trajectory membership.

Results

Four restless sleep trajectory groups were identified: good (69.7%, persistently low restless sleep probabilities), worsening (9.1%), improving (11.7%), and poor (9.5%, persistently high). Among 2 groups initially having low restless sleep prevalence, the worsening trajectory group had an increased likelihood of baseline cardiovascular disease (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.01–2.33), pulmonary disease (OR, 1.48; 95% CI, 1.07–2.05), lower physical activity (OR, 1.29; 95% CI, 1.03–1.61), knee pain (OR, 1.04; 95% CI, 1.00–1.07), depressive symptoms (OR, 1.03; 95% CI, 1.01–1.06), and a decreased likelihood of better mental health (OR, 0.97; 95% CI, 0.95–0.98) at baseline. Among 2 groups initially having high restless sleep prevalence, the poor group had an increased likelihood of baseline depressive symptoms (OR, 1.03; 95% CI, 1.00–1.05).

Conclusions

Four trajectories of restless sleep over 8 years were identified using data collected from over 4000 older adults aged 45 to 79 years with or at higher risk for knee OA. The presence of depressive symptoms, less physical activity, knee pain, poor mental health, cardiovascular disease, or pulmonary disease was each associated with unfavorable trajectories.
Stages of Lyme Arthritis
Authors: Miller John B. , Aucott John N.
Published: August 2020

Background/Historical Perspective

Lyme arthritis was described in 1977, after an apparent outbreak of juvenile idiopathic arthritis in Lyme, Connecticut. The evolution of the disease has been meticulously described with presentation dependent on disease duration and previous therapy.

Summary Integrating Published Literature

Erythema migrans is typically the first manifestation. Untreated patients often develop early disseminated disease, characterized by migratory polyarthralgia, potentially with cardiac and/or neurologic sequelae. If untreated, most patients develop late Lyme arthritis, characterized as a monoarthritis or oligoarthritis, typically involving the knees. Serologies are strongly positive at this stage; if positive, Lyme PCR from synovial fluid confirms the diagnosis. Doxycycline is recommended for late Lyme arthritis, although amoxicillin or ceftriaxone may be considered.

Initial antibiotic therapy for late Lyme arthritis is insufficient for a subset of patients. However, serologies and synovial fluid PCR are not useful at determining whether infection persists after oral therapy. As such, ceftriaxone is recommended in patients with inadequate response to doxycycline or amoxicillin.

Approximately 10% of patients have persistent arthritis despite antimicrobial therapy, termed postinfectious Lyme arthritis, which is thought to be related to prolonged inflammation and unique microbial and host interaction. Therapy at this stage relies on immunosuppression and/or synovectomy.

Major Conclusions and Future Research

Lyme arthritis provides unique insights into the complex interplay between microbes and host immunity. The progression from localized erythema migrans to early disseminated disease and late Lyme arthritis allows insight into arthritis initiation, and the study of postinfectious Lyme arthritis allows further insight into mechanisms of arthritis persistence.
The use of a new type of heart rate-controlled training system “HeartGo ®” for patients with chronic Heart failure on the pedelec
Authors: Friedrich Erik B. , Löllgen Herbert , Röder Helmut , Baltes Wolfgang , Adam Oliver , Schlickel Martin , Hennersdorf Günter
Published: August 2020

Background

The study “HI-Herz.BIKE Saar” (August 2017 - September 2019) examined the health benefits and training effect of e-bikes (pedelecs) in patients from ambulatory heart groups with moderate chronic heart failure (CHI).

Method

10 subjects with NYHA stage II-III and a left ventricular ejection fraction LVEF of <=50% were selected. The presented study is explicitly marked as a pilot study.

The new HeartGo® system used here for the first time allows heart rate controlled training on a special pedelec via a smartphone app. The groups were accompanied during the training rides by a doctor and a paramedic. No cardiac complications occurred. The training units were increased in duration, distance and target frequency every six months.

Frequency behaviour, pedaling and motor load on the pedelec as well as climatic data such as ejection fraction, a biomarker (NT-pro BNP), risk factors, arterial blood pressure and ergometric courses were measured.

Results

The power tolerance increased by almost 2.5 times, a discrete decrease of the resting heart rate by 3.7% was observed and pedaling power improved accordingly. In the clinical data the ergometric power increased by 44% and the LVEF improved by 29%. The NT-pro BNP value decreased by 27%. Body Mass Index BMI remained constant at 27 and cholesterol levels showed no significant changes.

Conclusions

Pedaling according to this pilot study with its methodological limitations of low number was safe and accompanied by significant health benefits. The subjects were enthusiastic and satisfied with this form of training. This training form can therefore be recommended to heart group participants under certain medical conditions and can be used in the training process. The results of this pilot study with its methodological weaknesses should be verified in a larger follow-up study.
Troxerutin acts on complement mediated inflammation to ameliorate arthritic symptoms in rats
Authors: Sahu Debasis , Bishwal Subasa Chandra , Malik Md. Zubbair , Sahu Sukanya , Kaushik Sandeep Rai , Sharma Shikha , Saini Ekta , Arya Rakesh , Rastogi Archana , Sharma Sandeep , Sen Shanta , Singh R. K. Brojen , Nanda Ranjan Kumar , Panda Amulya Kumar
Published: August 2020

Troxerutin (TXR), is a phytochemical reported to possess anti-inflammatory and hepatoprotective effects. In this study, we aimed to exploit anti-arthritic properties of TXR using an adjuvant induced arthritic (AIA) rat model. AIA induced rats showed highest arthritis score at disease onset and by oral administration of TXR (50, 100, 200 mg/kg body weight), reduced to basal level in a dose dependent manner. Isobaric tag for relative and absolute quantitative (iTRAQ) proteomics tool was employed to identify deregulated joint homogenate proteins in AIA and TXR treated rats to decipher probable mechanism of the TXR action in arthritis. iTRAQ analysis identified a set of 434 joint homogenate proteins with 65 deregulated proteins (log2case/control ≥1.5) in AIA. Expressions of a set of important proteins (AAT, T-kininogen, vimentin, desmin, and nucleophosmin) that could classify AIA from healthy were validated using Western blot analysis. Western blot data corroborated proteomics findings.In silicoprotein-protein interaction study of joint homogenate proteome revealed that complement component 9, the major building blocks of the membrane attack complex (MAC) responsible for sterile inflammation, gets perturbed in AIA. Our dosimetry study suggests that a TXR dose of 200 mg/kg body weight for 15 days is sufficient to bring the arthritis score to basal levels in AIA rats. We have shown the importance of TXR as an anti-arthritis agent in AIA model and after additional investigation its arthritis ameliorating properties could be exploited for clinical usability.
Methionine stress induces a ferroptotic gene signature in methionine dependent cancer cells
Authors: Wallis Katherine , Bird Jordan T. , Gies Allen , Mackintosh Sam G. , Tackett Alan J. , Byrum Stephanie , Miousse Isabelle R.
Published: August 2020

Dietary methionine restriction is associated with a reduction in tumor growth in preclinical studies and an increase in lifespan in animal models. The mechanism by which methionine restriction inhibits tumor growth while sparing normal cells is incompletely understood, except for the observation that normal cells can utilize methionine or homocysteine interchangeably (methionine independence) while most cancer cells are strictly dependent on methionine availability. Here, we compared a typical methionine dependent and a rare methionine independent melanoma cell line. We found that replacing methionine with homocysteine generally induced hypomethylation in gene promoters. We isolated nuclear proteins and submitted it for tandem mass tag (TMT) proteomics. This analysis revealed that several proteins involved in the mitochondrial integrated stress response (ISR) were upregulated in response to the replacement of methionine to homocysteine in both cell lines, but to a much greater degree in the methionine dependent cell line. Consistent with the ISR signature, a proteomic analysis of a subcellular fraction enriched for mitochondrial content revealed a strong enrichment for proteins involved in oxidative phosphorylation. Analysis of cellular bioenergetics confirmed that homocysteine induces a decrease in ATP production from oxidative phosphorylation and glycolysis, but to a similar extent in methionine dependent and methionine independent cells. The mitochondrial integrated stress response shared a signature with ferroptosis. Methionine dependent cells displayed a strong ferroptotic signature, which was decreased by half in methionine independent cells. Consistent with ferroptosis, lipid peroxidation was significantly increased in methionine independent cells grown in homocysteine, and viability could be rescued partially but significantly with the inhibitor ferrostatin. Therefore, we propose that methionine stress induces ferroptotic cell death in methionine dependent cancer cells.
nanotatoR: A tool for enhanced annotation of genomic structural variants
Authors: Bhattacharya Surajit , Barseghyan Hayk , Délot Emmanuèle C. , Vilain Eric
Published: August 2020

Whole genome sequencing is effective at identification of small variants but, because it is based on short reads, assessment of structural variants (SVs) is limited. The advent of Optical Genome Mapping (OGM), which utilizes long fluorescently labeled DNA molecules for de novo genome assembly and SV calling, has allowed for increased sensitivity and specificity in SV detection. However, compared to small variant annotation tools, OGM-based SV annotation software has seen little development, and currently available SV annotation tools do not provide sufficient information for determination of variant pathogenicity.

We developed an R-based package,nanotatoR, which provides comprehensive annotation as a tool for SV classification. nanotatoR uses both external (DGV; DECIPHER; Bionano Genomics BNDB) and internal (user-defined) databases to estimate SV frequency. Human genome reference GRCh37/38-based BED files are used to annotate SVs with overlapping, upstream, and downstream genes. Overlap percentages and distances for nearest genes are calculated and can be used for filtration. A primary gene list is extracted from public databases based on the patient’s phenotype and used to filter genes overlapping SVs, providing the analyst with an easy way to prioritize variants. If available, expression of overlapping or nearby genes of interest is extracted (e.g. from an RNA-Seq dataset, allowing the user to assess the effects of SVs on the transcriptome). Most quality-control filtration parameters are customizable by the user. The output is given in an Excel file format, subdivided into multiple sheets based on SV type and inheritance pattern (INDELs, inversions, translocations, de novo, etc.).

nanotatoRpassed all quality and run time criteria of Bioconductor, where it was accepted in the April 2019 release. We evaluatednanotatoR’sannotation capabilities using publicly available reference datasets: the singleton sample NA12878, mapped with two types of enzyme labeling, and the NA24143 trio.nanotatoRwas also able to accurately filter the known pathogenic variants in a cohort of patients with Duchenne Muscular Dystrophy for which we had previously demonstrated the diagnostic ability of OGM. The extensive annotation enables users to rapidly identify potential pathogenic SVs, a critical step toward use of OGM in the clinical setting.
Identification of potential key genes for SARS-CoV-2 infected human bronchial organoids based on bioinformatics analysis
Authors: Gu Hanming , Yuan Gongsheng
Published: August 2020

There is an urgent need to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) that leads to COVID-19 and respiratory failure. Our study is to discover differentially expressed genes (DEGs) and biological signaling pathways by using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profiles of the GSE150819 datasets were originally produced using an Illumina NextSeq 500 (Homo sapiens). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) were utilized to identify functional categories and significant pathways. KEGG and GO results suggested that the Cytokine-cytokine receptor interaction, P53 signaling pathway, and Apoptosis are the main signaling pathways in SARS-CoV-2 infected human bronchial organoids (hBOs). Furthermore, NFKBIA, C3, and CCL20 may be key genes in SARS-CoV-2 infected hBOs. Therefore, our study provides further insights into the therapy of COVID-19.
Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool that Exploits Genomic Data in Public Health and Clinical Microbiology Applications
Authors: Rodrigues Charlene M.C. , Jolley Keith A. , Smith Andrew , Cameron J. Claire , Feavers Ian M. , Maiden Martin C.J.
Published: August 2020

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole genome sequence data by non-specialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD), since their licensure in 2013/14. These vaccines have different components and different coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate including: (i) the presence of particular vaccine antigen variants; (ii) the expression of vaccine antigens; and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesised genomic and experimental data from published sources to develop and implement the ‘Meningococcal Deduced Vaccine Antigen Reactivity’ (MenDeVAR) Index, which is publicly-available on PubMLST (https://pubmlst.org). Using whole genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, MenDeVAR provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programmes. MenDeVAR has been developed in consultation with, but independently of, both vaccine manufacturers.
Autocorrelation-based method to identify disordered rhythm in Parkinson’s disease tasks: a novel approach applicable to multimodal devices
Authors: Sato Kenichiro , Mano Tatsuo , Iwata Atsushi , Toda Tatsushi
Published: August 2020

Objective

We aim to propose a novel method of evaluating the degree of rhythmic irregularity during repetitive tasks in Parkinson’s disease (PD) by using autocorrelation to extract serial perturbation in the periodicity of body part movements as recorded by objective devices.

Methods

We used publicly distributed sequential joint movement data recorded during a leg agility task or pronation-supination task. The sequences of body part trajectory were processed to extract their short-time autocorrelation (STACF) matrices; the sequences of single task conducted by participants were then divided into two clusters according to their similarity in terms of their STACF representation. The Unified Parkinson’s Disease Rating Scale sub-score rated for each task was compared with cluster membership to obtain the area under the curve (AUC) to evaluate the discrimination performance of the clustering. We compared the AUC with those obtained from the clustering of the raw sequence or short-time Fourier transform (STFT).

Results

In classifying the pose estimator-based trajectory data of the knee during the leg agility task, the AUC was the highest when the STACF sequence was used for clustering instead of other types of sequences with up to 0.815, being comparable to the results reported in the original analysis of the data using an approach different from ours. In addition, in classifying another dataset of accelerometer-based trajectory data of the wrist during a pronation-supination task, the AUC was again highest up to 0.785 when clustering was performed using the STACF rather than other types of sequence.

Conclusion

Our autocorrelation-based method achieved a fair performance in detecting sequences with irregular rhythm, suggesting that it might be used as another evaluation strategy that is potentially widely applicable to qualify the disordered rhythm of PD regardless of the kinds of task or the modality of devices, although further refinement is needed.
Nested versus independent sampling: Solving the mystery of contradictory species-area relationships
Authors: Reinhard Johannes , Drossel Barbara
Published: August 2020

Abstract

Species-area relationships (SARs) describe how the number of species increases with the size of the area surveyed, and they usually take the shape of a power law on regional spatial scales. A meta-review of empirical data has shown that the exponent of the power law is on average larger when the areas are sampled in a nested manner, compared to sampling of independent areas such as islands of different sizes. As this is in contrast to ecological reasoning, we performed computer simulations of three qualitatively different models that generate species distributions in space and time by the mechanisms of speciation, dispersal, and extinction. We find that in all cases and over a wide parameter range the SARs obtained by nested sampling have a smaller slope in the regional scale than those obtained by independent sampling. We explain the discrepancy to the empirical data by the different spatial scales on which the two types of empirical investigations were performed.
A Nanoluciferase biosensor to investigate endogenous chemokine secretion and receptor binding
Authors: White Carl W. , Pfleger Kevin D. G. , Hill Stephen J.
Published: August 2020

Secreted chemokines are critical mediators of cellular communication that elicit intracellular signalling by binding membrane-bound receptors. Here we demonstrate the development and use of a sensitive real-time approach to quantify secretion and receptor binding of native chemokines in live cells to better understand their molecular interactions and function. CRISPR/Cas9 genome-editing was used to tag the chemokine CXCL12 with the Nanoluciferase fragment HiBiT. CXCL12 secretion was subsequently monitored and quantified by luminescence output. Binding of tagged CXCL12 to either chemokine receptors or membrane glycosaminoglycans could be monitored due to the steric constraints of Nanoluciferase complementation. Furthermore, binding of native CXCL12-HiBiT to AlexaFluor488-tagged CXCR4 chemokine receptors could also be distinguished from glycosaminoglycan binding and pharmacologically analysed using BRET. These live cell approaches combine the sensitivity of Nanoluciferase with CRISPR/Cas9 genome-editing to detect, quantify and monitor binding of low levels of native secreted proteins in real time.
Gigantic Genomes Can Provide Empirical Tests of TE Dynamics Models — An Example from Amphibians
Authors: Wang Jie , Itgen Michael W. , Wang Huiju , Gong Yuzhou , Jiang Jianping , Li Jiatang , Sun Cheng , Sessions Stanley K. , Mueller Rachel Lockridge
Published: August 2020

Transposable elements (TEs) are a major determinant of eukaryotic genome size. The collective properties of a genomic TE community reveal the history of TE/host evolutionary dynamics and impact present-day host structure and function, from genome to organism levels. In rare cases, TE community/genome size has greatly expanded in animals, associated with increased cell size and altered anatomy and physiology. We characterize the TE landscape of the genome and transcriptome in an amphibian with a giant genome — the caecilianIchthyophis bannanicus, which we show has a genome size of 12.2 Gb. Amphibians are an important model system because the clade includes independent cases of genomic gigantism. TheI. bannanicusgenome differs compositionally from other giant amphibian genomes, but shares a low rate of ectopic-recombination-mediated deletion. We examine TE activity using expression and divergence plots; TEs account for 15% of somatic transcription, and most superfamilies appear active. We quantify TE diversity in the caecilian, as well as other vertebrates with a range of genome sizes, using diversity indices commonly applied in community ecology. We synthesize previous models integrating TE abundance, diversity, and activity, and we test whether the caecilian meets model predictions for genomes with high TE abundance. We propose thorough, consistent characterization of TEs to strengthen future comparative analyses. Such analyses will ultimately be required to reveal whether the divergent TE assemblages found across convergent gigantic genomes reflect fundamental shared features of TE/host genome evolutionary dynamics.