bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric-onset systemic lupus erythematosus with coronary artery dilation
Authors: Zhang Hui , Zhang Lijuan , Guo Nan
Published: January 2020

Introduction:

Though pediatric-onset systemic lupus erythematosus (SLE) is at high risk of coronary artery involvement, coronary artery dilation appears to be a rare characteristic of pediatric-onset SLE. In this article, we described 1 pediatric-onset SLE patient with coronary artery dilation at the diagnosis of SLE, in order to better diagnose and manage this cardiac complication of SLE in children.

Patient concerns:

A 13-year-old boy was admitted in hospital for daily fevers with the highest temperature of 39.2°C over 10 days, with rash, non-exudative conjunctivitis, cervical adenopathy, knee, and ankle arthralgi. The result of echocardiogram implicated coronary artery dilation and aortic regurgitation. Further laboratory tests showed: Coomb's test (+), decreased C3 complement. The results of immunologic tests were only to find ANA (+) with titer 1:3200, ds-DNA (+).

Diagnosis:

This patient was diagnosed as SLE complicated with coronary artery dilation.

Interventions:

The patient was treated with intravenous methylprednisolone pulse therapy. He was discharged home on prednisone maintain treatment.

Outcomes:

As soon as treatment, his temperature returned to normal, with recovery of rash, conjunctivitis, knee, and ankle arthralgi. However, the echocardiogram of this patient after 3 months also had dilation of left coronary artery (LCA) and right coronary artery (RCA).

Conclusions

: Cardiac complication can occur during the entire course of SLE, suggesting that routine echocardiogram surveillance may be necessary for all SLE patients to prevent morbidity and mortality from cardiovascular events.
The prevalence of spinal muscular atrophy carrier in China
Authors: Li Chao , Geng Yanfang , Zhu Xiaodan , Zhang Linghua , Hong Zhantong , Guo Xiaoling , Xia Chenglai
Published: January 2020

Introduction:

Spinal muscular atrophy (SMA) was the second most fatal autosomal recessive hereditary disease in clinic. There had been no detailed study to characterize the prevalence of SMA carrier among people in China. So, we conducted a systematic review and meta-analysis to obtain a reliable estimation of the prevalence of SMA carrier to characterize its epidemiology for the first time.

Methods:

We systematically searched for articles in kinds of important electronic databases, including PubMed, Embase, Wanfang Database and China National Knowledge Infrastructure (CNKI) to identify all relevant literatures about carrier rates of SMA in China. The prevalence was performed by forest plot choosing random effect models. The publication bias was evaluated by means of funnel plots and Egger test. The sensitivity analysis was carried out by the method of omitting any literature at a time. Combined with the results of subgroup analysis, the source of heterogeneity was also discussed absolutely.

Results:

A total of 10 studies published between 2005 and 2016 were included in our analysis at last. The sample size ranged from 264 to 107,611 in included studies. The random effect models of meta-analysis showed that the overall carrier rate of SMA was 2.0% (95% confidence interval [CI], 1.7%–2.3%) in a heterogeneous set of studies (I2 = 64%). There was a gradual rise trend observed in the SMA carrier rate during the study period. The funnel plots and Egger test (Coef = 0.02, t = −0.45, P = .667 > .05) showed no obvious potential risk of publication bias.

Conclusion:

The overall carrying rate of SMA was high as 2.0% and may be on a slow upward trend. So it was recommended that the countries should take active and effective measures to roll out routine prenatal screening and health genetic counseling for SMA as early as possible. What is more, further studies also need to be conducted to explore the etiology and epidemic factors of SMA to better control the risk of this common birth defect.
Performance of 68Ga-DOTA-SST PET/CT, octreoscan SPECT/CT and 18F-FDG PET/CT in the detection of culprit tumors causing osteomalacia: a meta-analysis
Authors: Jiang Yuanyuan , Hou Guozhu , Cheng Wuying
Published: January 2020

Objectives

The objective of this study was to assess and compare the performance of 68Ga-DOTA-conjugated-somatostatin-receptor-targeting-peptides (68Ga-DOTA-SST) PET/CT, octreoscan-SPECT/CT and 18F-FDG-PET/CT in the detection of tumor-induced osteomalacia (TIO).

Methods

Relevant studies reporting the performance 68Ga-DOTA-SST PET/CT, octreoscan-SPECT/CT and 18F-FDG-PET/CT in TIO were identified by searching PubMed, EMBASE, and Web of Science (last updated June 2019). Two authors independently extracted the numbers of true and false positives, and true and false negatives. The pooled estimates on a per-patient basis were calculated with 95% confidence interval (CI) obtained using a random-effects model.

Results

Fourteen studies comprising 346 patients were included in this meta-analysis. The meta-analysis provided the following results on a per-patient analysis. The pooled sensitivities of both 68Ga-DOTA-SST PET/CT (90%, 95% CI 82–95%) and octreoscan-SPECT/CT (83%, 95% CI 75–89%) were found to be significantly higher (P < 0.005) than that of 18F-FDG PET/CT (67%, 95% CI 53–80%). There was no statistically significant difference between the sensitivity of 68Ga-DOTA-SST PET/CT and octreoscan-SPECT/CT (P = 0.161). Owing to the low number of articles with true negative findings, the pooled specificities were not calculated. A total of 287 tumors were identified in 287 patients according to the data the included studies offered. The majority of the tumors were located in the lower extremities (59.6%, 171/287), followed by craniofacial regions (24.0%, 69/287), torso (9.4%%, 27/287), and upper extremities (6.9%, 20/287).

Conclusion

This meta-analysis demonstrates that somatostatin receptor-based imaging modalities outperformed 18F-FDG PET/CT in the detection of TIO, with 68Ga-DOTA-SST PET/CT performing slightly better than octreoscan-SPECT/CT.
Recent Surveys on Food Allergy Prevalence
Authors: Messina Mark , Venter Carina
Published: January 2020

Substantial numbers of children and adults report having immunoglobulin E–mediated food allergies. However, generating accurate food allergy prevalence data is difficult. Self-reported data can overestimate prevalence when compared with prevalence estimates established by more rigorous methods. As of 2004, in the United States, the Food Allergen Labeling and Consumer Protection Act mandated that the label should declare the source of the food if the product contains that food or a protein-containing ingredient from that food (not all proteins in a major food allergen cause allergic reactions) in the manner described by the law. The 8 major food allergens are milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soybeans, commonly referred to as the “Big 8.” These 8 allergens are thought to account for 90% of the food allergy reactions. Recently published large surveys of Americans and Canadian adults and children provide considerable insight into the prevalence of allergy for the major allergens. These data indicate that there is a large variation in prevalence among the Big 8. The prevalence of soy beans allergy is lower than the prevalence reported for each of the other 7 major allergens, which has been used to argue that soy could be removed from the Big 8 without risking harm to the public. However, the momentum appears to be in favor of expanding the Big 8. The US Food and Drug Administration is evaluating classification of sesame seed as a major allergen; it is already classified as a major allergen in Canada, Australia, and Europe. Europe classifies 14 foods as major allergens. There may be some advantage to standardizing major allergen lists globally, although it may be equally important to acknowledge differences in priority allergens based on cultural and dietary preferences. It is incumbent upon health professionals to help their patients and clients identify foods to which they are allergic and aid in planning diets that are nutritionally adequate despite elimination of these foods.
Comparison of Choroidal Thickness Measurements Using Semiautomated and Manual Segmentation Methods
Authors: Zhao Mei , Alonso-Caneiro David , Lee Roger , Cheong Allen M. Y. , Yu Wing-Yan , Wong Ho-Yin , Lam Andrew K. C.
Published: February 2020

SIGNIFICANCE

This study demonstrated that a semiautomated segmentation method could help inexperienced practitioners to obtain choroidal thickness as good as experienced practitioners.

PURPOSE

The purpose of this study was to compare choroidal thickness measurements obtained by semiautomated and manual segmentation methods.

METHODS

Optical coherence tomography images of 37 eyes from 37 healthy young subjects acquired by a spectral-domain optical coherence tomography device were reviewed retrospectively. Two naive examiners measured choroidal thickness using manual and semiautomated methods, whereas two experienced examiners used only the semiautomated method. The semiautomated method referred to a fully automated segmentation program customized based on MATLAB and followed manual verification. After highlighting the inner and outer choroidal boundaries through automated segmentation, examiners reviewed these boundaries in each B-scan and conducted manual revisions if segmentation errors occurred. After selecting points where correct boundary was located, the software used a spline fit to blend the corrected region with the rest of the boundary. All measurements were summarized in a 6-mm Early Treatment Diabetic Retinopathy Study grid. Operation time spent to complete retinal and choroidal segmentation on each eye was recorded. Between-examiner agreements, that is, intraclass correlation coefficient and coefficient of reproducibility (CoR), were calculated among four sets of semiautomated measurements, and within-examiner agreements were comparisons between manual and semiautomated results from the same naive examiners. Eyes with thin or thick choroids were also analyzed separately.

RESULTS

The between-examiner and within-examiner agreements were excellent with intraclass correlation coefficient of 0.976 or greater. Pairwise within-examiner CoRs ranged from 17.4 to 47.1 μm. Pairwise between-examiner CoRs were between 13.0 and 38.9 μm. Eyes with thin choroid had better agreements than those with thick choroids. On average, naive examiners saved 3 to 5 minutes per eye using the semiautomated method.

CONCLUSIONS

With the help of a dedicated software, inexperienced practitioners could obtain choroidal thickness measurements with accuracy similar to experienced practitioners. Processing time with the semiautomated method was also reduced.
Assessing the Impact of En Face Retinal Nerve Fiber Layer Imaging on Clinical Decision Making for Glaucoma Suspects
Authors: King Brett J. , Swanson William H. , Klemencic Stephanie A. , Chaglasian Michael , Teitelbaum Bruce A. , Clark Christopher A. , Speilburg Ashley M. , Grogg Jane Ann , Peabody Todd D.
Published: February 2020

SIGNIFICANCE

Assessing and managing glaucoma are a complicated process in which experience plays a key role in decision making. Although advanced glaucoma is more easily diagnosed, patients with early glaucoma or who present with suspicious findings are more complicated. A need to aid clinicians in the decision-making process exists.

PURPOSE

The purpose of this study was to assess the impact of en face ocular coherence tomography images to clinical decision making when added to standard presentations of circumpapillary retinal nerve fiber layer thickness and automated perimetry.

METHODS

Thirty participants from two centers presenting either as a glaucoma suspect or for an initial glaucoma evaluation were enrolled. Six masked investigators were given standard presentations of circumpapillary retinal nerve fiber layer thickness and perimetry. They were asked if glaucomatous damage was present as well as a recommended plan of management on 5-point Likert scales. They were then given en face images of the retinal nerve fiber layer in three different presentations coupled with the standard presentation, and the questions were repeated. An intraclass correlation coefficient (ICC) was generated.

RESULTS

The masked investigators had moderate agreement from the standard presentation for assessment (ICC = 0.67 [95% confidence interval {CI}, 0.54 to 0.80] and ICC = 0.69 [95% CI, 0.52 to 0.80], respectively), as well as with the addition of the en face images (ICC = 0.69; 95% CI, 0.56 to 0.81). The en face images tended to change decisions in both assessment and plan toward likely to have glaucoma and likely to start treatment.

CONCLUSIONS

The addition of en face images to a standard presentation has an impact on clinical decision making. Although en face images seem to influence the decision toward likely to have glaucoma and likely to treat, it is unclear if this leads to a more accurate decision. Further investigations seem warranted to assess sensitivity and specificity of this approach.
An 8-Year Retrospective Study on Suicides in Washington, DC
Authors: Cuchara Breanna , Diaz Francisco J.
Published: January 2020

The suicide rate in the United States has been increasing steadily over the previous 10 years. In DC, these results are not mirrored. The suicide rate has a tendency to be lower than the rest of the country. During this retrospective review of suicides in DC, factors such as medical history and toxicology results were examined.

In this study performed over 8 years (2009–2016), 394 suicides occurred. It was found that decedents committed suicide mostly by hanging (31.2%), firearms (20.3%), or drug intoxication (15.7%). The average age was 44.5 years. Similar to national statistics, male individuals committed suicide at a higher rate (77.9%) than did female individuals (22.1%). The toxicology data showed that ethanol (26.4%), antidepressants (20.1%), opioids (14.9%), and benzodiazepines (12.9%) were the drugs most frequently involved, although the finding of no drugs was most common (33.7%). Ethanol was present in 5 methods of suicide that include death by hanging, drowning, firearm, suffocation, and poisoning.

This research provides information that may be useful for public health officials when confronting the issue of suicide. It is hoped that it will encourage other medical examiner offices to perform toxicological analysis and autopsy of all suicide cases.
Early Recognition and Emergency Treatment of Sepsis and Septic Shock in Children
Authors: Hilarius Kristel W.E. , Skippen Peter W. , Kissoon Niranjan
Published: February 2020

Early diagnosis and treatment of sepsis and septic shock in children results in improved outcomes. However, diagnosis is hampered by lack of specific diagnostic tests and relies on the recognition of the alterations of vital signs and protean systemic manifestations associated with infections, signs that mimic many critical illnesses. As a result, the early diagnosis of sepsis is usually presumptive and is based on the suspicion or presence of an infection in combination with the systemic changes. Suspicion should be heightened in vulnerable risk groups such as those with immune compromise due to underlying disease or medication use. Thus, on many occasions, treatment of sepsis is initiated on clinical suspicion pending the outcomes of ongoing evaluations and laboratory findings.

What is of relevance to the emergency clinicians is the initial recognition, resuscitation, and treatment in the first few hours of presentation. To best accomplish these tasks, contemporary guidelines suggest that the use of a “recognition bundle” containing a trigger tool for rapid identification, a “resuscitation and stabilization bundle” to enable adherence to best practice, and a “performance bundle” to identify and overcome barriers to best practice be used.

Although there are no universally acceptable tools to accomplish these tasks, the various iterations used in quality improvement initiatives have consistently demonstrated better care processes and outcomes. In this article, we outline the contemporary approach to sepsis in the first hours after presentation.
Distraction Therapy to Correct Trismus Following Noma
Authors: Holle Jürgen , Kubiena Harald , Issa Ousmane Hamady
Published: January 2020

Trismus is a frequent complication of healed Noma infection and is caused by soft tissue and muscle contraction. Free-flap surgery is recommended to replace the missing oral mucosa and soft tissue. However, significant complications can occur if this surgery is performed in places like Africa, where conditions are usually less than optimal. In 2007, the authors started to treat patients with trismus in Niamey, Niger by distracting the soft tissue and muscle constriction between the jaws with a bone distractor continuously for 1 month with the aim of achieving a mouth opening of 3 cm. The distraction was limited to 1 mm/d. performed under local anesthesia with some sedation. Minor complications such as infection in the pin holes were easily managed. In 2009, 2 patients with trismus after Noma with a follow-up of 2 years were reported. Till date, the authors have successfully performed trismus release in more than 69 patients in Niamey and Guinea Bissau. The present study analyses the results of distraction therapy in 40 patients with follow-ups until 60 months. At the end of distraction, the mean interincisal distance was 2.7 ± 0.5 cm. Mouth opening 6 months after distraction had not reverted. However, 3 to 5 years after treatment, some signs of relapse were detected, with an average mouth opening of 1.5 ± 1.9 cm. Physiotherapy was unfortunately not feasible. The presented results strongly support the efficacy of distraction therapy to correct trismus in Noma patients.
New Insights Into the Molecular Mechanisms and Immune Control of Cytomegalovirus Reactivation
Authors: Heald-Sargent Taylor A. , Forte Eleonora , Liu Xuefeng , Thorp Edward B. , Abecassis Michael M. , Zhang Zheng Jenny , Hummel Mary A.
Published: January 2020

Cytomegalovirus (CMV) is a β-herpesvirus that establishes lifelong latency in infected hosts. Following transplantation of a latently infected organ, reactivation can occur and consists of a spectrum of clinically apparent syndromes from mild symptoms to tissue-invasive, resulting in both direct and indirect sequelae. Before the advent of effective antiviral agents, the primary treatment was reduction in immunosuppression (IS). While antiviral agents provide effective prophylaxis, there are several important caveats associated with their use, including drug toxicity and resistance. The traditional view attributes CMV reactivation and the ensuing clinical disease primarily to IS, either intrinsic to disease-related immune compromise or from the extrinsic administration of IS agents. However, previous data from both animal models and human subjects showed that inflammatory signals could induce upregulation of latent viral gene expression. New data demonstrate that ischemia/reperfusion is necessary and sufficient to induce CMV reactivation following murine transplantation of a latently infected graft. In this article, we review a growing body of evidence that suggests that reactivation of both human CMV and murine CMV is first triggered by molecular events that activate CMV gene expression and lytic infection and viral dissemination are then facilitated by IS. The initial activation of viral gene expression may be mediated by oxidative stress, DNA damage, or inflammatory cytokines, and these factors may act synergistically. New therapeutic approaches are needed to capture this complex array of targets.
A Review of Donor Acute Kidney Injury and Posttransplant Outcomes
Authors: Koyawala Neel , Parikh Chirag R.
Published: January 2020

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.
Reducing Donor-specific Antibody During Acute Rejection Diminishes Long-term Renal Allograft Loss: Comparison of Early and Late Rejection
Authors: Lichvar Alicia B. , Tremblay Simon , Leino Abbie D. , Shields Adele R. , Cardi Michael A. , Abu Jawdeh Bassam G. , Govil Amit , Kremer Joseph , Cuffy Madison , Paterno Flavio , Diwan Tayyab , Brailey Paul , Girnita Alin , Alloway Rita R. , Woodle E. Steve
Published: January 2020

Background.

Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor–based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival.

Methods.

Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor–based therapy from January 2005 to July 2015.

Results.

A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P < 0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction > 50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01).

Conclusions.

In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.
Biomimetic optics: liquid-based optical elements imitating the eye functionality
Authors: Ivanova Natalia
Published: February 2020

The optical systems mimicking the eye functions are of great importance in various applications including consumer electronics, medical equipment, machine vision systems and robotics. This optics offers advantages over traditional optical technologies such as the superior adaptation to changing conditions and the comprehensive range of functional characteristics at miniature sizes. This paper presents a review on the recent progress in the development of human eye-inspired optical systems. Liquid-based and elastomer-based tunable optical elements are discussed with the focus on the actuation mechanism, optical performance and the possibility of integration into artificial eye systems.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology (part 3)’.
Development of polyurethane-based superhydrophobic coatings on steel surfaces
Authors: Meena Mukesh Kumar , Tudu Balraj Krishnan , Kumar Aditya , Bhushan Bharat
Published: February 2020

In this study, a superhydrophobic coating on steel surface has been developed with polyurethane, SiO
2
nanoparticles and hexadecyltrimethoxysilane by using a spin-coating technique. Characterization of the coated steel surface was done by using the contact angle measurement technique, scanning electron microscopy and Fourier transform infrared spectroscopy. With a water tilt angle of 4° ± 2° and static contact angle of 165° ± 5°, the coated surface shows a superhydrophobic and self-cleaning nature. Chemical, thermal, mechanical stability tests and droplet dynamic studies were done to evaluate performance of the coating. Excellent self-cleaning, anti-fogging and anti-corrosion properties of coated steel surfaces make them ideal for industrial applications.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology (part 3)’.
A bioinspired strategy for designing well-ordered nanotubular structures by templateless electropolymerization of thieno[3,4-
b
]thiophene-based monomers
Authors: Bousrih Imen , El Kateb Mejda , Szczepanski Caroline R. , Beji Mohammed , Guittard Frédéric , Darmanin Thierry
Published: February 2020

Here, a bioinspired strategy is used to prepare well-ordered nanotubular structures, as observed in animals and plants, such as gecko toe pads or corals. The nanotubes are obtained by templateless electropolymerization of thieno[3,4-
b
]thiophene-based monomers with various aromatic groups in an organic solvent (dichloromethane). The most interesting and robust structures were obtained with carbazole and pyrene substituents to the base monomer structure, since these groups participate significantly in the polymerization and also have strong
π
-stacking interactions. The addition of water to electropolymerization solvent significantly impacted the formation of nanotubes, as it caused the release of a significant amount of H
2
and O
2
bubbles, depending on the electropolymerization method. Identifying templateless approaches to vary nanotubular structures is very interesting, as these materials are sought-after for applications in water harvesting systems.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology (part 3)’.
16S rRNA Gene PCR/Sequencing of Cerebrospinal Fluid in the Diagnosis of Post-operative Meningitis
Authors: Ramakrishna Jahanavi M. , Libertin Claudia R. , Yang Joshua N. , Diaz Mark A. , Nengue Anne L. , Patel Robin
Published: February 2020

Introduction. Post-operative meningitis (POM) is a life-threatening complication of neurosurgery. Diagnosis is often difficult due to pre-existing inflammation and antecedent antimicrobial use. Bacterial cerebrospinal fluid (CSF) cultures may reveal no growth, but empiric antibiotics are typically given due to the high morbidity and mortality associated with POM. 16S rRNA gene PCR/sequencing is a molecular methodology that can identify the presence of bacteria regardless of viability for culture.

Case Presentation. A patient presented with a rapid onset of fever associated with headache, neck pain, nausea and altered mental status 11 days after undergoing laser interstitial thermal therapy for treatment of recurrent astrocytoma at another hospital. Based on clinical presentation and imaging, POM was suspected, and empiric antibacterial therapy was started. Microbiological stains and cultures of CSF were negative. Due to persistent fevers, 16S rRNA gene PCR/sequencing was done on CSF; it detected a member of the order

Enterobacteriales

most closely resembling

Serratia

species. All antimicrobials were stopped except for cefepime, which was given for 2 weeks. The patient’s mental status fully recovered.

Conclusion. The application of 16S rRNA gene PCR/sequencing in the setting of POM is of value by improving the quality of patient care and decreasing costs by antimicrobial de-escalation. Further studies regarding the positive and negative predictive values of this test are required.
Gemmobacter caeruleus sp. nov., a novel species originating from lake sediment
Authors: Qu Jian-Hang , Ma Wen-Wen , Zhou Jia , Wang Xi-Feng , Lu Wen-Lan , Qu Ling-Bo , Wang Lin-Feng
Published: January 2020

An aerobic, Gram-stain-negative, non-spore-forming and rod-shaped bacterial strain, designated N8T, was isolated from the interfacial sediment of Taihu Lake in PR China. The strain formed white to blue colonies on R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain N8T represented a member of the genus

Gemmobacter

and was most closely related to

Gemmobacter aquaticus

A1-9T (97.97 %). The average nucleotide identity and digital DNA–DNAhybridization values between strain N8T and

G. aquaticus

A1-9T based on their whole genomes were 78.8 and 21.7 %, respectively. Q-10 was the main predominant ubiquinone. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 0 and C16 : 0. The G+C content of the genomic DNA was 66.1 mol%. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, two unidentified glycolipids and two unidentified lipids. Based on its physiological, biochemical and chemotaxonomic characteristics, strain N8T represents a novel species of the genus

Gemmobacter

, for which the name Gemmobacter caeruleus sp. nov. is proposed. The type strain is N8T=(KACC 21307T=MCCC 1K04036T).
Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis
Authors: Cepko Leah C. S. , Garling Eliotte E. , Dinsdale Madeline J. , Scott William P. , Bandy Loralee , Nice Tim , Faber-Hammond Joshua , Mellies Jay L.
Published: February 2020

Introduction. Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established.

Aim. Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative

Escherichia coli

(EAEC) while leaving the human microbiome intact.

Methodology. Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage, PDX, was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment.

Results.

Escherichia

virus PDX, a member of the strictly lytic family Myoviridae, killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of PDX (multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces. PDX also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and PDX, or with just PDX phage was not different statistically.

Conclusion.
PDX killed EAEC isolate EN1E-0007 in vivo and in vitro, while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller’s diarrhoea without causing dysbiosis.
Evaluation of Myocardial Perfusion and Immune Cell Response in Cardiac Allograft Dysfunction of Heart-Transplant Patients
Authors: Kim Paul J. , Contijoch Francisco , Morris Gerald P. , Wong Darrin , Chi Neil C. , Yarahmadi Pourya , Tada Yuko , Salmi Darren , Nguyen Patricia
Published: January 2020

Background

We investigated the myocardial perfusion differences and changes in immune cell response in heart-transplant patients with nonspecific graft dysfunction (NGD) compared to cardiac allograft vasculopathy (CAV) patients and normal heart-transplant patients.

Methods and Results

We prospectively studied 17 heart-transplant patients (59.8±14.1 years, 78% male) from January to June 2016. Regadenoson stress cardiac MRI was performed in the patients and peripheral blood obtained contemporaneously to isolate peripheral blood mononuclear cells (PBMCs). Stress myocardial perfusion showed significantly decreased myocardial perfusion using maximum upslope method in NGD and CAV patients compared to normal heart-transplant patients. Myocardial scar by late gadolinium enhancement also was significantly increased in nonspecific graft dysfunction patients compared to normal. Evaluation of PBMCs by flow cytometry showed a trend towards increased activated HLA-DR+T cells in NGD patients compared to normal. Clinical outcomes for cardiac hospitalization, allograft loss/retransplant, death were assessed at 8 years.

Conclusions

NGD shows decreased stress myocardial perfusion by cardiac MRI and a trend towards increased activated T cells in PBMCs, suggestive of an immune-mediated cause for allograft dysfunction.
Antigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine
Authors: Gouma Sigrid , Weirick Madison , Hensley Scott E.
Published: January 2020

The 2019-2020 Northern Hemisphere influenza vaccine includes antigens from 3c3.A H3N2 viruses; however, over half of circulating H3N2 viruses belong to subclade 3c2.A1b. Here, we analyzed antibody responses elicited by the egg-adapted 3c3.A H3N2 vaccine strain in ferrets and humans. We found that this vaccine strain elicits antibodies that have reduced reactivity to a wild-type 3c3.A strain and very limited reactivity to 3c2.A strains, including the currently circulating 3c2.A1b strain.
Antimicrobial treatment impacts resistance in off-target populations of a nosocomial bacterial pathogen: a case-control study
Authors: Kinnear Clare L. , Hansen Elsa , Forstchen Meghan , Read Andrew F. , Woods Robert J.
Published: January 2020

The antimicrobial resistance crisis has persisted despite broad attempts at intervention. Detailed studies of the population dynamics that lead to resistance could identify additional intervention points. An important driver of resistance in the most concerning antibiotic resistant pathogens can be selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations of E. faecium. We performed a case-control study in which the daptomycin resistance of E. faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance of E. faecium from the off-target population was on average 50% higher than resistance in the control group (n=428 independent E. faecium clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. Multiple samples over time were available from a subset of patients, and these demonstrate wide variability in temporal dynamics, from long-term maintenance of resistance to rapid return to sensitivity after daptomycin treatment stopped. Our results demonstrate that off-target gastrointestinal populations rapidly respond to intravenous antibiotic exposure. Gastrointestinal populations are the source for faecal transmission and so can be the driver for hospital-wide population level increases in resistance. Focusing on the off-target evolutionary dynamics may offer novel avenues to slow the spread of antibiotic resistance.
An empirical attack tolerance test alters the structure and species richness of plant-pollinator networks
Authors: Biella Paolo , Akter Asma , Ollerton Jeff , Nielsen Anders , Klečka Jan
Published: January 2020

Ecological network theory hypothesizes a link between structure and stability, but this has mainly been investigatedin-silico. In an experimental manipulation, we sequentially removed four generalist plants from real plant-pollinator networks and explored the effects on, and drivers of, species and interaction extinctions, network structure and interaction rewiring. Our results indicate that cumulative species and interaction extinctions increased faster with generalist plant loss than what was expected by co-extinction models, which predicted the survival or extinction of many species incorrectly. In addition, network nestedness decreased, modularity increased, and opportunistic random interactions and structural unpredictability emerged, which are all indicators of network instability and fragility. Conversely, interaction reorganization (rewiring) was high, asymmetries between network levels emerged as plants increased their centrality. From the experimental manipulations of real networks, our study shows how plant-pollinator network structure has low stability and changes towards a more fragile state when generalist plants are lost.
Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes
Authors: Heesterbeek Dani A. C. , Muts Remy M. , van Hensbergen Vincent P. , de Saint Aulaire Pieter , Wennekes Tom , Bardoel Bart W. , van Sorge Nina M. , Rooijakkers Suzan H.M.
Published: January 2020

Infections with Gram-negative bacteria form an increasing risk for human health, which is mainly due to the increase in antibiotic resistance. The cell envelope of Gram-negative bacteria consists of an inner membrane, a peptidoglycan layer and an outer membrane, which forms an impermeable barrier to many antibiotics and antimicrobial proteins. The complement system is an important factor of the human immune system that can efficiently kill Gram-negative bacteria via the formation of large pores in the bacterial outer membrane, called Membrane Attack Complexes (MACs). To better understand how these MAC pores damage the complex cell envelope of Gram-negative bacteria, we recently developed a fluorescent reporter system to study membrane damage inE. coli. Here, we used a similar experimental setup in combination with flow cytometry, confocal microscopy and conventional plating assays to elucidate how different components of the immune system act synergistically to effectively clear invading bacteria. We demonstrate how MAC-dependent outer membrane damage enhances the susceptibility ofE. colito further degradation of the cell envelope by lysozyme, leading to drastic changes in the morphology of these bacteria. Furthermore, we elucidate that the MAC enhances the susceptibility ofE. colito phospholipases, and to degradation and killing inside human neutrophils. Altogether, this study provides a detailed overview on how different players of the human immune system work closely together to degrade the complex cell envelope of Gram-negative bacteria. This knowledge may facilitate the development of new antimicrobials that could stimulate, or work synergistically with the immune system.
Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species
Authors: Dorant Yann , Cayuela Hugo , Wellband Kyle , Laporte Martin , Rougemont Quentin , Mérot Claire , Normandeau Eric , Rochette Rémy , Bernatchez Louis
Published: January 2020

Copy number variants (CNVs) are a major component of genotypic and phenotypic variation in genomes. To date, our knowledge of genotypic variation and evolution has largely been acquired by means of single nucleotide polymorphism (SNPs) analyses. Until recently, the adaptive role of structural variants (SVs) and particularly that of CNVs has been overlooked in wild populations, partly due to their challenging identification. Here, we document the usefulness of Rapture, a derived reduced-representation shotgun sequencing approach, to detect and investigate copy number variants (CNVs) alongside SNPs in American lobster (Homarus americanus) populations. We conducted a comparative study to examine the potential role of SNPs and CNVs in local adaptation by sequencing 1,141 lobsters from 21 sampling sites within the southern Gulf of St. Lawrence, which experiences the highest yearly thermal variance of the Canadian marine coastal waters. Our results demonstrated that CNVs accounts for higher genetic differentiation than SNP markers. Contrary to SNPs, for which no significant genetic-environment association was found, 48 CNV candidates were significantly associated with the annual variance of sea surface temperature, leading to the genetic clustering of sampling locations despite their geographic separation. Altogether, we provide a strong empirical case that CNVs putatively contribute to local adaptation in marine species and unveil stronger spatial signal of population structure than SNPs. Our study provides the means to study CNVs in non-model species and highlights the importance of considering structural variants alongside SNPs to enhance our understanding of ecological and evolutionary processes shaping adaptive population structure.
Implications of genetic heterogeneity for plant translocation during ecological restoration
Authors: Crow Taylor M. , Buerkle C. Alex , Runcie Daniel E. , Hufford Kristina M.
Published: January 2020

Ecological restoration often requires translocating plant material from distant sites. Yet published guidelines for seed transfer are available for very few species. Accurately predicting how plants will perform when transferred requires multi-year and multi-environment field trials and comprehensive follow-up work. In this study, we analyzed the genetic structure of an important shrub used in ecological restorations in the Southern Rocky Mountains called alder-leaf mountain mahogany (Cercocarpus montanus). We sequenced DNA from 1440 plants in 48 populations across a broad geographic range. We found that genetic heterogeneity among populations reflected the complex climate and topography across which the species is distributed. We identified several temperature and precipitation variables that were useful predictors of genetic differentiation and can be used to generate seed transfer recommendations. These results will be valuable for defining management and restoration practices for mountain mahogany and other widespread montane plant species.
Serine Phosphorylation Regulates the P-type Potassium pump KdpFABC
Authors: Sweet Marie E. , Dubey Vikas , Zhang Xihui , Erdjument-Bromage Hediye , Neubert Thomas A. , Pedersen Bjørn P. , Khandelia Himanshu , Stokes David L.
Published: January 2020

KdpFABC is an ATP-dependent K+pump that ensures bacterial survival in K+-deficient environments. Whereas transcriptional activation of kdpFABC expression is well studied, a mechanism for down regulation when K+levels are restored has not been described. Here we show that KdpFABC is inhibited when cells return to a K+-rich environment. The mechanism of inhibition involves phosphorylation of Ser162 on KdpB, which can be reversed in vitro by treatment with serine phosphatase. Mutating Ser162 to Alanine produces constitutive activity, whereas the phosphomimetic Ser162Asp mutation inactivates the pump. Analyses of the transport cycle show that serine phosphorylation uncouples the pump and blocks the cycle after formation of the catalytic aspartyl phosphate intermediate (E1∼P). Molecular dynamics simulations show that serine phosphorylation has allosteric effects that potentially explain the uncoupling. This regulatory mechanism, unique amongst P-type pumps, furthers our understanding of how bacteria control potassium homeostasis to maintain cell volume and osmotic potential.
StoHi-C: Using t-Distributed Stochastic Neighbor Embedding (t-SNE) to predict 3D genome structure from Hi-C Data
Authors: MacKay Kimberly , Kusalik Anthony
Published: January 2020

In order to comprehensively understand the structure-function relationship of the genome, 3D genome structures must first be predicted from biological data (like Hi-C) using computational tools. Many of these existing tools rely partially or completely on multi-dimensional scaling (MDS) to embed predicted structures in 3D space. MDS is known to have inherent problems when applied to high-dimensional datasets like Hi-C. Alternatively, t-Distributed Stochastic Neighbor Embedding (t-SNE) is able to overcome these problems but has not been applied to predict 3D genome structures. In this manuscript, we present a new workflow called StoHi-C (pronounced "stoic") that uses t-SNE to predict 3D genome structure from Hi-C data. StoHi-C was used to predict 3D genome structures for multiple, independent existing fission yeast Hi-C datasets. Overall, StoHi-C was able to generate 3D genome structures that more clearly exhibit the established principles of fission yeast 3D genomic organization.
Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes
Authors: Bacmeister Clara M. , Barr Helena J. , McClain Crystal R. , Thornton Michael A. , Nettles Dailey , Welle Cristin G. , Hughes Ethan G.
Published: January 2020

Oligodendrocyte loss in neurological disease leaves axons vulnerable to damage and degeneration, and activity-dependent myelination may represent an endogenous mechanism to improve remyelination following injury. Here, we report that while learning a forelimb reach task transiently suppresses oligodendrogenesis, it subsequently increases OPC differentiation, oligodendrocyte generation, and retraction of pre-existing myelin sheaths in the forelimb region of motor cortex. Immediately following demyelination, motor cortex neurons exhibit hyperexcitability, motor learning is impaired, and behavioral intervention provides no long-term benefit to remyelination. However, partial remyelination restores neuronal and behavioral function. Motor learning following partial remyelination increases oligodendrogenesis and enhances the ability of mature oligodendrocytes to generate new myelin sheaths, resulting in almost double the remyelination of denuded axons relative to untrained controls. Together, our findings demonstrate that the correct timing of behaviorally-induced neuronal circuit activation improves recovery from demyelinating injury via enhanced remyelination from new and surviving oligodendrocytes.
Encoding Innately Recognized Odors via a Generalized Population Code
Authors: Qiu Qiang , Wu Yunming , Ma Limei , Yu C. Ron
Published: January 2020

Odors carrying intrinsic values often trigger instinctive aversive or attractive responses. It is not known how innate valence is encoded. An intuitive model suggests that the information is conveyed through specific channels in hardwired circuits along the olfactory pathway, insulated from influences of other odors, to trigger innate responses. Here we show that in mice, mixing innately aversive or attractive odors with a neutral odor, and surprisingly, mixing two odors with the same valence, abolish the innate behavioral responses. Recordings from the olfactory bulb indicate that odors are not masked at the level of peripheral activation and glomeruli independently encode components in the mixture. In contrast, crosstalk among the mitral/tufted cells changes their patterns of activity such that those elicited by the mixtures can no longer be linearly decoded as separate components. The changes in behavioral and mitral/tufted cell responses are associated with reduced activation of brain areas linked to odor preferences. Thus, crosstalk among odor channels at the earliest processing stage in the olfactory pathway leads to re-coding of odor identity to abolish valence associated with the odors. These results are inconsistent with insulated labeled lines and support a model of a common mechanism of odor recognition for both innate and learned valence associations.