bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of an Iris Speculum for Retrolental Membrane Dissection for Stage 5 Prematurity of Retinopathy Complicated With Pupillary Adhesion
Authors: Lyu Jiao , Zhang Qi , Zhao Peiquan
Published: January 2020

Purpose:

To report a novel use of an iris speculum to assist with membrane dissection and trough separation for stage 5 retinopathy of prematurity–related funnel-shaped tractional retinal detachment complicated with pupillary adhesion.

Methods:

Limbus-based closed vitrectomy and membrane dissection were performed in 10 eyes (9 patients) with stage 5 retinopathy of prematurity–related tractional retinal detachment and pupillary adhesion. After synechiolysis, an iris speculum was positioned to enlarge the pupil for surgical visualization and maintain a neutral iris plane. The retrolental membrane was dissected bimanually and circumferentially along the peripheral trough and then toward the central retina with vertical scissors and end-gripping forceps.

Results:

In all 10 eyes, retrolental membranes were entirely removed and troughs were circumferentially unraveled. Follow-up examinations performed 6 to 18 months postoperatively showed reattachment of the retina in 3 eyes with an open-narrow funnel and 6 of 7 eyes with a narrow–narrow funnel. A near-circular pupil without recurrent pupillary adhesion was preserved in all nine eyes showing retinal reattachment.

Conclusion:

This use of the iris speculum effectively exposes the surgical field for the entire removal of retrolental tissue and interruption of the peripheral trough in stage 5 retinopathy of prematurity–related tractional retinal detachment complicated with pupillary adhesion. The pupil's configuration is well preserved postoperatively.
Immunization Against Hepatitis A in Migrant Children
Authors: Fahrni Olivia , Posfay-Barbe Klara M. , Wagner Noémie
Published: January 2020

Background:

Hepatitis A is endemic in many countries. Swiss guidelines recommend vaccinating patients native from endemic areas. In Geneva’s Children’s hospital, migrant children are screened and vaccinated if seronegative. Because hepatitis A’s prevalence is decreasing worldwide, more children are seronegative at arrival, highlighting the need for immunization in medical centers and refugee camps and questioning the benefits of systematic serology. Other Swiss hospitals vaccinate regardless of serostatus. This study’s aim is to assess migrant children’s immunity according to origin and age, and the cost-effectiveness of different immunization strategies.

Methods:

We retrospectively analyzed 329 children’s serostatus (1–16 years of age) between 2012 and 2015, using enzyme-linked fluorescent assay method. Serology and vaccine costs were based on local prices. Groups were compared with χ2 test and the age-seropositivity relationship was studied with linear regression.

Results:

The predominant regions were the Eastern Mediterranean and European Regions with mostly negative serologies (71% and 83%) and the African Region with mostly positive serologies (79%). Immunity varied depending on birth country. Regardless of region, seropositivity increased with age (P < 0.001). The most cost-effective vaccination strategy was an individualized approach based on age and origin, reducing costs by 2% compared with serology-guided immunization and by 17% compared with systematic vaccination.

Conclusions:

Many migrant children >5 years old are seronegative and at risk of clinical infection. They need to be immunized. New guidelines according to age and origin should be defined to reduce immunization costs. We recommend systematic vaccination for patients <5 years old or native from low endemicity areas (≤25.7% of seropositivity). For the others, we propose serology-based vaccination.
Human Herpesvirus 7-Related Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion
Authors: Syridou Garyfallia , Drikos Ioannis , Kapetanakis Minas , Vartzelis Giorgos , Horefti Elina , Triantafylou Evagelia , Bodozoglou Nikolaos , Zarganis Diagoras , Mentis Andreas , Tsolia Maria
Published: January 2020

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a recently described entity so far exclusively in East Asian children. AESD diagnosis is based on clinicoradiologic criteria, often without pleocytic CSF and characterized by hyperglycemia and transaminasemia. Here, we present the first case of human herpesvirus 7-related AESD in an immunocompetent child >2 years old and of Caucasian origin.
Measuring Council Health to Transform Shared Governance Processes and Practice
Authors: Hess Robert G. , Bonamer Jennifer I. , Swihart Diana , Brull Stacey
Published: January 2020

OBJECTIVE

The aim of this study was to develop a valid, reliable instrument to measure the effectiveness of shared governance councils

BACKGROUND

The work of shared governance, that is, the decisions, takes place in its structures, notably, the councils. A literature search yielded no formal instrument for evaluating how these councils function.

METHODS

A 4-phase process was used to generate valid items to measure shared governance council effectiveness, including content validity by experts, a pilot for feasibility, a larger pilot for internal consistency, and an exploratory factor analysis to delineate a final instrument.

RESULTS

More than a dozen experts and participants from nearly 30 healthcare organizations contributed to the final development of the 25-item Council Health Survey instrument. Items for measuring council effectiveness at either the unit or division level were grouped in areas of structure, activities, and membership.

CONCLUSIONS

When evaluating shared governance, nurses should focus on councils themselves, in which much of the work of shared governance occurs.
Quality of End of Life Care in Magnet® and Non-Magnet Hospitals
Authors: Lasater Karen B. , Schlak Amelia E.
Published: January 2020

OBJECTIVE

To examine whether end-of-life care quality is superior in Magnet® hospitals, a recognition designating nursing excellence.

BACKGROUND

Considerable research shows better patient outcomes in hospitals with excellent nurse work environments, but end-of-life care quality has not been studied in Magnet hospitals.

METHODS

An analysis of cross-sectional data was completed using surveys of nurses and hospitals. Multivariate logistic regression models were used to determine the association between Magnet hospitals and measures of end-of-life care quality.

RESULTS

Overall, nurses report poor quality of end-of-life care in US hospitals. In Magnet hospitals, nurses were significantly less likely to give their hospital an unfavorable rating on end-of-life care.

CONCLUSIONS

Hospital Magnet status may signal better quality in end-of-life care. Administrators looking to improve the quality of end-of-life care may consider improving aspects of nursing that distinguish Magnet hospitals.
Subclinical Peroneal Neuropathy Affects Ambulatory, Community-Dwelling Adults and Is Associated with Falling
Authors: Poppler Louis H. , Yu Jenny , Mackinnon Susan E.
Published: January 2020

Background:

Peroneal neuropathy with an overt foot drop is a known risk factor for falling. Subclinical peroneal neuropathy caused by compression at the fibular neck is subtler and does not have foot drop. A previous study found subclinical peroneal neuropathy in 31 percent of hospitalized patients. This was associated with having fallen. The purpose of this study was to determine the prevalence of subclinical peroneal neuropathy in ambulatory adults and investigate if it is associated with falling.

Methods:

A cross-sectional study of 397 ambulatory adults presenting to outpatient clinics at a large academic hospital was conducted from 2016 to 2017. Patients were examined for dorsiflexion weakness and signs of localizing peroneal nerve compression to the fibular neck. Fall risk was assessed with the Activities-Specific Balance Confidence Scale and self-reported history of falling. Multivariate logistic regression was used to correlate subclinical peroneal neuropathy with fall risk and a history of falls.

Results:

The mean patient age was 54 ± 15 years and 248 patients (62 percent) were women. Thirteen patients (3.3 percent) were found to have subclinical peroneal neuropathy. After controlling for various factors known to increase fall risk, patients with subclinical peroneal neuropathy were 3.74 times (95 percent CI, 1.06 to 13.14) (p = 0.04) more likely to report having fallen multiple times in the past year than patients without subclinical peroneal neuropathy. Similarly, patients with subclinical peroneal neuropathy were 7.22 times (95 percent CI, 1.48 to 35.30) (p = 0.02) more likely to have an elevated fall risk on the Activities-Specific Balance Confidence fall risk scale.

Conclusion:

Subclinical peroneal neuropathy affects 3.3 percent of adult outpatients and may predispose them to falling.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Efavirenz-Based Antiretroviral Therapy Reduces Artemether–Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women
Authors: Hughes Emma , Mwebaza Norah , Huang Liusheng , Kajubi Richard , Nguyen Vy , Nyunt Myaing M. , Orukan Francis , Mwima Moses W. , Parikh Sunil , Aweeka Francesca
Published: January 2020

Background:

The choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether–lumefantrine (AL) because no studies have isolated the impact of efavirenz for HIV-infected pregnant women.

Methods:

A prospective clinical pharmacokinetic (PK) study compared HIV-infected, efavirenz-treated pregnant women with HIV-uninfected pregnant women in Tororo, Uganda. All women received the standard 6-dose AL treatment regimen for Plasmodium falciparum malaria with intensive PK samples collected over 21 days and 42-days of clinical follow-up. PK exposure parameters were calculated for artemether, its active metabolite dihydroartemisinin (DHA), and lumefantrine to determine the impact of efavirenz.

Results:

Nine HIV-infected and 30 HIV-uninfected pregnant women completed intensive PK evaluations. Relative to controls, concomitant efavirenz therapy lowered the 8-hour artemether concentration by 76% (P = 0.013), DHA peak concentration by 46% (P = 0.033), and day 7 and 14 lumefantrine concentration by 61% and 81% (P = 0.046 and 0.023), respectively. In addition, there were nonsignificant reductions in DHA area under the concentration–time curve0–8hr (35%, P = 0.057) and lumefantrine area under the concentration–time curve0–∞ (34%, P = 0.063) with efavirenz therapy.

Conclusions:

Pregnant HIV-infected women receiving efavirenz-based antiretroviral therapy during malaria treatment with AL showed reduced exposure to both the artemisinin and lumefantrine. These data suggest that malaria and HIV coinfected pregnant women may require adjustments in AL dosage or treatment duration to achieve exposure comparable with HIV-uninfected pregnant women.
Clinical and Economic Impact of Ibalizumab for People With Multidrug-Resistant HIV in the United States
Authors: Millham Lucia R.I. , Scott Justine A. , Sax Paul E. , Shebl Fatma M. , Reddy Krishna P. , Losina Elena , Walensky Rochelle P. , Freedberg Kenneth A.
Published: January 2020

Background:

We projected the clinical outcomes, cost-effectiveness, and budget impact of ibalizumab plus an optimized background regimen (OBR) for people with multidrug-resistant (MDR) HIV in the United States.

Methods:

Using the Cost-Effectiveness of Preventing AIDS Complications microsimulation model and a health care sector perspective, we compared 2 treatment strategies for MDR HIV: (1) IBA + OBR—ibalizumab plus OBR and (2) OBR—OBR alone. Ibalizumab efficacy and cohort characteristics were from trial data: mean age 49 years, 85% male, and mean CD4 150/µL. Six-month viral suppression was 50% with IBA + OBR and 0% with OBR. The ibalizumab loading dose cost $10,500, and subsequent ibalizumab injections cost $8400/month; OBR cost $4500/month. Incremental cost-effectiveness ratios (ICERs) were calculated using discounted (3%/year) quality-adjusted life years (QALYs) and costs. ICERs ≤$100,000/QALY were considered cost-effective. We performed sensitivity analysis on key parameters and examined budget impact.

Results:

In the base case, 5-year survival increased from 38% with OBR to 47% with IBA + OBR. Lifetime costs were $301,700/person with OBR and $661,800/person with IBA + OBR; the ICER for IBA + OBR compared with OBR was $260,900/QALY. IBA + OBR was not cost-effective even with 100% efficacy. IBA + OBR became cost-effective at base case efficacy if ibalizumab cost was reduced by ≥88%. For an estimated 12,000 people with MDR HIV in the United States, IBA + OBR increased care costs by $1.8 billion (1.5% of total treatment budget) over 5 years.

Conclusions:

For people with MDR HIV lacking other treatment options, ibalizumab will substantially increase survival when effective. Although adding ibalizumab to OBR is not cost-effective, the low number of eligible patients in the United States makes the budget impact relatively small.
Prevalence of and Risk Factors for Low Bone Mineral Density Assessed by Quantitative Computed Tomography in People Living With HIV and Uninfected Controls
Authors: Thomsen Magda T. , Wiegandt Yaffah L. , Gelpi Marco , Knudsen Andreas D. , Fuchs Andreas , Sigvardsen Per E. , Kühl Jørgen T. , Nordestgaard Børge , Køber Lars , Lundgren Jens , Hansen Ann-Brit E. , Kofoed Klaus F. , Jensen Jens-Erik B. , Nielsen Susanne D.
Published: January 2020

Background:

Low bone mineral density (BMD) has been described in people living with HIV (PLWH). We examined the prevalence of low BMD measured by quantitative computed tomography (QCT), a method that allows 3-dimensional volumetric density measures at the thoracic spine, in well-treated PLWH and uninfected controls and assessed risk factors for reduced BMD.

Methods:

Cross-sectional study including 718 PLWH from the Copenhagen Co-Morbidity in HIV infection (COCOMO) study and 718 uninfected controls matched on age and sex from the Copenhagen General Population Study (CGPS). Trabecular BMD was determined by QCT.

Results:

Median BMD was 144.2 mg/cm3 in PLWH vs. 146.6 mg/cm3 in controls (P = 0.580). HIV status was not associated with BMD in univariable or multivariable linear analyses. However, a higher prevalence of very low BMD (T-score ≤ −2.5) was found in PLWH (17.2% vs. 11.0% in controls, P = 0.003). In unadjusted analysis, HIV was associated with very low BMD (odds ratio 1.68 [95% confidence interval: 1.24–2.27], P = 0.001), but this association was not significant after adjusting for age, sex, smoking, alcohol, body mass index, physical activity, and ethnicity. Previous AIDS-defining disease was associated with lower BMD, but no other associations with HIV-specific variables were identified.

Conclusion:

Using QCT, we found a higher prevalence of very low BMD in PLWH than in controls. However, HIV status was not independently associated with BMD indicating that traditional risk factors contribute to the difference in prevalence of very low BMD. Focus on improvement of lifestyle factors, especially in PLWH with previous AIDS-defining disease, may prevent very low BMD in PLWH.
From Nonadherence to Adherence
Authors: Kuypers Dirk R.J.
Published: January 2020

Medication nonadherence (MNA) after solid organ transplantation is highly prevalent and associated with (late) (sub)clinical acute rejection, graft dysfunction and graft loss, development of donor-specific anti-HLA antibodies, and antibody-mediated rejection. MNA is predominantly unintentional and originates from barriers to adherence that are often multifactorial and complex. Tools to establish an early diagnosis of MNA include incorporation of MNA as a vital sign in daily clinical practice, self-reporting using validated questionnaires, calculating intrapatient variability in drug exposure and applying electronic monitoring, and recent audio and video technologies such as in home telemonitoring. MNA is a modifiable risk factor after organ transplantation, and treatment is most effective if a multimodal approach is used. Management of MNA comprises education (cognitive) and counseling (behavioral) that require the involvement of a trained multidisciplinary team [ideally physician, nurse (specialist), social worker, transplant coordinator, psychologist, clinical pharmacist], electronic reminder and support systems (eg, Medication Event Monitoring System, smartphone), and different types of novel mobile health applications as well as simplification of the medication dosing regimen. Future studies that evaluate novel therapeutic approaches for MNA should assure the use of reliable MNA measures, focus on multimodal individualized therapy for enriched nonadherent target populations (eg, adolescents), and incorporate clinically relevant endpoints. Costs, time, and personnel investments should be taken into account when assessing scalability and cost-effectiveness of novel therapeutic strategies. This review provides suggestions how different types of transplant centers can set up a dedicated MNA program according to available resources to define and achieve realistic clinical goals in managing MNA.
Stoma-Related Complications Following Ostomy Surgery in 3 Acute Care Hospitals
Authors: Pearson Robert , Knight Stephen R. , Ng James C. K. , Robertson Isabell , McKenzie Clare , Macdonald Angus M.
Published: January 2020

PURPOSE:

The aim of this study was to evaluate both surgical and patient-centered stomal complications after stoma formation, with emphasis on underreported symptoms and complaints.

DESIGN:

Prospective, single-group study.

SUBJECTS AND SETTING:

Patients undergoing emergency and elective ostomy surgery between January 1, 1999, and June 1, 2016, in 3 acute care hospitals were followed up by stoma care nurse specialists in NHS Lanarkshire, Scotland.

METHODS:

Data were collected on surgery type (emergency or elective), stoma type (ileostomy or colostomy), stoma-related complications including surgical complications (stenosis, retractions, hernia, and prolapse) and so-called “patient-centered” complications (skin changes, odor, leakage, soiling, and nighttime emptying) at 5 time points: 10 days, 3 months, 6 months, 1 year, and 2 years postoperatively. For this study, we report comparisons at 10 days and 2 years, using frequencies reported as percentages.

RESULTS:

Data from 3509 consecutive stoma surgeries were analyzed. Complication rates were similar in both emergency and elective cases. The nighttime symptoms of leakage and soiling were significantly greater in the ileostomy group and worsened over the 2-year period. The parastomal hernia rate was 34.5% at 2 years, a finding more common in the colostomy group (46.4% vs 20.1%, P < .001). However, the rate of clinically significant hernia was similar when comparing the colostomy group with the ileostomy group (3.6% vs 2.2%, P = .38). Emergency stoma surgeries (40.2%) were preoperatively sited compared with 95.9% of elective cases.

CONCLUSIONS:

Our prospective multicenter study demonstrated that stoma-related complications are similar irrespective of whether the stoma was formed via an elective surgery or emergency surgery. Nighttime symptoms of leakage, soiling, and emptying were high post–stoma formation, particularly in the ileostomy group, and worsened over the 2-year period. Findings from our study highlight the presence and persistence of complications. We believe our work highlights the importance of having frequent discussions with patients about making decisions about approaches to reduce complications to enhance patient outcomes.
Importance of adipocyte browning in the evolution of endothermy
Authors: Jastroch Martin , Seebacher Frank
Published: January 2020

Endothermy changes the relationship between organisms and their environment fundamentally, and it is therefore of major ecological and evolutionary significance. Endothermy is characterized by non-shivering thermogenesis, that is metabolic heat production in the absence of muscular activity. In many eutherian mammals, brown adipose tissue (BAT) is an evolutionary innovation that facilitates non-shivering heat production in mitochondria by uncoupling food-derived substrate oxidation from chemical energy (ATP) production. Consequently, energy turnover is accelerated resulting in increased heat release. The defining characteristics of BAT are high contents of mitochondria and vascularization, and the presence of uncoupling protein 1. Recent insights, however, reveal that a range of stimuli such as exercise, diet and the immune system can cause the browning of white adipocytes, thereby increasing energy expenditure and heat production even in the absence of BAT. Here, we review the molecular mechanisms that cause browning of white adipose tissue, and their potential contribution to thermoregulation. The significance for palaeophysiology lies in the presence of adipose tissue and the mechanisms that cause its browning and uncoupling in all amniotes. Hence, adipocytes may have played a role in the evolution of endothermy beyond the more specific evolution of BAT in eutherians.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Pushing the limits of recovery in chronic stroke survivors: User perceptions of the Queen Square Upper Limb Neurorehabilitation Programme
Authors: Kelly K , Brander F , Strawson A , Ward NS , Hayward KS
Published: January 2020

Introduction

The Queen Square Upper Limb (QSUL) Neurorehabilitation Programme is a clinical service within the National Health Service in the United Kingdom that provides 90 hours of therapy over three weeks to stroke survivors with persistent upper limb impairment. This study aimed to explore the perceptions of participants of this programme, including clinicians, stroke survivors and carers.

Design

Descriptive qualitative.

Setting

Clinical outpatient neurorehabilitation service.

Participants

Clinicians (physiotherapists, occupational therapists, rehabilitation assistants) involved in the delivery of the QSUL Programme, as well as stroke survivors and carers who had participated in the programme were purposively sampled. Each focus group followed a series of semi-structured, open questions that were tailored to the clinical or stroke group. One independent researcher facilitated all focus groups, which were audio-recorded, transcribed verbatim and analysed by four researchers using a thematic approach to identify main themes.

Results

Four focus groups were completed: three including stroke survivors (n = 16) and carers (n =2), and one including clinicians (n = 11). The main stroke survivor themes related to psychosocial aspects of the programme (“you feel valued as an individual”), as well as the behavioural training provided (“gruelling, yet rewarding”). The main clinician themes also included psychosocial aspects of the programme (“patient driven ethos – no barriers, no rules”), and knowledge, skills and resources of clinicians (“it is more than intensity, it is complex”).

Conclusions

As an intervention, the QSUL Programme is both comprehensive and complex. The impact of participation in the programme spans psychosocial and behavioural domains from the perspectives of both the stroke survivor and clinician.

Strengths and limitations

Descriptive qualitative study of the perception of users (stroke survivor, carer, clinician) engaged in the delivery of the Queen Square Upper Limb Neurorehabilitation Programme, which is run at a single centre in the United Kingdom.

Focus groups were completed by a researcher independent of the programme, without the involvement of senior management to facilitate open discussion and critical reflection of the programme.

This study involved a sample of users that were involved in the programme in the previous 12-months.

Data coding was performed by four researchers enhancing the validity of the results.

As only two carers were included in the focus groups, their experience has limited representation in the results.
Expanding cancer predisposition genes with ultra-rare cancer-exclusive human variations
Authors: Rasnic Roni , Linial Nathan , Linial Michal
Published: January 2020

It is estimated that up to 10% of cancer incidents are attributed to inherited genetic alterations. Despite extensive research, there are still gaps in our understanding of genetic predisposition to cancer. It was theorized that ultra-rare variants partially account for the missing heritable component. We harness the UK BioBank dataset of ∼500,000 individuals, 14% of which were diagnosed with cancer, to detect ultra-rare, possibly high-penetrance cancer predisposition variants. We report on 115 cancer-exclusive ultra-rare variations (CUVs) and nominate 26 variants with additional independent evidence as cancer predisposition variants. We conclude that population cohorts are valuable source for expanding the collection of novel cancer predisposition genes.
Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility
Authors: Gouma Sigrid , Kim Kangchon , Weirick Madison , Gumina Megan E. , Branche Angela , Topham David J. , Martin Emily T. , Monto Arnold S. , Cobey Sarah , Hensley Scott E.
Published: January 2020

Most humans are infected with influenza viruses by 3-4 years of age (1) and have high antibody titers against viral strains encountered early in life (2). Early childhood influenza exposures can leave lifelong ‘immunological imprints’ that affect how an individual responds to antigenically distinct viral strains later in life (3,4). H3N2 influenza viruses began circulating in humans in 1968 and have evolved substantially over the past 51 years (5). Therefore, an individual’s birth year largely predicts which specific type of H3N2 virus they first encountered in childhood. Here, we completed a large serological survey to elucidate the specificity of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We found that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. Most importantly, we found that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility.
Dissecting the genetic overlap of education, socioeconomic status, and mental health
Authors: Wendt F. R. , Pathak G. A. , Lencz T. , Krystal J. H. , Gelernter J. , Polimanti R.
Published: January 2020

Socioeconomic status (SES) and education (EDU) are phenotypically associated with psychiatric disorders and behavior. It remains unclear how these associations influence the genetic risk for mental health traits and EDU/SES individually. Using information from >1 million individuals, we conditioned the genetic risk for psychiatric disorders, personality traits, brain imaging phenotypes, and externalizing behaviors with genome-wide data for EDU/SES. Accounting for EDU/SES significantly affected the observed heritability of psychiatric traits ranging from 2.44% h2decrease for bipolar disorder to 29.0% h2decrease for Tourette syndrome. Neuroticism h2significantly increased by 20.23% after conditioning with SES. After EDU/SES conditioning, novel neuronal cell-types were identified for risky behavior (excitatory), major depression (inhibitory), schizophrenia (excitatory and GABAergic), and bipolar disorder (excitatory). Conditioning with EDU/SES also revealed unidirectional causality between brain morphology and mental health phenotypes. Our results indicate genetic discoveries of mental health outcomes may be limited by genetic overlap with EDU/SES.
Melanopsin Carboxy-terminus Phosphorylation Plasticity and Bulk Negative Charge, not Strict Site Specificity, Achieves Phototransduction Deactivation
Authors: Valdez-Lopez Juan C. , Gulati Sahil , Ortiz Elelbin A. , Palczewski Krzysztof , Robinson Phyllis R.
Published: January 2020

Melanopsin is a visual pigment expressed in a small subset of ganglion cells in the mammalian retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) and is implicated in regulating non-image forming functions such as circadian photoentrainment and pupil constriction and contrast sensitivity in image formation. Mouse melanopsin’s Carboxy-terminus (C-terminus) possesses 38 serine and threonine residues, which can potentially serve as phosphorylation sites for a G-protein Receptor Kinase (GRK) and be involved in the deactivation of signal transduction. Previous studies suggest that S388, T389, S391, S392, S394, S395 on the proximal region of the C-terminus of mouse melanopsin are necessary for melanopsin deactivation. We expressed a series of mouse melanopsin C-terminal mutants in HEK293 cells and using calcium imaging, and we found that the necessary cluster of six serine and threonine residues, while being critical, are insufficient for proper melanopsin deactivation. Interestingly, the additional six serine and threonine residues adjacent to the required six sites, in either proximal or distal direction, are capable of restoring wild-type deactivation of melanopsin. These findings suggest an element of plasticity in the molecular basis of melanopsin phosphorylation and deactivation. In addition, C-terminal chimeric mutants and molecular modeling studies support the idea that the initial steps of deactivation and β-arrestin binding are centered around these critical phosphorylation sites (S388-S395). This degree of functional versatility could help explain the diverse ipRGC light responses as well as non-image and image forming behaviors, even though all six sub types of ipRGCs express the same melanopsin gene OPN4.
Viral Sequence Identification in Metagenomes using Natural Language Processing Techniques
Authors: Abdelkareem Aly O. , Khalil Mahmoud I. , Elbehery Ali H. A. , Abbas Hazem M.
Published: January 2020

Viral reads identification is one of the important steps in metagenomic data analysis. It shows up the diversity of the microbial communities and the functional characteristics of microorganisms. There are various tools that can identify viral reads in mixed metagenomic data using similarity and statistical tools. However, the lack of available genome diversity is a serious limitation to the existing techniques. In this work, we applied natural language processing approaches for document classification in analyzing metagenomic sequences. Text featurization is presented by treating DNA similar to natural language. These techniques reveal the importance of using the text feature extraction pipeline in sequence identification by transforming DNA base pairs into a set of characters with a term frequency and inverse document frequency techniques. Various machine learning classification algorithms are applied to viral identification tasks such as logistic regression and multi-layer perceptron. Moreover, we compared classical machine learning algorithms with VirFinder and VirNet, our deep attention model for viral reads identification on generated fragments of viruses and bacteria for benchmarking viral reads identification tools. Then, as a verification of our tool, It was applied to a simulated microbiome and virome data for tool verification and real metagenomic data of Roche 454 and Illumina for a case study.
The snowmelt niche differentiates three microbial life strategies that influence soil nitrogen availability during and after winter
Authors: Sorensen Patrick O. , Beller Harry R. , Bill Markus , Bouskill Nicholas J. , Hubbard Susan S. , Karaoz Ulas , Polussa Alexander , Steltzer Heidi , Wang Shi , Williams Kenneth H. , Wu Yuxin , Brodie Eoin L.
Published: January 2020

Soil microbial biomass can reach its annual maximum pool size beneath the winter snowpack and is known to decline abruptly following snowmelt in seasonally snow-covered ecosystems. Observed differences in winter versus summer microbial taxonomic composition also suggests that phylogenetically conserved traits may permit winter-versus summer-adapted microorganisms to occupy distinct niches. In this study, we sought to identify archaea, bacteria, and fungi that are associated with the soil microbial bloom overwinter and the subsequent biomass collapse following snowmelt at a high-altitude watershed in central Colorado, USA. Archaea, bacteria, and fungi were categorized into three life strategies (Winter-Adapted, Snowmelt-Specialist, Spring-Adapted) based on changes in abundance during winter, the snowmelt period, and after snowmelt in spring. We calculated indices of phylogenetic relatedness (archaea and bacteria) or assigned functional attributes (fungi) to organisms within life strategies to infer whether phylogenetically conserved traits differentiate Winter-Adapted, Snowmelt-Specialist, and Spring-Adapted groups. We observed that the soil microbial bloom was correlated in time with a pulse of snowmelt infiltration, which commenced 65 days prior to soils becoming snow-free. A pulse of nitrogen (N, as nitrate) occurred after snowmelt, along with a collapse in the microbial biomass pool size, and an increased abundance of nitrifying archaea and bacteria (e.g., Thaumarchaeota, Nitrospirae). Winter- and Spring-Adapted archaea and bacteria were phylogenetically clustered, suggesting that phylogenetically conserved traits allow Winter- and Spring-Adapted archaea and bacteria to occupy distinct niches. In contrast, Snowmelt-Specialist archaea and bacteria were phylogenetically overdispersed, suggesting that the key mechanism(s) of the microbial biomass crash are likely to be density-dependent (e.g., trophic interactions, competitive exclusion) and affect organisms across a broad phylogenetic spectrum. Saprotrophic fungi were the dominant functional group across fungal life strategies, however, ectomycorrhizal fungi experienced a large increase in abundance in spring. If well-coupled plant-mycorrhizal phenology currently buffers ecosystem N losses in spring, then changes in snowmelt timing may alter ecosystem N retention potential. Overall, we observed that the snowmelt separates three distinct soil niches that are occupied by ecologically distinct groups of microorganisms. This ecological differentiation is of biogeochemical importance, particularly with respect to the mobilization of nitrogen during winter, before and after snowmelt.
Plant-pollinator interaction linkage rules are altered by agricultural intensification
Authors: Morrison Beth M. L. , Brosi Berry J. , Dirzo Rodolfo
Published: January 2020

Determining linkage rules that govern the formation of species interactions is a critical goal of ecologists, especially considering that biodiversity, species interactions, and the ecosystem processes they maintain are changing at rapid rate worldwide. Species traits and abundance play a role in determining plant-pollinator interactions, but we illustrate here that linkage rules of plant-pollinator interactions change with disturbance context, switching from predominantly trait-based linkage rules in undisturbed, natural habitats, to abundance-based linkage rules in intensive agricultural habitats. The transition from trait-based to abundance-based linkage rules corresponds with a decline in floral trait diversity and an increase in opportunistic interaction behavior as agricultural intensification increases. These findings suggest that agricultural intensification is changing the very rules determining the realization of interactions and the formation of communities, making it challenging to use the structure of undisturbed systems to predict interactions within disturbed communities.
Deep Learning Identifies Cardiomyocyte Nuclei in Murine Tissue with High Precision
Authors: Ali Shah R. , Nguyen Dan , Wang Brandon , Jiang Steven , Sadek Hesham A.
Published: January 2020

Proper identification and annotation of cells in mammalian tissues is of paramount importance to biological research. Various approaches are currently used to identify and label cell types of interest in complex tissues. In this report, we generated an artificial intelligence (AI) deep learning model that uses image segmentation to predict cardiomyocyte nuclei in mouse heart sections without a specific cardiomyocyte nuclear label. This tool can annotate cardiomyocytes highly sensitively and specifically (AUC 0.94) using only cardiomyocyte structural protein immunostaining and a global nuclear stain. We speculate that our method is generalizable to other tissues to annotate specific cell types and organelles in a label-free way.
The relationship between the waiting time of postoperative radiotherapy and the prognosis of high grade glioma:a systemic review and meta-analysis
Authors: Li Guang-lie , Lv Shuang , Xu Ying , Zhang Hai-bo , Yan Ying
Published: January 2020

Objective: The relationship between the waiting time of postoperative radiotherapy and the prognosis of patients with high-grade glioma is still inconclusive, and we addressed this issue through a systematic review and meta-analysis. Methods: Twenty studies published between 1975 and 2019 about waiting times (WT) of radiotherapy with high-grade glioma were retrieved for meta-analysis.The meta-analysis was performed by converting the effect sizes of different WT into regression coefficients (β) and standard error (SE) to indicate the daily impact of delay on OS. Results: A total of 8462 high-grade glioma patients were included in the 20 studies, and no correlation between WT delay and OS was found in the unadjusted model through meta-analysis (HR=1, 95%CI=0.99-1.01,p=0.962). Meta-regression was used to adjust for other prognostic factors and no clear evidence of the relationship between WT delay and OS was found. Conclusion: This meta-analysis suggests that there is no clear evidence for the effect of delayed radiotherapy on OS with high-grade glioma patients.
Inactive variants of death receptor p75NTRreduce Alzheimer’s neuropathology by interfering with APP internalization
Authors: Yi Chenju , Goh Ket Yin , Wong Lik-Wei , Tanaka Kazuhiro , Sajikumar Sreedharan , Ibáñez Carlos F.
Published: January 2020

A prevalent model of Alzheimer’s disease (AD) pathogenesis postulates the generation of neurotoxic fragments derived from the amyloid precursor protein (APP) after its internalization to endocytic compartments. However, the molecular pathways that regulate APP internalization and intracellular trafficking in neurons are unknown. Here we report that 5xFAD mice, an animal model of AD, expressing signaling-deficient variants of the p75 neurotrophin receptor (p75NTR) show greater neuroprotection from AD neuropathology than animals lacking this receptor. p75NTRknock-in mice lacking the death domain or transmembrane Cys259showed lower levels of Aβ species, amyloid plaque burden, gliosis, mitochondrial stress and neurite dystrophy than global knock-outs. Strikingly, long-term synaptic plasticity and memory, which are completely disrupted in 5xFAD mice, were fully recovered in the knock-in mice. Mechanistically, we found that p75NTRinteracts with APP and regulates its internalization in hippocampal neurons. Inactive p75NTRvariants internalized much slower and to lower levels than wild type p75NTR, favoring non-amyloidogenic APP cleavage by reducing APP internalization and colocalization with BACE1, the critical protease for generation of neurotoxic APP fragments. These results reveal a novel pathway that directly and specifically regulates APP internalization, amyloidogenic processing and disease progression, and suggest that inhibitors targeting the p75NTRtransmembrane domain may be an effective therapeutic strategy in AD.
Study of application times gibberellic acid and 2,4-Dichlorophenoxyacetic acid in the plant regeneration from wheat haploid embryos in chromosome elimination method
Authors: Modirrousta Hamed , Khademian Raheleh , Bozorgipour Reza
Published: January 2020

Wheat is one of the most important cereals, which is very valuable in food. Haploid plants are of particular importance in plant breeding. The wheat seeds produced in the crosses between wheat and maize in the chromosome elimination method without of endosperm and are immature embryo, to prevent the abortions haploid embryos, they must have embryo rescue. Increasing production of haploid plants from produced embryos can improve production efficiency. In this study, With attention their effects gibberellic acid and 2,4-Dichlorophenoxyacetic acid on growth, cell size and cell division, Their use in the production of wheat haploid plant were studied. There was a significant difference at level 1% between the not use and use of gibberellic acid in difference times in the production of haploid from embryos, So that the most haploid plant produced in the use of gibberellic acid in the 4 days after pollination. Also, the use of 2,4-Dichlorophenoxyacetic acid in tiller maintenance liquid culture medium was evaluated at times 48 and 72 hours after pollination. There were a significant difference between these treatments at the 1% level and the most was obtained for wheat haploid plant production with application of 2,4-Dichlorophenoxyacetic acid treatment for 72 hours.

Highlight

production of haploid plants plays an important role in wheat breeding. This technique is done to get doubled haploid and absolute homozygous plants in a very short duration of time.
Chemogenetic analysis of how receptors for short chain fatty acids regulate the gut-brain axis
Authors: Barki Natasja , Bolognini Daniele , Börjesson Ulf , Jenkins Laura , Riddell John , Hughes David I. , Ulven Trond , Hudson Brian D. , Ulven Elisabeth Rexen , Dekker Niek , Tobin Andrew B. , Milligan Graeme
Published: January 2020

The gut-brain axis allows bi-directional communication between the enteric and central nervous systems. Short chain fatty acids (SCFAs) generated by the gut microbiota are important regulators of this interface. However, defining mechanisms by which SCFAs do so has been challenging because, amongst various roles, they co-activate both of a pair of closely related and poorly characterized G protein-coupled receptors, FFA2 and FFA3. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) can provide an important approach in defining receptor-specific functions. By screening a library of carboxylate-containing small molecules we identified 4-methoxy-3-methyl-benzoic acid (MOMBA) as a specific agonist of a DREADD variant of FFA2 which is not activated by SCFAs. Using mice engineered to replace FFA2 with this FFA2-DREADD, whilst retaining FFA3 expression, combinations of MOMBA and the now FFA3 receptor selective SCFAs defined key, but distinct, roles of FFA2 and FFA3 in each of gut transit time, secretion of entero-endocrine hormones, and communication from the gut to each of autonomic and somatic sensory ganglion cells and the spinal cord. These studies map mechanisms and signalling pathways by which each of FFA2 and FFA3 act to link the gut and the brain and provide both animal models and novel tool compounds to further explore this interface.
Differential contributions of synaptic and intrinsic inhibitory currents to speech segmentation via flexible phase-locking in neural oscillators
Authors: Pittman-Polletta Benjamin R. , Wang Yangyang , Stanley David A. , Schroeder Charles E. , Whittington Miles A. , Kopell Nancy J.
Published: January 2020

Current hypotheses suggest that speech segmentation – the initial division and grouping of the speech stream into candidate phrases, syllables, and phonemes for further linguistic processing – is executed by a hierarchy of oscillators in auditory cortex. Theta (~3-12 Hz) rhythms play a key role by phase-locking to recurring acoustic features marking syllable boundaries. Reliable synchronization to quasi-rhythmic inputs, whose variable frequency can dip below cortical theta frequencies (down to ~1 Hz), requires “flexible” theta oscillators whose underlying neuronal mechanisms remain unknown. Using biophysical computational models, we found that the flexibility of phase-locking in neural oscillators depended on the types of hyperpolarizing currents that paced them. Simulated cortical theta oscillators flexibly phase-locked to slow inputs when these inputs caused both (i) spiking and (ii) the subsequent buildup of outward current sufficient to delay further spiking until the next input. The greatest flexibility in phase-locking arose from a synergistic interaction between intrinsic currents that was not replicated by synaptic currents at similar timescales. Flexibility in phase-locking enabled improved entrainment to speech input, optimal at mid-vocalic channels, which in turn supported syllabic-timescale segmentation through identification of vocalic nuclei. Our results suggest that synaptic and intrinsic inhibition contribute to frequency-restricted and -flexible phase-locking in neural oscillators, respectively. Their differential deployment may enable neural oscillators to play diverse roles, from reliable internal clocking to adaptive segmentation of quasi-regular sensory inputs like speech.

Author summary

Oscillatory activity in auditory cortex is believed to play an important role in auditory and speech processing. One suggested function of these rhythms is to divide the speech stream into candidate phonemes, syllables, words, and phrases, to be matched with learned linguistic templates. This requires brain rhythms to flexibly synchronize with regular acoustic features of the speech stream. How neuronal circuits implement this task remains unknown. In this study, we explored the contribution of inhibitory currents to flexible phase-locking in neuronal theta oscillators, believed to perform initial syllabic segmentation. We found that a combination of specific intrinsic inhibitory currents at multiple timescales, present in a large class of cortical neurons, enabled exceptionally flexible phase-locking, which could be used to precisely segment speech by identifying vowels at mid-syllable. This suggests that the cells exhibiting these currents are a key component in the brain’s auditory and speech processing architecture.
Simplitigs as an efficient and scalable representation of de Bruijn graphs
Authors: Břinda Karel , Baym Michael , Kucherov Gregory
Published: January 2020

De Bruijn graphs play an essential role in computational biology. However, despite their widespread use, they lack a universal scalable representation suitable for different types of genomic data sets. Here, we introduce simplitigs as a compact, efficient and scalable representation and present a fast algorithm for their computation. On examples of several model organisms and two bacterial pan-genomes, we show that, compared to the best existing representation, simplitigs provide a substantial improvement in the cumulative sequence length and their number, especially for graphs with many branching nodes. We demonstrate that this improvement is amplified with more data available. Combined with the commonly used Burrows-Wheeler Transform index of genomic sequences, simplitigs substantially reduce both memory and index loading and query times, as illustrated with large-scale examples of GenBank bacterial pan-genomes.