bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Perspectives in Facilitated Angioplasty
Authors: Crişan Simina , Petriş Antoniu Octavian , Petrescu Lucian , Luca Constantin Tudor
Published: March 2019

Background:

Ischemic heart disease represents the most important cause of mortality worldwide, and the management of patients with ST-elevation myocardial infarction (STEMI) still remains a great challenge. For a great number of patients who do not have immediate access to primary percutaneous coronary intervention (PCI), facilitated angioplasty may be a reasonable therapeutic option.

Areas of Uncertainty:

The goal of reperfusion therapy is achieving repermeabilization of the infarct-related artery. However, the restoration of normal epicardial flow is not always followed by microvascular tissue perfusion and the presence of myocardial blush. Early studies assessing the benefits of facilitated angioplasty over primary PCI encountered disappointing results, with an increased number of bleeding complications. The invasive strategy following fibrinolysis mainly consists in angiography and PCI of the infarct-related artery between 2 and 24 hours after successful fibrinolysis or rescue PCI in failed fibrinolysis, hemodynamic, electrical instability, or worsening ischemia. Currently, a strategy of routine early angiography after fibrinolysis is recommended, taking into account studies that have demonstrated a reduced rate of reinfarction and recurrent ischemia, without an increased risk of stroke or major bleeding complications.

Therapeutic Advances:

After evaluating 1892 patients with STEMI within 3 hours after the onset of symptoms and revealing, beyond clear benefit of fibrinolysis, an increased risk of bleeding complications, the STREAM trial was the one that led to halving the tenecteplase dose for patients aged >75 years. A safety profile of adjusted-dose fibrinolytic therapy in elderly patients with STEMI will be further investigated by the ongoing STREAM-2 trial.

Conclusions:

With the current increased burden of acute coronary syndromes and the lack of immediate primary PCI facilities for all patients with STEMI, facilitated angioplasty seems a feasible therapeutic option. Another benefit of facilitated angioplasty may be represented by a major contribution of thrombolytic therapy in re-establishing microvascular myocardial blood flow.
New Directions in the Management of Peripheral Artery Disease
Authors: Chioncel Valentin , Brezeanu Radu , Sinescu Crina
Published: March 2019

Background:

Peripheral artery disease represents an important chapter of cardiovascular pathology in which atherosclerosis (promoted by major risk factors—hypertension, smoking, dyslipidemia, and diabetes mellitus) is the major etiology. The severity of this pathology is not only due to local injury but also due to frequent association with atherosclerotic disease with other localizations, thus increasing cardiovascular morbidity and mortality in these patients. Diagnosis is based on clinical data, functional tests (the ankle–brachial index is very useful in these cases) and imagistic methods (Doppler ultrasonography, computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography). Therapeutic options vary depending on the location and severity of the lesions but also on the chronic or acute nature of the disease. Thus, in addition to pharmacological treatment and nonpharmacological measures (related to lifestyle), revascularization therapy is a very important step.

Areas of Uncertainty:

There are still many things that need to be clarified in this pathology: importance of developing national registries (because epidemiological data are often poor), role of drug-eluting stents/drug-eluting balloons in femoropopliteal lesions, optimal duration of double antiplatelet treatment after stenting, and more. Current guidelines for the management of peripheral artery disease are built from the results of many trials and research groups regarding to the evaluation and therapy of these patients.

Therapeutic Advances:

Endovascular therapy is particularly targeted for cases with short lesions/occlusions or in patients with high surgical risk; instead, surgical revascularization (bypass) brings benefits in patients with long or distal stenoses/occlusions or where anatomy does not allow for interventional intervention. Anticoagulant and thrombolytic treatment plays an important role in acute limb ischemia.

Conclusions:

So, in the patients with peripheral artery disease (especially acute limb ischemia), early diagnosis and prompt application of therapeutic measures are the cornerstone of management in these cases.
Immunotherapy in Bladder Cancer
Authors: Konala Venu Madhav , Adapa Sreedhar , Aronow Wilbert S.
Published: March 2019

Background:

Bladder cancer is the fifth most common cancer in the United States. Cisplatin-based chemotherapy is the current standard of care in stage IV bladder cancer. It has increased overall survival but rarely results in complete remission, with an overall survival of 14–15 months. The most significant breakthrough in cancer therapy over the last decade was the development of immunotherapy.

Data sources:

KEYNOTE-045, IMvigor211, CheckMate275, Javelin Solid Tumor, MEDI4736, and KEYNOTE-0528 clinical trials.

Areas of Uncertainty:

There are ongoing clinical trials using combination of immunotherapy and chemotherapy as first line of therapy in the setting of metastatic urothelial cancer and also to determine the duration of treatment.

Therapeutic Advances:

Immunotherapy is approved as a second-line treatment for metastatic urothelial cancer. Their use as a first-line agent is only limited to patients who are ineligible for cisplatin-based treatments. Five drugs are approved by Food and Drug Administration for metastatic urothelial cancer including 3 Programmed cell-death protein 1 (PD-1) inhibitors and 2 programmed cell-death ligand 1 (PD-L1) inhibitors in patients who have progressed during or after platinum-based therapy. Pembrolizumab, nivolumab, and atezolizumab are PD-1 inhibitors. Durvalumab and avelumab are PD-L1 inhibitors. However, only 2 drugs were approved based on phase III clinical trials—pembrolizumab and atezolizumab, of which only KEYNOTE study performed with pembrolizumab showed overall survival difference. Atezolizumab and pembrolizumab are the Food and Drug Administration–approved checkpoint inhibitors in cisplatin-ineligible patients.

Conclusion:

This review article summarizes the significance of immunotherapy in treatment of bladder cancer, its side effects, and limitations.
Current status of graft-versus-host disease after intestinal transplantation
Authors: Ganoza Armando , Mazariegos George V. , Khanna Ajai
Published: March 2019

Purpose of review

Over the past decades, visceral transplantation has become the standard of care for patients with irreversible intestinal failure who suffer complications of total parenteral nutrition (TPN). Graft-versus-host disease (GVHD) after solid organ transplantation is a rare but often fatal complication with high mortality. GVHD after intestinal transplantation, given the large lymphoid content of the graft, is more frequent compared with other solid organs. It is a complex condition that may have varied clinical presentations. The therapy of GVHD is multifactorial and has evolved with visceral transplantation.

Recent findings

In recent large series of intestinal transplantation performed in centers around the world, GVHD remained an important cause of death (40–70%). Advances in immunology and current treatment options come from the hematopoietic stem-cell transplantation (HSCT) experience given the high prevalence of GVHD in that patient population. Therapeutic options for GVHD are based on disease classification, overall grading, organs involved, and associated symptoms.

Graft-versus-host disease (GVHD) is a serious complication that can occur after solid organ and allogenic HSCT. Intestinal or multivisceral transplantation have the highest incidence of GVHD among all solid organ transplants with very high mortality rates. Increased risk of GVHD is present after multivisceral and liver-included transplants compared with isolated intestinal transplant. Visceral transplantation is the all-encompassing term used for transplant that includes small bowel. It includes isolated small bowel transplant, small bowel/pancreas transplant, liver/small bowel/ pancreas transplant, stomach/pancreas/small bowel (modified multivisceral transplant), and stomach/liver/pancreas/small bowel (multivisceral). Each of these may or may not include the colon as part of the allograft. Steroids remain the first line of treatment along with modulation of the primary immunosuppression. Steroid-refractory patients remain a challenge and, to date, no consensus has been achieved for a single agent second-line therapy. Successful outcome depends on early diagnosis and prompt treatment.
Integration of Authentic Leadership Lens for Building High Performing Interprofessional Collaborative Practice Teams
Authors: Shirey Maria R. , White-Williams Connie , Hites Lisle
Published: March 2019

Interprofessional collaborative practice (IPCP) models facilitate collaboration and teamwork across the health care continuum. Success of high performing IPCP teams is dependent on compassionate, authentic leaders who invest in helping their teams thrive amidst complexity. This article presents the integration of an authentic leadership lens for building high performing IPCP teams. Using their experience with implementation of an innovative IPCP model to improve health outcomes for an underserved patient population in the southeastern United States, the authors share targeted strategies using an authentic leadership lens to develop high performing teams. Data collected for 3 years reflect positive team performance outcomes related to collaboration and teamwork, which contributed to enhanced access to care, exceptional patient experience, improved physical and mental health outcomes, reduced hospital readmissions, and decreased cost of care. An innovative IPCP model of care is an effective approach to improve health outcomes and care transitions. However, it may not be fully successful if health care professionals practicing within these models cannot collaborate effectively or maintain personal well-being. The value of using an authentic leadership lens to guide IPCP team development cannot be underestimated.
Engaging Stakeholders to Co-design an Academic Practice Strategic Plan in an Integrated Health System
Authors: Jeffs Lianne , Merkley Jane , Sinno Maya , Thomson Nicole , Peladeau Nathalie , Richardson Sandy
Published: March 2019

As key members of the executive team, nurse executives play an integral role in the planning process and operationalization of strategic imperatives to ensure the overall success of the organization. Nurse executives are leading organizations through transition periods that require transformational leadership. Leaders must design a shared vision and set strategic priorities; empower others to lead; ensure access to resources needed for safe care delivery; and inspire people to meet the demands of the future. Paramount to effective strategic planning and achievement of positive outcomes is a leadership team that engages key stakeholders in the strategic planning process. This article provides an overview of a recently integrated health system's strategic planning process that included the engagement of patients and caregivers. This can serve as a blueprint for others in their efforts to implement a systematic approach for enhancing collaborative academic practice in their organizations.
Nursing's Leadership Role in Advancing Professional Practice/Work Environments as Part of the Quadruple Aim
Authors: Bowles John R. , Batcheller Joyce , Adams Jeffrey M. , Zimmermann Deb , Pappas Sharon
Published: March 2019

Development of healthy professional practice/work environments (PPWEs) for nursing practice is critical to optimizing patient safety and workforce satisfaction while limiting turnover. Healthy PPWEs are linked with improved outcomes for patients, the workforce, and organizations. Nurses constitute the greatest professional segment of the US health care workforce and influence PPWEs, patient experience, health care quality, and cost per capita, all aspects of the quadruple aim. This article shares a model of leadership identified by executive nurse leaders to address and foster healthy PPWEs. A focus group of 16 expert nurse leaders convened an invitational meeting in Richmond, Virginia, to discuss nurse leaders' roles in optimizing the quadruple aim. The discussions led to shared perceptions about the prevalence of barriers to optimizing PPWEs; nursing leaders' responsibility to address the barriers to supporting improvement of the work-life of nursing professionals; and the need for early integration of leadership education, theory, and practice in every nurse's career.
Mastering Your Distinctive Strengths as an Introverted Nurse Leader
Authors: Wisser Kathleen Z. , Massey Robert L.
Published: March 2019

This article contrasts the nursing leadership styles of introverts and extraverts and examines what each brings to the nurse leader role. While introverts and extraverts bring unique strengths, it may appear to introverts that extraverts garner the preponderance of attention in meetings and committee work. Strategies for the self-identified introvert nurse leader to successfully lead in an extraversion-centric workplace are described. The article ends with the personal journey of 2 nurse leaders who embraced their introversion traits and learned ways to flourish in health care and academic settings.
Addressing Unconscious Bias
Authors: Persaud Sabita
Published: March 2019

The nurse leader is ethically responsible for creating diverse and inclusive spaces for both nurses and those we care for. The leader must openly acknowledge and address the negative influence of bias and prejudice within health care organizations. This requires both an awareness of the influence of unconscious bias within the organization and appropriate actions to mitigate its impact. This process begins with an in-depth examination of one's own biases and continues through actions at the individual and organizational levels. Nurse leaders are well positioned to address and mitigate the negative influence of bias within organizations. This article discusses the influence of unconscious bias as well as strategies that the nurse leader can use to build diverse and inclusive organizations.
Relationship Between Control Over Nursing Practice and Job Satisfaction and Quality of Patient Care
Authors: Al-Hamdan Zaid , Smadi Eman , Ahmad Muayyad , Bawadi Hala , Mitchell Ann M.
Published: March 2019

Background:

Control over nursing practice (CONP) in the work setting is associated with several positive consequences such as increased job satisfaction, support of teamwork, decreased patient mortality, and improved quality of care.

Purpose:

The purpose of this study was to examine the level of perceived CONP among Jordanian registered nurses (RNs) and determine its relationship with their job satisfaction and quality of patient care.

Method:

A descriptive, cross-sectional correlational design was used. A convenience sample of 230 RNs was recruited from 4 hospitals.

Result:

The RNs had a moderate level of perceived CONP. This control was positively correlated with their work satisfaction and perception of the quality of patient care that they delivered.

Conclusion:

Nurse managers should be encouraged to take into consideration nurses' perceived CONP to improve working conditions for nurses.
Evaluation of a Rapid Syphilis Test in an Emergency Department Setting in Detroit, Michigan
Authors: Fakile Yetunde F. , Markowitz Norman , Zhu Weiming , Mumby Kimberly , Dankerlui Doreen , McCormick Josh K. , Ham David C. , Hopkins Andre , Manteuffel Jake , Sun Yongcheng , Huang Ya-lin A. , Peters Philip J. , Hoover Karen W.
Published: March 2019

Background

Syphilis transmission can be prevented by prompt diagnosis and treatment of primary and secondary infection. We evaluated the performance of a point-of-care rapid syphilis treponemal (RST) test in an emergency department (ED) setting.

Methods

Between June 2015 and April 2016, men aged 18 to 34 years seeking services in a Detroit ED, and with no history of syphilis, were screened for syphilis with the RST test, rapid plasma reagin (RPR) test, and Treponema pallidum particle agglutination assay (TP-PA). A positive reference standard was both a reactive RPR and a reactive TP-PA. We compared test results in self-reported men who have sex with men (MSM) to non-MSM.

Results

Among 965 participants, 10.9% of RST tests were reactive in MSM and only 1.5% in non-MSM (P < 0.001). Sensitivity of the RST test was 76.9% and specificity was 99.0% (positive predictive value, 50.0%) compared with the positive reference standard. Three discordant specimens found negative with the RST test but positive with the reference standard had an RPR titer of 1:1, compared with 10 specimens with concordant positive results that had a median RPR titer of 1:16. The RST sensitivity was 50.0% (positive predictive value, 68.4%) compared to the TP-PA test alone. Among men seeking care in an ED, the RST detected 76.9% of participants with a reactive RPR and TP-PA.

Conclusions

The RST test detected all of the participants with an RPR titer ≥1:2 but less than 20% of participants with a positive TP-PA and negative RPR. The RST test was useful to detect a high proportion of participants with an active syphilis in an urban ED.
Unplanned Return Visits to a Pediatric Emergency Department
Authors: Seiler Michelle , Furrer Pascal Raffael , Staubli Georg , Albisetti Manuela
Published: March 2019

Objectives

Unplanned return visits (URVs) to emergency departments (EDs) account internationally for 2.5% to 5.2% of all consultations. ED crowding is an increasing challenge, and URVs seem to contribute to this problem. This study aimed to assess factors for URVs at the ED of a tertiary children's hospital to analyze if they are jointly responsible for the steadily rising amount of treated patients.

Methods

All patients with an URV to a pediatric ED in Switzerland between January and December 2013 were included in the study. Data were taken retrospectively from the electronic patient files, and different variables were defined and analyzed.

Results

URVs occurred at an incidence of 4.6%, and mostly concerned infants and toddlers (46%). URVs were independent of weekdays and mostly occurred between 10 am and 10 pm. In 84.2% of the cases, the URVs were judged as unnecessary, and in 15.8%, a hospitalization was indicated, mainly for children with a worsening respiratory illness.

Conclusions

The occurrence of URVs in our ED was within the incidence reported in the literature. While URVs lead to hospitalization in some patients, the majority of URVs were unnecessary from a medical point of view. These results indicate that a correct evaluation of the child's health state by parents is often challenging and requires repeated medical attendance following a first ED visit, especially in infants with airway diseases and infections. Intensive counseling and scheduled short-term follow-up consultation at the pediatrician's office could prevent URVs to the ED.
Nonfatal Pediatric Injuries Associated With Consumer Products and Sports and Recreational Activities in the United States
Authors: Kamboj Amrit K. , Chounthirath Thitphalak , Hodges Nichole L. , Smith Gary A.
Published: March 2019

Objective

The aim of this study was to investigate the epidemiology of nonfatal consumer product– and sports and recreational activity–related injuries among US children.

Methods

National Electronic Injury Surveillance System data regarding children younger than 18 years who were treated in US emergency departments (EDs) for nonfatal consumer product– or sports and recreational activity–related injuries were analyzed.

Results

From 1990 through 2012, an estimated 121,489,024 (95% confidence interval, 104,226,323–138,751,726) children younger than 18 years were treated in US EDs for nonfatal injuries meeting study criteria, yielding an average of 5,282,131 children annually, or 74.12 injuries per 1000 children. During 1990 to 2005, the overall annual injury rate decreased by 14.0% (P < 0.001), followed by an increase of 7.3% (P = 0.157) during 2005 to 2012. The concussion/closed head injury rate increased by 199.3% (P < 0.001) from 1996 to 2012. Injury rates were highest among children 0 to 4 years old and lowest among children 5 to 9 years old. Sports and recreational activities accounted for 46.5% of all injuries. Falls (40.2%) and “struck-by” (22.6%) were the leading mechanisms of injury, and 62.3% of all injuries were among boys. Injuries often occurred to the head/neck (37.8%) or upper extremities (31.9%), were frequently diagnosed as lacerations (29.0%) or soft tissue injuries (21.0%), and 2.7% were admitted to the hospital.

Conclusions

On average, a child was treated in a US ED for a nonfatal consumer product– or sports and recreational activity–related injury every 6 seconds. Although injury rates decreased early in the study period, there was a nonsignificant increasing trend from 2005 to 2012. Multilevel injury prevention efforts are recommended.
Longitudinal Analysis of Syndemic Psychosocial Problems Predicting HIV Risk Behavior Among a Multicity Prospective Cohort of Sexually Active Young Transgender Women in the United States
Authors: Mimiaga Matthew J. , Hughto Jaclyn M.W. , Biello Katie B. , Santostefano Christopher M. , Kuhns Lisa M. , Reisner Sari L. , Garofalo Robert
Published: March 2019

Background:

Worldwide, young transgender women (YTW) contend with exceptionally high risks of HIV infection. Cross-sectional studies have suggested that co-occurring epidemics or “syndemics” of psychosocial problems may accelerate HIV acquisition and transmission through elevated sexual risk behavior among transgender women. We aimed to examine how a syndemic of 7 psychosocial problems potentiates HIV sexual risk behavior among a multicity, longitudinal cohort of sexually active YTW in the United States.

Methods:

Between 2012 and 2015, 233 YTW from Boston, MA, and Chicago, IL, completed behavioral surveys at baseline, 4, 8, and 12 months. We used generalized estimating equations to examine the prospective relationship of overlapping psychosocial problems and HIV sexual risk behavior (ie, condomless anal or vaginal sex) among YTW.

Results:

The prevalence of 7 psychosocial syndemic problems was substantial at baseline and remained high at each time point: 6.4% reported polydrug use in the past 4 months (excluding stimulants); 7.7% reported heavy alcohol use in the past 4 months; 10% reported a history of childhood sexual abuse; 15.9% reported stimulant use in the past 4 months; 41.7% reported experiencing lifetime intimate partner violence; 42.1% reported clinically significant depressive symptoms; and 68.6% reported lifetime transgender-specific victimization. We identified a statistically significant positive “dose–response” relationship between the number of psychosocial syndemic problems and condomless anal or vaginal sex over time.

Conclusions:

The accumulation of “syndemic” psychosocial problems predicted HIV sexual risk behavior in a prospective cohort of YTW. Given the high prevalence of psychosocial problems and HIV sexual risk behavior, as well as having the highest HIV incidence among any risk group, the HIV prevention agenda requires a shift toward improved assessment of psychosocial comorbidities and stronger integration with gender-affirming and supportive mental health, violence recovery, and addiction treatment services for this population.
The Value of 1H-MRS and MRI in Combined Methylmalonic Aciduria and Homocystinuria
Authors: Cheng Ailan , Yao Rong , Cao Wenjun , Yu Hong
Published: March 2019

Objective

The aims of this study were to describe the brain magnetic resonance imaging (MRI) features of methylmalonic aciduria and homocystinuria and to evaluate the additional value of 1H-MRS.

Patients and Methods

Twenty-eight children with methylmalonic aciduria and homocystinuria were included in this study. The control group included 21 healthy children. All the cases underwent MRI and 1H-MRS before treatment. We measured the N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myoinositol (mI) peaks in the basal ganglia regions. The NAA/Cr, Cho/Cr, mI/Cr, and NAA/Cho ratios were calculated. We also observed whether there were lactic acid peaks.

Result

We identified that NAA/Cr and NAA/Cho significantly decreased in the basal ganglia and that 3 patients showed lactate peaks, but other metabolites were not significantly altered. Hydrocephalus and diffuse supratentorial white matter edema were the primary MR findings; 7 patients had thinning of the corpus callosum, and 2 patients had subdural hematoma. Six patients showed normal brain MRI findings.

Conclusions

Methylmalonic aciduria and homocystinuria patients with metabolite changes in the basal ganglia demonstrate compromised neuronal integrity, and anerobic metabolism occurs in acute encephalopathic episodes. 1H-MRS is a useful tool for evaluating brain damage. Hydrocephalus and diffuse supratentorial white matter edema are the main MRI features.
Removal of the Dental Implant Displaced Into the Maxillary Sinus Through the Inferior Nasal Meatus via Transnasal Endoscopy
Authors: Jin Tingting , Wang Yan , Li Shihao , Cai Qian , Huang Zhiquan
Published: March 2019

Worldwide, the reconstruction of the posterior edentulous maxilla with dental implants has become a common practice in clinical settings. However, the poor bone condition in this area is sometimes accompanied by complications. Dental implant displacement into the maxillary sinus is viewed as a rare complication. A case of a 72-year-old man in whom an endoscopic technique was used to remove a dental implant that had been mistakenly planted into the maxillary sinus was reported in this study. The authors approached the sinus through the inferior nasal meatus, and the dental implant was removed through the widened ostium. The endoscopic surgical approach described in this study is reliable and minimally invasive for removing residual roots displaced into the maxillary sinus. Therefore, it has been concluded that this clinical procedure is worth using.
The Global Catalogue of Microorganisms (GCM) 10K type strain sequencing project: providing services to taxonomists for standard genome sequencing and annotation
Authors: Wu Linhuan , Ma Juncai
Published: March 2019

The World Federation of Culture Collections and the World Data Center for Microorganisms (wdcm) initiated an international community-led project to sequence and annotate newly described prokaryotic taxa. This sequencing project aims to cooperate with international culture collections and the International Journal of Systematic and Evolutionary Microbiology and contribute to the expansion of whole genome sequencing databases for type strains. It will provide global microbial taxonomists with free standard genome sequencing and annotation services. Taxonomists are encouraged to contact the wdcm and participant culture collections to submit a type strain sequencing proposal.
ICTV Virus Taxonomy Profile: Polycipiviridae
Authors: Olendraite Ingrida , Brown Katherine , Valles Steven M. , Firth Andrew E. , Chen Yanping , Guérin Diego M. A. , Hashimoto Yoshifumi , Herrero Salvador , de Miranda Joachim R. , Ryabov Eugene ,   ICTV Report Consortium
Published: March 2019

Polycipiviridae is a family of picorna-like viruses with non-segmented, linear, positive-sense RNA genomes of approximately 10–12 kb. Unusually for viruses within the order Picornavirales, their genomes are polycistronic, with four (or more) consecutive 5′-proximal open reading frames (ORFs) encoding structural (and possibly other) proteins and a long 3′ ORF encoding the replication polyprotein. Members of species within the family have all been detected in ants or via arthropod transcriptomic datasets. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the Polycipiviridae, which is available at www.ictv.global/report/polycipiviridae.
ICTV Virus Taxonomy Profile: Solinviviridae
Authors: Brown Katherine , Olendraite Ingrida , Valles Steven M. , Firth Andrew E. , Chen Yanping , Guérin Diego M. A. , Hashimoto Yoshifumi , Herrero Salvador , de Miranda Joachim R. , Ryabov Eugene ,   ICTV Report Consortium
Published: March 2019

Solinviviridae is a family of picorna/calici-like viruses with non-segmented, linear, positive-sense RNA genomes of approximately 10–11 kb. Unusually, their capsid proteins are encoded towards the 3′-end of the genome where they can be expressed both from a subgenomic RNA and as an extension of the replication (picorna-like helicase–protease–polymerase) polyprotein. Members of two species within the family infect ants, but related unclassified virus sequences derive from a large variety of insects and other arthropods. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the Solinviviridae, which is available at www.ictv.global/report/solinviviridae.
Hippocampal volume across age: Nomograms derived from over 19,700 people in UK Biobank
Authors: Nobis Lisa , Manohar Sanjay G. , Smith Stephen M. , Alfaro-Almagro Fidel , Jenkinson Mark , Mackay Clare E. , Husain Masud
Published: March 2019

Measurement of hippocampal volume has proven useful to diagnose and track progression in several brain disorders, most notably in Alzheimer’s disease (AD). For example, an objective evaluation of a patient’s hippocampal volume status may provide important information that can assist diagnosis or risk stratification of AD. However, clinicians and researchers require access to age-related normative percentiles to reliably categorise a patient’s hippocampal volume as being pathologically small. Here we analysed effects of age, sex, and hemisphere on the hippocampus and neighbouring temporal lobe volumes, in 19,793 generally healthy participants in the UK Biobank. A key finding of the current study is a significant acceleration in the rate of hippocampal volume loss in middle age, more pronounced in females than in males. In this report, we provide normative values for hippocampal and total grey matter volume as a function of age for reference in clinical and research settings. These normative values may be used in combination with our online, automated percentile estimation tool to provide a rapid, objective evaluation of an individual’s hippocampal volume status. The data provide a large-scale normative database to facilitate easy age-adjusted determination of where an individual hippocampal and temporal lobe volume lies within the normal distribution.
A Cryo-EM Grid Preparation Device for Time-Resolved Structural Studies
Authors: Kontziampasis Dimitrios , Klebl David P. , Iadanza Matthew G. , Scarff Charlotte A. , Kopf Florian , Sobott Frank , Monteiro Diana C.F. , Trebbin Martin , Muench Stephen P. , White Howard D.
Published: March 2019

Structural biology generally provides static snapshots of protein conformations that can inform on the functional mechanisms of biological systems. Time-resolved structural biology provides a means to visualise, at near-atomic resolution, the dynamic conformational changes that macromolecules undergo as they function. Recent advances in the resolution obtainable by electron microscopy (EM) and the broad range of samples that can be studied makes it ideally suited to time-resolved studies. Here we describe a cryo-electron microscopy grid preparation device that permits rapid mixing, voltage assisted spraying, and vitrification of samples. We show that the device produces grids of sufficient ice quality to enable data collection from single grids that results in a sub 4 Å reconstruction. Rapid mixing can be achieved by blot and spray or mix and spray approaches with a delay of ~10 ms, providing greater temporal resolution than previously reported approaches.
Optogenetic control of cell morphogenesis on protein micropatterns
Authors: Zieske Katja , Dyche Mullins R
Published: March 2019

Cell morphogenesis is critical for embryonic development, tissue formation, and wound healing. Our ability to manipulate endogenous mechanisms to control cell shape, however, remains limited. Here we combined surface micropatterning of adhesion molecules with optogenetic activation of intracellular signaling pathways to control the nature and morphology of cellular protrusions. We employed geometry-dependent pre-organization of cytoskeletal structures together with acute activation of signaling pathways that control actin assembly to create a tool capable of generating membrane protrusions at defined cellular locations. Further, we find that the size of microfabricated patterns of adhesion molecules influences the molecular mechanism of cell protrusion: larger patterns enable cells to create actin-filled lamellipodia while smaller patterns promote formation of spherical blebs. Optogenetic perturbation of signaling pathways in these cells changes the size of blebs and convert them into lamellipodia. Our results demonstrate how the coordinated manipulation of adhesion geometry and cytoskeletal dynamics can be used to control membrane protrusion and cell morphogenesis.
Functional RNA Structures in the 3’UTR of Tick-Borne, Insect-Specific and No-Known-Vector Flaviviruses
Authors: Ochsenreiter Roman , Hofacker Ivo L. , Wolfinger Michael T.
Published: March 2019

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3’UTR of tick-borne, insect-specific and no-known-vector flavivirusesin silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs (xrRNAs) within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3’UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs.
Systems biology of cold adaptation in the polyextremophilic red algaGaldieria sulphuraria
Authors: Rossoni Alessandro W. , Weber Andreas P.M.
Published: March 2019

Rapid fluctuation of environmental conditions can impose severe stress upon living organisms. Surviving such episodes of stress requires a rapid acclimation response, e.g., by transcriptional and post-transcriptional mechanisms. Persistent change of the environmental context, however, requires longer-term adaptation at the genetic level. Fast-growing unicellular aquatic eukaryotes enable analysis of adaptive responses at the genetic level in a laboratory setting. In this study, we applied continuous cold stress (28°C) to the thermoacidophile red algaG. sulphuraria,which is 14°C below its optimal growth temperature of 42°C. Cold stress was applied for more than 100 generations to identify components that are critical for conferring thermal adaptation. After cold exposure for more than 100 generations, the cold-adapted samples grew ~30% faster than the starting population. Whole-genome sequencing revealed 757 variants located on 429 genes (6.1% of the transcriptome) encoding molecular functions involved in cell cycle regulation, gene regulation, signaling, morphogenesis, microtubule nucleation, and transmembrane transport. CpG islands located in the intergenic region accumulated a significant number of variants, which is likely a sign of epigenetic remodeling. We present 20 candidate genes and three putative cis-regulatory elements with various functions most affected by temperature. Our work shows that natural selection towards temperature tolerance is a complex systems biology problem that involves gradual reprogramming of an intricate gene network and deeply nested regulators.
Multiple elements of addiction vulnerability are independently heritable in rats
Authors: Eid Maya , Pullmann Dominika , Li Hao , Thomas Alen , Jhou Thomas C.
Published: March 2019

Background

Although cocaine is powerfully rewarding, only a fraction of drug-exposed individuals actually transition to become drug-dependent users, possibly due in part to genetic influences, as addictions are among the most heritable of human neuropsychiatric disorders. Consistent with addiction being a complex disorder, prior studies have noted many factors that predict addiction vulnerability, such as drug-induced aversive effects, behavioral responses to novelty, and sensitivity to punishment.

Methods

We tested different inbred strains of rats, as well as selectively bred Sprague-Dawley (SD) or Heterogeneous Stock (HS) rats, on cocaine avoidance, sensitivity to punishment, and locomotor responses to novelty, and calculated heritability estimates of these behaviors. We tested animals on additional control tasks (progressive ratio, shock avoidance) to control for alternate interpretations of addiction-like behaviors.

Results

Conditioned avoidance to cocaine varied greatly between individual rats as measured using either the runway operant task or conditioned place aversion (CPA). Cocaine avoidance responded rapidly to selective breeding, yielding heritability estimates of 0.70 and 0.58 in SD and HS rats. Resistance to punishment was also highly heritable in inbred rats (estimated h2= 0.62), and varied independently of cocaine avoidance despite both behaviors being mediated by the RMTg. Furthermore, cocaine avoidance correlated positively with cocaine-induced c-Fos induction in the RMTg, negatively with initial rates of acquisition of intravenous cocaine self-administration, and positively with both cued and cocaine-primed reinstatement.

Conclusions

Cocaine avoidance and resistance to punishment are strongly and independently heritable behaviors that may both control different aspects of individual propensity to acquire and maintain drug-seeking.
Disentangling presentation and processing times in the brain
Authors: Caplette Laurent , Ince Robin A. A. , Jerbi Karim , Gosselin Frédéric
Published: March 2019

Visual object recognition seems to occur almost instantaneously. However, not only does it require hundreds of milliseconds of processing, but our eyes also typically fixate the object for hundreds of milliseconds. Consequently, information reaching our eyes at different moments is processed in the brain together. Moreover, information received at different moments during fixation is likely to be processed differently, notably because different features might be selectively attended at different moments. Here, we introduce a novel reverse correlation paradigm that allows us to uncover with millisecond precision the processing time course of specific information received on the retina at specific moments. Using faces as stimuli, we observed that processing at several electrodes and latencies was different depending on the moment at which information was received. Some of these variations were caused by a disruption occurring 160-200 ms after the face onset, suggesting a role of the N170 ERP component in gating information processing; others hinted at temporal compression and integration mechanisms. Importantly, the observed differences were not explained by simple adaptation or repetition priming, they were modulated by the task, and they were correlated with differences in behavior. These results suggest that top-down routines of information sampling are applied to the continuous visual input, even within a single eye fixation.
NMDA receptors enhance the fidelity of synaptic integration
Authors: Li Chenguang , Gulledge Allan T.
Published: March 2019

Excitatory synaptic transmission in many neurons is mediated by two co-expressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in their kinetics, ion-selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here we report that the voltage-dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of excitatory postsynaptic potentials (EPSPs) across spatial and voltage domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees revealed that the combined presence of AMPA and NMDA conductances reduces the variability of somatic responses to spatiotemporal patterns of excitatory synaptic input presented at different initial membrane potentials and/or in different dendritic domains. This moderating effect of the NMDA conductance on synaptic integration was robust across a wide range of AMPA-to-NMDA ratios, and results from synergistic interaction of NMDA kinetics (which reduces variability across membrane potential) and voltage-dependence (which favors stabilization across dendritic location). When combined with AMPA conductance, the NMDA conductance balances voltage- and impedance-dependent changes in synaptic driving force, and distance-dependent attenuation of synaptic potentials arriving at the axon, to increase the fidelity of synaptic integration and EPSP-spike coupling across neuron state (i.e., initial membrane potential) and dendritic location of synaptic input. Thus, synaptic NMDA receptors convey advantages for synaptic integration that are independent of, but fully compatible with, their importance for coincidence detection and synaptic plasticity.

Significance Statement

Glutamate is an excitatory neurotransmitter that, at many synapses, gates two coexpressed receptor subtypes (AMPA and NMDA receptors). Computational simulations reveal that the combined synaptic presence of AMPA and NMDA receptors reduces variability in synaptic integration in response to identical patterns of synaptic input delivered to different dendritic locations and/or at different initial membrane potentials. This results from synergistic interaction of the slower kinetics and voltage-dependence of NMDA receptors, which combine to enhance synaptic currents when synaptic driving forces are otherwise reduced (e.g., at depolarized membrane potentials or in distal, high-impedance dendrites). By stabilizing synaptic integration across dendritic location and initial membrane potential, NMDA receptors provide advantages independent of, but fully compatible with, their well-known contribution to synaptic plasticity.
Uncovering hypergraphs of cell-cell interaction from single cell RNA-sequencing data
Authors: Tsuyuzaki Koki , Ishii Manabu , Nikaido Itoshi
Published: March 2019

Complex biological systems can be described as a multitude of cell-cell interactions (CCIs). Recent single-cell RNA-sequencing technologies have enabled the detection of CCIs and related ligand-receptor (L-R) gene expression simultaneously. However, previous data analysis methods have focused on only one-to-one CCIs between two cell types. To also detect many-to-many CCIs, we proposescTensor, a novel method for extracting representative triadic relationships (hypergraphs), which include (i) ligand-expression, (ii) receptor-expression, and (iii) L-R pairs. When applied to simulated and empirical datasets,scTensorwas able to detect some hypergraphs including paracrine/autocrine CCI patterns, which cannot be detected by previous methods.
Non-responder phenotype reveals microbiome-wide antibiotic resistance in the murine gut
Authors: Diener Christian , Hoge Anna C. H. , Kearney Sean M. , Erdman Susan E. , Gibbons Sean M.
Published: March 2019

Broad spectrum antibiotics can cause both transient and lasting damage to the ecology of the gut microbiome. Loss of gut bacterial diversity has been linked to immune dysregulation and disease susceptibility. Antibiotic-resistant populations of cells are known to arise spontaneously in single-strain systems. Furthermore, prior work on subtherapeutic antibiotic treatment in humans and therapeutic treatments in non-human animals have suggested that entire gut communities may exhibit spontaneous resistance phenotypes. In this study, we validate the existence of these community resistance phenotypes in the murine gut and explore how antibiotic duration or diet influence the frequency of this phenotype. We find that almost a third of mice exhibit whole-community resistance to a therapeutic concentration of theβ-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or xenobiotic dietary amendment. These non-responder (i.e. resistant) microbiota were protected from biomass depletion, transient ecological community collapse, and lasting diversity loss seen in the susceptible microbiota. There were no major differences between non-responder microbiota and untreated control microbiota at the community structure level. However, gene expression was vastly different between non-responder microbiota and controls during antibiotic treatment, with non-responder communities showing an upregulation of antimicrobial resistance genes and a down-regulation of central metabolism. Thus, non-responder phenotypes appear to combat antibiotic assault through a combination of efflux transporter upregulation and a reduced growth rate across the entire gut community. Future work should focus on what factors are responsible for tipping entire communities from susceptible to resistant phenotypes so that we might harness this phenomenon to protect our microbiota from exposure to therapeutic antibiotic treatment regimes.
Deconvolving the contributions of cell-type heterogeneity on cortical gene expression
Authors: Patrick Ellis , Taga Mariko , Ergun Ayla , Ng Bernard , Casazza William , Cimpean Maria , Yung Christina , Schneider Julie A , Bennett David A , Gaiteri Chris , Jager Philip L De , Bradshaw Elizabeth M , Mostafavi Sara
Published: March 2019

Complexity of cell-type composition has created much skepticism surrounding the interpretation of brain bulk-tissue transcriptomic studies. We generated paired tissue genome-wide gene expression data and immunohistochemistry data, enabling us to assess statistical methods for modeling and estimating cellular heterogeneity in the brain. We demonstrate that several algorithms that rely on single-cell and cell-sorted data to define cell marker gene sets yield accuraterelativeandabsoluteestimates of constituent cell-type proportions.
Testing for correlation between traits under directional evolution
Authors: Royer-Carenzi Manuela , Didier Gilles
Published: March 2019

Being confounding factors, directional trends are likely to make two quantitative traits appear as spuriously correlated. By determining the probability distributions of independent contrasts when traits evolve following Brownian motions with linear trends, we show that the standard independent contrasts can not be used to test for correlation in this situation. We propose a multiple regression approach which corrects the bias caused by directional evolution.

We show that our approach is equivalent to performing a Phylogenetic Generalized Least Squares (PGLS) analysis with tip times as covariables by providing a new and more general proof of the equivalence between PGLS and independent contrasts methods.

Our approach is assessed and compared with three previous correlation tests on data simulated in various situations and overall outperforms all the other methods. The approach is next illustrated on a real dataset to test for correlation between hominin cranial capacity and body mass.