bluuebunny/crossref_metadata_2025 huggingface dataset:
One Hundred Mitochondrial Genomes of Cicadas
Authors: Łukasik Piotr , Chong Rebecca A , Nazario Katherine , Matsuura Yu , Bublitz De Anna C , Campbell Matthew A , Meyer Mariah C , Van Leuven James T , Pessacq Pablo , Veloso Claudio , Simon Chris , McCutcheon John P
Published: December 2018

Mitochondrial genomes can provide valuable information on the biology and evolutionary histories of their host organisms. Here, we present and characterize the complete coding regions of 107 mitochondrial genomes (mitogenomes) of cicadas (Insecta: Hemiptera: Auchenorrhyncha: Cicadoidea), representing 31 genera, 61 species, and 83 populations. We show that all cicada mitogenomes retain the organization and gene contents thought to be ancestral in insects, with some variability among cicada clades in the length of a region between the genes nad2 and cox1, which encodes 3 tRNAs. Phylogenetic analyses using these mitogenomes recapitulate a recent 5-gene classification of cicadas into families and subfamilies, but also identify a species that falls outside of the established taxonomic framework. While protein-coding genes are under strong purifying selection, tests of relative evolutionary rates reveal significant variation in evolutionary rates across taxa, highlighting the dynamic nature of mitochondrial genome evolution in cicadas. These data will serve as a useful reference for future research into the systematics, ecology, and evolution of the superfamily Cicadoidea.
Mean Platelet Volume, Platelet Distribution Width, and Platelet Count, in Connection with Immune Thrombocytopenic Purpura and Essential Thrombocytopenia
Authors: Lee Eunyup , Kim Miyoung , Jeon Kibum , Lee Jiwon , Lee Jee-Soo , Kim Han-Sung , Kang Hee Jung , Lee Young Kyung
Published: December 2018

Objective

To examine the kinetic characteristics of platelet (PLT) destruction and thrombopoiesis by using mean platelet volume (MPV) and platelet distribution width (PDW).

Methods

Using the ADVIA2120i instrument, we measured PLT counts, MPV, and PDW in 153 healthy individuals, 35 patients with immune thrombocytopenic purpura (ITP), and 48 patients with essential thrombocytopenia (ET).

Results

In the ITP group, the MPV and PDW were higher than those values in healthy individuals. In the ET group, the MPV was lower than in the ITP group and in healthy individuals, and the PDW was lower than in the ITP group. When the ITP group was subdivided (PLT counts <45 × 103/µL vs ≥ 45 × 103/µL), the MPV and PDW tended to be higher in patients with PLT counts less than 45 × 103 per µL. When patients with ET were subdivided (PLT counts <770 × 103/µL vs ≥770 × 103/µL), the MPV and PDW were lower in patients with PLT count of 770 or greater × 103 per µL.

Conclusions

In ITP, the overall PLT composition varies, and PLT sequestration is nondiscriminatory. In ET, PLTs quickly shrink and remain small, resulting in a high proportion of small-sized PLTs.
Predictors of Time to Effective and Optimal Antimicrobial Therapy in Patients With Positive Blood Cultures Identified via Molecular Rapid Diagnostic Testing
Authors: Beganovic Maya , Timbrook Tristan T , Wieczorkiewicz Sarah M
Published: December 2018

Antimicrobial stewardship (AMS) programs integrated with rapid diagnostic tests optimize patient outcomes and reduce time to effective therapy (TTET) and time to optimal therapy (TTOT). This study identifies predictors of TTET and TTOT among patients with positive blood cultures and identifies limitations to current TTOT definitions and outcomes.
Preoperative Long-Acting Opioid Use Is Associated with Increased Length of Stay and Readmission Rates After Elective Surgeries
Authors: Doan Lisa V , Wang Jing , Padjen Kristoffer , Gover Adam , Rashid Jawad , Osmani Bijan , Avraham Shirley , Kendale Samir
Published: December 2018

Objectives To compare postoperative outcomes in patients prescribed long-acting opioids vs opioid-naïve patients who underwent elective noncardiac surgeries.

Design Retrospective cohort study.

Setting Single urban academic institution.

Methods and Subjects We retrospectively compared postoperative outcomes in long-acting opioid users vs opioid-naïve patients who underwent elective noncardiac surgeries. Inpatient and ambulatory surgery cohorts were separately analyzed. Preoperative medication lists were queried for the presence of long-acting opioids or absence of opioids. Multivariable logistic regression was performed to analyze the impact of long-acting opioid use on readmission rate, respiratory failure, and adverse cardiac events. Multivariable zero-truncated negative binomial regression was used to examine length of stay.

Results After exclusions, there were 93,644 adult patients in the study population, 23,605 of whom underwent inpatient surgeries and 70,039 of whom underwent ambulatory surgeries. After adjusting for potential confounders and inpatient surgeries, preoperative long-acting opioid use was associated with increased risk of prolonged length of stay (incidence rate ratio = 1.1, 99% confidence interval [CI] = 1.0–1.2, P < 0.01) but not readmission. For ambulatory surgeries, preoperative long-acting opioid use was associated with increased risk of all-cause as well as pain-related readmission (odds ratio [OR] = 2.1, 99% CI = 1.5–2.9, P < 0.001; OR = 2.0, 99% CI = 0.85–4.2, P = 0.02, respectively). There were no significant differences for respiratory failure or adverse cardiac events.

Conclusions The use of preoperative long-acting opioids was associated with prolonged length of stay for inpatient surgeries and increased risk of all-cause and pain-related readmission for ambulatory surgeries. Timely interventions for patients on preoperative long-acting opioids may be needed to improve these outcomes.
Mild-to-moderate sleep apnea is associated with incident hypertension: age effect
Authors: Vgontzas Alexandros N , Li Yun , He Fan , Fernandez-Mendoza Julio , Gaines Jordan , Liao Duanping , Basta Maria , Bixler Edward O
Published: December 2018

Study Objectives

Mild-to-moderate obstructive sleep apnea (OSA) is highly prevalent in the general population; however, previous studies on its association with incident hypertension are mixed. We examined the association between mild and moderate OSA and incident hypertension in a large random general population sample.

Methods

From 1741 adults of the Penn State Cohort, 744 adults without hypertension or severe OSA (i.e. apnea/hypopnea index [AHI] ≥ 30 events/hour) were followed-up after 9.2 years. Mild OSA was defined as an AHI of 5 to 14.9 events/hour (n = 71), while moderate OSA as an AHI of 15 to 29.9 events/hour (n = 32). Incident hypertension was defined by a self-report of receiving antihypertensive medication and/or history of a diagnosis since their baseline study.

Results

After adjusting for multiple potential confounders, mild-to-moderate OSA was significantly associated with increased risk of incident hypertension (overall hazard ratio [HR] = 2.94, 95% confidence interval (CI) = 1.96–4.41; HR = 3.24, 95% CI = 2.08–5.03 for mild OSA and HR = 2.23, 95% CI = 1.10–4.50 for moderate OSA). Importantly, this association was modified by age (p-interaction < 0.05); while strong in young and middle-aged adults (HR = 3.62, 95% CI = 2.34–5.60), the association was lost in adults older than 60 years (HR = 1.36 95% CI = 0.50–3.72). Furthermore, the association of mild-to-moderate OSA with components of metabolic syndrome was strongest in young and middle-aged adults.

Conclusions

Mild-to-moderate OSA, even when asymptomatic, is associated with increased risk of incident hypertension, but the strength of association significantly decreases with age. Although older participants with asymptomatic mild-to-moderate OSA are not at significant risk of developing hypertension, early detection and intervention, including improving metabolic indices, is especially warranted in young and middle-aged adults.
Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species
Authors: Calisher Charles H , Briese Thomas , Brister J Rodney , Charrel Rémi N , Dürrwald Ralf , Ebihara Hideki , Fulhorst Charles F , Gāo George Fú , Groschup Martin H , Haddow Andrew D , Hyndman Timothy H , Junglen Sandra , Klempa Boris , Klingström Jonas , Kropinski Andrew M , Krupovic Mart , LaBeaud A Desiree , Maes Piet , Nowotny Norbert , Nunes Márcio Roberto Teixeira , Payne Susan L , Radoshitzky Sheli R , Rubbenstroth Dennis , Sabanadzovic Sead , Sasaya Takahide , Stenglein Mark D , Varsani Arvind , Wahl Victoria , Weaver Scott C , Zerbini Francisco Murilo , Vasilakis Nikos , Kuhn Jens H
Published: December 2018

The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (phyla to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV’s official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world, and therefore, have limited use for ICTV-devised taxa. Instead, these professionals look to the ICTV as an expert point source that provides the most current taxonomic affiliations of viruses of interests to facilitate document writing. These needs are currently unmet as an ICTV-supported, easily searchable database that includes all published virus names and abbreviations linked to their taxa is not available. In addition, in stark contrast to other biological taxonomic frameworks, virus taxonomy currently permits individual species to have several members. Consequently, confusion emerges among those who are not aware of the difference between taxa and viruses, and because certain well-known viruses cannot be located in ICTV publications or be linked to their species. In addition, the number of duplicate names and abbreviations has increased dramatically in the literature. To solve this conundrum, the ICTV could mandate listing all viruses of established species and all reported unclassified viruses in forthcoming online ICTV Reports and create a searchable webpage using this information. The International Union of Microbiology Societies could also consider changing the mandate of the ICTV to include the nomenclature of all viruses in addition to taxon considerations. With such a mandate expansion, official virus names and virus name abbreviations could be catalogued and virus nomenclature could be standardized. As a result, the ICTV would become an even more useful resource for all stakeholders in virology.
Strategy to blend leftover finisher feed to nursery pigs in a wean-to-finish production system1
Authors: Wu Fangzhou , Coble Kyle F , Hastad Chad W , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Dritz Steve S , Goodband Robert D
Published: December 2018

In wean-to-finish pig production, leftover finisher feed from the previous group is commonly blended with nursery diets as weanling pigs enter the facility. Two experiments were conducted to evaluate feeding the last finisher diet to nursery pigs. The timing (phase) and dose were evaluated. Each experiment used 1,260 pigs from two commercial research rooms with 21 pigs per pen and 30 pens per room (15 pens per treatment). Pigs were fed commercial nursery diets in a five-phase feeding program, and phase changes were based on a feed budget. In experiment 1, pens of pigs (initially 5.83 kg) were blocked by body weight, gender, and room and allotted to one of four treatments. Treatments included standard nursery diets throughout (control) or standard diets with 2.5 kg/pig of the last finisher feed blended at the beginning of phase 2, 3, or 4. Growth responses during the intermediate periods were promptly decreased (P < 0.05) once the finisher feed was introduced regardless of phase in which it was blended. However, during the overall nursery period, blending the finisher diet into phase 2 decreased (P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI), but did not affect gain:feed ratio (G:F), compared with control pigs or those that had blended diet in phase 4 with blending of phase 3 diet intermediate. In experiment 2, weaned pigs were fed common phase 1 and 2 diets before the start of the experiment. At the beginning of phase 3, pens of pigs (initially 10.6 kg) were blocked by body weight and room and allotted to one of four treatments. Treatments consisted of a dose-titration of blending increasing amounts of finisher feed (0, 1.25, 2.50, and 3.75 kg/pig) into the phase 3 nursery diet. Overall, blending increasing amounts of the last finisher feed with phase 3 nursery diet decreased ADG (linear, P = 0.050) and tended to decrease (linear, P < 0.07) ADFI and final body weight. However, there was no evidence for difference in overall G:F. In conclusion, blending finisher feed into the early nursery diets decreased overall ADG and ADFI; however, pigs greater than 11 kg had improved ability to compensate for the negative effects of blending the last finisher feed on overall growth performance. Nevertheless, increasing the amounts of finisher feed fed to 11-kg pigs from 0 to 3.75 kg/pig resulted in a linear decrease in overall ADG and ADFI. Economic analysis indicated no change in income-over-feed-cost due to the timing and dose of blending finisher feed into nursery diets.
Wireless Physical Activity Monitor Use Among Adults Living With HIV: A Scoping Review
Authors: Dagenais Matthieu , Cheng Darren , Salbach Nancy M. , Brooks Dina , O'Brien Kelly K.
Published: December 2018

Introduction:

Physical activity (PA) can help promote healthy aging while addressing health-related challenges experienced with HIV infection. To determine the benefits of PA or consequences of inactivity, it is critical to ensure that we have accurate ways of measuring PA in the context of HIV infection. Wireless physical activity monitors (WPAMs) are increasingly used for measuring PA; however, evidence of their use in the context of HIV infection is unclear. Our aim was to characterize the literature (nature and extent and gaps in evidence) pertaining to WPAM use among adults living with HIV.

Methods:

We conducted a scoping review using the Arskey and O'Malley framework. We answered the following question: “What is the nature and extent of evidence pertaining to WPAMs and their use among adults living with HIV?” We searched databases including MEDLINE, EMBASE, CINAHL, PubMed, Cochrane, and PsycINFO from 1980 to September 2016. Two authors independently reviewed titles and abstracts, followed by full texts for inclusion. Two authors independently piloted and then extracted data from included articles. We described characteristics of included studies using frequencies and medians and collated results from text data using content analytical techniques.

Results:

Our search strategy yielded 1315 citations, of which 25 articles were included. The majority of articles (76%) were published between 2011 and 2016. Among a total sample of 1212 adults living with HIV in the included studies, 56% were women. Across the 20 studies, 23 WPAMs were used including actigraphs (n = 10 WPAMs), accelerometers (n = 8), and pedometers (n = 5) to measure PA. WPAMs were used primarily as an outcome measure of PA. No included studies assessed measurement properties of WPAMs among adults living with HIV.

Conclusion:

WPAM use in the context of HIV infection primarily involved measuring PA. Areas to address in future research include examining the effectiveness of WPAMs for enhancing PA and assessing measurement properties of WPAMs to ensure they accurately assess PA among adults living with HIV.
HIV/AIDS in Southern and East Africa: The Pandemic and Interface With Rehabilitation
Authors: Myezwa Hellen
Published: December 2018

The literature out of Southern and Eastern Africa contributes to understanding of the HIV/AIDS-related disability. The research has extended to assess interventions and their policy implications in the African setting. This commentary explores the trend of research in HIV-associated disability in the region in the last decade. There is an increasing body of knowledge on the burden of HIV/AIDS-associated disability, and there is a need for the inclusion of disability management in HIV/AIDS care.
The IASP classification of chronic pain for ICD-11: chronic secondary visceral pain
Authors: Aziz Qasim , Giamberardino Maria Adele , Barke Antonia , Korwisi Beatrice , Baranowski Andrew P. , Wesselmann Ursula , Rief Winfried , Treede Rolf-Detlef ,   The IASP Taskforce for the Classification of Chronic Pain
Published: December 2018

Chronic visceral pain is a frequent and disabling condition. Despite high prevalence and impact, chronic visceral pain is not represented in ICD-10 in a systematic manner. Chronic secondary visceral pain is chronic pain secondary to an underlying condition originating from internal organs of the head or neck region or of the thoracic, abdominal, or pelvic regions. It can be caused by persistent inflammation, by vascular mechanisms or by mechanical factors. The pain intensity is not necessarily fully correlated with the disease process, and the chronic visceral pain may persist beyond successful treatment of the underlying cause. This article describes how a new classification of chronic secondary visceral pain is intended to facilitate the diagnostic process and to enable the collection of accurate epidemiological data. Furthermore, it is hoped that the new classification will improve the tailoring of patient-centered pain treatment of chronic secondary visceral pain and stimulate research. Chronic secondary visceral pain should be distinguished from chronic primary visceral pain states that are considered diseases in their own right.
The IASP classification of chronic pain for ICD-11: chronic cancer-related pain
Authors: Bennett Michael I. , Kaasa Stein , Barke Antonia , Korwisi Beatrice , Rief Winfried , Treede Rolf-Detlef ,   The IASP Taskforce for the Classification of Chronic Pain
Published: December 2018

Worldwide, the prevalence of cancer is rising and so too is the number of patients who survive their cancer for many years thanks to the therapeutic successes of modern oncology. One of the most frequent and disabling symptoms of cancer is pain. In addition to the pain caused by the cancer, cancer treatment may also lead to chronic pain. Despite its importance, chronic cancer-related pain is not represented in the current International Classification of Diseases (ICD-10). This article describes the new classification of chronic cancer-related pain for ICD-11. Chronic cancer-related pain is defined as chronic pain caused by the primary cancer itself or metastases (chronic cancer pain) or its treatment (chronic postcancer treatment pain). It should be distinguished from pain caused by comorbid disease. Pain management regimens for terminally ill cancer patients have been elaborated by the World Health Organization and other international bodies. An important clinical challenge is the longer term pain management in cancer patients and cancer survivors, where chronic pain from cancer, its treatment, and unrelated causes may be concurrent. This article describes how a new classification of chronic cancer-related pain in ICD-11 is intended to help develop more individualized management plans for these patients and to stimulate research into these pain syndromes.
The IASP classification of chronic pain for ICD-11: chronic secondary musculoskeletal pain
Authors: Perrot Serge , Cohen Milton , Barke Antonia , Korwisi Beatrice , Rief Winfried , Treede Rolf-Detlef ,   The IASP Taskforce for the Classification of Chronic Pain
Published: December 2018

Chronic musculoskeletal pain is defined as chronic pain arising from musculoskeletal structures such as bones or joints. Although comprising the most prevalent set of chronic pain conditions, it was not represented appropriately in the 10th edition of the International Classification of Diseases (ICD-10), which was organized mainly according to anatomical sites, was strongly focused on musculoskeletal disease or local damage, and did not consider the underlying mechanisms of pain. The new ICD-11 classification introduces the concept of chronic primary and secondary musculoskeletal pain, and integrates the biomedical axis with the psychological and social axes that comprise the complex experience of chronic musculoskeletal pain. Chronic primary musculoskeletal pain is a condition in its own right, not better accounted for by a specific classified disease. Chronic secondary musculoskeletal pain is a symptom that arises from an underlying disease classified elsewhere. Such secondary musculoskeletal pain originates in persistent nociception in musculoskeletal structures from local or systemic etiologies, or it may be related to deep somatic lesions. It can be caused by inflammation, by structural changes, or by biomechanical consequences of diseases of the nervous system. It is intended that this new classification will facilitate access to patient-centered multimodal pain management and promote research through more accurate epidemiological analyses.
The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain
Authors: Schug Stephan A. , Lavand'homme Patricia , Barke Antonia , Korwisi Beatrice , Rief Winfried , Treede Rolf-Detlef ,   The IASP Taskforce for the Classification of Chronic Pain
Published: December 2018

Chronic pain after tissue trauma is frequent and may have a lasting impact on the functioning and quality of life of the affected person. Despite this, chronic postsurgical and posttraumatic pain is underrecognised and, consequently, undertreated. It is not represented in the current International Classification of Diseases (ICD-10). This article describes the new classification of chronic postsurgical and posttraumatic pain for ICD-11. Chronic postsurgical or posttraumatic pain is defined as chronic pain that develops or increases in intensity after a surgical procedure or a tissue injury and persists beyond the healing process, ie, at least 3 months after the surgery or tissue trauma. In the classification, it is distinguished between tissue trauma arising from a controlled procedure in the delivery of health care (surgery) and forms of uncontrolled accidental damage (other traumas). In both sections, the most frequent conditions are included. This provides diagnostic codes for chronic pain conditions that persist after the initial tissue trauma has healed and that require specific treatment and management. It is expected that the representation of chronic postsurgical and posttraumatic pain in ICD-11 furthers identification, diagnosis, and treatment of these pain states. Even more importantly, it will make the diagnosis of chronic posttraumatic or postsurgical pain statistically visible and, it is hoped, stimulate research into these pain syndromes.
The IASP classification of chronic pain for ICD-11: chronic secondary headache or orofacial pain
Authors: Benoliel Rafael , Svensson Peter , Evers Stefan , Wang Shuu-Jiun , Barke Antonia , Korwisi Beatrice , Rief Winfried , Treede Rolf-Detlef ,   The IASP Taskforce for the Classification of Chronic Pain
Published: December 2018

This article describes chronic secondary headache and chronic orofacial pain (OFP) disorders with respect to the new International Classification of Diseases (ICD-11). The section refers extensively to the International Classification of Headache Disorders (ICHD-3) of the International Headache Society that is implemented in the chapter on Neurology in ICD-11. The ICHD-3 differentiates between primary (idiopathic) headache disorders, secondary (symptomatic) headache disorders, and OFP disorders including cranial neuralgias. Chronic headache or OFP is defined as headache or OFP that occurs on at least 50% of the days during at least 3 months and lasting at least 2 hours per day. Only chronic secondary headache and chronic secondary OFP disorders are included here; chronic primary headache or OFP disorders are listed under chronic primary pain syndromes that have been described in a companion publication. The subdivisions of chronic secondary OFP of ICHD-3 are complemented by the Diagnostic Criteria for Temporomandibular Disorders and contributions from the International Association for the Study of Pain Special Interest Group on Orofacial and Head Pain and include chronic dental pain. The ICD-11 codes described here are intended to be used in combination with codes for the underlying diseases, to identify patients who require specialized pain management. In addition, these codes shall enhance visibility of these disorders in morbidity statistics and motivate research into their mechanisms.
Effects of Dementia-Specific Education for Nursing Students
Authors: Kimzey Michelle , Mastel-Smith Beth , Seale Ashlie
Published: December 2018

Background

The numbers of people living with dementia are overwhelming. Dementia education is important to prepare nursing students to care for this population.

Purpose

The purpose of this study was to determine the effects of a virtual dementia experience on nursing students' attitudes and empathy for people with dementia, dementia knowledge, and self-confidence for dementia care.

Methods

The design was a 2-group, pretest-posttest using a convenience sample of undergraduate nursing students (n = 112). The intervention group (n = 56) participated in a virtual dementia experience.

Results

Both groups experienced improved attitudes toward people with dementia, increased dementia knowledge, improved self-confidence for dementia care, and improved empathy (Perspective Taking). However, the virtual dementia experience did not lead to improved outcomes compared to the standard teaching approaches.

Conclusions

Dementia-specific education had a significant influence on students' attitudes, knowledge, self-confidence, and empathy, whereas the type of education did not impact outcomes.
The Experiences of Black Nursing Alumni at a Predominantly White Institution
Authors: Gona Clara , Pusey-Reid Eleonor , Lussier-Duynstee Patricia , Gall Gail
Published: December 2018

Background

Despite increasing minority enrollment in nursing programs, student attrition remains a persistent problem.

Purpose

The purpose of this study was to describe the experiences of a diverse group of black alumni at a predominantly white institution in the United States.

Method

In this qualitative descriptive study, researchers conducted focus group interviews with 16 recent graduates of accelerated baccalaureate and direct-entry nurse practitioner programs.

Results

Four themes emerged as barriers to success: burden of exclusion and isolation, lack of diversity among students and faculty, struggling to find mentors, and cultural assumptions. Five themes captured the strategies alumni adopted to succeed: strength in numbers, helpful mentors, resilience, faith, and self-silencing.

Conclusion

Participants experienced challenges but successfully navigated the program until they graduated. The study findings lay the groundwork for the development of programs that foster success for all students.
Social Networks and Its Impact on Women's Awareness, Interest, and Uptake of HIV Pre-exposure Prophylaxis (PrEP): Implications for Women Experiencing Intimate Partner Violence
Authors: Willie Tiara C. , Stockman Jamila K. , Keene Danya E. , Calabrese Sarah K. , Alexander Kamila A. , Kershaw Trace S.
Published: December 2018

Background:

In the United States, women represent less than 5% of all pre-exposure prophylaxis (PrEP) users. Social networks may promote and/or inhibit women's PrEP awareness, which could influence PrEP intentions. Furthermore, women experiencing intimate partner violence (IPV) may have smaller, less supportive networks, which could deter or have no impact on PrEP care engagement. This study examined associations between network characteristics and women's PrEP awareness, interest, uptake, and perceived candidacy and analyzed IPV as an effect modifier.

Setting/Methods:

From 2017 to 2018, data were collected from a prospective cohort study of 218 PrEP-eligible women with (n = 94) and without (n = 124) IPV experiences in Connecticut. Women completed surveys on demographics, IPV, social networks, and PrEP care continuum outcomes.

Results:

Adjusted analyses showed that PrEP awareness related to having more PrEP-aware alters. PrEP intentions related to having more alters with favorable opinions of women's potential PrEP use and a smaller network size. Viewing oneself as an appropriate PrEP candidate related to having more PrEP-aware alters and more alters with favorable opinions of women's potential PrEP use. IPV modified associations between network characteristics and PrEP care. Having members who were aware of and/or used PrEP was positively associated with PrEP care engagement for women without IPV experiences but had either no effect or the opposite effect for women experiencing IPV.

Conclusion:

Improving PrEP attitudes might improve its utilization among women. Social network interventions might be one way to increase PrEP uptake among many US women but may not be as effective for women experiencing IPV.
Diagnostic Accuracy of Noninvasive Markers of Steatosis, NASH, and Liver Fibrosis in HIV-Monoinfected Individuals at Risk of Nonalcoholic Fatty Liver Disease (NAFLD): Results From the ECHAM Study
Authors: Lemoine Maud , Assoumou Lambert , De Wit Stephane , Girard Pierre-Marie , Valantin Marc Antoine , Katlama Christine , Necsoi Coca , Campa Pauline , Huefner Anja D. , Schulze zur Wiesch Julian , Rougier Hayette , Bastard Jean-Philippe , Stocker Hartmut , Mauss Stefan , Serfaty Lawrence , Ratziu Vlad , Menu Yves , Schlue Jerome , Behrens Georg , Bedossa Pierre , Capeau Jacqueline , Ingiliz Patrick , Costagliola Dominique ,   on behalf of the ANRS-ECHAM Group
Published: December 2018

Background:

HIV-monoinfected individuals are at high risk of nonalcoholic fatty liver disease. Noninvasive tests of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis have been poorly assessed in this population. Using liver biopsy (LB) as a reference, we assessed the accuracy of noninvasive methods for their respective diagnosis: magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), FibroScan/controlled attenuation parameter (CAP), and biochemical tests.

Methods:

We enrolled antiretroviral therapy–controlled participants with persistently elevated transaminases and/or metabolic syndrome, and/or lipodystrophy. All had hepatic MRI-PDFF, FibroScan/CAP, FibroTest/NashTest/SteatoTest, APRI, FIB-4, and nonalcoholic fatty liver disease–fibrosis score. A LB was indicated if suspected significant fibrosis (FibroScan ≥7.1 kPa and/or FibroTest ≥0.49). Performance was considered as good if area under a receiver operating characteristic curves (AUROCs) was >0.80.

Results:

Among the 140 patients with suspected significant fibrosis out of the 402 eligible patients, 49 had had a LB: median age of 54 years (53–65), body mass index: 26 kg/m2 (24–30), steatosis in 37 (76%), NASH in 23 (47%), and fibrosis in 31 (63%) patients [F2: 7 (14%); F3: 6 (12%); and F4: 2 (4%)]. Regarding steatosis, MRI-PDFF had excellent and CAP good performances with AUROCs at 0.98 (95% confidence interval: 0.96 to 1.00) and 0.88 (0.76 to 0.99), respectively, whereas the AUROCs of SteatoTest was 0.68 (0.51 to 0.85). Regarding fibrosis (≥F2), APRI and FIB-4 had good performance with AUROCs at 0.86 (0.74 to 0.98) and 0.81 (0.67 to 0.95). By contrast, FibroScan and FibroTest had poor AUROCs [0.61 (0.43 to 0.79) and 0.61 (0.44 to 0.78)], with very low specificity. Regarding NASH, alanine aminotransferase ≥36 IU/L had good performance with AUROCs of 0.83 (0.71 to 0.94), whereas the NashTest had an AUROC of 0.60 (0.44 to 0.76).

Conclusions:

In HIV-monoinfected patients, MRI-PDFF and FibroScan/CAP are highly accurate for the diagnosis of steatosis. The alanine aminotransferase level and APRI should be considered for the detection of NASH and fibrosis.
Etiology and Severity of Liver Disease in HIV-Positive Patients With Suspected NAFLD: Lessons From a Cohort With Available Liver Biopsies
Authors: Iogna Prat Laura , Roccarina Davide , Lever Robert , Lombardi Rosa , Rodger Alison , Hall Andrew , Luong Tu Vinh , Bhagani Sanjay , Tsochatzis Emmanuel A.
Published: December 2018

Background:

Spectrum of liver injury among HIV-positive people is wide; in particular, prevalence of nonalcoholic fatty liver disease (NAFLD) seems to be higher compared with HIV-negative people.

Methods:

We retrospectively evaluated all liver biopsies performed at Royal Free Hospital from 2000 to 2017 in HIV monoinfected patients with abnormal transaminases, to assess the underlying cause of liver disease and to characterize the extent of fibrosis. We furthermore evaluated the diagnostic accuracy of FIB4 and FibroScan as noninvasive tools for fibrosis assessment.

Results:

Ninety-seven patients were included. Most common histological findings were NAFLD (28%), nonspecific changes (26%), and normal histology (13%). Twenty percent of the patients had significant fibrosis and 11% had advanced fibrosis. FIB4, at a cutoff of 1.3, had a specificity of 82% and negative predictive value (NPV) of 95% for exclusion of advanced fibrosis. FibroScan was available in 28% patients and 33% had a liver stiffness ≥7.5 kPa. FibroScan showed a specificity of 77% and NPV of 94% for exclusion of significant fibrosis. Among patients with NAFLD (n = 27), 18% had advanced fibrosis, whereas the majority (56%) did not have any fibrosis. The NPV of FIB4 for advanced fibrosis in these patients was 93%.

Conclusions:

Among HIV-positive patients with elevated transaminases, a surprisingly high number of patients had nonsignificant changes or even normal histological findings. The prevalence of NAFLD was lower than reported in other series. Use of noninvasive tools with a high NPV for significant fibrosis can help reduce the number of required biopsies.
Radiation conditions for a semi-infinite elastic strip
Authors: Babenkova E , Kaplunov J
Published: December 2018

High-frequency vibrations of a semi-infinite elastic strip with traction-free faces are considered. The conditions on end data that are derived do not allow non-radiating in Sommerfeld's sense of polynomial modes at thickness resonance frequencies. These represent a high-frequency analogue of the well-known decay conditions in statics that agree with the classical Saint-Venant principle. The proposed radiation conditions are applied to the construction of boundary conditions in the theories of high-frequency long-wave vibrations describing slow-varying motions in the vicinity of thickness resonance frequencies. The derivation is based on the Laplace transform technique along with the asymptotic methodology that is typical for thin plates and shells.
ElectroPen: An ultralow-cost piezoelectric electroporator
Authors: Byagathvalli Gaurav , Sinha Soham , Zhang Yan , Styczynski Mark P. , Standeven Janet , Bhamla M. Saad
Published: December 2018

Electroporation is a basic yet powerful method for delivering small molecules (RNA, DNA, drugs) across cell membranes by application of an electrical field. Due to its vital role, electroporation has wide applicability from genetically engineering cells, to drug- and DNA-based vaccine delivery. Despite its broad applications in biological research, the high cost of electroporators is an obstacle for many budget-conscious laboratories. To address this need, we describe a simple, inexpensive, and hand-held electroporator inspired by a common household piezoelectric gas lighter. The proposed “ElectroPen” device costs about 20 cents, is portable (13 g), is fabricated on-demand using 3D-printing, and delivers repeatable exponentially decaying pulses of about 2000 V in 5 ms. We provide a proof-of-concept demonstration by genetically transforming plasmids into E. coli strains and show comparable transformation efficiency and cell growth with commercial devices, but at a fraction of the cost. Our results are validated by an independent team across the globe, providing a real-world example of democratizing science through frugal tools. Thus, the simplicity, accessibility, and affordability of our device holds potential for making modern synthetic biology accessible in high-school, community, and field-ecology laboratories.
Cancer-Induced Immunosuppression can enable Effectiveness of Immunotherapy through Bistability Generation: a mathematical and computational Examination
Authors: Garcia Victor , Bonhoeffer Sebastian , Fu Feng
Published: December 2018

Cancer immunotherapies rely on how interactions between cancer and immune system cells are constituted. The more essential to the emergence of the dynamical behavior of cancer growth these are, the more effectively they may be used as mechanisms for interventions. Mathematical modeling can help unearth such connections, and help explain how they shape the dynamics of cancer growth. Here, we explored whether there exist simple, consistent properties of cancer-immune system interaction (CISI) models that might be harnessed to devise effective immunotherapy approaches. We did this for a family of three related models of increasing complexity. To this end, we developed a base model of CISI, which captures some essential features of the more complex models built on it. We find that the base model and its derivates can plausibly reproduce biological behavior that is consistent with the notion of animmunological barrier. This behavior is also in accord with situations in which the suppressive effects exerted by cancer cells on immune cells dominate their proliferative effects. Under these circumstances, the model family may display a pattern ofbistability, where two distinct, stable states (a cancer-free, and a full-grown cancer state) are possible. Increasing the effectiveness of immune-caused cancer cell killing may remove the basis for bistability, and abruptly tip the dynamics of the system into a cancer-free state. Additionally, in combination with the administration of immune effector cells, modifications in cancer cell killing may be harnessed for immunotherapy without the need for resolving the bistability. We use these ideas to test immunotherapeutic interventionsin silicoin a stochastic version of the base model. This bistability-reliant approach to cancer interventions might offer advantages over those that comprise gradual declines in cancer cell numbers.
Whole genome sequencing of a sporadic primary immunodeficiency cohort
Authors: Thaventhiran James E. D. , Allen Hana Lango , Burren Oliver S. , Rae William , Greene Daniel , Staples Emily , Zhang Zinan , Farmery James H. R. , Simeoni Ilenia , Rivers Elizabeth , Maimaris Jesmeen , Penkett Christopher J , Stephens Jonathan , Deevi Sri V.V. , Sanchis-Juan Alba , Gleadall Nicholas S , Thomas Moira J. , Sargur Ravishankar B. , Gordins Pavels , Baxendale Helen E. , Brown Matthew , Tuijnenburg Paul , Worth Austen , Hanson Steven , Linger Rachel , Buckland Matthew S. , Rayner-Matthews Paula J. , Gilmour Kimberly C. , Samarghitean Crina , Seneviratne Suranjith L. , Sansom David M. , Lynch Andy G. , Megy Karyn , Ellinghaus Eva , Ellinghaus David , Jorgensen Silje F. , Karlsen Tom H , Stirrups Kathleen E. , Cutler Antony J. , Kumararatne Dinakantha S. , Chandra Anita , Edgar J. David M. , Herwadkar Archana , Cooper Nichola , Grigoriadou Sofia , Huissoon Aarnoud , Goddard Sarah , Jolles Stephen , Schuetz Catharina , Boschann Felix ,   NBR-RD PID Consortium,   NIHR BioResource, Lyons Paul A. , Hurles Matthew E. , Savic Sinisa , Burns Siobhan O. , Kuijpers Taco W. , Turro Ernest , Ouwehand Willem H. , Thrasher Adrian J. , Smith Kenneth G. C.
Published: December 2018

Primary immunodeficiency (PID) is characterised by recurrent and often life-threatening infections, autoimmunity and cancer, and it presents major diagnostic and therapeutic challenges. Although the most severe forms present in early childhood, the majority of patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent, and up to 10% develop lymphoid malignancies1–3. Consequently, in sporadic PID genetic diagnosis is difficult and the role of genetics is not well defined. We addressed these challenges by performing whole genome sequencing (WGS) of a large PID cohort of 1,318 participants. Analysis of coding regions of 886 index cases found disease-causing mutations in known monogenic PID genes in 10.3%, while a Bayesian approach (BeviMed4) identified multiple potential new candidate genes, including IVNS1ABP. Exploration of the non-coding genome revealed deletions in regulatory regions which contribute to disease causation. Finally, a genome-wide association study (GWAS) identified PID-associated loci and uncovered evidence for co-localisation of, and interplay between, novel high penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to variable penetrance and phenotypic complexity in PID. Thus, a cohort-based WGS approach to PID diagnosis can increase diagnostic yield while deepening our understanding of the key pathways influencing human immune responsiveness.
Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
Authors: Velten Lars , Story Benjamin A. , Hernández-Malmierca Pablo , Raffel Simon , Leonce Daniel R. , Milbank Jennifer , Paulsen Malte , Demir Aykut , Szu-Tu Chelsea , Frömel Robert , Lutz Christoph , Nowak Daniel , Jann Johann-Christoph , Pabst Caroline , Boch Tobias , Hofmann Wolf-Karsten , Müller-Tidow Carsten , Trumpp Andreas , Haas Simon , Steinmetz Lars M.
Published: December 2018

Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with i the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance and high similarity to healthy hematopoietic stem cells (HSCs). Here, we demonstrate that LSCs, HSCs, and pre-leukemic stem cells can be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants. While mutational status discriminates between healthy and cancerous cells, gene expression distinguishes stem cells and progenitor cell populations. Our approach enables the identification of LSC-specific gene expression programs and the characterization of differentiation blocks induced by leukemic mutations. Taken together, we demonstrate the power of single-cell multi-omic approaches in characterizing cancer stem cells.
Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression ofoskartranslation
Authors: Dold Annabelle , Han Hong , Liu Niankun , Hildebrandt Andrea , Brüggemann Mirko , Rücklé Cornelia , Busch Anke , Beli Petra , Zarnack Kathi , König Julian , Roignant Jean-Yves , Lasko Paul
Published: December 2018

Makorins are evolutionary conserved proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. InDrosophilamaternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation ofoskar. We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and bindsosk3’ UTR in a region adjacent to A-rich sequences. This binding site overlaps with Bruno1 (Bru1) responsive elements (BREs), which regulateosktranslation. We observe increased association of the translational repressor Bru1 withoskmRNA upon depletion of Mkrn1, indicating that both proteins compete foroskbinding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries fromMkrn1females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activatingosktranslation by displacing Bru1 from its 3’ UTR.

Author Summary

To ensure accurate development of theDrosophilaembryo, proteins and mRNAs are positioned at specific sites within the embryo. Many of these proteins and mRNAs are produced and localized during the development of the egg in the mother. One protein essential for this process that has been heavily studied is Oskar (Osk), which is positioned at the posterior pole. During the localization ofoskmRNA, its translation is repressed by the RNA-binding protein Bruno1 (Bru1), ensuring that Osk protein is not present outside of the posterior where it is harmful. At the posterior pole,oskmRNA is activated through mechanisms that are not yet understood. In this work, we show that the conserved protein Makorin 1 (Mkrn1) is a novel factor involved in the translational activation ofosk. Mkrn1 binds specifically tooskmRNA in a region that overlaps with the binding site of Bru1, thus alleviating the association of Bru1 withosk. Moreover, Mkrn1 is stabilized by poly(A) binding protein, a translational activator that bindsoskmRNA in close proximity to Mkrn1. Our work thus helps to answer a long-standing question in the field, providing insight about the function of Mkrn1 and more generally into embryonic patterning in animals.
Detection of acute TLR-7 agonist-induced hemorrhagic myocarditis in mice by refined multi-parametric quantitative cardiac MRI
Authors: Baxan Nicoleta , Papanikolaou Angelos , Salles-Crawley Isabelle , Lota Amrit , Chowdhury Rasheda , Dubois Olivier , Branca Jane , Hasham Muneer G. , Rosenthal Nadia , Prasad Sanjay K. , Zhao Lan , Harding Sian E. , Sattler Susanne
Published: December 2018

BACKGROUND

Hemorrhagic myocarditis is a potentially fatal complication of excessive levels of systemic inflammation. It has been reported in viral infection, but is also possible in systemic autoimmunity. Cardiac magnetic resonance (CMR) imaging is the current gold standard for non-invasive detection of suspected inflammatory damage to the heart and changes in T1 and T2 relaxation times are commonly used to detect edema associated with immune cell infiltration and fibrosis. These measurements also form the basis of the Lake Louise Criteria, which define a framework for the CMR-based diagnosis of myocarditis. However, they do not take into account the possibility of hemorrhage leading to tissue iron deposition which strongly influences T1 and T2 measurements and may complicate interpretation based on these two parameters only.

METHODS

Systemic inflammation was induced in CFN mice by application of the TLR-7 agonist Resiquimod. Histopathology was performed on heart sections to assess immune cell infiltration (Hematoxylin & Eosin), fibrosis (PicoSirius Red) and tissue iron deposition (Perl’s Prussian Blue). A multi-parametric cardiac MRI tissue mapping approach measuring T1, T2, and T2* relaxation times was established to non-invasively identify these parameters in this small rodent model.

RESULTS

Resiquimod-treated mice developed severe thrombocytopenia and hemorrhagic myocarditis. We identified patches of cardiac hemorrhage based on the presence of two major MRI phenotypes. Increased T2 with normal T1 and T2* values correlated with infiltration/edema only, while decreased T1, T2, and T2* values identify areas with infiltration/edema in the presence of iron indicating hemorrhagic myocarditis.

CONCLUSION

We show that over-activation of the TLR-7 pathway by Resiquimod treatment of CFN mice induces an early immune response reminiscent of excessive systemic inflammation due to viral infection. This causes internal bleeding which manifests most prominently as severe hemorrhagic myocarditis. We optimized a comprehensive noninvasive in vivo MRI approach based on quantitative measurement of T1, T2 and T2* to demonstrate the presence of diffuse myocardial edema, infiltration and iron deposition without the need of contrast agent administration. We propose that adding quantitative T2* mapping to CMR protocols for detection of myocarditis will improve diagnostic sensitivity and interpretation of disease mechanisms.