bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of abacavir/lamivudine plus rilpivirine as a first-line regimen in treatment-naïve HIV-1 infected adults
Authors: Ho Sharlene , Wong Joshua Guoxian , Ng Oon Tek , Lee Cheng Chuan , Leo Yee Sin , Lye David Chien Boon , Wong Chen Seong 
Published: May 2020

AbstractBackgroundThe anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients.MethodsA retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial anti-retroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events.Results170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n = 24) in the RPV group and 87% (n = 26) in the comparator group achieved viral suppression at 48 weeks (p = 0.28). Median (interquartile range) time to viral suppression was similar: 17 (14–24) weeks in the RPV group, and 21 (13–26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n = 9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n = 31) from the comparator group (p = 0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p < 0.01). One patient in each group had virologic failure.ConclusionRPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings.
The impact of reimbursement negotiations on cost and availability of new pharmaceuticals: evidence from an online experiment
Authors: Wettstein Dominik J. , Boes Stefan 
Published: May 2020

AbstractBackgroundThe necessity to measure and reward “value for money” of new pharmaceuticals has become central in health policy debates, as much as the requirement to assess the “willingness to pay” for an additional, quality-adjusted life year (QALY). There is a clear need to understand the capacity of “value-based” pricing policies to impact societal goals, like timely access to new treatments, sustainable health budgets, or incentivizing research to improve patient outcomes. Not only the pricing mechanics, but also the process of value assessment and price negotiation are subject to reform demands. This study assesses the impact of a negotiation situation for life-extending pharmaceuticals on societal outcomes. Of interest were general effects of the bargaining behaviour, as well as differences caused by the assigned role and the magnitude of prices.MethodsWe ran an online experiment (n = 404) on Amazon Mechanical Turk (MTurk). Participants were randomly assigned into four treatment groups for a reimbursement negotiation between two roles (health minister, pharma representative) in two price framings. Payoff to players consisted of a fixed salary and a potential bonus, depending on their preferences, their price offer and the counter offer of a randomly paired negotiation partner. Success had real social consequences on other MTurk users (premium payers, investors) and via donations to a patient association.ResultsMargins between reservation prices and price offers increased throughout the game. Yet, 47% of players reduced at least once and 15% always their bonus probability to zero in favour of an agreement. 61% of simulated negotiation pairs could have reached an agreement, based on their preferences. 63% of these were successful, leaving 61% of patients with no access to the new treatment. The group with “real world” prices had lower prices and less agreements than the unconverted payoff group. The successful markets redistributed 20% of total assets from premium payers to investors over five innovation cycles.ConclusionsThe negotiation situation for pharmaceutical reimbursement has notable impact on societal outcomes. Further research should evaluate policies that align preferences and increase negotiation success.
The microbiome as a biosensor: functional profiles elucidate hidden stress in hosts
Authors: Zolti Avihai , Green Stefan J. , Sela Noa , Hadar Yitzhak , Minz Dror 
Published: May 2020

Abstract
Background
Microbial communities are highly responsive to environmental cues, and both their structure and activity can be altered in response to changing conditions. We hypothesized that host-associated microbial communities, particularly those colonizing host surfaces, can serve as in situ sensors to reveal environmental conditions experienced by both microorganisms and the host. For a proof-of-concept, we studied a model plant-soil system and employed a non-deterministic gene-centric approach. A holistic analysis was performed using plants of two species and irrigation with water of low quality to induce host stress. Our analyses examined the genetic potential (DNA) and gene expression patterns (RNA) of plant-associated microbial communities, as well as transcriptional profiling of host plants.

Results
Transcriptional analysis of plants irrigated with treated wastewater revealed significant enrichment of general stress-associated root transcripts relative to plants irrigated with fresh water. Metagenomic analysis of root-associated microbial communities in treated wastewater-irrigated plants, however, revealed enrichment of more specific stress-associated genes relating to high levels of salt, high pH and lower levels of oxygen. Meta-analysis of these differentially abundant genes obtained from other metagenome studies, provided evidence of the link between environmental factors such as pH and oxygen and these genes. Analysis of microbial transcriptional response demonstrated that enriched gene content was actively expressed, which implies contemporary response to elevated levels of pH and salt.

Conclusions
We demonstrate here that microbial profiling can elucidate stress signals that cannot be observed even through interrogation of host transcriptome, leading to an alternate mechanism for evaluating in situ conditions experienced by host organisms.
This study is a proof-of-concept for the use of microbial communities as microsensors, with great potential for interrogation of a wide range of host systems.
Feasibility and predictors of change of narrative exposure therapy for displaced populations: a repeated measures design
Authors: Ghafoerkhan Rina S. , van Heemstra Henriette E. , Scholte Willem F. , van der Kolk Joriene R. J. , ter Heide Jackie June F. , de la Rie Simone M. , Verhaak Linda M. , Snippe Evelien , Boelen Paul A. 
Published: May 2020

AbstractBackgroundDisplaced victims of interpersonal violence, such as refugees, asylum seekers, and victims of sexual exploitation, are growing in numbers and are often suffering from a post-traumatic stress disorder (PTSD). At the same time, these victims are known to benefit less from trauma-focused therapy (TFT) and to be less compliant to treatment. The objective of this paper is to describe the rationale and research protocol of an ongoing trial that aims to evaluate different variables that might influence the feasibility of TFT for the study population. Specifically, perceived daily stress, emotion regulation, and mood are investigated as predictors of change in PTSD symptoms during a trauma-focused therapy (narrative exposure therapy (NET)). The feasibility of administering measures tapping these constructs repeatedly during treatment will also be evaluated.Methods/designUsing an observational treatment design, 80 displaced victims of interpersonal violence will be measured before, during, and after partaking in NET. Several questionnaires tapping PTSD plus the aforementioned possible predictors of PTSD change will be administered: Post-traumatic Stress Disorder Checklist-5, Perceived Stress Scale, Difficulties in Emotion Regulation Scale-18 (pre-test, post-test, and follow-up),subscale impulsivity of the Difficulties in Emotion Regulation Scale-18, Perceived Stress Scale short version, Primary Care Post-traumatic Stress Disorder and a single Mood item (each session). Multilevel modelling will be used to examine the relation between the possible predictors and treatment outcome.DiscussionThe present study is the first to examine the interplay of facilitating and interfering factors possibly impacting treatment feasibility and effectiveness in displaced victims of interpersonal violence with PTSD receiving NET, using repeated measures. The current study can help to improve future treatment based on individual characteristics.Trial registrationNetherlands Trial Register:NTR7353, retrospectively registered. Date of registration: July 11, 2018.
New Frontiers in Retina: highlights of the 2020 angiogenesis, exudation and degeneration symposium
Authors: Puliafito Carmen A. , Wykoff Charles C. 
Published: May 2020

AbstractWe summarize the most important findings presented at the 2020 angiogenesis, exudation and degeneration symposium in five topic areas: (1) epidemiology of retinal vascular disease and macular degeneration; (2) dry AMD and geographic atrophy; (3) neovascular age-related macular degeneration; (4) drug delivery and devices and (5) diabetic retinopathy.
Subacute Thyroiditis After Sars-COV-2 Infection
Authors: Brancatella Alessandro , Ricci Debora , Viola Nicola , Sgrò Daniele , Santini Ferruccio , Latrofa Francesco 
Published: May 2020

Abstract

Context
Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak.

Objectives
The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection.

Methods
We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2–positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days.

Results
At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days.

Conclusions
We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.
Longitudinal Study on Metabolic Health in Adults SGA During 5 Years After GH With or Without 2 Years of GnRHa Treatment
Authors: Goedegebuure Wesley J , van der Steen Manouk , Kerkhof Gerthe F , Hokken-Koelega Anita C S 
Published: May 2020

Abstract

Background
In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH.

Methods
A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and β-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans.

Findings
In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group.

Interpretation
This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood.

Clinical trial registration
ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389.
The Association of ARMC5 with the Renin-Angiotensin-Aldosterone System, Blood Pressure, and Glycemia in African Americans
Authors: Joseph Joshua J , Zhou Xiaofei , Zilbermint Mihail , Stratakis Constantine A , Faucz Fabio R , Lodish Maya B , Berthon Annabel , Wilson James G , Hsueh Willa A , Golden Sherita H , Lin Shili 
Published: May 2020

Abstract

Context
Armadillo repeat containing 5 (ARMC5) on chromosome 16 is an adrenal gland tumor suppressor gene associated with primary aldosteronism, especially among African Americans (AAs). We examined the association of ARMC5 variants with aldosterone, plasma renin activity (PRA), blood pressure, glucose, and glycosylated hemoglobin A1c (HbA1c) in community-dwelling AAs.

Methods
The Jackson Heart Study is a prospective cardiovascular cohort study in AAs with baseline data collection from 2000 to 2004. Kernel machine method was used to perform a single joint test to analyze for an overall association between the phenotypes of interest (aldosterone, PRA, systolic and diastolic blood pressure [SBP, DBP], glucose, and HbA1c) and the ARMC5 single nucleotide variants (SNVs) adjusted for age, sex, BMI, and medications; followed by Baysian Lasso methodology to identify sets of SNVs in terms of associated haplotypes with specific phenotypes.

Results
Among 3223 participants (62% female; mean age 55.6 (SD ± 12.8) years), the average SBP and DBP were 127 and 76 mmHg, respectively. The average fasting plasma glucose and HbA1c were 101 mg/dL and 6.0%, respectively. ARMC5 variants were associated with all 6 phenotypes. Haplotype TCGCC (ch16:31476015-31476093) was negatively associated, whereas haplotype CCCCTTGCG (ch16:31477195-31477460) was positively associated with SBP, DBP, and glucose. Haplotypes GGACG (ch16:31477790-31478013) and ACGCG (ch16:31477834-31478113) were negatively associated with aldosterone and positively associated with HbA1c and glucose, respectively. Haplotype GCGCGAGC (ch16:31471193-ch16:31473597(rs114871627) was positively associated with PRA and negatively associated with HbA1c.

Conclusions
ARMC5 variants are associated with aldosterone, PRA, blood pressure, fasting glucose, and HbA1c in community-dwelling AAs, suggesting that germline mutations in ARMC5 may underlie cardiometabolic disease in AAs.
Yotsi’tsishon and the Language of the Seed in the Haudenosaunee Story of Earth’s Creation
Authors: Adams Amber Meadow 
Published: May 2020

AbstractKanyen’keha and Onoñda’gega’ versions of the Haudenosaunee story of Earth’s creation transcribed in the late 1880s by J. N. B. Hewitt contain ethnobotanical detail not present in many other recorded versions of the story. They also, especially the version told by Skanyatarí:yo John Arthur Gibson, build nuanced actors and articulate the negotiations of relationship through dialogue, imagery, and arcs of naming. Using close readings of these versions, I argue that the narrative arc of biome, as described through ethnobotanical detail, and of the story’s dynamic actors, as described through the poetic devices present in fuller versions, inform one another. The intersection of these arcs encodes a matrix of human responses to catastrophic climate change specific to the narrative’s home biome.
Indigenous Narratives of Creation and Origin in Embrace of the Serpent, by Ciro Guerra
Authors: Albites Enrique Bernales 
Published: May 2020

Abstract
In Ciro Guerra’s film Embrace of the Serpent (2015), cultural exchanges between the central characters reveal the origin narratives and the curative power of plants valued by Indigenous cultures of the Amazon. This article analyzes how Embrace of the Serpent expresses Indigenous rationality in the origin narratives as the shaman Karamakate confronts Western travelers and scientists. For these Indigenous cultures, knowledge and its reproduction are equivalent to ancestral songs and rituals such as the ceremony of the Ayahuasca. This article supports these ideas not in a filmic analysis but by exploring central aspects and scenes in the film associated with intercultural exchanges and the ritual of Ayahuasca. Finally, Embrace of the Serpent highlights the difficulty of distinguishing between the rationality of orality and writing with which Native cultures of the Americas understand the world that surrounds them.
The Influence of Climate Fiction
Authors: Schneider-Mayerson Matthew 
Published: May 2020

AbstractClimate fiction—literature explicitly focused on climate change—has exploded over the last decade, and is often assumed to have a positive ecopolitical influence by enabling readers to imagine potential climate futures and persuading them of the gravity and urgency of climate change. Does it succeed? And whom does it reach? A qualitative survey of 161 American readers of 19 works of climate fiction finds that these readers are younger, more liberal, and more concerned about climate change than nonreaders of climate fiction. Drawing on concepts from ecocriticism, environmental psychology, and environmental communication, this article suggests that “cli-fi” reminds concerned readers of the severity of climate change while impelling them to imagine environmental futures and consider the impact of climate change on human and nonhuman life. However, the actions that resulted from readers’ heightened consciousness reveal that awareness is only as valuable as the cultural messages about efficacious action that are in circulation. Moreover, the affective responses of many readers suggest that most works of climate fiction are leading readers to associate climate change with intensely negative emotions, which could prove counterproductive to efforts at environmental engagement or persuasion. Based on one of the first studies to empirically examine the reception of environmental literature, this article demonstrates a novel interdisciplinary approach to environmental literature (empirical ecocriticism) and points the way to future research in this vein.
Polarized epidermal growth factor secretion ensures robust vulval cell fate specification in Caenorhabditis elegans
Authors: Mereu Louisa , Morf Matthias K. , Spiri Silvan , Gutierrez Peter , Escobar-Restrepo Juan M. , Daube Michael , Walser Michael , Hajnal Alex 
Published: May 2020

ABSTRACT
The anchor cell (AC) in C. elegans secretes an epidermal growth factor (EGF) homolog that induces adjacent vulval precursor cells (VPCs) to differentiate. The EGF receptor in the nearest VPC sequesters the limiting EGF amounts released by the AC to prevent EGF from spreading to distal VPCs. Here, we show that not only EGFR localization in the VPCs but also EGF polarity in the AC is necessary for robust fate specification. The AC secretes EGF in a directional manner towards the nearest VPC. Loss of AC polarity causes signal spreading and, when combined with MAPK pathway hyperactivation, the ectopic induction of distal VPCs. In a screen for genes preventing distal VPC induction, we identified sra-9 and nlp-26 as genes specifically required for polarized EGF secretion. sra-9(lf) and nlp-26(lf) mutants exhibit errors in vulval fate specification, reduced precision in VPC to AC alignment and increased variability in MAPK activation. sra-9 encodes a seven-pass transmembrane receptor acting in the AC and nlp-26 a neuropeptide-like protein expressed in the VPCs. SRA-9 and NLP-26 may transduce a feedback signal to channel EGF secretion towards the nearest VPC.
Pitx2-Sox2-Lef1 interactions specify progenitor oral/dental epithelial cell signaling centers
Authors: Yu Wenjie , Sun Zhao , Sweat Yan , Sweat Mason , Venugopalan Shankar Rengasamy , Eliason Steven , Cao Huojun , Paine Michael L. , Amendt Brad A. 
Published: May 2020

ABSTRACT
Epithelial signaling centers control epithelial invagination and organ development, but how these centers are specified remains unclear. We report that Pitx2 (the first transcriptional marker for tooth development) controls the embryonic formation and patterning of epithelial signaling centers during incisor development. We demonstrate using Krt14Cre/Pitx2flox/flox (Pitx2cKO) and Rosa26CreERT/Pitx2flox/flox mice that loss of Pitx2 delays epithelial invagination, and decreases progenitor cell proliferation and dental epithelium cell differentiation. Developmentally, Pitx2 regulates formation of the Sox2+ labial cervical loop (LaCL) stem cell niche in concert with two signaling centers: the initiation knot and enamel knot. The loss of Pitx2 disrupted the patterning of these two signaling centers, resulting in tooth arrest at E14.5. Mechanistically, Pitx2 transcriptional activity and DNA binding is inhibited by Sox2, and this interaction controls gene expression in specific Sox2 and Pitx2 co-expression progenitor cell domains. We demonstrate new transcriptional mechanisms regulating signaling centers by Pitx2, Sox2, Lef1 and Irx1.
Cell-fate plasticity, adhesion and cell sorting complementarily establish a sharp midbrain-hindbrain boundary
Authors: Kesavan Gokul , Machate Anja , Hans Stefan , Brand Michael 
Published: May 2020

ABSTRACT
The formation and maintenance of sharp boundaries between groups of cells play a vital role during embryonic development as they serve to compartmentalize cells with similar fates. Some of these boundaries also act as organizers, with the ability to induce specific cell fates and morphogenesis in the surrounding cells. The midbrain-hindbrain boundary (MHB) is such an organizer: it acts as a lineage restriction boundary to prevent the intermingling of cells with different developmental fates. However, the mechanisms underlying the lineage restriction process remain unclear. Here, using novel fluorescent knock-in reporters, live imaging, Cre/lox-mediated lineage tracing, atomic force microscopy-based cell adhesion assays and mutant analysis, we analyze the process of lineage restriction at the MHB and provide mechanistic details. Specifically, we show that lineage restriction occurs by the end of gastrulation, and that the subsequent formation of sharp gene expression boundaries in the developing MHB occur through complementary mechanisms, i.e. cell-fate plasticity and cell sorting. Furthermore, we show that cell sorting at the MHB involves differential adhesion among midbrain and hindbrain cells that is mediated by N-cadherin and Eph-ephrin signaling.