bluuebunny/crossref_metadata_2025_split huggingface dataset:
Position Review: Functional Selectivity in Mammalian Olfactory Receptors
Authors: Ache Barry W 
Published: June 2020

Abstract
There is increasing appreciation that G-protein-coupled receptors (GPCRs) can initiate diverse cellular responses by activating multiple G proteins, arrestins, and other biochemical effectors. Structurally different ligands targeting the same receptor are thought to stabilize the receptor in multiple distinct active conformations such that specific subsets of signaling effectors are engaged at the exclusion of others, creating a bias toward a particular outcome, which has been referred to as ligand-induced selective signaling, biased agonism, ligand-directed signaling, and functional selectivity, among others. The potential involvement of functional selectivity in mammalian olfactory signal transduction has received little attention, notwithstanding the fact that mammalian olfactory receptors comprise the largest family of mammalian GPCRs. This position review considers the possibility that, although such complexity in G-protein function may have been lost in the specialization of olfactory receptors to serve as sensory receptors, the ability of olfactory receptor neurons (ORNs) to function as signal integrators and growing appreciation that this functionality is widespread in the receptor population suggest otherwise. We pose that functional selectivity driving 2 opponent inputs have the potential to generate an output that reflects the balance of ligand-dependent signaling, the direction of which could be either suppressive or synergistic and, as such, needs to be considered as a mechanistic basis for signal integration in mammalian ORNs.
Not All Emotions Are Equal: Fear Chemosignals Lower Awareness Thresholds Only for Fearful Faces
Authors: Silva Fábio , Gomes Nuno , Korb Sebastian , Semin Gün R 
Published: June 2020

Abstract
Exposure to body odors (chemosignals) collected under different emotional states (i.e., emotional chemosignals) can modulate our visual system, biasing visual perception. Recent research has suggested that exposure to fear body odors, results in a generalized faster access to visual awareness of different emotional facial expressions (i.e., fear, happy, and neutral). In the present study, we aimed at replicating and extending these findings by exploring if these effects are limited to fear odor, by introducing a second negative body odor—that is, disgust. We compared the time that 3 different emotional facial expressions (i.e., fear, disgust, and neutral) took to reach visual awareness, during a breaking continuous flash suppression paradigm, across 3 body odor conditions (i.e., fear, disgust, and neutral). We found that fear body odors do not trigger an overall faster access to visual awareness, but instead sped-up access to awareness specifically for facial expressions of fear. Disgust odor, on the other hand, had no effects on awareness thresholds of facial expressions. These findings contrast with prior results, suggesting that the potential of fear body odors to induce visual processing adjustments is specific to fear cues. Furthermore, our results support a unique ability of fear body odors in inducing such visual processing changes, compared with other negative emotional chemosignals (i.e., disgust). These conclusions raise interesting questions as to how fear odor might interact with the visual processing stream, whilst simultaneously giving rise to future avenues of research.
The Safety of Delayed Versus Immediate Antibiotic Prescribing for Upper Respiratory Tract Infections
Authors: van Staa Tjeerd Pieter , Palin Victoria , Brown Benjamin , Welfare William , Li Yan , Ashcroft Darren M 
Published: June 2020

Abstract

Background
This study aimed to evaluate the clinical safety of delayed antibiotic prescribing for upper respiratory tract infections (URTIs), which is recommended in treatment guidelines for less severe cases.

Methods
Two population-based cohort studies used the English Clinical Practice Research Databank and Welsh Secure Anonymized Information Linkage, containing electronic health records from primary care linked to hospital admission records. Patients with URTI and prescriptions of amoxicillin, clarithromycin, doxycycline, erythromycin, or phenoxymethylpenicillin were identified. Patients were stratified according to delayed and immediate prescribing relative to URTI diagnosis. Outcome of interest was infection-related hospital admission after 30 days.

Results
The population included 1.82 million patients with an URTI and antibiotic prescription; 91.7% had an antibiotic at URTI diagnosis date (immediate) and 8.3% had URTI diagnosis in 1–30 days before (delayed). Delayed antibiotic prescribing was associated with a 52% increased risk of infection-related hospital admissions (adjusted hazard ratio, 1.52; 95% confidence interval, 1.43–1.62). The probability of delayed antibiotic prescribing was unrelated to predicted risks of hospital admission. Analyses of the number needed to harm showed considerable variability across different patient groups (median with delayed antibiotic prescribing, 1357; 2.5% percentile, 295; 97.5% percentile, 3366).

Conclusions
This is the first large population-based study examining the safety of delayed antibiotic prescribing. Waiting to treat URTI was associated with increased risk of hospital admission, although delayed antibiotic prescribing was used similarly between high- and low-risk patients. There is a need to better target delayed antibiotic prescribing to URTI patients with lower risks of complications.
Outcomes of Reflex Cryptococcal Antigen (CrAg) Screening in Human Immunodeficiency Virus (HIV)-Positive Patients With CD4 Counts of 100–200 Cells/µL in Botswana
Authors: Tenforde Mark W , Milton Thandi , Rulaganyang Ikanyeng , Muthoga Charles , Tawe Leabaneng , Chiller Tom , Greene Gregory , Jordan Alexander , Williams Christopher G , Owen Leah , Leeme Tshepo B , Boose Amber , Ngidi Julia , Mine Madisa , Jarvis Joseph N 
Published: June 2020

Abstract
Increasing the CD4-count threshold for cryptococcal antigen (CrAg) screening from ≤100 to ≤200 cells/µL resulted in a 3-fold increase in numbers screened. CrAg-prevalence was 3.5% at CD4 101–200 and 6.2% ≤100 cells/µL. Six-month mortality was 21.4% (9/42) in CrAg-positive CD4 ≤100 cells/µL and 3.2% (1/31) in CrAg-positive CD4 101–200 cells/µL.
Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV
Authors: Ehinger Erik , Ghosheh Yanal , Pramod Akula Bala , Lin Juan , Hanna David B , Mueller Karin , Durant Christopher P , Baas Livia , Qi Qibin , Wang Tao , Buscher Konrad , Anastos Kathryn , Lazar Jason M , Mack Wendy J , Tien Phyllis C , Cohen Mardge H , Ofotokun Igho , Gange Stephen , Heath Sonya L , Hodis Howard N , Tracy Russell P , Landay Alan L , Kaplan Robert C , Ley Klaus 
Published: June 2020

Abstract

Aims
During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability.

Methods and results
Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women’s Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women’s Interagency HIV Study and deep-sequenced their mRNA (n = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV−sCVD−) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production.

Conclusion
Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD.
Short- and long-term treatment with TNF-α inhibits the induction of osteoblastic differentiation in cyclic tensile-stretched periodontal ligament fibroblasts
Authors: Papadopoulou Adamantia , Cantele Aurelie , Koletsi Despina , Eliades Theodore , Kletsas Dimitris 
Published: June 2020

SummaryBackgroundCyclic tensile stretching (CTS) induces osteoblastic differentiation of periodontal ligament fibroblasts (PDLF). On the other hand, increased concentrations of tumour necrosis factor-α (TNF-α) are found in inflammatory conditions, leading to periodontal disease and tooth loss. Accordingly, our aim was to investigate the short- and long-term effect of TNF-α on the response of human PDLF to CTS and its implication on osteoblastic differentiation.MethodsPDLF were either pre-incubated for 4 hours or were repeatedly exposed to TNF-α for up to 50 days and then subjected to CTS. Gene expression was determined by quantitative real-time polymerase chain reaction. Activation of mitogen-activated protein kinase (MAPK) was monitored by western analysis and cell proliferation by bromodeoxyuridine incorporation. Intracellular reactive oxygen species were determined by the 2´, 7´-dichlorofluorescein-diacetate assay and osteoblastic differentiation by Alizarin Red-S staining after an osteo-inductive period of 21 days.ResultsCTS of PDLF induced an immediate upregulation of the c-fos transcription factor and, further downstream the overexpression of alkaline phosphatase and osteopontin, two major osteoblast marker genes. A 4-hour pre-incubation with TNF-α repressed these effects. Similarly, long-term propagation of PDLF along with TNF-α diminished their osteoblastic differentiation capacity and suppressed cells’ CTS-elicited responses. The observed phenomena were not linked with TNF-α-induced premature senescence or oxidative stress. While CTS induced the activation of MAPKs, involved in mechanotransduction, TNF-α treatment provoked a small delay in the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase.ConclusionIncreased concentrations of TNF-α, such as those recorded in many inflammatory diseases, suppress PDLF’s immediate responses to mechanical forces compromising their osteoblastic differentiation potential, possibly leading to tissue’s impaired homeostasis.
Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial
Authors: Stuber Mirah J , Moutzouri Elisavet , Feller Martin , Del Giovane Cinzia , Bauer Douglas C , Blum Manuel R , Collet Tinh-Hai , Gussekloo Jacobijn , Mooijaart Simon P , McCarthy Vera J C , Aujesky Drahomir , Westendorp Rudi , Stott David J , Glynn Nancy W , Kearney Patricia M , Rodondi Nicolas 
Published: June 2020

AbstractBackgroundFatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue.MethodThis study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60–19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight &lt;50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose.ResultsAmong 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p &lt; .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI −1.8 to 2.1; p = .88), or mental fatigability (−1.0; 95% CI −2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI −3.6 to 2.8, p = .79) and −2.2 (95% CI −8.8 to 4.5, p = .51).ConclusionsLevothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability.
Localization and coalescence of seismicity before large earthquakes
Authors: Ben-Zion Yehuda , Zaliapin Ilya 
Published: June 2020

SUMMARY
We examine localization processes of low magnitude seismicity in relation to the occurrence of large earthquakes using three complementary analyses: (i) estimated production of rock damage by background events, (ii) evolving occupied fractional area of background seismicity and (iii) progressive coalescence of individual earthquakes into clusters. The different techniques provide information on different time scales and on the spatial extent of weakened damaged regions. Techniques (i) and (ii) use declustered catalogues to avoid the occasional strong fluctuations associated with aftershock sequences, while technique (iii) examines developing clusters in entire catalogue data. We analyse primarily earthquakes around large faults that are locked in the interseismic periods, and examine also as a contrasting example seismicity from the creeping Parkfield section of the San Andreas fault. Results of analysis (i) show that the M &gt; 7 Landers 1992, Hector Mine 1999, El Mayor-Cucapah 2010 and Ridgecrest 2019 main shocks in Southern and Baja California were preceded in the previous decades by generation of rock damage around the eventual rupture zones. Analysis (ii) reveals localization (reduced fractional area) 2–3 yr before these main shocks and before the M &gt; 7 Düzce 1999 earthquake in Turkey. Results with technique (iii) indicate that individual events tend to coalesce rapidly to clusters in the final 1–2 yr before the main shocks. Corresponding analyses of data from the Parkfield region show opposite delocalization patterns and decreasing clustering before the 2004 M6 earthquake. Continuing studies with these techniques, combined with analysis of geodetic data and insights from laboratory experiments and model simulations, might improve the ability to track preparation processes leading to large earthquakes.
Improved approach for stress drop estimation and its application to an induced earthquake sequence in Oklahoma
Authors: Chen X , Abercrombie R E 
Published: June 2020

SUMMARYWe calculate source parameters for fluid-injection induced earthquakes near Guthrie, Oklahoma, guided by synthetic tests to quantify uncertainties. The average stress drop during an earthquake is a parameter fundamental to ground motion prediction and earthquake source physics, but it has proved hard to measure accurately. This has limited our understanding of earthquake rupture, as well as the spatio-temporal variations of fault strength. We use synthetic tests based on a joint spectral-fitting method to define the resolution limit of the corner frequency as a function of the maximum frequency of usable signal, for both individual spectra and the average from multiple stations. Synthetic tests based on stacking analysis find that an improved stacking approach can recover the true input stress drop if the corner frequencies are within the resolution limit defined by joint spectral-fitting. We apply the improved approach to the Guthrie sequence, using different wave types and signal-to-noise criteria to understand the stability of the calculated stress drop values. The results suggest no systematic scaling relationship of stress drop for M ≤ 3.1 earthquakes, but larger events (M ≥ 3.5) tend to have higher average stress drops. Some robust spatio-temporal variations can be linked to the triggering processes and indicate possible stress heterogeneity within the fault zone. Tight clustering of low stress drop events at the beginning stage of the sequence suggests that pore pressure influences earthquake source processes. Events at shallow depth have lower stress drop compared to deeper events. The largest earthquake occurred within a cluster of high stress drop events, likely rupturing a strong asperity.
Exact extrapolation and immersive modelling with finite-difference injection
Authors: van Manen Dirk-Jan , Li Xun , Vasmel Marlies , Broggini Filippo , Robertsson Johan 
Published: June 2020

SUMMARY
In numerical modelling of wave propagation, the finite-difference (FD) injection method enables the re-introduction of simulated wavefields in model subdomains with machine precision, enabling the efficient calculation of waveforms after localized model alterations. By rewriting the FD-injection method in terms of sets of equivalent sources, we show how the same principles can be applied to achieve on-the-fly wavefield extrapolation using Kirchhoff–Helmholtz (KH)-like integrals. The resulting extrapolation methods are numerically exact when used in conjunction with FD-computed Green’s functions. Since FD injection only relies on the linearity of the wave equation and compactness of FD stencils in space, the methods can be applied to both staggered and non-staggered discretizations with arbitrary-order spatial operators. Examples for both types of discretizations show how these extrapolators can be used to truncate models with exact absorbing or immersive boundary conditions. Such immersive modelling involves the evaluation of KH-type extrapolation and representation integrals in the same simulation, which include the long-range interactions missing from conventional FD injection.
Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms
Authors: Prasasya Rexxi , Grotheer Kristen V , Siracusa Linda D , Bartolomei Marisa S 
Published: June 2020

AbstractTemple syndrome (TS) and Kagami-Ogata syndrome (KOS) are imprinting disorders caused by absence or overexpression of genes within a single imprinted cluster on human chromosome 14q32. TS most frequently arises from maternal UPD14 or epimutations/deletions on the paternal chromosome, whereas KOS most frequently arises from paternal UPD14 or epimutations/deletions on the maternal chromosome. In this review, we describe the clinical symptoms and genetic/epigenetic features of this imprinted region. The locus encompasses paternally expressed protein-coding genes (DLK1, RTL1 and DIO3) and maternally expressed lncRNAs (MEG3/GTL2, RTL1as and MEG8), as well as numerous miRNAs and snoRNAs. Control of expression is complex, with three differentially methylated regions regulating germline, placental and tissue-specific transcription. The strong conserved synteny between mouse chromosome 12aF1 and human chromosome 14q32 has enabled the use of mouse models to elucidate imprinting mechanisms and decipher the contribution of genes to the symptoms of TS and KOS. In this review, we describe relevant mouse models and highlight their value to better inform treatment options for long-term management of TS and KOS patients.
Evolution of the Dentition in Holocephalans (Chondrichthyes) Through Tissue Disparity
Authors: Johanson Zerina , Manzanares Esther , Underwood Charlie , Clark Brett , Fernandez Vincent , Smith Moya 
Published: June 2020

AbstractThe Holocephali is a major group of chondrichthyan fishes, the sister taxon to the sharks and rays (Elasmobranchii). However, the dentition of extant holocephalans is very different from that of the elasmobranchs, lacking individual tooth renewal, but comprising dental plates made entirely of self-renewing dentine. This renewal of all tissues occurs at the postero-lingual plate surface, as a function of their statodont condition. The fossil record of the holocephalans illuminates multiple different trends in the dentition, including shark-like teeth through to those with dentitions completely lacking individual teeth. Different taxa illustrate developmental retention of teeth but with fusion in their serial development. Dentine of different varieties comprises these teeth and composite dental plates, whose histology includes vascularized tubes within coronal dentine, merging with basal trabecular dentine. In this coronal vascularized dentine, extensive hypermineralization forms a wear resistant tissue transformed into a variety of morphologies. Through evolution, hypermineralized dentine becomes enclosed within the trabecular dentine, and specialized by reduction into specific zones within a composite dental plate, with these increasing in morphological disparity, all reflecting loss of defined teeth but retention of dentine production from the inherited developmental package.
Clinical Outcomes and Immunologic Characteristics of Coronavirus Disease 2019 in People With Human Immunodeficiency Virus
Authors: Ho Hsi-en , Peluso Michael J , Margus Colton , Matias Lopes Joao Pedro , He Chen , Gaisa Michael M , Osorio Georgina , Aberg Judith A , Mullen Michael P 
Published: June 2020

Abstract
We performed a retrospective study of coronavirus disease 2019 (COVID-19) in people with human immunodeficiency virus (PWH). PWH with COVID-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin 6, interleukin 8, and tumor necrosis factor α were commonly elevated. In all, 19 of 72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of COVID-19 despite antiretroviral therapy and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.
Monitoring via the Courts: Judicial Oversight and Police Violence in India
Authors: Hu Shengkuo , Conrad Courtenay R 
Published: June 2020

AbstractCan the creation of court-mandated accountability institutions improve human rights? In this article, we investigate the extent to which court-ordered accountability institutions decrease government repression in the form of police violence. We argue that the creation of regional bodies to which citizens report allegations of police abuse provides “fire-alarm” oversight by which police officers can be monitored for abuses of power. To test the implications of our theory, we take advantage of variance in the implementation of Prakash Singh and Others v. Union of India and Others, a 2006 judgment by the Supreme Court of India requiring states and districts to establish local Police Complaints Authorities (PCAs). Using a difference-in-difference design, we show the implementation of state PCAs to be associated with statistically and substantively significant decreases in human rights violations by Indian police officers.