bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Pre-exposure Prophylaxis (PrEP) Uptake Among Gay and Bisexual Men in Australia and Factors Associated With the Nonuse of PrEP Among Eligible Men: Results From a Prospective Cohort Study
Authors: Hammoud Mohamed A. , Vaccher Stefanie , Jin Fengyi , Bourne Adam , Maher Lisa , Holt Martin , Bavinton Benjamin R. , Haire Bridget , Degenhardt Louisa , Grulich Andrew , Prestage Garrett P. 
Published: April 2019

Background:
HIV pre-exposure prophylaxis (PrEP) is a highly effective biomedical HIV prevention strategy, yet some gay and bisexual men (GBM) who are eligible to access PrEP are not using it. We report the incidence of PrEP uptake, factors predicting its initiation, and identify characteristics associated with nonuptake of PrEP among Australian GBM who meet the eligibility criteria.

Methods:
The Following Lives Undergoing Change (Flux) Study is a national, online, prospective observational study among GBM focusing on licit and illicit drug use. Participants (N = 1257) responded to baseline and 6-monthly follow-up questionnaires. Incidence per 100 person-years and incidence rate ratios of PrEP initiation are presented. Multivariate Poisson regression was used to examine associations with PrEP initiation and logistic regression to examine associations with nonuptake of PrEP among eligible GBM.

Results:
Among GBM who met the eligibility criteria, 69.8% of men did not commence PrEP. Factors independently associated with nonuptake of PrEP were younger age, living in an Australian state without a PrEP trial, lower social engagement with other gay men, less use of illicit party drugs or use of illicit party drugs for sex, and less likely to have engaged in HIV sexual risk behaviors such as group sex or any condomless anal intercourse.

Conclusions:
Despite meeting formal eligibility criteria for PrEP, men who were relatively less sexually active or less socially connected were less likely to initiate PrEP. Men who did not initiate PrEP may assess their risk as insufficient relative to others to warrant using PrEP because they engaged in less frequent “risky” behaviors.
HIV Positivity and Referral to Treatment Following Testing of Partners and Children of PLHIV Index Patients in Public Sector Facilities in South Africa
Authors: Joseph Davey Dvora , Wall Kristin M. , Serrao Claire , Prins Marlien , Feinberg Madaline , Mtonjana Ntokozo , Hlophe Khanyo , Zuma Lindiwe , Sejake Senate , Malone Todd 
Published: April 2019

Background:
There is an imperative need for innovative interventions to identify people living with HIV and initiate them on antiretroviral therapy. The objective of this study was to determine the feasibility of providing index partner/child testing of people living with HIV.

Methods:
We trained 86 nurses and counsellors in 56 public health facilities in 6 high HIV burden Districts in South Africa 2017 to provide index partner/child testing (tracing and testing of partners/children of people living with HIV). We collected programmatic data including index partner/child HIV positivity by age, gender, and location of testing. In subanalyses, we evaluated factors associated with identifying HIV-positive partners and children in separate models using multivariable logistic regression.

Results:
We tested 16,033 partners and children of index patients between October 2017 and June 2018. Most of those tested were women (61%) and 20–39 years old (39%). Overall, 6.4% were 10–14 years old, 9.5% were 15–19 years, and 8% were ≥50 years. HIV positivity was 38% [95% confidence interval (CI) = 36% to 40%]. In children ages 10–14 years, 13% were HIV-infected (95% CI = 11% to 14%). In subanalyses, HIV positivity in partners was associated with their increased age [adjusted odds ratio (aOR) for increase in 5-year age category = 1.21; 95% CI = 1.04 to 1.42], female gender (aOR = 1.38; 95% CI = 1.04 to 1.82), and index partner bringing the partner in for HIV testing vs. referring the partner through the provider or recommending testing to the partner (aOR = 1.94, 95% CI = 1.43 to 2.63), adjusting for location of testing. Almost all patients diagnosed (97%) were referred to antiretroviral therapy.

Conclusions:
Providing index partner/child testing was feasible and we identified a very high yield when testing partners and children of index patients. Index partner and children testing should be offered to all patients living with HIV to improve case finding.
HIV Disease Severity Is Sensitive to Temporal Changes in Alcohol Use: A National Study of VA Patients With HIV
Authors: Williams Emily C. , McGinnis Kathleen A. , Tate Janet P. , Matson Theresa E. , Rubinsky Anna D. , Bobb Jennifer F. , Lapham Gwen T. , Edelman E. Jennifer , Catz Sheryl L. , Satre Derek D. , Bryant Kendall J. , Marshall Brandon D. L. , Kraemer Kevin L. , Bensley Kara M. , Richards Julie E. , Skanderson Melissa , Justice Amy C. , Fiellin David A. , Bradley Katharine A. 
Published: April 2019

Background:
Alcohol use influences HIV disease severity through multiple mechanisms. Whether HIV disease severity is sensitive to changes in alcohol use among people with HIV (PWH) is understudied.

Setting:
National Veterans Health Administration.

Methods:
Pairs of AUDIT-C screens within 9–15 months (February 1, 2008–September 30, 2014) were identified among PWH from the Veterans Aging Cohort Study (VACS). Initial and follow-up VACS Index 2.0 pairs obtained 0–270 days after initial and follow-up AUDIT-Cs, respectively, determined change in VACS Index 2.0, a composite HIV severity measure. Change in VACS Index 2.0 was regressed on AUDIT-C change scores (−12 to +12) adjusted for demographics, initial VACS Index 2.0, and days between VACS Index measures.

Results:
Among 23,297 PWH (76,202 observations), most had no (51%) or low-level (38%) alcohol use initially. Most (54%) had no subsequent change; 21% increased and 24% decreased drinking. Initial VACS Index 2.0 scores ranged from 0 to 134, change scores ranged from −65 to +73, with average improvement of 0.76 points (SD 9.48). AUDIT-C change was associated with VACS Index 2.0 change (P < 0.001). Among those with stable alcohol use (AUDIT-C change ≤ │1│ point), VACS Index 2.0 improvements ranged 0.36–0.60 points. For those with maximum AUDIT-C increase (change from 0 to 12), VACS Index 2.0 worsened 3.74 points (95% CI: −4.71 to −2.78); for those with maximum AUDIT-C decrease (change from 12 to 0), VACS Index 2.0 changed minimally [−0.60 (95% CI: −1.43 to 0.23)].

Conclusions:
In this national sample, improvement in HIV severity was generally greatest among those with stable alcohol use (primarily those with no use).
Mandibular Spatial Reorientation and Morphological Alteration of Crouzon and Apert Syndrome
Authors: Lu Xiaona , Sawh-Martinez Rajendra , Forte Antonio Jorge , Wu Robin , Cabrejo Raysa , Wilson Alexander , Steinbacher Derek M. , Alperovich Michael , Alonso Nivaldo , Persing John A. 
Published: April 2019

Background
From infancy to adulthood, the mandible develops increased ramus height, prominence of the chin, and laterally widened gonial angles. In Crouzon and Apert syndromes, both relative retrognathia and prognathic jaws have been reported. Growth is influenced by a variety of factors, including the growth and relative position of the skull base, functional coordination, and the spatial influence of the laryngopharynx. Thus, this study aimed to explore in detail the evolution of the mandible in both syndromes and its relationship with the entire facial structure and skull base.

Methods
One hundred twenty-three preoperative computed tomographic scans (Crouzon, n = 36; Apert, n = 33; control, n = 54) were included and divided into 5 age subgroups. Computed tomographic scans were measured using Materialise software. Cephalometrics relating to the mandible, facial structures, and cranial base were collected. Statistical analyses were performed using t test and statistical power analysis.

Results
In Crouzon syndrome, the angle between the cranial base and gnathion was increased prior to 6 months of age by 10.29 degrees (P < 0.001) and by adulthood to 11.95 degrees (P = 0.003) compared with normal. After 6 months of age, the distance between bilateral mandibular condylions (COR-COL) was narrower by 15% (P < 0.001) in Crouzon syndrome compared with control subjects. Before 6 months of age, Apert COR-COL decreased 16% (P < 0.001) compared with control subjects and 13% (P = 0.006) narrower than Crouzon. During 2 to 6 years of age, Apert mandibular ramus height caught up to, and became longer than, Crouzon by 12% (P = 0.011). The nasion-sella-articulare angle of the Apert skull was 5.04 degrees (P < 0.001) less than Crouzon overall.

Conclusions
In Crouzon syndrome, the changes of the spatial relationship of the mandible to the cranial base develop earlier than the mandibular shape deformity, whereas in Apert syndrome, the spatial and morphological changes are synchronous. The morphological changes of the mandible are disproportional in 3 directions, initially significant shortening of the mandibular width and length, and, subsequently, reduced height. Crouzon has more shortening in mandibular height compared with Apert, reflecting the more shortened posterior cranial base length. The narrowed angle between the mandible and the posterior cranial base in Apert skulls is consistent with the more limited nasopharyngeal and oropharyngeal airway space.
A Design for the Dual Skin Paddle Circumflex Scapular Artery Perforator Flap for the Reconstruction of Complex Soft-Tissue Defects in Children
Authors: Qing Liming , Wu Panfeng , Zhou Zhengbing , Yu Fang , Tang Maolin , Tang Juyu 
Published: April 2019

Background
The main drawbacks of the use of the circumflex scapular artery perforator (CSAP) flap for complex soft-tissue defect repair are the limitation of skin paddle size, which can be harvested to allow precise wound coverage and primary closure of the donor site. We developed a variant of the dual skin paddle CSAP flap to extend its applications and minimize donor-site morbidity when reconstructing complex soft-tissue defects in children.

Methods
A detailed anatomical investigation of circumflex scapular artery (CSA) branches was conducted using a standardized injection of lead oxide in 25 fresh cadavers. Dual skin paddle CSAP flaps were harvested for the reconstruction of complex defects in the extremities in 16 children. Three types of dual skin paddle CSAP flap were used in this study: transverse chain-shaped, oblique chain-shaped, and trefoil-shaped flaps.

Results
Three CSA branching patterns with superior branch diameters were observed: 34% of CSAs were of the transverse branch dominant type, 54% were of the descending branch dominant type, and 12% were of the codominant type. Sixteen dual skin paddle CSAP flaps were elevated successfully; they were of the transverse chain-shaped type in 2 cases, the oblique chain-shaped type in 9 cases, and the trefoil-shaped type in 5 cases. All flaps survived postoperatively. Primary closure of the donor site was achieved in all cases.

Conclusions
The CSA system is an appropriate source for harvesting dual skin paddle CASP flap. Use of this flap for the reconstruction of complex soft-tissue defects in the extremities in children is an alternative approach that reduces morbidity and improves the cosmetic outcome at the donor site.
Definition of the Rectum
Authors: D'Souza Nigel , de Neree tot Babberich Michael P. M. , d’Hoore Andre , Tiret Emmanuel , Xynos Evaghelos , Beets-Tan Regina G. H. , Nagtegaal Iris D. , Blomqvist Lennart , Holm Torbjorn , Glimelius Bengt , Lacy Antonio , Cervantes Andres , Glynne-Jones Robert , West Nicholas P. , Perez Rodrigo O. , Quadros Claudio , Lee Kil Yeon , Madiba Thandinkosi E. , Wexner Steven D. , Garcia-Aguilar Julio , Sahani Dushyant , Moran Brendan , Tekkis Paris , Rutten Harm J. , Tanis Pieter J. , Wiggers Theo , Brown Gina 
Published: April 2019

Background:
The wide global variation in the definition of the rectum has led to significant inconsistencies in trial recruitment, clinical management, and outcomes. Surgical technique and use of preoperative treatment for a cancer of the rectum and sigmoid colon are radically different and dependent on the local definitions employed by the clinical team. A consensus definition of the rectum is needed to standardise treatment.

Methods:
The consensus was conducted using the Delphi technique with multidisciplinary colorectal experts from October, 2017 to April, 2018.

Results:
Eleven different definitions for the rectum were used by participants in the consensus. Magnetic resonance imaging (MRI) was the most frequent modality used to define the rectum (67%), and the preferred modality for 72% of participants. The most agreed consensus landmark (56%) was “the sigmoid take-off,” an anatomic, image-based definition of the junction of the mesorectum and mesocolon. In the second round, 81% of participants agreed that the sigmoid take-off as seen on computed tomography or MRI achieved consensus, and that it could be implemented in their institution. Also, 87% were satisfied with the sigmoid take-off as the consensus landmark.

Conclusion:
An international consensus definition for the rectum is the point of the sigmoid take-off as visualized on imaging. The sigmoid take-off can be identified as the mesocolon elongates as the ventral and horizontal course of the sigmoid on axial and sagittal views respectively on cross-sectional imaging. Routine application of this landmark during multidisciplinary team discussion for all patients will enable greater consistency in tumour localisation.
Fluorescent and Iodized Emulsion for Preoperative Localization of Pulmonary Nodules
Authors: Rho Jiyun , Lee Jae Wook , Quan Yu Hua , Choi Byeong Hyeon , Shin Bong Kyung , Han Kook Nam , Kim Beop-Min , Choi Young Ho , Yong Hwan Seok , Kim Hyun Koo 
Published: April 2019

Objective:
This study was conducted to develop a fluorescent iodized emulsion comprising indocyanine green (ICG) solution and lipiodol (ethiodized oil) and evaluate its feasibility for use in a clinical setting.

Background:
ICG use for the preoperative localization of pulmonary nodules is limited in terms of penetration depth and diffusion.

Methods:
First, fluorescent microscopy was used to investigate the distribution of ICG-lipiodol emulsions prepared using different methods. The emulsions were injected in 15 lung lobes of 3 rabbits under computed tomography fluoroscopy guidance; evaluation with imaging and radiography was conducted after thoracotomy. Subsequently, the emulsions were used to preoperatively localize 29 pulmonary nodules in 24 human subjects, and wedge resections were performed using fluorescent imaging and C-arm fluoroscopy.

Results:
The optimal emulsion of 10% ICG and 90% lipiodol mixed through 90 passages had even distribution and the highest signal intensity under fluorescent microscopy; it also had the best consistency in the rabbit lungs, which persisted for 24 hours at the injection site. In human subjects, the mean diameter of pulmonary nodules was 0.9 ± 0.4 cm, and depth from the pleura was 1.2 ± 0.8 cm. All emulsion types injected were well localized around the target nodules without any side effects or procedure-related complications. Wedge resection with minimally invasive approach was successful in all pulmonary nodules with a free resection margin.

Conclusions:
A fluorescent iodized emulsion prepared by mixing ICG with lipiodol enabled accurate localization and resection of pulmonary nodules.
Disruption of membrane cholesterol organization impairs the concerted activity of PIEZO1 channel clusters
Authors: Ridone P. , Pandzic E. , Vassalli M. , Cox C. D. , Macmillan A. , Gottlieb P.A. , Martinac B. 
Published: April 2019

ABSTRACTThe human mechanosensitive ion channel PIEZO1 is gated by membrane tension and regulates essential biological processes such as vascular development and erythrocyte volume homeostasis. Currently, little is known about PIEZO1 plasma membrane localization and organization. Using a PIEZO1-GFP fusion protein, we investigated whether cholesterol enrichment or depletion by methyl-β-Cyclodextrin (MBCD) and disruption of membrane cholesterol organization by dynasore affects PIEZO1-GFP’s response to mechanical force. Electrophysiological recordings in the cell-attached configuration revealed that MBCD caused a rightward shift in the PIEZO1-GFP pressure-response curve, increased channel latency in response to mechanical stimuli and markedly slowed channel inactivation. The same effects were seen in native PIEZO1 in N2A cells. STORM super-resolution imaging revealed that, at the nano-scale, PIEZO1-GFP channels in the membrane associate as clusters sensitive to membrane manipulation. Both cluster distribution and diffusion rates were affected by treatment with MBCD (5 mM). Supplementation of poly-unsaturated fatty acids appeared to sensitize the PIEZO1-GFP response to applied pressure. Together, our results indicate that PIEZO1 function is directly dependent on the membrane mechanical properties and lateral organization of membrane cholesterol domains which coordinates the concerted activity of PIEZO1 channels.SUMMARYThe essential mammalian mechanosensitive channel PIEZO1 organizes in the plasma membrane into nanometric clusters which depend on the integrity of cholesterol domains to rapidly detect applied force and especially inactivate syncronously, the most commonly altered feature of PIEZO1 in pathology.
Social information drives ecological outcomes among competing species
Authors: Gil M.A. , Baskett M.L. , Schreiber S.J. 
Published: April 2019

AbstractThrough its behavior, an organism intentionally or unintentionally produces information. Use of this ‘social information’ by surrounding conspecifics or heterospecifics is a ubiquitous phenomenon that can drive strong correlations in fitness-associated behaviors, such as predator avoidance, enhancing survival within and among competing species. By eliciting indirect positive interactions between competing individuals or species, social information might alter overall competitive outcomes. To test this potential, we present new theory that quantifies the effect of social information, modeled as predator avoidance signals/cues, on the outcomes from intraspecific and interspecific competition. Our analytical and numerical results reveal that social information can rescue populations from extinction and can shift the long-term outcome of competitive interactions from mutual exclusion to coexistence, or vice versa, depending on the relative strengths of intraspecific and interspecific social information and competition. Our findings highlight the importance of social information in determining ecological outcomes.
Bayesian Estimation of Population Size Changes by Sampling Tajima’s Trees
Authors: Palacios Julia A. , Véber Amandine , Cappello Lorenzo , Wang Zhangyuan , Wakeley John , Ramachandran Sohini 
Published: April 2019

AbstractThe large state space of gene genealogies is a major hurdle for inference methods based on Kingman’s coalescent. Here, we present a new Bayesian approach for inferring past population sizes which relies on a lower resolution coalescent process we refer to as “Tajima’s coalescent”. Tajima’s coalescent has a drastically smaller state space, and hence it is a computationally more efficient model, than the standard Kingman coalescent. We provide a new algorithm for efficient and exact likelihood calculations for data without recombination, which exploits a directed acyclic graph and a correspondingly tailored Markov Chain Monte Carlo method. We compare the performance of our Bayesian Estimation of population size changes by Sampling Tajima’s Trees (BESTT) with a popular implementation of coalescent-based inference in BEAST using simulated data and human data. We empirically demonstrate that BESTT can accurately infer effective population sizes, and it further provides an efficient alternative to the Kingman’s coalescent. The algorithms described here are implemented in theRpackagephylodyn, which is available for download athttps://github.com/JuliaPalacios/phylodyn.
RhoA mediates epithelial cell shape changes via mechanosensitive endocytosis
Authors: Cavanaugh Kate E. , Staddon Michael F. , Munro Ed , Banerjee Shiladitya , Gardel Margaret L. 
Published: April 2019

AbstractMorphogenetic movements require tight spatiotemporal control over cell-cell junction lengths. Contractile forces, acting at adherens junctions, alter cell-cell contact lengths in a cyclic fashion as a mechanical ratchet. Pulsatile RhoA activity is thought to drive ratcheting through acute periods of junction contraction followed by stabilization. Currently, we lack a mechanistic understanding of if and how RhoA activity governs junction length and subsequent cell shape within epithelia. In this study we use optogenetics to exogenously control RhoA activity in model Caco-2 epithelium. We find that at short timescales, RhoA activation drives reversible junction contraction. Sustained RhoA activity drives irreversible junction shortening but the amount of shortening saturates for a single pulse. To capture these data, we develop a vertex model modified to include strain-dependent junction length and tension remodeling. We find that, to account for experimental data, tension remodeling requires a strain-dependent threshold. Our model predicts that temporal structuring of RhoA activity allows for subsequent tension remodeling events to overcome the limited shortening within a single pulse and this is confirmed by our experimental data. We find that RhoA-mediated junction remodeling requires activities of formin and dynamin, indicating the closely inter-connected activities of contractility, E-cadherin clustering, and endocytosis. Junction length is therefore regulated by the coordinated action of RhoA-mediated contractility, membrane trafficking, and adhesion receptor remodeling. Altogether these data provide insights into the underlying molecular and biophysical mechanisms of RhoA-mediated regulation of epithelial cell shape.