bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With Poor Linkage to HIV Care in South Africa: Secondary Analysis of Data From the Thol'impilo Trial
Authors: Dorward Jienchi , Mabuto Tonderai , Charalambous Salome , Fielding Katherine L. , Hoffmann Christopher J. 
Published: September 2017

Background:
Poor linkage to HIV care is impeding achievement of the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets. This study aims to identify risk factors for poor linkage-to-care after HIV counseling and testing, thereby informing strategies to achieve 90-90-90.

Setting:
The Thol'impilo trial was a large randomized controlled trial performed between 2012 and 2015 in South Africa, comparing different strategies to improve linkage-to-care among adults aged ≥18 years who tested HIV-positive at mobile clinic HIV counseling and testing.

Methods:
In this secondary analysis, sociodemographic factors associated with time to linkage-to-care were identified using Cox regression.

Results:
Of 2398 participants, 61% were female, with median age 33 years (interquartile range: 27–41) and median CD4 count 427 cells/mm3 (interquartile range: 287–595). One thousand one hundred one participants (46%) had clinic verified linkage-to-care within 365 days of testing HIV-positive. In adjusted analysis, younger age [≤30 vs >40 years: adjusted hazard ratio (aHR): 0.58, 95% CI: 0.50 to 0.68; 31–40 vs >40 years: aHR: 0.81, 95% CI: 0.70 to 0.94, test for trend P < 0.001], being male (aHR: 0.86, 95% CI: 0.76 to 0.98, P = 0.028), not being South African (aHR: 0.79, 95% CI: 0.66 to 0.96, P = 0.014), urban district (aHR: 0.82, 95% CI: 0.73 to 0.93, P = 0.002), being employed (aHR: 0.81, 95% CI: 0.72 to 0.92, P = 0.001), nondisclosure of HIV (aHR: 0.63, 95% CI: 0.56 to 0.72, P < 0.001), and having higher CD4 counts (test for trend P < 0.001) were all associated with decreased hazard of linkage-to-care.

Conclusion:
Linkage-to-care was low in this relatively large cohort. Increasing linkage-to-care requires innovative, evidence-based interventions particularly targeting individuals who are younger, male, immigrant, urban, employed, and reluctant to disclose their HIV status.
The Effect of PrEP on HIV Incidence Among Men Who Have Sex With Men in the Context of Condom Use, Treatment as Prevention, and Seroadaptive Practices
Authors: LeVasseur Michael T. , Goldstein Neal D. , Tabb Loni P. , Olivieri-Mui Brianne L. , Welles Seth L. 
Published: September 2017

Background:
HIV preexposure prophylaxis (PrEP) is an effective tool in preventing HIV infection among high-risk men who have sex with men (MSM). It is unknown how effective PrEP is in the context of other implemented HIV prevention strategies, including condom use, seroadaption, and treatment as prevention (TasP). We evaluate the impact of increasing uptake of PrEP in conjunction with established prevention strategies on HIV incidence in a high-risk population of MSM through simulation.

Methods:
Agent-based simulation models representing the sexual behavior of high-risk, urban MSM in the United States over the period of 1 year were used to evaluate the effect of PrEP on HIV infection rates. Simulations included data for 10,000 MSM and compared increasing rates of PrEP uptake under 8 prevention paradigms: no additional strategies, TasP, condom use, seroadaptive behavior, and combinations thereof.

Results:
We observed a mean of 103.2 infections per 10,000 MSM in the absence of any prevention method. PrEP uptake at 25% without any additional prevention strategies prevented 30.7% of infections. In the absence of PrEP, TasP, condom use, and seroadaptive behavior independently prevented 27.1%, 48.8%, and 37.7% of infections, respectively, and together prevented 72.2%. The addition of PrEP to the 3 aforementioned prevention methods, at 25% uptake, prevented an additional 5.0% of infections.

Conclusions:
To achieve a 25% reduction in HIV infections by 2020, HIV prevention efforts should focus on significantly scaling up access to PrEP in addition to HIV testing, access to antiretroviral therapy, and promoting condom use.
Surgical Outcome of Simplified Horse-Shoe Technique With the Traditional Procedure in Children With Trigonocephaly
Authors: Kalantar Hormozi Abdoljalil , Dastgerdi Vahid , Ghalambor Abdolazim 
Published: September 2017

Abstract
Trigonocephaly is one of the most common types of craniosynostosis leading to triangular-shaped head and neurodevelopmental complications. Several surgical techniques have been suggested for its correction, but the newly suggested technique seems to have optimal outcomes compared with the traditional methods. Thus, the authors retrospectively evaluated the outcomes of the simplified horse-shoe technique with previous procedures performed on 169 children severe trigonocephaly during 1996 to 2015 at Mofid Hospital, Tehran, Iran. Demographic data of the patients and the surgical outcomes and complications and the need for reoperation were recorded and scored using the Whitaker system. The male-to-female ratio was 2.75:1. The mean ±  standard deviation age of all the patients at the time of surgery was 7.09 ± 7.5, 9.95 ± 7.71, 10.53 ± 6.57, and 10.59 ± 7.96 months for the traditional, horse-shoe, and simplified horse-shoe techniques, respectively. The total reoperation rate was 6.5% (4.7% in the traditional technique, 1.2% in the horse-shoe, and 0.6% in the simplified horse-shoe technique) (P < 0.001). The main reason for reoperation was hardware removal (in the traditional technique). Whitaker scoring showed no patients of class IV in any of the groups and no patients of class III and IV in simplified horse-shoe technique, but the difference in the Whitaker scores among the 3 groups was not statistically significant (P = 1.176). The new surgical technique is easier and simpler with fewer complications than the traditional technique and is suggested to be recommended for surgical treatment in children with trigonocephaly, especially in younger children.
What is next after anamorelin?
Authors: Garcia Jose M. 
Published: September 2017

Purpose of review
In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical trials is anamorelin. Its development, along with that of other agents for this indication, will be reviewed here, with a focus on the gaps in the current knowledge and future directions.

Recent findings
In spite of several targets showing promising results in early development, their difficulties obtaining regulatory approval underscore the need to reconsider the current strategies in drug development and the challenges in the field of CACS.

Summary
Further research is needed in order to meet the challenges of developing treatments for CACS. Preclinical studies should expand our understanding about key regulators of appetite, muscle, and energy metabolism in this setting using models that can be translated reliably to humans. Clinical research efforts should focus on validating the entry criteria, endpoints, outcomes, and the potential synergistic effects and interaction between different targets, nutrition, and exercise interventions. Clinical meaningfulness and significance should be taken into account in the design of clinical trials. It is essential that all key stakeholders are included in the design of future strategies.
Practical approaches to managing cancer patients with weight loss
Authors: Del Fabbro Egidio , Orr Tamara A. , Stella Susan M. 
Published: September 2017

Purpose of review
Poor appetite and weight loss are a source of family conflict, psychological distress, and associated with poor tolerance to chemotherapy, impaired quality of life, and decreased survival. Despite clinicians’ concern about the effect of cachexia on their patients, few oncological professional organizations provide guidelines for the treatment of cancer-related weight loss.

Recent findings
Recent publications indicate there is an unmet need for addressing cachexia in patients with cancer. Studies also reveal that patients are often consuming inadequate calories and protein. Inadequate oral intake may be mitigated by a multimodal interdisciplinary approach that uses pharmacological and nonpharmacological measures such as exercise and counseling. Other positive clinical outcomes include decreased symptom burden, improved quality of life, and enhanced physical performance.

Summary
Experience from specialist cachexia clinics and published literature indicates that simple assessments and interventions can be applied more broadly in clinical practice and that the interdisciplinary multimodal approach is important for achieving successful outcomes. The positive influence of this approach on clinical outcomes also has to be considered in clinical trial design.
Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia
Authors: Dunne Richard F. , Mustian Karen M. , Garcia Jose M. , Dale William , Hayward Reid , Roussel Breton , Buschmann Mary M. , Caan Bette J. , Cole Calvin L. , Fleming Fergal J. , Chakkalakal Joe V. , Linehan David C. , Hezel Aram F. , Mohile Supriya G. 
Published: September 2017

Purpose of review
Cancer cachexia remains understudied and there are no standard treatments available despite the publication of an international consensus definition and the completion of several large phase III intervention trials in the past 6 years. In September 2015, The University of Rochester Cancer Center NCORP Research Base led a Symposium on Cancer Cachexia and Sarcopenia with goals of reviewing the state of the science, identifying knowledge gaps, and formulating research priorities in cancer cachexia through active discussion and consensus.

Recent findings
Research priorities that emerged from the discussion included the implementation of morphometrics into clinical decision making, establishing specific diagnostic criteria for the stages of cachexia, expanding patient selection in intervention trials, identifying clinically meaningful trial endpoints, and the investigation of exercise as an intervention for cancer cachexia.

Summary
Standardizing how we define and measure cancer cachexia, targeting its complex biologic mechanisms, enrolling patients early in their disease course, and evaluating exercise, either alone or in combination, were proposed as initiatives that may ultimately result in the improved design of cancer cachexia therapeutic trials.
Reconstruction of developmental landscapes by optimal-transport analysis of single-cell gene expression sheds light on cellular reprogramming
Authors: Schiebinger Geoffrey , Shu Jian , Tabaka Marcin , Cleary Brian , Subramanian Vidya , Solomon Aryeh , Liu Siyan , Lin Stacie , Berube Peter , Lee Lia , Chen Jenny , Brumbaugh Justin , Rigollet Philippe , Hochedlinger Konrad , Jaenisch Rudolf , Regev Aviv , Lander Eric S. 
Published: September 2017

AbstractUnderstanding the molecular programs that guide cellular differentiation during development is a major goal of modern biology. Here, we introduce an approach, WADDINGTON-OT, based on the mathematics of optimal transport, for inferring developmental landscapes, probabilistic cellular fates and dynamic trajectories from large-scale single-cell RNA-seq (scRNA-seq) data collected along a time course. We demonstrate the power of WADDINGTON-OT by applying the approach to study 65,781 scRNA-seq profiles collected at 10 time points over 16 days during reprogramming of fibroblasts to iPSCs. We construct a high-resolution map of reprogramming that rediscovers known features; uncovers new alternative cell fates including neuraland placental-like cells; predicts the origin and fate of any cell class; highlights senescent-like cells that may support reprogramming through paracrine signaling; and implicates regulatory models in particular trajectories. Of these findings, we highlightObox6, which we experimentally show enhances reprogramming efficiency. Our approach provides a general framework for investigating cellular differentiation.
No evidence that inbreeding avoidance is up-regulated during the ovulatory phase of the menstrual cycle
Authors: Holzleitner Iris J. , Driebe Julie C. , Arslan Ruben C. , Hahn Amanda C. , Lee Anthony J. , O’Shea Kieran J. , Gerlach Tanja M. , Penke Lars , Jones Benedict C. , DeBruine Lisa M. 
Published: September 2017

AbstractMate preferences and mating-related behaviors are hypothesized to change over the menstrual cycle in ways that function to increase reproductive fitness. Results of recent large-scale studies suggest that many of these hormone-linked behavioral changes are less robust than was previously thought. One specific hypothesis that has not yet been subject to a large-scale test is the proposal that women’s preference for associating with male kin is down-regulated during the ovulatory (high-fertility) phase of the menstrual cycle. Consequently, we used a longitudinal design to investigate the relationship between changes in women’s steroid hormone levels and their perceptions of faces experimentally manipulated to possess kinship cues (Study 1). Analyses suggested that women viewed men’s faces displaying kinship cues more positively (i.e., more attractive and trustworthy) when estradiol-to-progesterone ratio was high. Since estradiol-to-progesterone ratio is positively associated with conception risk during the menstrual cycle, these results directly contradict the hypothesis that women’s preference for associating with male kin is down-regulated during the ovulatory (high-fertility) phase of the menstrual cycle. Study 2 employed a daily diary approach and found no evidence that women reported spending less time in the company of male kin or thought about male kin less often during the fertile phase of the menstrual cycle. Thus, neither study found evidence that inbreeding avoidance is up-regulated during the ovulatory phase of the menstrual cycle.
Estimation of genetic correlation using linkage disequilibrium score regression and genomic restricted maximum likelihood
Authors: Ni Guiyan , Moser Gerhard ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Wray Naomi R. , Lee S. Hong 
Published: September 2017

ABSTRACTGenetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e. linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on ~150,000 individuals give a higher accuracy than LDSC estimates based on ~400,000 individuals (from combined meta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-data sets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.
A preliminary analysis of the association between perceived stigma and HIV-related pain
Authors: Wadley Antonia L , Pincus Tamar , Evangeli Michael 
Published: September 2017

AbstractObjectiveHIV stigma remains common and has been associated with severity of HIV-related symptoms. Associations between HIV stigma and HIV-related pain, one of the most common symptoms in HIV, have not been investigated however. Data from low back pain populations suggest that stigma associates with worse pain intensity and so we hypothesised that the same would be the case in HIV. In a small pilot study we assessed the association between HIV stigma and pain intensity in PLWH with chronic pain while controlling for depression, a well-established correlate of pain.MethodsMediation analysis was used to assess the effect of depression on the relationship between stigma and pain intensity in a cross-sectional cohort of 50 PLWH and chronic pain (pain most days of the week for > 3 months) recruited in Johannesburg, South Africa. All participants were assessed using: HIV/AIDS stigma instrument – PLWA (HASI-P), 11-point numerical pain rating scale, and the Beck Depression Inventory II.Results88% (44/50) of participants reported experiencing some form of HIV stigma (HIV stigma scale score ≥ 1). Worst pain intensity and depressive symptoms individually correlated with total stigma score (Spearman’s r = 0.33, p = 0.02 for both). The mediation analysis highlighted that mediation of the relationship by depression was equivocal (b = −0.002, bootstrapped CI −0.02 to 0.00).ConclusionsWhilst these preliminary data are marginal, they do suggest that associations between HIV stigma and HIV-related pain warrant further investigation. Future study should also include potential mechanisms, which may include mediation through depression.
Hydrogel encapsulation of living organisms for long-term microscopy
Authors: Burnett Kyra , Edsinger Eric , Albrecht Dirk R. 
Published: September 2017

AbstractImaging living organisms at high spatial resolution requires effective and innocuous immobilization. Long-term imaging, across development or behavioral states, places further demands on sample mounting with minimal perturbation of the organism. Here we present a simple and inexpensive method for rapid encapsulation of small animals of any developmental stage within a photocrosslinked polyethylene glycol (PEG) hydrogel, gently restricting movement within their confined spaces. Immobilized animals maintained a normal, uncompressed morphology in a hydrated environment and could be exposed to different aqueous chemicals. We focus in particular on the nematodeC. elegans, an organism that is typically viewed with paralyzing reagents, nanobeads, adhesives, or microfluidic traps. The hydrogel is optically clear, non-autofluorescent, and nearly index-matched with water for use with light-sheet microscopy. We captured volumetric images of optogenetically-stimulated responses in multiple sensory neurons over 14 hours using a diSPIM light-sheet microscope, and immobilized worms were recoverable and viable after 24 hours encapsulation. We further imaged living pygmy squid hatchlings to demonstrate size scalability, characterized immobilization quality for various crosslinking parameters and identified paralytic-free conditions suitable for high-resolution single cell imaging. PEG hydrogel encapsulation enables continuous observation for hours of small living organisms, from yeast to zebrafish, and is compatible with multiple microscope mounting geometries.
Low cost and open source multi-fluorescence imaging system for teaching and research in biology and bioengineering
Authors: Isaac Nuñez , Tamara Matute , Roberto Herrera , Juan Keymer , Tim Marzullo , Tim Rudge , Fernán Federici 
Published: September 2017

AbstractThe advent of easy-to-use open source microcontrollers, off-the-shelf electronics and customizable manufacturing technologies has facilitated the development of inexpensive scientific devices and laboratory equipment. In this study, we describe an imaging system that integrates low-cost and open-source hardware, software and genetic resources. The multi-fluorescence imaging system consists of readily available 470 nm LEDs, a Raspberry Pi camera and a set of filters made with low cost acrylics. This device allows imaging in scales ranging from single colonies to entire plates. We developed a set of genetic components (e.g. promoters, coding sequences, terminators) and vectors following the standard framework of Golden Gate, which allowed the fabrication of genetic constructs in a combinatorial, low cost and robust manner. In order to provide simultaneous imaging of multiple wavelength signals, we screened a series of long stokes shift fluorescent proteins that could be combined with cyan/green fluorescent proteins. We found CyOFP1, mBeRFP and sfGFP to be the most compatible set for 3-channel fluorescent imaging. We developed open source Python code to operate the hardware to run time-lapse experiments with automated control of illumination and camera and a Python module to analyze data and extract meaningful biological information. To demonstrate the potential application of this integral system, we tested its performance on a diverse range of imaging assays often used in disciplines such as microbial ecology, microbiology and synthetic biology. We also assessed its potential for STEM teaching in a high school environment, using it to teach biology, hardware design, optics, and programming. Together, these results demonstrate the successful integration of open source hardware, software, genetic resources and customizable manufacturing to obtain a powerful, low cost and robust system for STEM education, scientific research and bioengineering. All the resources developed here are available under open source licenses.
Arabidopsis phenotyping through Geometric Morphometrics
Authors: Manacorda Carlos A. , Asurmendi Sebastian 
Published: September 2017

AbstractIn recent years, much technical progress has been done regarding plant phenotyping including the model speciesArabidopsis thaliana. With automated, high-throughput platforms and the development of improved algorithms for the rosette segmentation task, it is now possible to massively extract reliable shape and size parameters for genetic, physiological and environmental studies. The development of low-cost phenotyping platforms and freeware resources make it possible to widely expand phenotypic analysis tools for Arabidopsis. However, objective descriptors of shape parameters that could be used independently of platform and segmentation software used are still lacking and shape descriptions still rely onad hocor even sometimes contradictory descriptors, which could make comparisons difficult and perhaps inaccurate. Modern geometric morphometrics is a family of methods in quantitative biology proposed to be the main source of data and analytical tools in the emerging field of phenomics studies. It has been used for taxonomists and paleontologists for decades and is now a mature discipline. By combining geometry, multivariate analysis and powerful statistical techniques, it offers the possibility to reproducibly and accurately account for shape variations amongst groups. Based on the location of homologous landmarks points over photographed or scanned specimens, these tools could identify the existence and degree of shape variation and measure them in standard units. Here, it is proposed a particular scheme of landmarks placement on Arabidopsis rosette images to study shape variation in the case study of viral infection processes. Several freeware-based geometric morphometric tools are applied in order to exemplify the usefulness of this approach to the study of phenotypes in this model plant. These methods are concisely presented and explained. Shape differences between controls and infected plants are quantified throughout the infectious process and visualized with the appealing graphs that are a hallmark of these techniques and render complex mathematical analysis simple outcomes to interpret. Quantitative comparisons between two unrelated ssRNA+ viruses are shown and reproducibility issues are assessed. Combined with the newest automatons and plant segmentation procedures, geometric morphometric tools could boost phenotypic features extraction and processing in an objective, reproducible manner.