bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient acceptability and satisfaction with a low-dose solubilized vaginal estradiol softgel capsule, TX-004HR
Authors: Kingsberg Sheryl A. , Kroll Robin , Goldstein Irwin , Kushner Harvey , Bernick Brian , Graham Shelli , Mirkin Sebastian , Constantine Ginger D. 
Published: February 2017

Abstract

Objective:
TX-004HR is an investigational, muco-adhesive, vaginal, softgel capsule containing low-dose, solubilized, 17β-estradiol designed to treat postmenopausal vulvar and vaginal atrophy (VVA) and improve user experience without an applicator and less mess.

Methods:
As part of the 12-week, placebo-controlled, double-blind, phase 3 REJOICE trial evaluating the efficacy/safety of 4-, 10-, and 25-μg TX-004HR in 764 postmenopausal women with VVA, a five-question product survey was administered. Pearson correlation coefficients were used to evaluate correlations between clinical endpoints (vaginal physiology, dyspareunia, and vaginal dryness) and patient acceptability and satisfaction.

Results:
Majority of the women receiving TX-004HR or placebo reported that the product was easy to use (85.4%-92.1%) and rated ease of capsule insertion as “good” to “excellent” (75.0%-82.6%). A significantly greater percentage of women reported being “very satisfied” or “satisfied” with TX-004HR (68.6%-76.3%) than with placebo (56.8%, P < 0.05 for all). A greater percentage of women “somewhat” or “very much” preferred TX-004HR over their previous treatment versus those taking placebo (P < 0.05). Significantly more women receiving TX-004HR (72.8%-80.5%) versus placebo (62.5%, P < 0.05) would “probably” or “definitely” consider using the product again. Dyspareunia and vaginal dryness reductions were correlated with higher product satisfaction and the percentage of women who would consider re-using TX-004HR.

Conclusions:
TX-004HR had a high level of product acceptability, and more women were satisfied with TX-004HR, preferred it over their previous treatment, and would consider using it again versus placebo. Women may find TX-004HR to be a more acceptable product than current options to treat their dyspareunia associated with postmenopausal VVA.
Resolution of Primary Lymphedema: A Case Report
Authors: Goss Jeremy A. , Maclellan Reid A. , Beijnen Usha E. A. , Greene Arin K. 
Published: February 2017

Summary:
Primary lymphedema is a rare, progressive disease that typically affects the lower extremity. The condition is not curable, and the limb enlarges over time because of subcutaneous fibroadipose deposition. We present a patient with clinical and radiographical evidence of resolution of primary lymphedema. This observation may provide greater insight into the pathophysiology of the disease.
Pharmacoepidemiologic analyses of opioid use among OEF/OIF/OND veterans
Authors: Hudson Teresa J. , Painter Jacob T. , Martin Bradley C. , Austen Mark A. , Williams James S. , Fortney John C. , Sullivan Mark D. , Edlund Mark J. 
Published: February 2017

Abstract
There is a great deal of concern about opioid use in veterans, particularly those who served in Afghanistan (OEF) and Iraq (OIF and OND). The current study provides a detailed pharmacoepidemiologic analysis of opioid use among OEF/OIF/OND veterans from FY09 to FY12. Data from 3 data repositories from the Veterans Health Administration (VHA) were used to describe demographic, clinical, and medication characteristics associated with opioid use among OEF/OIF/OND veterans and among those with TBI. Logistic regression models were used to identify risks associated with chronic opioid use in FY12. Approximately 23% of all OEF/OIF/OND veterans and 35% of those with TBI received any opioid medications. Most received moderate doses ranging from 26 to 30 mg morphine equivalent dose daily. Median days of opioid use for all OEF/OIF/OND veterans were 30 to 40 days. Factors associated with chronic use in both groups included young age, male sex, white race, being married, and living in rural areas. A diagnosis of PTSD (odds ratio [OR] = 1.22, P < 0.0001), major depressive disorder (OR = 1.14, P < 0.0001), and tobacco use disorder (OR = 1.18, P < 0.0001) were strongly associated with chronic opioid use. Back pain was also strongly associated with chronic use (OR = 2.50, P < 0.0001). As pain severity increased the odds of chronic opioid use also increased: mild pain (OR = 3.76, P < 0.0001), moderate pain (OR = 6.80, P < 0.0001), and severe pain (OR = 8.49, P < 0.0001). Opioid use among OEF/OIF/OND veterans is characterized by moderate doses that are used over relatively long periods of time by a minority of veterans.
Treatment Duration With Long-Acting Injectable Antipsychotics After In-hospital Initiation
Authors: Rittmannsberger Hans , Rosenleitner Jan , Malsiner-Walli Gertraud , Werl Regina , Rittmannsberger Barbara , Yazdi Kurosch 
Published: February 2017

Abstract

Purpose
Long-acting injectable (LAI) antipsychotics are recommended especially for patients with multiple admissions and poor adherence. The empirical basis of this strategy is a matter of debate.

Methods
In a retrospective cohort study extending over 6 years, all patients admitted for inpatient treatment with a diagnosis of psychotic disorders according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision (F2) were screened for treatment episodes with a new start of an LAI. Indication for LAI treatment was based primarily on previous medication default. All-cause discontinuation was used as a measure of treatment efficiency. Patients with early dropout (termination of LAI treatment within 6 months) were compared with patients with longer treatment (treatment >6 months) for sociodemographic and treatment variables using bivariate and multivariate analyses.

Results
A total of 194 treatment episodes with new start of LAIs were identified. Almost one half dropped out within 6 months (early dropout: n = 95 [49%]; mean duration, 2.2 months). Termination of treatment was mainly due to patients’ refusal to continue. However, almost a third of patients (61; 31.4%) had a treatment duration of more than 2 years. In a multivariate Cox regression model, longer treatment duration was associated with older age (P = 0.05), not being single (P = 0.04), fewer admissions during the year preceding the index episode (P = 0.02), and better ratings for adherence at the index episode (P = 0.03).

Conclusions
There are both more patients than expected leaving the treatment early and more patients than expected staying for long periods, even among patients with a history of poor adherence.
NIACE score for hepatocellular carcinoma patients treated by surgery or transarterial chemoembolization
Authors: Adhoute Xavier , Pénaranda Guillaume , Raoul Jean Luc , Bollon Emilie , Pol Bernard , Letreut Yves P. , Perrier Hervé , Bayle Olivier , Monnet Olivier , Beaurain Patrick , Muller Cyril , Hardwigsen Jean , Lefolgoc Gaëlle , Castellani Paul , Bronowicki Jean P. , Bourlière Marc 
Published: February 2017

Background and aims
Hepatocellular carcinoma (HCC) prognostic scores could be useful in addition to the Barcelona Clinic Liver Cancer (BCLC) system to clarify patient prognosis and guide treatment decision. The NIACE (tumor Nodularity, Infiltrative nature of the tumor, serum Alpha-fetoprotein level, Child–Pugh stage, ECOG performance status) score distinguishes different prognosis groups among BCLC A, B, and C HCC patients. Our aims are to evaluate the NIACE score and its additive value in two HCC cohorts treated either by surgery or by chemoembolization, and then according to the BCLC recommendations.

Patients and methods
This was a retrospective multicenter study with two BCLC A, B, and C HCC cohorts treated either by surgery (n=207) or by chemoembolization (n=168) carried out between 2008 and 2013. We studied survival time according to the baseline NIACE score and compared it with the Cancer of the Liver Italian Program score and the BCLC system.

Results
The NIACE score differentiates between subgroups of patients with different prognosis within each BCLC class. Among BCLC A patients treated by surgery and BCLC B patients treated by chemoembolization, the NIACE score differentiates between two subgroups with a significant difference in survival time: 68 (55–81) months versus 35 (21–56) months (P=0.0004) and 20 (17–24) months versus 13 (7–17) months (P=0.0008), respectively. Among those subgroups, the NIACE score has a significantly better prognostic value than the BCLC system or the Cancer of the Liver Italian Program score.

Conclusion
In this study, among HCC patients treated according to the BCLC recommendations, the NIACE score predicts more accurately than any other system the survival time.
Development and validation of a prognostic model for acute-on-chronic hepatitis B liver failure
Authors: Gao Fangyuan , Sun Le , Ye Xieqiong , Liu Yao , Liu Huimin , Geng Mingfan , Li Xiaoshu , Yang Xue , Li Yuxin , Wang Rui , Chen Jialiang , Wan Gang , Jiang Yuyong , Wang Xianbo 
Published: February 2017

Aim
The CANONIC study proposed the Chronic Liver Failure Consortium acute-on-chronic liver failure (CLIF-C ACLF) prognostic model at the European Association for the Study of the Liver-CLIF diagnosis. This study aimed to develop and validate a prognostic model for predicting the short-term mortality of hepatitis B virus (HBV) ACLF as defined by the Asia-Pacific Association for the Study of the Liver.

Patients and methods
A retrospective cohort of 381 HBV ACLF patients and a prospective cohort of 192 patients were included in this study. Independent predictors of disease progression were determined using univariate and multivariate Cox proportional hazard regression analysis, and a regression model for predicting prognosis was established. Patient survival was estimated by Kaplan–Meier analysis and subsequently compared by log-rank tests. The area under the receiver operating characteristic curve was used to compare the performance of various current prognostic models.

Results
Our model was constructed with five independent risk factors: hepatic encephalopathy, international normalized ratio, neutrophil–lymphocyte ratio, age, and total bilirubin, termed as the HINAT ACLF model, which showed the strongest predictive values compared with CLIF-C ACLF, CLIF-C Organ Failure, Sequential Organ Failure Assessment, CLIF-Sequential Organ Failure Assessment, Model for End-stage Liver Disease, Model for End-stage Liver Disease-sodium, and Child–Turcotte–Pugh scores; this model reduced the corresponding prediction error rates at 28 and 90 days by 16.4–54.5% after ACLF diagnosis in both the derivation cohort and the validation cohorts.

Conclusion
The HINAT ACLF model can accurately predict the short-term mortality of patients with HBV ACLF as defined by Asia-Pacific Association for the Study of the Liver.
TRIAD VIII: Nationwide Multicenter Evaluation to Determine Whether Patient Video Testimonials Can Safely Help Ensure Appropriate Critical Versus End-of-Life Care
Authors: Mirarchi Ferdinando L. , Cooney Timothy E. , Venkat Arvind , Wang David , Pope Thaddeus M. , Fant Abra L. , Terman Stanley A. , Klauer Kevin M. , Williams-Murphy Monica , Gisondi Michael A. , Clemency Brian , Doshi Ankur A. , Siegel Mari , Kraemer Mary S. , Aberger Kate , Harman Stephanie , Ahuja Neera , Carlson Jestin N. , Milliron Melody L. , Hart Kristopher K. , Gilbertson Chelsey D. , Wilson Jason W. , Mueller Larissa , Brown Lori , Gordon Bradley D. 
Published: February 2017

Objective
End-of-life interventions should be predicated on consensus understanding of patient wishes. Written documents are not always understood; adding a video testimonial/message (VM) might improve clarity. Goals of this study were to (1) determine baseline rates of consensus in assigning code status and resuscitation decisions in critically ill scenarios and (2) determine whether adding a VM increases consensus.

Methods
We randomly assigned 2 web-based survey links to 1366 faculty and resident physicians at institutions with graduate medical education programs in emergency medicine, family practice, and internal medicine. Each survey asked for code status interpretation of stand-alone Physician Orders for Life-Sustaining Treatment (POLST) and living will (LW) documents in 9 scenarios. Respondents assigned code status and resuscitation decisions to each scenario. For 1 of 2 surveys, a VM was included to help clarify patient wishes.

Results
Response rate was 54%, and most were male emergency physicians who lacked formal advanced planning document interpretation training. Consensus was not achievable for stand-alone POLST or LW documents (68%–78% noted “DNR”). Two of 9 scenarios attained consensus for code status (97%–98% responses) and treatment decisions (96%–99%). Adding a VM significantly changed code status responses by 9% to 62% (P ≤ 0.026) in 7 of 9 scenarios with 4 achieving consensus. Resuscitation responses changed by 7% to 57% (P ≤ 0.005) with 4 of 9 achieving consensus with VMs.

Conclusions
For most scenarios, consensus was not attained for code status and resuscitation decisions with stand-alone LW and POLST documents. Adding VMs produced significant impacts toward achieving interpretive consensus.
Subtle changes in the landmark panorama disrupt visual navigation in a nocturnal bull ant
Authors: Narendra Ajay , Ramirez-Esquivel Fiorella 
Published: February 2017

The ability of ants to navigate when the visual landmark information is altered has often been tested by creating large and artificial discrepancies in their visual environment. Here, we had an opportunity to slightly modify the natural visual environment around the nest of the nocturnal bull antMyrmecia pyriformis. We achieved this by felling three dead trees, two located along the typical route followed by the foragers of that particular nest and one in a direction perpendicular to their foraging direction. An image difference analysis showed that the change in the overall panorama following the removal of these trees was relatively little. We filmed the behaviour of ants close to the nest and tracked their entire paths, both before and after the trees were removed. We found that immediately after the trees were removed, ants walked slower and were less directed. Their foraging success decreased and they looked around more, including turning back to look towards the nest. We document how their behaviour changed over subsequent nights and discuss how the ants may detect and respond to a modified visual environment in the evening twilight period.This article is part of the themed issue ‘Vision in dim light’.
Ontogenetic adaptations in the visual systems of deep-sea crustaceans
Authors: Frank Tamara M. 
Published: February 2017

For all visually competent organisms, the driving force behind the adaptation of photoreceptors involves obtaining the best balance of resolution to sensitivity in the prevailing light regime, as an increase in sensitivity often results in a decrease in resolution. A number of marine species have an additional problem to deal with, in that the juvenile stages live in relatively brightly lit shallow (100–200 m depth) waters, whereas the adult stages have daytime depths of more than 600 m, where little downwelling light remains. Here, I present the results of electrophysiological analyses of the temporal resolution and irradiance sensitivity of juvenile and adult stages of two species of ontogenetically migrating crustaceans (Gnathophausia ingensandSystellaspis debilis) that must deal with dramatically different light environments and temperatures during their life histories. The results demonstrate that there are significant effects of temperature on temporal resolution, which help to optimize the visual systems of the two life-history stages for their respective light environments.This article is part of the themed issue ‘Vision in dim light’.
Behavioural and physiological limits to vision in mammals
Authors: Field Greg D. , Sampath Alapakkam P. 
Published: February 2017

Human vision is exquisitely sensitive—a dark-adapted observer is capable of reliably detecting the absorption of a few quanta of light. Such sensitivity requires that the sensory receptors of the retina, rod photoreceptors, generate a reliable signal when single photons are absorbed. In addition, the retina must be able to extract this information and relay it to higher visual centres under conditions where very few rods signal single-photon responses while the majority generate only noise. Critical to signal transmission are mechanistic optimizations within rods and their dedicated retinal circuits that enhance the discriminability of single-photon responses by mitigating photoreceptor and synaptic noise. We describe behavioural experiments over the past century that have led to the appreciation of high sensitivity near absolute visual threshold. We further consider mechanisms within rod photoreceptors and dedicated rod circuits that act to extract single-photon responses from cellular noise. We highlight how these studies have shaped our understanding of brain function and point out several unresolved questions in the processing of light near the visual threshold.This article is part of the themed issue ‘Vision in dim light’.
Processing of single-photon responses in the mammalian On and Off retinal pathways at the sensitivity limit of vision
Authors: Takeshita Daisuke , Smeds Lina , Ala-Laurila Petri 
Published: February 2017

Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods. The On pathway provides the brain with a thresholded, low-noise readout and the Off pathway with a noisy, linear readout. We outline the mechanistic basis of these different coding strategies and analyse their implications for detecting the weakest light signals. We show that high-fidelity, nonlinear signal processing in the On pathway comes with costs: more single-photon responses are lost and their propagation is delayed compared with the Off pathway. On the other hand, the responses of On ganglion cells allow better intensity discrimination compared with the Off ganglion cell responses near visual threshold.This article is part of the themed issue ‘Vision in dim light’.
Insect photoreceptor adaptations to night vision
Authors: Honkanen Anna , Immonen Esa-Ville , Salmela Iikka , Heimonen Kyösti , Weckström Matti 
Published: February 2017

Night vision is ultimately about extracting information from a noisy visual input. Several species of nocturnal insects exhibit complex visually guided behaviour in conditions where most animals are practically blind. The compound eyes of nocturnal insects produce strong responses to single photons and process them into meaningful neural signals, which are amplified by specialized neuroanatomical structures. While a lot is known about the light responses and the anatomical structures that promote pooling of responses to increase sensitivity, there is still a dearth of knowledge on the physiology of night vision. Retinal photoreceptors form the first bottleneck for the transfer of visual information. In this review, we cover the basics of what is known about physiological adaptations of insect photoreceptors for low-light vision. We will also discuss major enigmas of some of the functional properties of nocturnal photoreceptors, and describe recent advances in methodologies that may help to solve them and broaden the field of insect vision research to new model animals.This article is part of the themed issue ‘Vision in dim light’.
Plaques formed by mutagenized viral populations have elevated co-infection frequencies
Authors: Aguilera Elizabeth R. , Erickson Andrea K. , Jesudhasan Palmy R. , Robinson Christopher M. , Pfeiffer Julie K. 
Published: February 2017

ABSTRACTThe plaque assay is a common technique used to measure virus concentrations and is based upon the principle that each plaque represents a single infectious unit. As such, plaque number is expected to correlate linearly with the virus dilution plated and each plaque should be formed by a single founder virus. Here, we examined whether more than one virus can contribute to plaque formation. By using genetic and phenotypic assays with genetically marked polioviruses, we found that multiple parental viruses are present in 5-7% of plaques, even at an extremely low multiplicity of infection. We demonstrated through visual and biophysical assays that, like many viral stocks, our viral stocks contain both single particles and aggregates. These data suggest that aggregated virions are capable of inducing co-infection and chimeric plaque formation. In fact, inducing virion aggregation via exposure to low pH increased co-infection in a flow cytometry-based assay. We hypothesized that plaques generated by viruses with high mutation loads may have higher co-infection frequencies due to fitness restoring processes such as complementation and recombination. Indeed, we found that co-infection frequency correlated with mutation load, with 17% chimeric plaque formation for heavily mutagenized viruses. Importantly, the frequency of chimeric plaques may be underestimated by up to three-fold, since co-infection with the same parental virus cannot be scored in our assay. This work indicates that more than one virus can contribute to plaque formation and that co-infection may assist plaque formation in situations where the amount of genome damage is high.
Integrative cross tissue analysis of gene expression identifies novel type 2 diabetes genes
Authors: Torres Jason M. , Barbeira Alvaro N. , Bonazzola Rodrigo , Morris Andrew P. , Shah Kaanan P. , Wheeler Heather E. , Bell Graeme I. , Cox Nancy J. , Im Hae Kyung 
Published: February 2017

AbstractTo understand the mechanistic underpinnings of type 2 diabetes (T2D) loci mapped through GWAS, we performed a tissue-specific gene association study in a cohort of over 100K individuals (ncases≈ 26K,ncontrols≈ 84K) across 44 human tissues using MetaXcan, a summary statistics extension of PrediXcan. We found that 90 genes significantly (FDR < 0.05) associated with T2D, of which 24 are previously reported T2D genes, 29 are novel in established T2D loci, and 37 are novel genes in novel loci. Of these, 13 reported genes, 15 novel genes in known loci, and 6 genes in novel loci replicated (FDRrep< 0.05) in an independent study (ncases≈ 10K,ncontrols≈ 62K). We also found enrichment of significant associations in expected tissues such as liver, pancreas, adipose, and muscle but also in tibial nerve, fibroblasts, and breast. Finally, we found that monogenic diabetes genes are enriched in T2D genes from our analysis suggesting that moderate alterations in monogenic (severe) diabetes genes may promote milder and later onset type 2 diabetes.