bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition
Authors: Ding Xiaohui , Zhang Xiujuan , Chong Huihui , Zhu Yuanmei , Wei Huamian , Wu Xiyuan , He Jinsheng , Wang Xinquan , He Yuxian 
Published: June 2017

ABSTRACT

The peptide drug enfuvirtide (T20) is the only viral fusion inhibitor used in combination therapy for HIV-1 infection, but it has relatively low antiviral activity and easily induces drug resistance. Emerging studies demonstrate that lipopeptide-based fusion inhibitors, such as LP-11 and LP-19, which mainly target the gp41 pocket site, have greatly improved antiviral potency and
in vivo
stability. In this study, we focused on developing a T20-based lipopeptide inhibitor that lacks pocket-binding sequence and targets a different site. First, the C-terminal tryptophan-rich motif (TRM) of T20 was verified to be essential for its target binding and inhibition; then, a novel lipopeptide, termed LP-40, was created by replacing the TRM with a fatty acid group. LP-40 showed markedly enhanced binding affinity for the target site and dramatically increased inhibitory activity on HIV-1 membrane fusion, entry, and infection. Unlike LP-11 and LP-19, which required a flexible linker between the peptide sequence and the lipid moiety, addition of a linker to LP-40 sharply reduced its potency, implying different binding modes with the extended N-terminal helices of gp41. Also, interestingly, LP-40 showed more potent activity than LP-11 in inhibiting HIV-1 Env-mediated cell-cell fusion while it was less active than LP-11 in inhibiting pseudovirus entry, and the two inhibitors displayed synergistic antiviral effects. The crystal structure of LP-40 in complex with a target peptide revealed their key binding residues and motifs. Combined, our studies have not only provided a potent HIV-1 fusion inhibitor, but also revealed new insights into the mechanisms of viral inhibition.

IMPORTANCE
T20 is the only membrane fusion inhibitor available for treatment of viral infection; however, T20 requires high doses and has a low genetic barrier for resistance, and its inhibitory mechanism and structural basis remain unclear. Here, we report the design of LP-40, a T20-based lipopeptide inhibitor that has greatly improved anti-HIV activity and is a more potent inhibitor of cell-cell fusion than of cell-free virus infection. The binding modes of two classes of membrane-anchoring lipopeptides (LP-40 and LP-11) verify the current fusion model in which an extended prehairpin structure bridges the viral and cellular membranes, and their complementary effects suggest a vital strategy for combination therapy of HIV-1 infection. Moreover, our understanding of the mechanism of action of T20 and its derivatives benefits from the crystal structure of LP-40.
Case-Control Comparison of Enteric Viromes in Captive Rhesus Macaques with Acute or Idiopathic Chronic Diarrhea
Authors: Kapusinszky Beatrix , Ardeshir Amir , Mulvaney Usha , Deng Xutao , Delwart Eric 
Published: June 2017

ABSTRACT

Diarrhea is the major cause of non-research-associated morbidity and mortality affecting the supply of rhesus macaques and, potentially, their responses to experimental treatments. Idiopathic chronic diarrhea (ICD) in rhesus macaques also resembles ulcerative colitis, one form of human inflammatory bowel disease. To test for viral etiologies, we characterized and compared the fecal viromes from 32 healthy animals, 31 animals with acute diarrhea, and 29 animals with ICD. The overall fractions of eukaryotic viral reads were 0.063% for the healthy group, 0.131% for the acute-diarrhea group, and 0.297% for the chronic-diarrhea group. Eukaryotic viruses belonging to 6 viral families, as well as numerous circular Rep-encoding single-stranded DNA (CRESS DNA) viral genomes, were identified. The most commonly detected sequences were from picornaviruses, making up 59 to 88% of all viral reads, followed by 9 to 17% for CRESS DNA virus sequences. The remaining 5 virus families,
Adenoviridae
,
Astroviridae
,
Anelloviridae
,
Picobirnaviridae
, and
Parvoviridae
, collectively made up 1 to 3% of the viral reads, except for parvoviruses, which made up 23% of the viral reads in the healthy group. Detected members of the families
Picornaviridae
and
Parvoviridae
were highly diverse, consisting of multiple genera, species, and genotypes. Coinfections with members of up to six viral families were detected. Complete and partial viral genomes were assembled and used to measure the number of matching short sequence reads in feces from the 92 animals in the two clinical and the healthy control groups. Several enterovirus genotypes and CRESS DNA genomes were associated with ICD relative to healthy animals. Conversely, higher read numbers from different parvoviruses were associated with healthy animals. Our study reveals a high level of enteric coinfections with diverse viruses in a captive rhesus macaque colony and identifies several viruses positively or negatively associated with ICD.
Can an FDA-Approved Alzheimer’s Drug Be Repurposed for Alleviating Neuronal Symptoms of Zika Virus?
Authors: Sirohi Devika , Kuhn Richard J. 
Published: June 2017

ABSTRACT

Zika virus caught the world by surprise by its rapid spread and frightening disease outcomes. This major epidemic motivated many scientists to focus their attention on controlling this emerging pathogen. As many as 45 vaccine candidates are being developed, but progress in the antiviral arena has been slower. In a recent article (mBio 8:e00350-17, 2017,
https://doi.org/10.1128/mBio.00350-17
), Costa and colleagues showed that an FDA-approved drug used to treat Alzheimer’s disease may moderate Zika virus-induced neuronal damage. This work is based on the premise that overstimulation of
N
-methyl-
d
-aspartate receptors (NMDARs) may drive neurodegeneration and that this may be responsible for neuronal cell death associated with Zika virus infection of the central nervous system (CNS). Thus, blockage of the NMDAR channel activity with FDA-approved memantine or other antagonists may reduce neurological complications associated with Zika virus infection. Repurposing a preapproved drug and targeting the host represent intriguing strategies and yet require more analysis prior to moving into clinical trials.
Physiological and Molecular Understanding of Bacterial Polysaccharide Monooxygenases
Authors: Agostoni Marco , Hangasky John A. , Marletta Michael A. 
Published: June 2017

SUMMARYBacteria have long been known to secrete enzymes that degrade cellulose and chitin. The degradation of these two polymers predominantly involves two enzyme families that work synergistically with one another: glycoside hydrolases (GHs) and polysaccharide monooxygenases (PMOs). Although bacterial PMOs are a relatively recent addition to the known biopolymer degradation machinery, there is an extensive amount of literature implicating PMO in numerous physiological roles. This review focuses on these diverse and physiological aspects of bacterial PMOs, including facilitating endosymbiosis, conferring a nutritional advantage, and enhancing virulence in pathogenic organisms. We also discuss the correlation between the presence of PMOs and bacterial lifestyle and speculate on the advantages conferred by PMOs under these conditions. In addition, the molecular aspects of bacterial PMOs, as well as the mechanisms regulating PMO expression and the function of additional domains associated with PMOs, are described. We anticipate that increasing research efforts in this field will continue to expand our understanding of the molecular and physiological roles of bacterial PMOs.
Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer
Authors: Bang Yung-Jue , Cho Jae Yong , Kim Yeul Hong , Kim Jin Won , Di Bartolomeo Maria , Ajani Jaffer A. , Yamaguchi Kensei , Balogh Agnes , Sanchez Teresa , Moehler Markus 
Published: June 2017

Abstract
Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte–associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.
Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS).
Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61–5.16 vs. 4.90 months, 95% CI, 3.45–6.54, HR = 1.44; 80% CI, 1.09–1.91; P = 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5–18.9) and 12.1 months (95% CI, 9.3–not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients.
Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer. Clin Cancer Res; 23(19); 5671–8. ©2017 AACR.
Health Insurance Expansion and Incidence of Out‐of‐Hospital Cardiac Arrest: A Pilot Study in a US Metropolitan Community
Authors: Stecker Eric C. , Reinier Kyndaron , Rusinaru Carmen , Uy‐Evanado Audrey , Jui Jon , Chugh Sumeet S. 
Published: June 2017

Background
Health insurance has many benefits including improved financial security, greater access to preventive care, and better self‐perceived health. However, the influence of health insurance on major health outcomes is unclear. Sudden cardiac arrest prevention represents one of the major potential benefits from health insurance, given the large impact of sudden cardiac arrest on premature death and its potential sensitivity to preventive care.

Methods and Results

We conducted a pre–post study with control group examining out‐of‐hospital cardiac arrest (
OHCA
) among adult residents of Multnomah County, Oregon (2015 adult population 636 000). Two time periods surrounding implementation of the Affordable Care Act were evaluated: 2011–2012 (“pre‐expansion”) and 2014–2015 (“postexpansion”). The change in
OHCA
incidence for the middle‐aged population (45–64 years old) exposed to insurance expansion was compared with the elderly population (age ≥65 years old) with constant near‐universal coverage. Rates of
OHCA
among middle‐aged individuals decreased from 102 per 100 000 (95%
CI
: 92–113 per 100 000) to 85 per 100 000 (95%
CI
: 76–94 per 100 000),
P
value 0.01. The elderly population experienced no change in
OHCA
incidence, with rates of 275 per 100 000 (95%
CI
: 250–300 per 100 000) and 269 per 100 000 (95%
CI
: 245–292 per 100 000),
P
value 0.70.

Conclusions

Health insurance expansion was associated with a significant reduction in
OHCA
incidence. Based on this pilot study, further investigation in larger populations is warranted and feasible.
Toward a New Estimate of “Time of Emergence” of Anthropogenic Warming: Insights from Dynamical Adjustment and a Large Initial-Condition Model Ensemble
Authors: Lehner Flavio , Deser Clara , Terray Laurent 
Published: June 2017

Abstract
Time of emergence of anthropogenic climate change is a crucial metric in risk assessments surrounding future climate predictions. However, internal climate variability impairs the ability to make accurate statements about when climate change emerges from a background reference state. None of the existing efforts to explore uncertainties in time of emergence has explicitly explored the role of internal atmospheric circulation variability. Here a dynamical adjustment method based on constructed circulation analogs is used to provide new estimates of time of emergence of anthropogenic warming over North America and Europe from both a local and spatially aggregated perspective. After removing the effects of internal atmospheric circulation variability, the emergence of anthropogenic warming occurs on average two decades earlier in winter and one decade earlier in summer over North America and Europe. Dynamical adjustment increases the percentage of land area over which warming has emerged by about 30% and 15% in winter (10% and 5% in summer) over North America and Europe, respectively. Using a large ensemble of simulations with a climate model, evidence is provided that thermodynamic factors related to variations in snow cover, sea ice, and soil moisture are important drivers of the remaining uncertainty in time of emergence. Model biases in variability lead to an underestimation (13%–22% over North America and &lt;5% over Europe) of the land fraction emerged by 2010 in summer, indicating that the forced warming signal emerges earlier in observations than suggested by models. The results herein illustrate opportunities for future detection and attribution studies to improve physical understanding by explicitly accounting for internal atmospheric circulation variability.
Memantine improves semantic memory in patients with amnestic mild cognitive impairment: A single-photon emission computed tomography study
Authors: Ilhan Algin Demet , Dagli Atalay Suna , Ozkan Serhat , Ozbabalik Adapinar Demet , Ak Sivrioz Ilknur 
Published: June 2017

Objective This study was performed to assess the efficacy of memantine in patients with amnestic mild cognitive impairment (aMCI). Methods Thirty healthy controls and 45 patients diagnosed with aMCI based on the Petersen criteria were classified into 3 groups. Group 1 comprised patients who received a single memantine dose following examination (n = 25), Group 2 comprised patients who did not receive memantine treatment following examination (n = 20), and Group 3 comprised healthy age-matched volunteers (n = 30). Neuropsychological testing was performed, and the response to memantine was examined at baseline and at 12, 24, and 48 weeks. Single-photon emission computed tomography was performed at baseline and at 48 weeks in patients who received memantine treatment. Results Memantine treatment significantly improved the symptoms of aMCI according to the Wechsler Adult Intelligence Scale-Revised vocabulary subtest, backward digit span, and Blessed Dementia Rating Scale, all of which were recorded for the duration of the study. Conclusion These data indicate that patients with aMCI receiving memantine develop an improved semantic memory compared with no treatment. Further studies including larger patient cohorts are necessary to validate these findings.
Minimally invasive treatment of unstable pelvic ring injuries with modified pedicle screw–rod fixator
Authors: Wu Xiao-Tian , Liu Zuo-Qing , Fu Wen-Qin , Zhao Shan 
Published: June 2017

Objective To evaluate the clinical application of the minimally invasive modified pedicle screw–rod fixator for unstable pelvic ring injuries, including its feasibility, merits, and limitations. Methods Twenty-three patients (13 males, 10 females; average age, 36.3 years) with unstable pelvic ring injuries underwent anterior fixation using a modified pedicle screw–rod fixator with or without posterior fixation using a transiliac internal fixator. The clinical findings were assessed using Majeed scores. The quality of reduction was evaluated using the Matta criteria. Results Clinical results at 1 year postoperatively were excellent in 14 patients, good in 7, and fair in 2. The two patients with fair results had intermittent pain at the sacroiliac joint because of the posterior implant. One woman complained of persistent pain at the pubic tubercle during sexual intercourse. Iatrogenic neuropraxia of the unilateral lateral femoral cutaneous nerve occurred in three patients. Unilateral femoral nerve palsy occurred in one patient. The quality of fracture reduction was excellent in 12 patients, good in 8, and fair in 3. Heterotopic ossification occurred in eight patients; all were asymptomatic. Conclusions Minimally invasive modified pedicle screw-rod fixation is an effective alternative treatment for pelvic ring injuries.
Effect of team training on efficiency of trauma care in a Chinese hospital
Authors: Hong Yucai , Cai Xiujun 
Published: June 2017

Objective Multidisciplinary trauma teams are the standard of care in the USA, but staffing differences and lack of advanced trauma life support training hinder replication of this system in Chinese hospitals. We investigated the effect of simulation team training on initial trauma care. Methods Over 15 months, we compared grade I trauma patients cared for by the trained team and those cared for using traditional practice on times from emergency room arrival to tests/procedures. Propensity-score analysis was performed to improve between-group comparisons. Results During the study, 144 grade I trauma patients were treated. Trained team patients showed shorter times from emergency room arrival to initiation of hemostasis (31.0 [13.5–58.5] vs. 113.5 [77–150.50] min), blood routine report (8 [5–10.25] vs. 13 [10–21] min), other blood tests (21 [14.75–25.75] vs. 31 [25–37] min), computed tomography scan (29.5 [20.25–65] vs. 58.5 [30.25–71.25] min) and tranexamic acid administration (31 [13–65] vs. 90 [65–200] min). Similar results were obtained for the propensity-score matched cohort. Conclusion Simulation team training could help reduce time to blood routine reports, scans and hemostasis. Assessment of available resources and development of targeted team training could improve care in resource-limited hospitals.
Augmentation Mammaplasty with Saline-Filled Textured Implants: Review of 9 Years' Experience and Results of Patient Survey
Authors: Haiavy Jacob , Tobin Howard A. 
Published: June 2017

Introduction: In June of 2000 the FDA approved saline-filled breast implants as safe prosthetic devices based on results of clinical testing presented by the manufacturers. The corresponding author has been using saline-filled implants since 1992. It was decided to review his experience and assess the incidence of postoperative complications as reported by the patients and to identify factors related to their satisfaction. Materials and Methods: A survey was mailed out to a cohort of 460 patients. The survey included questions pertaining to possible postoperative complications and the patient's overall satisfaction. Overall, 207 surveys were returned after 2 mailings. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software. Results: The patient's age at the time of surgery ranged from 18 to 62 years, with a mean of 33.8 years. Follow-up time ranged from 6 months to 102 months postoperatively, with a mean of 37.2 months. Forty-two out of 193 patients were smokers. Implant volumes ranged from 180 to 800 mL, with an average of 380 mL. Implant types used were McGhan (55.5%), Mentor (40.5%), and Microcell (4%). All implants had surface texturing. Most of the implants (90.7%) were placed in a submuscular position. Sixty-five percent of the patients preferred a transaxillary approach, whereas 35% preferred the periareolar approach. Discussion: Capsular contracture remains one of the main factors affecting patient satisfaction. Implant volume and position had no significant effect on the risk of developing capsular contracture. Furthermore, the volume of an implant did not have a significant impact on the risk of developing pain, loss of nipple sensation, or wrinkling. In this study, a significant number of patients reported wrinkling (44.4%) and alteration of nipple sensation (40.6%), which reflects the fact that this is a subjective patient-reported result. Overall satisfaction rate reported was 96.6%.
Dignity realization of patients with stroke in hospital care: A grounded theory
Authors: Rannikko Sunna , Stolt Minna , Suhonen Riitta , Leino-Kilpi Helena 
Published: June 2017

Background: Dignity is seen as an important but complex concept in the healthcare context. In this context, the discussion of dignity includes concepts of other ethical principles such as autonomy and privacy. Patients consider dignity to cover individuality, patient’s feelings, communication, and the behavior of healthcare personnel. However, there is a lack of knowledge concerning the realization of patients’ dignity in hospital care and the focus of the study is therefore on the realization of dignity of the vulnerable group of patients with stroke. Aim: The aim of the study was to create a theoretical construct to describe the dignity realization of patients with stroke in hospital care. Research design and participants: Patients with stroke (n = 16) were interviewed in 2015 using a semi-structured interview containing open questions concerning dignity. The data were analyzed using constant comparison of Grounded Theory. Ethical considerations: Ethical approval for the research was obtained from the Ethics Committee of the University. The permission for the research was given by the hospital. Informed consent was obtained from participants. Findings: The “Theory of Dignity Realization of Patients with Stroke in Hospital Care” consists of a core category including generic elements of the new situation and dignity realization types. The core category was identified as “Dignity in a new situation” and the generic elements as health history, life history, individuality and stroke. Dignity of patients with stroke is realized through specific types of realization: person-related dignity type, control-related dignity type, independence-related dignity type, social-related dignity type, and care-related dignity type. Discussion: The theory has similar elements with the previous literature but the whole construct is new. The theory reveals possible special characteristics in dignity realization of patients with stroke. Conclusion: For healthcare personnel, the theory provides a frame for a better understanding and recognition of how dignity of patients with stroke is realized.