bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urban point sources of nutrients were the leading cause for the historical spread of hypoxia across European lakes
Authors: Jenny Jean-Philippe , Normandeau Alexandre , Francus Pierre , Taranu Zofia Ecaterina , Gregory-Eaves Irene , Lapointe François , Jautzy Josue , Ojala Antti E. K. , Dorioz Jean-Marcel , Schimmelmann Arndt , Zolitschka Bernd 
Published: October 2016

SignificanceUsing a compilation of data arising from over 1,500 European watersheds, we have identified the relative role of different drivers in initiating hypolimnetic hypoxia, a critical indicator of lake health. In particular, our regional synthesis of laminated lake sediments indicated a significant acceleration in the spread of lacustrine hypoxia in the 1900s, which occurred well before the general use of commercial fertilizers in the mid-20th century and the onset of supraregional climate warming in the 1970s. The spread of hypoxia was best explained by urban expansion and the associated intensification of anthropogenic point sources of phosphorus, whereby changes in lifestyle increased the discharge of nutrients from treated and raw sewage, and ultimately led to enhanced lacustrine biological productivity.
Geometry-induced capillary emptying
Authors: Rascón Carlos , Parry Andrew O. , Aarts Dirk G. A. L. 
Published: October 2016

Significance
We present a precise mathematical criterion that determines whether the liquid in a capillary of arbitrary cross-section will remain in it or will flow out when the capillary is at a horizontal position. The rich phenomenology found can be used to construct very sensitive microfluidics devices.
Increased risk of dementia in the aftermath of the 2011 Great East Japan Earthquake and Tsunami
Authors: Hikichi Hiroyuki , Aida Jun , Kondo Katsunori , Tsuboya Toru , Matsuyama Yusuke , Subramanian S. V. , Kawachi Ichiro 
Published: October 2016

Significance
Recovery after major disaster poses potential risks of dementia for the elderly population. However, no previous studies have examined exposure to natural disaster and changes in risk factors as predictors of deterioration in cognitive function. We prospectively examined whether housing damage and loss of relatives or friends were associated with cognitive decline in the aftermath of the 2011 Great East Japan Earthquake and Tsunami. In this study, which included 3,566 survivors who are 65 y old or older, the severity of housing damage was significantly associated with cognitive decline after controlling changes of covariates and risk factors during the follow-up period. The cognitive decline should be listed as a health risk of older survivors in the aftermath of natural disasters.
Adaptive integration of habits into depth-limited planning defines a habitual-goal–directed spectrum
Authors: Keramati Mehdi , Smittenaar Peter , Dolan Raymond J. , Dayan Peter 
Published: October 2016

Significance
Solving complex tasks often requires estimates of the future consequences of current actions. Estimates could be learned from past experience, but they then risk being out of date, or they could be calculated by a form of planning into the future, a process that is computationally taxing. We show that humans integrate learned estimates into their planning calculations, saving mental effort and time. We also show that increasing time pressure leads to reliance on learned estimates after fewer steps of planning. We suggest a normative rationale for this effect using a computational model. Our results provide a perspective on how the brain combines different decision processes collaboratively to exploit their comparative computational advantages.
Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen
Authors: Kong Leopold , Lee David E. , Kadam Rameshwar U. , Liu Tong , Giang Erick , Nieusma Travis , Garces Fernando , Tzarum Netanel , Woods Virgil L. , Ward Andrew B. , Li Sheng , Wilson Ian A. , Law Mansun 
Published: October 2016

Significance
Hepatitis C virus is an important human pathogen, and its E2 envelope glycoprotein is the major target of neutralizing antibodies (NAbs) and, hence, a promising vaccine candidate. Many broadly NAbs (bNAbs) to E2 recognize the conserved receptor-binding site, but immunization with soluble E2 antigen rarely elicits a potent bNAb response. Here, we show that soluble E2 is highly stable except for the receptor-binding site and variable loops. Thus, despite high sequence conservation, structural flexibility at the receptor-binding site may distract the immune system from eliciting bNAbs that recognize the conformation required for its function on virions. Stabilization of the E2 CD81 receptor-binding site (CD81bs) by structure-based design may improve its performance as a vaccine candidate.
Universality in human cortical folding in health and disease
Authors: Wang Yujiang , Necus Joe , Kaiser Marcus , Mota Bruno 
Published: October 2016

SignificanceDespite of the enormous diversity in size and function of the mammalian cerebral cortex, it has been shown that the cortices of different species fold according to a simple universal law. In this study, we investigate if this law also applies to variation within a single species—our own. Specifically, we examine how the law is affected by sex, age, or the presence of Alzheimer’s disease. By investigating and quantifying what remains invariant and what changes in each case, we shed some light on the underlying mechanisms through which the cortex changes in health and disease and argue that morphological complexity could emerge from a few simple rules.
Probing the free energy landscapes of ALS disease mutants of SOD1 by NMR spectroscopy
Authors: Sekhar Ashok , Rumfeldt Jessica A. O. , Broom Helen R. , Doyle Colleen M. , Sobering Ryan E. , Meiering Elizabeth M. , Kay Lewis E. 
Published: October 2016

Significance
A series of amyotrophic lateral sclerosis disease-causing mutants of superoxide dismutase have been studied using NMR experiments probing sparsely populated, transiently formed protein conformers. Focusing on the most immature enzyme form, which is monomeric, metal-free, and lacking a stabilizing disulfide bond, we show that the ground states for the wild-type and disease mutant proteins are similar, with an intact eight-stranded β-barrel structure resembling the structure of the mature enzyme. In contrast, conformationally excited states can be affected by mutation, both in terms of the number and types of structures accessible to the mutant. These excited states can play roles in both maturation and aggregation processes and, in the latter case, can provide a variety of possible pathways for aberrant interactions.
Expression of multiplecbb3cytochromecoxidase isoforms by combinations of multiple isosubunits inPseudomonas aeruginosa
Authors: Hirai Takehiro , Osamura Tatsuya , Ishii Masaharu , Arai Hiroyuki 
Published: October 2016

SignificanceThecbb3cytochromecoxidase has high affinity for oxygen and is typically used for respiration in many pathogenic bacteria in hypoxic environments. Here we show that the opportunistic human pathogenPseudomonas aeruginosahas a capability to produce 16 differentcbb3isoforms by combinations of multiple isosubunits. Utilization of multiple isoforms with different properties contributes to the robustness of the bacterium under hypoxic growth conditions and might have practical implications for resistance to antibiotics and formations of biofilms and persister cells. Our findings indicate that the mechanism for the production of the isoforms could be possible therapeutic targets for treating chronicP. aeruginosainfection.
Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens
Authors: Shaffer J. Scott , Moore Penny L. , Kardar Mehran , Chakraborty Arup K. 
Published: October 2016

SignificanceThe design of vaccination strategies that generate potent Abs directed against diverse strains of highly mutable pathogens, like HIV and malaria, will significantly impact global health. Such Abs are called broadly neutralizing Abs (bnAbs). Abs are produced by a Darwinian evolutionary process called affinity maturation. Induction of bnAbs will likely require vaccination with diverse mutant antigens. How affinity maturation occurs in the presence of multiple diverse antigens is not well-understood, thus hindering rational design of immunization strategies. We study this issue using computer simulations and statistical mechanical theory. Our results provide guides for the rational design of optimal vaccination strategies, and they reveal mechanistic principles at a crossroad of immunology and evolutionary biology.
Polynomial matrix equivalences: system transformations and structural invariants
Authors: Vologiannidis S , Antoniou E N , Karampetakis N P , Vardulakis A I G 
Published: October 2016

Abstract
The present article is a survey on linear multivariable systems equivalences. We attempt a review of the most significant forms of system equivalence having as a starting point matrix transformations preserving certain aspects of their spectral structure. From a system theoretic point of view, the need for a variety of forms of polynomial matrix equivalences, arises from the fact that different types of spectral invariants give rise to different types of dynamics of the underlying linear system. A historical perspective of the key results and their contributors is also given.
An Interprofessional Curriculum on Antimicrobial Stewardship Improves Knowledge and Attitudes Toward Appropriate Antimicrobial Use and Collaboration
Authors: MacDougall Conan , Schwartz Brian S. , Kim Lisa , Nanamori Mari , Shekarchian Sharmin , Chin-Hong Peter V. 
Published: October 2016

AbstractBackgroundInappropriate antimicrobial use can threaten patient safety and is the focus of collaborative physician and pharmacist antimicrobial stewardship teams. However, antimicrobial stewardship is not comprehensively taught in medical or pharmacy school curricula. Addressing this deficiency can teach an important concept as well as model interprofessional healthcare.MethodsWe created an antimicrobial stewardship curriculum consisting of an online learning module and workshop session that combined medical and pharmacy students, with faculty from both professions. Learners worked through interactive, branched-logic clinical cases relating to appropriate antimicrobial use. We surveyed participants before and after the curriculum using validated questions to assess knowledge and attitudes regarding antimicrobial stewardship and interprofessional collaboration. Results were analyzed using paired χ2 and t tests and mixed-effects logistic regression.ResultsAnalysis was performed with the 745 students (425 medical students, 320 pharmacy students) who completed both pre- and postcurriculum surveys over 3 years. After completing the curriculum, significantly more students perceived that they were able to describe the role of each profession in appropriate antimicrobial use (34% vs 82%, P &lt; .001), communicate in a manner that engaged the interprofessional team (75% vs 94%, P &lt; .001), and describe collaborative approaches to appropriate antimicrobial use (49% vs 92%, P &lt; .001). Student favorability ratings were high for the online learning module (85%) and small group workshop (93%).ConclusionsA curriculum on antimicrobial stewardship consisting of independent learning and an interprofessional workshop significantly increased knowledge and attitudes towards collaborative antimicrobial stewardship among preclinical medical and pharmacy students.
Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study
Authors: Santoro Nanette , Allshouse Amanda , Neal-Perry Genevieve , Pal Lubna , Lobo Rogerio A. , Naftolin Frederick , Black Dennis M. , Brinton Eliot A. , Budoff Matthew J. , Cedars Marcelle I. , Dowling N. Maritza , Dunn Mary , Gleason Carey E. , Hodis Howard N. , Isaac Barbara , Magnani Maureen , Manson JoAnn E. , Miller Virginia M. , Taylor Hugh S. , Wharton Whitney , Wolff Erin , Zepeda Viola , Harman S. Mitchell 
Published: October 2016

Abstract

Objective:
The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years.

Methods:
A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ2 tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling.

Results:
Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity.

Conclusions:
Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.
Collagenopathies—Implications for Abdominal Wall Reconstruction: A Systematic Review
Authors: Harrison Bridget , Sanniec Kyle , Janis Jeffrey E. 
Published: October 2016

Background:
The etiology of hernia formation is strongly debated and includes mechanical strain, prior surgical intervention, abnormal embryologic development, and increased intraabdominal pressure. Although the most common inciting cause in ventral hernias is previous abdominal surgery, many other factors contribute. We explore this etiology through an examination of the current literature and existing evidence on patients with collagen vascular diseases, such as Ehlers–Danlos syndrome.

Methods:
A systematic review of the published literature was performed of all available Spanish and English language PubMed and Cochrane articles containing the key words “collagenopathies,” “collagenopathy,” “Ehlers-Danlos,” “ventral hernia,” and “hernia.”

Results:
Three hundred fifty-two articles were identified in the preliminary search. After review, 61 articles were included in the final review.

Conclusions:
Multiple authors suggest a qualitative or quantitative defect in collagen formation as a common factor in hernia formation. High-level clinical data clearly linking collagenopathies and hernia formation are lacking. However, a trend in pathologic studies suggests a link between abnormal collagen production and/or processing that is likely associated with hernia development.
Integra-based Reconstruction of Large Scalp Wounds: A Case Report and Systematic Review of the Literature
Authors: Johnson Maxwell B. , Wong Alex K. 
Published: October 2016

Background:
Large complex scalp wounds that have traditionally required free vascularized tissue transfer have been successfully reconstructed with skin substitutes such as Integra. Although there are multiple reports of Integra-based reconstructions of scalp wounds, there has not been a comprehensive assessment of this body of literature that critically examines this method. Our goal was to conduct a systematic review to determine the effectiveness of Integra-based reconstructions of scalp wounds, with emphasis on large defects.

Methods:
A comprehensive systematic review was completed using key search terms, including Integra, dermal regeneration template, bovine collagen, skin substitute, forehead, and scalp. Selected articles reported characteristics of patients and their reconstructions. The primary outcome measures were wound complications and percent graft take.

Results:
Thirty-four articles were included in this systematic review. Wound sizes ranged from 5.7 to 610 cm2, with 35.3% of articles reporting a mean defect size >100 cm2. Thirty-two articles reported mean percent take of skin graft ≥90%. Sixteen articles reported a minor complication. There were no major complications associated with the reconstructions.

Conclusions:
There is a substantial evidence base for the use of Integra to reconstruct scalp wounds. To date, the dermal regeneration template is generally reserved for salvage procedures or when the patient cannot tolerate free tissue transfer. Based on the findings of this systematic review and the authors’ clinical experience, Integra can be used to achieve predictable results in large complex scalp defects.
Aesthetic Surgery in Patients with Lung Cancer: A Paradigm Shift
Authors: Hidalgo David A. , Baranski Jan , Sinno Sammy 
Published: October 2016

Background:
Lung cancer is the most common cancer worldwide and the leading cause of cancer death. With the development of targeted therapy against causative driver mutations, some patients have experienced dramatic responses that have converted their disease into a chronic, stable form. Shifting concerns away from survival and back to quality-of-life issues has led some of these patients to seek aesthetic surgery.

Methods:
Three patient examples are presented to illustrate current lung cancer treatment modalities, disease responses, and subsequent experiences with aesthetic surgical procedures. Two patients presented for blepharoplasty and the third for revisional breast augmentation surgery.

Results:
Two patients were treated for lung cancer with targeted therapy and a third with more traditional chemotherapy before undergoing aesthetic surgery. All 3 patients experienced a normal recovery from surgery without any untoward results. Two remain free of disease and one has chronic stable disease. All have returned to normal, active lives.

Conclusions:
Recent developments in lung cancer treatment are transforming this entity into a less formidable diagnosis for some patients, much like breast cancer and prostate cancer. Plastic surgeons should be aware of this paradigm shift. Successfully treated patients should be considered as reasonable candidates for aesthetic surgery, particularly when they have the full support of their oncologist. Beyond the typical psychological benefits that plastic surgery can produce, it also provides affirmation in this patient population of a return to normalcy, thereby imparting hope and optimism for the future.
Measures of Patient Activation and Social Support in a Peer-Led Support Network for Women With Cardiovascular Disease
Authors: Witt Dawn , Benson Gretchen , Campbell Susan , Sillah Arthur , Berra Kathy 
Published: October 2016

PURPOSE:
Social support has been associated with beneficial effects on many disease states and overall health and well-being. However, there is limited research exploring the impact of peer-led support models among women living with coronary heart disease. This study describes the structure of peer-led support groups offered by WomenHeart (WH): The National Coalition for Women Living with Heart Disease, and assesses WH participants' quality of life and social, emotional, and physical health.

METHODS:
Participants were recruited from 50 WH groups. A 70-item online survey was administered, and the main analytic sample included 157 women. Multivariate logistic regression was used to examine the association between patient activation levels (lower activation levels: 1, 2 vs higher activation levels: 3, 4) and social support scores (range: lowest 8 to highest 34), adjusting for age.

RESULTS:
High levels of social support, patient activation, physical activity, and low levels of stress, anxiety, and depression were reported. Those who were at or above the median for the social support measures (indicating high levels of social support) had greater odds of high levels of patient activation (level 3 or 4) than individuals reporting low levels of social support (OR = 2.23; 95% CI, 1.04-4.76; P = .012).

CONCLUSIONS:
Women who regularly attended a support group by a trained peer leader were highly engaged in their health care and had low levels of stress, anxiety, and depression. These findings lend credibility to the value of the peer support model and could potentially be replicated in other disease states to enhance patient care.
TRAUMATIC PROLIFERATIVE VITREORETINOPATHY
Authors: Jin Ying , Chen Huijin , Xu Xiaojian , Hu Yuntao , Wang Changguan , Ma Zhizhong 
Published: October 2016

Purpose:
To determine the phases of traumatic proliferative vitreoretinopathy after open globe injury by assessing cellular components, extracellular matrix constituents of proliferative vitreoretinopathy membranes, and intraretinal changes over time.

Methods:
Twenty-one epiretinal and/or subretinal membrane specimens were obtained from 21 patients with open globe injuries. The patients were divided into Groups A (≤28 days), B (29–120 days), and C (>120 days) according to the interval between injury and vitrectomy. The staining intensity and percentage of positive cells in membranes were compared among the groups, and proliferative indices for Ki-67 and proliferating cell nuclear antigen were assessed. Intraretinal changes were evaluated through histology and immunohistochemistry. Fundus photography was performed during vitrectomy.

Results:
The proliferating cell nuclear antigen proliferative index was significantly higher in Group B (P = 0.002) than in Group A, and lower in Group C (P < 0.001) than in Group B. α-smooth muscle actin expression increased from day 29 to 120 after injury. Meanwhile, intraretinal gliosis and fibrosis developed.

Conclusion:
Active proliferation and contraction in proliferative vitreoretinopathy membranes continue until 120 days after injury, and are accompanied by the initiation of intraretinal gliosis and fibrosis. These findings provide further insight into the optimal timing of vitrectomy after trauma.