bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress and Addiction: When a Robust Stress Response Indicates Resiliency
Authors: al'Absi Mustafa 
Published: August 2017

ABSTRACTObjectiveStress reactivity research has traditionally focused on the idea that exaggerated responses to stress may have adverse effects on health. Accumulating evidence suggests that attenuated responses to stress and delayed recovery may also be problematic.MethodsThis review focuses on the role of the stress response of the hypothalamic-pituitary-adrenocortical axis, the endogenous opioid system, and the cardiovascular system in hypertension, pain perception, and addictive behaviors. Results from multiple methods of assessment and stress paradigms conducted in our laboratory over the past two decades are integrated with research from other investigators and with existing theories.ResultsResearch indicates that exaggerated biological and physiological responses to stress and attenuated pain perception are associated with hypertension and risk for cardiovascular diseases. This research complements work linking reduced stress responses with enhanced pain sensitivity and discomfort. Multiple studies have also demonstrated that an attenuated stress response is linked to exacerbation of withdrawal symptoms and relapse in nicotine addiction. Evidence indicates important moderators (i.e., sex, personality traits, and early life adversity) and hypothalamic-pituitary-adrenocortical– and endogenous opioid system–related mechanisms in the altered response to stress. I integrate these findings in a conceptual model emphasizing that robust stress responses in the context of addiction and relapse should be considered as a marker of resiliency.ConclusionsA blunted stress response may indicate long-term physiological dysregulation that could usher harmful consequences for cardiovascular disease, pain perception, and addictive disorders. The impact of dysregulation is influenced by multiple individual and situational factors that should be considered in evaluating the clinical significance of stress response dysregulation.
Estimated Coverage to Address Financial Barriers to HIV Preexposure Prophylaxis Among Persons With Indications for Its Use, United States, 2015
Authors: Smith Dawn K. , Van Handel Michelle , Huggins Rebecca 
Published: August 2017

Background:
An estimated 1.2 million American adults engage in sexual and drug use behaviors that place them at significant risk of acquiring HIV infection. Engagement in health care for the provision of daily oral antiretroviral medication as preexposure prophylaxis (PrEP), when clinically indicated, could substantially reduce the number of new HIV infections in these persons. However, resources to cover the financial cost of PrEP care are anticipated barriers for many of the populations with high numbers of new HIV infections.

Methods:
Using nationally representative data, we estimated the current national met and unmet need for financial assistance with covering the cost of PrEP medication, clinical visits, and laboratory tests among adults with indications for its use, overall and by transmission risk population.

Results:
This study found that of the 1.2 million adults estimated to have indications for PrEP use, <1% (∼7300) are in need of financial assistance for both PrEP medication and clinical care, at an estimated annual cost of $89 million. An additional 7% (∼86,300) are in need of financial assistance only for PrEP clinical care at an estimated annual cost of $119 million.

Conclusions:
This information on PrEP care costs, insurance coverage, and unmet financial need among persons in key HIV transmission risk subpopulations can inform policy makers at all levels as they consider how to address remaining financial barriers to the use of PrEP and accommodate any changes in eligibility for various insurance and financial assistance programs that may occur in coming years.
Low-Dose Radioactive Iodine Ablation Is Sufficient in Patients With Small Papillary Thyroid Cancer Having Minor Extrathyroidal Extension and Central Lymph Node Metastasis (T3 N1a)
Authors: Seo Minjung , Kim Yon Seon , Lee Jong Cheol , Han Myung Woul , Kim Eun Sook , Kim Kyung Bin , Park Seol Hoon 
Published: August 2017

Purpose
The aim of this study was to evaluate the effectiveness of low-dose radioactive iodine (RAI) ablation in patients with small papillary thyroid cancer (PTC) exhibiting microscopic extrathyroidal extension (mETE) and central lymph node (CLN) metastasis.

Methods
Among patients who underwent RAI ablation between March 2007 and February 2014, those who had small PTCs (≤2 cm), as well as mETE and CLN metastasis (T3 N1a M0), were enrolled. Response to ablation and long-term outcomes were assessed and compared according to the administered RAI dose. Factors associated with unsuccessful ablation were also determined.

Results
A total of 180 patients were included in the study. Eighty-eight patients had been treated with 1110 MBq (low-dose group) and 92 with 2960 MBq (high-dose group) of RAI. There were no significant differences in the responses to ablation (P = 0.810) and long-term outcomes (P = 0.663) between both groups. Among all patients enrolled, 13 did not achieve successful ablation at long-term follow-up. Logistic regression found that a high ratio of metastatic nodes was a significant factor for predicting unsuccessful ablation.

Conclusions
Low-dose RAI ablation did not produce significantly different responses or long-term outcomes in patients with small PTCs exhibiting mETE and CLN metastasis. These findings suggest that low-dose ablation may be sufficient in this specific group of intermediate-risk patients, although careful selection is required for patients with a high ratio of metastatic nodes.
Small Hepatocellular Carcinoma With Low Tumor Marker Expression Benefits More From Anatomical Resection Than Tumors With Aggressive Biology
Authors: Jung Dong-Hwan , Hwang Shin , Lee Young-Joo , Kim Ki-Hun , Song Gi-Won , Ahn Chul-Soo , Moon Deok-Bog , Lee Sung-Gyu 
Published: August 2017

Objective:
We assessed prognostic advantage of anatomical resection (AR) over nonanatomical resection (NAR) for hepatocellular carcinoma (HCC) according to multiplication of α-fetoprotein, des-γ-carboxyprothrombin, and tumor volume (ADV) scores.

Background:
Superiority of AR over NAR is debated. ADV score is surrogate marker of postresection prognosis for solitary HCC.

Methods:
This study included 1572 patients who underwent curative resection for solitary HCC of 2.0 to 5.0 cm between 2006 and 2014.

Results:
Preoperative patient profiles were not statistically different between AR and NAR groups. In 1324 naïve patients without preoperative treatment, AR group showed lower recurrence rates (P = 0.003) and higher patient survival rates (P = 0.012) than NAR group. AR group showed lower recurrence rates in patients with ADV ≤5 log (P ≤ 0.046). ADV scores >4 log and >3 log were independent risk factors for tumor recurrence and patient survival in treatment-naïve patients, respectively. In treatment-naïve group with preserved hepatic functional reserve, AR group showed lower recurrence rates in patients with ADV ≤4 log (P = 0.026). Absence of microvascular invasion also showed lower recurrence rates (P = 0.007) in AR group. In 248 patients with preoperative treatment, AR group showed lower recurrence rates (P = 0.001) and higher patient survival rates (P = 0.006). AR group showed lower recurrence rates in patients with ADV ≤4 log (P < 0.001) and higher survival rates in patients with ADV ≤5 log (P ≤ 0.043).

Conclusions:
Prognostic benefit of AR was evident in patients with ADV score ≤4 log or absence of microvascular invasion. Patients with less aggressive tumor biology benefit more from AR than NAR, thus being reasonably indicated for AR.
Characteristics of Effective Mentorship for Academic Surgeons
Authors: Cochran Amalia , Elder William B. , Neumayer Leigh A. 
Published: August 2017

Objective:
The authors sought to describe characteristics of effective mentoring relationships in academic surgery based upon lived experiences of mid-career and senior female academic surgeons.

Background:
Prior qualitative work describes characteristics of successful mentoring relationships. However, no model exists of effective mentorship that is specific to academic surgery.

Methods:
The authors conducted in-depth interviews with mid-career and senior female US academic surgeons about the impact of mentoring on professional development during 2014 and 2015. Purposive selection aimed to maximize institutional, specialty, years in career, and racial diversity. Grounded theory method was used to generate a conceptual model of effective mentoring relationships. Data saturation occurred following 15 interviews.

Results:
Interviewees described the need for multiple mentors over time with each mentor addressing a unique domain. Interviewees suggested that mentees should seek mentors who will serve as strategic advisors, who will be unselfish, and who engage with diverse mentees.

Conclusions:
This study identified a need for multiple mentors across time and disciplines, and identified 3 key characteristics of effective mentoring relationships in academic surgery. Future work in this area should generate an operational definition of mentorship that supports quantitative evaluation of mentor and mentoring panel performance.
Delayed Onset Cranial Nerve Palsies After Endovascular Coil Embolization of Direct Carotid-Cavernous Fistulas
Authors: Bou Ghannam Alaa , Subramanian Prem S. 
Published: August 2017

Background:
Late recurrence of visual symptoms associated with carotid-cavernous fistula (CCF), including diplopia, is uncommon and raises concern for new or recurrent fistula formation.

Methods:
We report 2 patients with traumatic CCFs, where cranial nerve paresis resolved after endovascular CCF treatment only to reappear years later.

Results:
No evidence of recurrent or new fistula formation was found. Both were treated successfully with strabismus surgery.

Conclusions:
Although the cause of delayed onset diplopia after successful treatment is still unknown, theories include late compression of cranial nerves within the cavernous sinus due to coil mass that can cause chronic ischemia, delayed inflammation due to a thrombophilic nidus created by the coil mass, or injury to the cranial nerves that manifests later due to decompensated strabismus.
Tim-3 co-stimulation promotes short-term effector T cells, restricts memory precursors and is dispensable for T cell exhaustion
Authors: Avery Lyndsay , Szymczak-Workman Andrea L. , Kane Lawrence P. 
Published: August 2017

AbstractTim-3 is highly expressed on a subset of T cells during T cell exhaustion, in settings of chronic viral infection and tumors (1, 2). Using LCMV Clone-13, a model for chronic infection, we have found that Tim-3 is neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted development of short-term effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3 deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, but may also contribute to exhaustion, by restricting development of long-lived memory T cells, including PD-1int“stem-like” exhausted T cells that expand during PD-1 pathway blockade. Taken together, our results suggest that Tim-3 is actually more similar to co-stimulatory receptors that are upregulated after T cell activation, rather than a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents.SignificanceDuring a chronic viral infection, prolonged exposure to viral antigens leads to dysfunction or “exhaustion” of T cells specific to the virus, a condition also observed in T cells that infiltrate tumors. The exhausted state is associated with expression of specific cell-surface proteins, some of which may inhibit T cell activation. Expression of Tim-3 is associated with acquisition of T cell exhaustion, although it is also expressed transiently during acute infection. Here we provide evidence that a major function of Tim-3 is to enhance T cell activation, during either acute or chronic viral infection. However, Tim-3 is not required for development of exhaustion. Thus, we propose that Tim-3 would be better described as a stimulatory, rather than inhibitory, protein.
Index hopping on the Illumina HiseqX platform and its consequences for ancient DNA studies
Authors: Valk Tom van der , Vezzi Francesco , Ormestad Mattias , Dalén Love , Guschanski Katerina 
Published: August 2017

AbstractThe high-throughput capacities of the Illumina sequencing platforms and the possibility to label samples individually have encouraged a wide use of sample multiplexing. However, this practice results in read misassignment (usually <1%) across samples sequenced on the same lane. Alarmingly high rates of read misassignment of up to 10% were reported for the latest generation of lllumina sequencing machines. This may make future use of the newest generation of platforms prohibitive, particularly in studies that rely on low quantity and quality samples, such as historical and archaeological specimens. Here, we rely on barcodes, short sequences that are ligated to both ends of the DNA insert, to directly quantify the rate of index hopping in 100-year old museum-preserved gorilla (Gorilla beringei) samples. Correcting for multiple sources of noise, we identify on average 0.470% of reads containing a hopped index. We show that sample-specific quantity of misassigned reads depend on the number of reads that any given sample contributes to the total sequencing pool, so that samples with few sequenced reads receive the greatest proportion of misassigned reads. Ancient DNA samples are particularly affected, since they often differ widely in endogenous content. Through extensive simulations we show that even low index-hopping rates lead to biases in ancient DNA studies when multiplexing samples with different quantities of input material.
Generation and validation of afloxed FosBmouse line
Authors: Ohnishi Yoshinori N. , Eagle Andrew L. , Ohnishi Yoko H. , Cahill Michael E. , Wirtz Alexis J. , Robison Alfred J. , Nestler Eric J. 
Published: August 2017

AbstractExpression of theFosBgene has been studied extensively in many fields using a variety of tools. However, previous techniques have had a variety of caveats, from potential off-target effects (e.g., overexpression of FosB, ΔFosB, or a dominant negative mutant of JunD, termed ΔJunD) or confounding developmental effects (e.g., the constitutiveFosBknockout mouse). Therefore, we sought to create afloxed FosBmouse line that will allow true silencing of theFosBgene with both spatial and temporal control. Here, we detail the cloning strategy, production, and validation of thefloxed FosBmouse. We demonstrate methodology for breeding and genotyping, and show that viral-mediated expression of Cre recombinase in a targeted, discrete brain region ablates expression of theFosBgene infloxedbut not wild type mice. Thus, thefloxed FosBmouse presented here represents an important new tool for the continued investigation of this critical gene.
PDB-NMA of a Protein Homodimer Reproduces Distinct Experimental Motility Asymmetry
Authors: Tirion Monique M. , ben-Avraham Daniel 
Published: August 2017

AbstractWe have extended our analytically derived PDB-NMA formulation, ATMAN [1], to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3Å resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50Å sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures. The vibrational analysis of this PDB entry, together with biochemical and crystallographic data, demonstrates the cooperative nature of the dimeric interaction of the two subunits and suggests a mechanical model for subunit interconversion during the catalytic cycle.
Global transcriptome analysis ofAedes aegyptimosquitoes in response to Zika virus infection
Authors: Etebari Kayvan , Hegde Shivanand , Saldaña Miguel A , Widen Steven G , Wood Thomas G , Asgari Sassan , Hughes Grant L 
Published: August 2017

AbstractZika virus (ZIKV) of theFlaviviridaefamily is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquitoAedes aegyptithat also vectors dengue virus, however little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of wholeAe. aegyptimosquitoes in response to ZIKV infection at 2, 7, and 14 days post-infection using RNA-Seq. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic process, cellular process and proteolysis. In addition, 486 long intergenic non-coding RNAs were identified that were altered upon ZIKV infection. Further, we found correlational changes of a number of potential mRNA target genes with that of altered host microRNAs. The outcomes provide a basic understanding ofAe. aegyptiresponses to ZIKV and helps to determine host factors involved in replication or mosquito host anti-viral response against the virus.ImportanceVector-borne viruses pose great risks on human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response ofAedes aegyptimosquitoes to Zika virus infection. Results showed large changes both in coding and long non-coding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.
SeroBA: rapid high-throughput serotyping ofStreptococcus pneumoniaefrom whole genome sequence data
Authors: Epping Lennard , van Tonder Andries J. , Gladstone Rebecca A. ,   The Global Pneumococcal Sequencing Consortium, Bentley Stephen D. , Page Andrew J. , Keane Jacqueline A. 
Published: August 2017

ABSTRACTStreptococcus pneumoniaeis responsible for 240,000 - 460,000 deaths in children under 5 years of age each year. Accurate identification of pneumococcal serotypes is important for tracking the distribution and evolution of serotypes following the introduction of effective vaccines. Recent efforts have been made to infer serotypes directly from genomic data but current software approaches are limited and do not scale well. Here, we introduce a novel method, SeroBA, which uses a hybrid assembly and mapping approach. We compared SeroBA against real and simulated data and present results on the concordance and computational performance against a validation dataset, the robustness and scalability when analysing a large dataset, and the impact of varying the depth of coverage in thecpslocus region on sequence-based serotyping. SeroBA can predict serotypes, by identifying thecpslocus, directly from raw whole genome sequencing read data with 98% concordance using ak-mer based method, can process 10,000 samples in just over 1 day using a standard server and can call serotypes at a coverage as low as 10x. SeroBA is implemented in Python3 and is freely available under an open source GPLv3 license from:https://github.com/sanger-pathogens/seroba.DATA SUMMARYThe reference genomeStreptococcus pneumoniaeATCC 700669 is available from National Center for Biotechnology Information (NCBI) with the accession number: FM211187Simulated paired end reads for experiment 2 have been deposited in FigShare:https://doi.org/10.6084/m9.figshare.5086054.v1Accession numbers for all other experiments are listed in Supplementary Table S1 and Supplementary Table S2.I/We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ⊠IMPACT STATEMENTThis article describes SeroBA, a A-mer based method for predicting the serotypes ofStreptococcus pneumoniaefrom Whole Genome Sequencing (WGS) data. SeroBA can identify 92 serotypes and 2 subtypes with constant memory usage and low computational costs. We showed that SeroBA is able to reliably predict serotypes at a depth of coverage as low as 10x and is scalable to large datasets.
The neural encoding of information prediction errors during non-instrumental information seeking
Authors: Brydevall Maja , Bennett Daniel , Murawski Carsten , Bode Stefan 
Published: August 2017

ABSTRACTIn a dynamic world, accurate beliefs about the environment are vital for survival, and individuals should therefore regularly seek out new information with which to update their beliefs. This aspect of behaviour is not well captured by standard theories of decision making, and the neural mechanisms of information seeking remain unclear. One recent theory posits that valuation of information results from representation of informative stimuli within canonical neural reward-processing circuits, even if that information lacks instrumental use. We investigated this question by recording EEG from twenty-three human participants performing a non-instrumental information-seeking task. In this task, participants could pay a monetary cost to receive advance information about the likelihood of receiving reward in a lottery at the end of each trial. Behavioural results showed that participants were willing to incur considerable monetary costs to acquire early but non-instrumental information. Analysis of the event-related potential elicited by informative cues revealed that the feedback-related negativity independently encoded both an information prediction error and a reward prediction error. These findings are consistent with the hypothesis that information seeking results from processing of information within neural reward circuits, and suggests that information may represent a distinct dimension of valuation in decision making under uncertainty.