bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreases in the Late Positive Potential to Alcohol Images Among Alcohol Treatment Seekers Following Mindfulness-Based Relapse Prevention
Authors: Brown Darin R , Jackson Trevor C J , Claus Eric D , Votaw Victoria R , Stein Elena R , Robinson Charles S H , Wilson Adam D , Brandt Emma , Fratzke Violet , Clark Vincent P , Witkiewitz Katie 
Published: October 2019

Abstract

Aim
Heightened craving among individuals with alcohol use disorder (AUD) has been attributed to a hypersensitivity to alcohol cues in attentional brain networks. Active mindfulness training has been shown to help improve attentional control. Here, we examined alcohol cue-related hypersensitivity among individuals with AUD who received rolling group mindfulness-based relapse prevention (MBRP) in combination with transcranial direct current stimulation (tDCS), over right inferior frontal gyrus.

Methods
Participants (n = 68) viewed a series of emotionally negative, emotionally neutral and alcohol-related images. Following image presentation, participants were asked to rate their level of craving for the alcohol cues, and their level of negative affect evoked by neutral and negative cues. During the task, electroencephalogram (EEG) was recorded to capture an event-related component shown to relate to emotionally salient stimuli: the late positive potential (LPP). Participants who completed a follow-up EEG (n = 37) performed the task a second time after up to eight sessions of MBRP coupled with active or sham tDCS.

Results
We found that both craving ratings and the LPP significantly decreased in response to alcohol cues from pre- to post-treatment, but not for other image cues. The magnitude of alcohol image craving reductions was associated with the number of MBRP group sessions attended. Active tDCS was not associated with craving ratings, but it was associated with greater LPP amplitudes across image types.

Conclusions
Taken together, these results suggest that disruption of alcohol-cue hypersensitivity in people with AUD may be a target mechanism of MBRP.
Deep learning of pharmacogenomics resources: moving towards precision oncology
Authors: Chiu Yu-Chiao , Chen Hung-I Harry , Gorthi Aparna , Mostavi Milad , Zheng Siyuan , Huang Yufei , Chen Yidong 
Published: October 2019

AbstractThe recent accumulation of cancer genomic data provides an opportunity to understand how a tumor’s genomic characteristics can affect its responses to drugs. This field, called pharmacogenomics, is a key area in the development of precision oncology. Deep learning (DL) methodology has emerged as a powerful technique to characterize and learn from rapidly accumulating pharmacogenomics data. We introduce the fundamentals and typical model architectures of DL. We review the use of DL in classification of cancers and cancer subtypes (diagnosis and treatment stratification of patients), prediction of drug response and drug synergy for individual tumors (treatment prioritization for a patient), drug repositioning and discovery and the study of mechanism/mode of action of treatments. For each topic, we summarize current genomics and pharmacogenomics data resources such as pan-cancer genomics data for cancer cell lines (CCLs) and tumors, and systematic pharmacologic screens of CCLs. By revisiting the published literature, including our in-house analyses, we demonstrate the unprecedented capability of DL enabled by rapid accumulation of data resources to decipher complex drug response patterns, thus potentially improving cancer medicine. Overall, this review provides an in-depth summary of state-of-the-art DL methods and up-to-date pharmacogenomics resources and future opportunities and challenges to realize the goal of precision oncology.
SMARTS: the social media-based addiction recovery and intervention targeting server
Authors: Jha Deeptanshu , Singh Rahul 
Published: October 2019

Abstract

Motivation
Substance abuse and addiction is a significant contemporary health crisis. Modeling its epidemiology and designing effective interventions requires real-time data analysis along with the means to contextualize addiction patterns across the individual-to-community scale. In this context, social media platforms have begun to receive significant attention as a novel source of real-time user-reported information. However, the ability of epidemiologists to use such information is significantly stymied by the lack of publicly available algorithms and software for addiction information extraction, analysis and modeling.

Results
SMARTS is a public, open source, web-based application that addresses the aforementioned deficiency. SMARTS is designed to analyze data from two popular social media forums, namely, Reddit and Twitter and can be used to study the effect of various intoxicants including, opioids, weed, kratom, alcohol and cigarettes. The SMARTS software analyzes social media posts using natural language processing, and machine learning to characterize drug use at both the individual- and population-levels. Included in SMARTS is a predictive modeling functionality that can, with high accuracy, identify individuals open to addiction recovery interventions. SMARTS also supports extraction, analysis and visualization of a number of key informational and demographic characteristics including post topics and sentiment, drug- and recovery-term usage, geolocation and age. Finally, the distributions of the aforementioned characteristics as derived from a set of 170 097 drug users are provided as part of SMARTS and can be used by researchers as a reference.

Availability and implementation
The SMARTS web server and source code are available at: http://haddock9.sfsu.edu/.

Supplementary information
Supplementary data are available at Bioinformatics online.
EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2
Authors: Chen Shengnan , Youhong Tang , Tan Yixin , He Yuxiang , Ban Yuanyuan , Cai Jing , Li Xiaoling , Xiong Wei , Zeng Zhaoyang , Li Guiyuan , Yi Mei , Liu Wei , Xiang Bo 
Published: October 2019

Abstract
Nasopharyngeal carcinoma (NPC) is notorious for its aggressiveness and high metastatic potential. NPC patients with distant metastasis have a particularly poor prognosis; however, evaluating metastatic potential by expression profiles of primary tumors is challenging. This study aimed to investigate the association between activation of epidermal growth factor receptor (EGFR) signaling and NPC metastasis and the underlying mechanisms. We found an association between EGFR protein overexpression and intense EGFR immunostaining in NPC samples with advanced tumor node metastasis stage, clinical stage, and distant metastasis in NPC patients. Exogenous EGF stimulates NPC mobility and invasiveness in vitro. Activation of EGFR signaling prompted PKM2 translocation to the nucleus. Silencing either EGFR or PKM2 attenuates NPC cell aggressiveness in vitro and in vivo. Blocking EGFR signaling with cetuximab suppressed NPC cell invasiveness in vitro and metastatic potential in vivo. Comprehensive analyses of transcriptome profiles indicated that the EGFR-PKM2 axis activates a number of novel metastasis promoters, including F3, FOSL1, EPHA2, ANTXR2, and AKR1C2. Finally, we found that the metastasis-promoting function of the EGFR-PKM2 axis is dependent on nuclear PKM2 regulation of the transcription of metastasis-related genes, including FOSL1 and ANTXR2. Our study indicates that EGFR-PKM2 signaling promotes NPC cell invasion and metastasis through induction of FOSL1 and ANTXR2 and identifies EGFR as a promising biomarker for predicting the risk of distant metastasis.
Cultivating Empathy and Resonance for Muslim Lives Through Affective Images of the Chapel Hill Victims
Authors: Peterson Kristin M 
Published: October 2019

AbstractThis article examines the creative projects that circulated in digital media following the murder of three Muslim college students in Chapel Hill, NC, in February 2015. Through an engagement with affect theory and digital mourning studies, this article critically analyzes the limitations of affect in the digital moment, as the complex lives of the victims were reduced to simple but highly resonate icons. Despite the limitations of these affective icons, I argue that the contradictory emotions of successful happiness and unimaginable grief that adhered to these images enabled Muslims to cultivate feelings of resonance. At the same time, Muslims were expected to perform constant affective labor to prove the worth and equality of their lives. Finally, my analysis of this case illustrates how these heavily affective images reinforced that Muslim lives are only valued if they are positive, harmless and apolitical.
Intersectionality and gender: community practice with low-income migrant women
Authors: Hung Suet-lin , Fung Kwok-kin , Lau Siu-mei 
Published: October 2019

AbstractEchoing the call to incorporate the intersectionality framework into studies of gender structure, this paper applied the framework to re-analyse the quantitative and qualitative findings of an evaluation study on a women empowerment community project in Hong Kong. This effort revealed the importance of the gender structure’s dimension of sexual division of labour and the intersectional effects of gender, race and class in explaining the mixed traditional and progressive views in different items within a domain and across different domains of the gender division of labour, specifically the marital, parental, employment, social activities and education domains. The low-income migrant women have upheld different traditional ideas in these domains. However, in contrast with the richer and local women who also shared these traditional views, low-income migrant women in this study questioned some prevailing ideas in these domains, due to their need to survive the conditions defined by the intersection of gender, race and class. The findings of this study, despite being preliminary and limited, demonstrate the significance and feasibility of studying gender structure adopting the perspective of intersectionality. Arguably, this lack of understanding of the intersectional effects diminishes the effectiveness of community intervention. In light of the paucity of research adopting the intersectionality framework in the community development field in general, and a similar deficit in the feminist and community development fields in Hong Kong in particular, the failure to adopt the intersectionality framework by the community project under consideration is understandable. It is likely that as this framework becomes more prominent in the future, given its potential to offer deeper insight into the dynamics of gender structure, community interventions for women of different identities could be strengthened.
Comparative Genomics Analysis Reveals High Levels of Differential Retrotransposition among Primates from the Hominidae and the Cercopithecidae Families
Authors: Tang Wanxiangfu , Liang Ping 
Published: October 2019

Abstract
Mobile elements (MEs), making ∼50% of primate genomes, are known to be responsible for generating inter- and intra-species genomic variations and play important roles in genome evolution and gene function. Using a bioinformatics comparative genomics approach, we performed analyses of species-specific MEs (SS-MEs) in eight primate genomes from the families of Hominidae and Cercopithecidae, focusing on retrotransposons. We identified a total of 230,855 SS-MEs, with which we performed normalization based on evolutionary distances, and we also analyzed the most recent SS-MEs in these genomes. Comparative analysis of SS-MEs reveals striking differences in ME transposition among these primate genomes. Interesting highlights of our results include: 1) the baboon genome has the highest number of SS-MEs with a strong bias for SINEs, while the crab-eating macaque genome has a sustained extremely low transposition for all ME classes, suggesting the existence of a genome-wide mechanism suppressing ME transposition; 2) while SS-SINEs represent the dominant class in general, the orangutan genome stands out by having SS-LINEs as the dominant class; 3) the human genome stands out among the eight genomes by having the largest number of recent highly active ME subfamilies, suggesting a greater impact of ME transposition on its recent evolution; and 4) at least 33% of the SS-MEs locate to genic regions, including protein coding regions, presenting significant potentials for impacting gene function. Our study, as the first of its kind, demonstrates that mobile elements evolve quite differently among these primates, suggesting differential ME transposition as an important mechanism in primate evolution.
Negative Regulator of Ubiquitin-Like Protein 1 modulates the autophagy–lysosomal pathway via p62 to facilitate the extracellular release of tau following proteasome impairment
Authors: Guarascio Rosellina , Salih Dervis , Yasvoina Marina , Edwards Frances A , Cheetham Michael E , van der Spuy Jacqueline 
Published: October 2019

Abstract
Negative regulator of ubiquitin-like protein 1 (NUB1) and its longer isoform NUB1L are ubiquitin-like (UBL)/ubiquitin-associated (UBA) proteins that facilitate the targeting of proteasomal substrates, including tau, synphilin-1 and huntingtin. Previous data revealed that NUB1 also mediated a reduction in tau phosphorylation and aggregation following proteasome inhibition, suggesting a switch in NUB1 function from targeted proteasomal degradation to a role in autophagy. Here, we delineate the mechanisms of this switch and show that NUB1 interacted specifically with p62 and induced an increase in p62 levels in a manner facilitated by inhibition of the proteasome. NUB1 moreover increased autophagosomes and the recruitment of lysosomes to aggresomes following proteasome inhibition. Autophagy flux assays revealed that NUB1 affected the autophagy–lysosomal pathway primarily via the UBA domain. NUB1 localized to cytosolic inclusions with pathological forms of tau, as well as LAMP1 and p62 in the hippocampal neurons of tauopathy mice. Finally, NUB1 facilitated the extracellular release of tau following proteasome inhibition. This study thus shows that NUB1 plays a role in regulating the autophagy–lysosomal pathway when the ubiquitin proteasome system is compromised, thus contributing to the mechanisms targeting the removal of aggregation-prone proteins upon proteasomal impairment.
Mosquito Exposure and Malaria Morbidity: A Microlevel Analysis of Household Mosquito Populations and Malaria in a Population-Based Longitudinal Cohort in Western Kenya
Authors: O’Meara Wendy Prudhomme , Simmons Ryan , Bullins Paige , Freedman Betsy , Abel Lucy , Mangeni Judith , Taylor Steve M , Obala Andrew A 
Published: October 2019

Abstract

Background
Malaria morbidity is highly overdispersed in the population. Fine-scale differences in mosquito exposure may partially explain this heterogeneity in individual malaria outcomes.

Methods
In 38 households we explored the effect of household-level mosquito exposure and individual insecticide-treated net (ITN) use on relative risk (RR) of confirmed malaria. We conducted monthly active surveillance (n = 254; 2624 person-months) and weekly mosquito collection (2092 household-days of collection), and used molecular techniques to confirm human blood feeding and exposure to infectious mosquitoes.

Results
Of 1494 female Anopheles (89.8% Anopheles gambiae sensu lato), 88.3% were fed, 51.9% had a human blood meal, and 9.2% were sporozoite infected. In total, 168 laboratory-confirmed malaria episodes were reported (incidence rate 0.064 episodes per person-month at risk; 95% confidence interval [CI], .055–.074). Malaria risk was directly associated with exposure to sporozoite-infected mosquitoes (RR, 1.24; 95% CI, 1.11–1.38). No direct effect was measured between ITN use and malaria morbidity; however, ITN use did moderate the effect of mosquito exposure on morbidity.

Conclusions
Malaria risk increases linearly with vector density and feeding success for persons with low ITN use. In contrast, malaria risk among high ITN users is consistently low and insensitive to variation in mosquito exposure.
Two-Locus Local Adaptation by Additive or Epistatic Gene Combinations in Autotetraploids Versus Diploids
Authors: Mostafaee Navid , Griswold Cortland K 
Published: October 2019

AbstractIn this article, we present a theoretical comparison of local adaptation between diploid and autotetraploid populations when fitness is determined by either additive or epistatic interactions between alleles at 2 loci. A continent-island model of local adaptation is derived, with 1-way migration from the continent to the island and distinct genotypes adaptive on the continent versus the island. The meiotic component of the model accounts for multivalent formation and the processes of chromosomal gametic disequilibrium and double reduction, which are unique to autotetraploids. Both the adaptability and efficiency of adaptation are investigated, where adaptability asks whether a population adapts and efficiency is the rate of adaptation. With an additive genetic basis to fitness, diploids experience better adaptability and efficiency than autotetraploids. With epistasis, our results indicate a limited parameter space in which autotetraploids have greater adaptability than diploids, but results indicate an interesting difference between adaptability and efficiency of adaptation. Oftentimes, diploids exhibit greater adaptability whereas autotetraploids exhibit greater efficiency of adaptation. These findings provide evidence for the advantage of epistasis within autotetraploids when efficiency of adaptation is of interest. Although autotetraploids are more efficient, under the same conditions and at equilibrium, diploid populations often have higher mean local fitness. Overall, the most ideal situation for autotetraploid local adaptation compared to diploids is when epistasis is strong, mutation is weak, recombination is high, selection is strong, deleterious selection is additive, chromosomal gametic disequilibrium is present, and double reduction is absent.
A Systematic Review and Meta-Analysis of Bevacizumab in First-Line Metastatic Breast Cancer: Lessons for Research and Regulatory Enterprises
Authors: Hey Spencer Phillips , Gyawali Bishal , D’Andrea Elvira , Kanagaraj Manoj , Franklin Jessica M , Kesselheim Aaron S 
Published: October 2019

Abstract

Background
The US Food and Drug Administration’s accelerated approval and later withdrawal of bevacizumab in patients with metastatic breast cancer (mBC) is a seminal case for ongoing debates about the validity of using progression-free survival (PFS) as a surrogate measure for overall survival (OS) in cancer drug approvals. We systematically reviewed and meta-analyzed the evidence around bevacizumab’s regulatory approval and withdrawal in mBC.

Methods
We searched for all published phase II or III clinical trials testing bevacizumab as a first-line therapy for patients with mBC. Data were extracted on trial demographics, interventions, and outcomes. Descriptive analysis was stratified by whether the trial was initiated before, during, or after the accelerated approval. We used a cumulative random-effects meta-analysis to assess the evolution of evidence of the effect of bevacizumab on PFS and OS. We estimated the association between the trial-level PFS and OS effect using a nonlinear mixed-regression model.

Results
Fifty-two studies were included. Trial activity dramatically dropped after the accelerated approval was withdrawn. Eight clinical trials reported hazard ratios (hazard ratios) and were meta-analyzed. The cumulative hazard ratio for PFS was 0.72 (95% CI = 0.65 to 0.79), and the cumulative hazard ratio for OS was 0.90 (95% CI = 0.80 to 1.01). The regression model showed a statistically nonsignificant association between PFS benefit and OS benefit (β = 0.43, SE = 0.81).

Conclusion
The US Food and Drug Administration’s decision-making in this case was consistent with the evolving state of evidence. However, the fact that seven clinical trials are insufficient to conclude validity (or lack thereof) for a trial-level surrogate suggests that it would be more efficient to conduct trials using the more clinically meaningful endpoints.
Differential diagnosis for a ring-enhancing lesion on CT/MRI brain: retained cotton ball pledget
Authors: Hughes Luke D 
Published: October 2019

Abstract
New or persisting symptoms require careful evaluation and investigation. We present a case report of a 58-year-old man who underwent a craniotomy for a subdural haematoma and presented a decade later with worsening neurological symptoms. Investigation revealed the cause to be a delayed foreign body reaction to a retained cotton wool pledget.
Antibiotic resistance patterns of Escherichia coli in migrants vs non-migrants: a study of 14 561 urine samples
Authors: Sloth Louise B , Nielsen Rikke T , Østergaard Christian , Nellums Laura B , Hargreaves Sally , Friedland Jon S , Norredam Marie 
Published: October 2019

Abstract

Background
To investigate the distribution of urine isolates and antibiotic resistance patterns in the predominant uropathogen Escherichia coli in migrant and non-migrant individuals.

Methods
We linked a cohort consisting of all migrants obtaining residence as refugees or family-reunited migrants in Denmark between January 1993 and December 2015 to hospital urine samples examined from January 2000 to December 2015 at the Department of Microbiology, University Hospital Hvidovre, Denmark. Samples from non-migrant individuals, Danish-born from Danish parents, were included as comparison. Analysis was carried out using multivariate logistic regression.

Results
There were 14 561 first-time urine samples included, with E. coli being the most prevalent bacterial pathogen. Of the identified isolates, 4686/11 737 were E. coli among non-migrants and 1032/2824 among migrants.
Sulfamethoxazol–Trimethoprim (SXT) resistance was found in 34.3% (350/1020) of E. coli isolates among migrants and 23.2% (1070/4619) among non-migrant patients [odds ratio (OR) 1.73, 95% confidence interval (CI): 1.47–2.03]. Ciprofloxacin resistance was found in 5.8% (36/618) of isolates among migrants and 2.2% (67/3092) among non-migrants (OR 2.20, 95% CI: 1.37–3.53). Gentamicin (GEN) resistance was seen in 10.8% (61/565) and 4.7% (110/2328) of isolates (OR 2.33, 95% CI:1.63–3.34), Cefuroxime resistance in 8.5% (87/1019) and 3.4% (158/4618) (OR 2.40, 95% CI:1.77–3.24), Ampicillin (AMP) resistance in 51.4% and 40.8% (OR 1.65, 95% CI: 1.42–1.92) and Piperacillin–Tazobactam resistance in 6.9% (30/432) and 4.2% (65/1532) for migrant and non-migrant patients, respectively. When stratifying according to migrant status, family-reunited had higher odds of resistance than refugees for SXT, GEN and AMP.

Conclusions
Prevalence of antibiotic resistance was significantly higher in E. coli isolates among migrants, both refugees and family-reunited, than non-migrant patients. Differences could not be explained by comorbidity or income. The results emphasize the importance of urine sample testing in both local-born and migrants before antibiotic start-up and point to the benefit of considering migration to secure individual treatment and equal health outcomes.