bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the serological response to syphilis treatment in men living with HIV
Authors: Ren Melody , Szadkowski Leah , Walmsley Sharon L. 
Published: August 2020

Objective:
To examine syphilis serology after treatment in people living with HIV. No unanimous guidelines exist in the era of increasing coinfection.

Design:
Retrospective review using a tertiary care clinic in Toronto from 2000 to 2017.

Methods:
The 2015 Centers for Diseases Control and Prevention syphilis guidelines were used to define an adequate serologic response. Cumulative distribution estimates and proportional hazards models accounting for interval censoring estimated the time to serologic response and seroreversion. Multistate models were used to investigate extended periods of serofast serology.

Results:
A total of 171 patients with syphilis met our inclusion criteria (16 primary, 53 secondary, 26 early latent, 46 late latent, 30 neurosyphilis). Serologic response was achieved by 12 months for 65 (94%) patients and by 12–18 months for four (6%) patients with primary/secondary syphilis. For latent and neurosyphilis, 94 (92%) achieved serologic response by 24 months and one (1%) at 24.1 months. 84 (49%) patients achieved seroreversion with a median (95% confidence interval) time of 2 (1.44, 2.68) years. Latent syphilis was associated with a lower likelihood of achieving serologic response [hazard ratio (HR) = 0.52, P = 0.05] and seroreversion (HR = 0.27, P < 0.001) compared with primary/secondary syphilis. The probability of moving from a new infection state to a serofast state within 1 year was high (0.65) but the 1-year probability of transitioning from a serofast state to seroreversion was low (0.27).

Conclusion:
The majority of people living with HIV infected with syphilis will achieve an adequate serologic response as per the Centers for Diseases Control and Prevention guidelines. Seroreversion was observed in about half but can take years to occur.
Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV–hepatitis B coinfection
Authors: Dezanet Lorenza N.C. , Maylin Sarah , Gabassi Audrey , Rougier Hayette , Miailhes Patrick , Lascoux-Combe Caroline , Chas Julie , Girard Pierre-Marie , Delaugerre Constance , Zoulim Fabien , Lacombe Karine , Boyd Anders 
Published: August 2020

Objective:
To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection.

Design:
Cross-sectional study of 31 HIV–HBV-infected patients (total liver biopsies, n = 38) from a well defined cohort.

Methods:
Spearman's rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA : total intrahepatic-DNA ratio].

Results:
At biopsy, 22 (71.0%) patients were hepatitis B ‘e’ antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n = 34), 0.26 copies/cell (0.4–2.89); total intrahepatic-DNA (n = 38), 2.38 copies/cell (0.58–207.9), and cccDNA : total intrahepatic-DNA ratio (n = 34), 0.05 (interquartile range = 0.01–0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho = 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho = 0.57, P < 0.001) or cccDNA : total intrahepatic-DNA ratio (Rho = −0.45, P = 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA : total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P = 0.5).

Conclusion:
qHBcrAg is a potential surrogate marker of cccDNA in HIV–HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.
The predictors of pain extent in people living with HIV
Authors: Sabin Caroline A. , Harding Richard , Bagkeris Emmanouil , Geressu Adam , Nkhoma Kennedy , Post Frank A. , Sachikonye Memory , Boffito Marta , Anderson Jane , Mallon Patrick W.G. , Williams Ian , Vera Jaime , Johnson Margaret A. , Babalis Daphne , Winston Alan 
Published: August 2020

Objective:
To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage.

Design:
Cross-sectional analysis of cohort study in the United Kingdom and Ireland.

Methods:
Pain information was collected during the baseline visit (conducted from 2013 to 2015) through a self-completed manikin identifying pain at 15 sites from five body regions. Pain was classified as widespread if reported at at least four regions and at least seven sites, or regional otherwise. Chi-squared tests, Kruskal–Wallis tests and ordinal logistic regression were used to consider associations between pain extent and sociodemographic and HIV-related factors.

Results:
Among the 1207 participants (614 PWH ≥ 50 years, 330 PWH < 50 years, 263 HIV-negative controls ≥50 years), pain was most commonly reported at the upper (left: 28.9%, right: 28.0%) and lower (left: 25.7%; right: 24.5%) leg, upper (18.6%) and lower (29.7%) back and shoulders (left: 16.0%; right: 16.8%). Widespread pain was more commonly reported in PWH than in HIV-negative controls (PWH ≥ 50 years: 18.7%; PWH < 50 years: 12.7%; HIV-negative ≥50 years: 9.5%) with regional pain reported in 47.6, 44.8 and 49.8%, respectively (global P = 0.001). In multivariable analyses, pain extent was greater in those with lower educational attainment, those exposed to more ART drugs, and those with a higher current CD4+ cell count but longer exposure to immunosuppression.

Conclusion:
Widespread pain is commonly reported in PWH and is associated with longer duration of exposure to HIV, immunosuppression and ART. Our findings call for greater awareness, and interventions to support the management, of pain in PWH.
Updates on defining and detecting diarrheagenic Escherichia coli pathotypes
Authors: Jesser Kelsey J. , Levy Karen 
Published: August 2020

Purpose of review
Several types of Escherichia coli cause acute diarrhea in humans and are responsible for a large burden of disease globally. The purpose of this review is to summarize diarrheagenic Escherichia coli (DEC) pathotype definitions and discuss existing and emerging molecular, genomic, and gut microbiome methods to detect, define, and study DEC pathotypes.

Recent findings
DEC pathotypes are currently diagnosed by molecular detection of unique virulence genes. However, some pathotypes have defied coherent molecular definitions because of imperfect gene targets, and pathotype categories are complicated by hybrid strains and isolation of pathotypes from asymptomatic individuals. Recent progress toward more efficient, sensitive, and multiplex DEC pathotype detection has been made using emerging PCR-based technologies. Genomics and gut microbiome detection methods continue to advance rapidly and are contributing to a better understanding of DEC pathotype diversity and functional potential.

Summary
DEC pathotype categorizations and detection methods are useful but imperfect. The implementation of molecular and sequence-based methods and well designed epidemiological studies will continue to advance understanding of DEC pathotypes. Additional emphasis is needed on sequencing DEC genomes from regions of the world where they cause the most disease and from the pathotypes that cause the greatest burden of disease globally.
Outcomes in Kidney Transplantation Between Veterans Affairs and Civilian Hospitals
Authors: Kesseli Samuel J. , Samoylova Mariya L. , Moris Dimitrios , Connor Ashton A. , Schmitz Robin , Shaw Brian I. , Gloria Jared N. , Abraham Nader , McElroy Lisa M. , Sudan Debra L. , Knechtle Stuart J. , Barbas Andrew S. 
Published: August 2020

Objective:
We sought to compare kidney transplantation outcomes between Veterans Affairs (VA) and non-VA transplant centers.

Summary Background Data:
Transplant care at the VA has previously been scrutinized due to geographic and systematic barriers. The recently instituted MISSION Act entered effect June 6th, 2019, which enables veteran access to surgical care at civilian hospitals if certain eligibility criteria are met.

Methods:
We evaluated observed-to-expected outcome ratios (O:E) for graft loss and mortality using the Scientific Registry of Transplant Recipients database for all kidney transplants during a 15-year period (July 1, 2001–June 30, 2016). Of 229,188 kidney transplants performed during the study period, 1508 were performed at VA centers (N = 7), 7750 at the respective academic institutions affiliated with these VA centers, and 227,680 at non-VA centers nationwide (N = 286).

Results:
Aggregate O:E ratios for mortality were lower in VA centers compared with non-VA centers at 1 month and 1 year (O:E = 0.27 vs 1.00, P = 0.03 and O:E = 0.62 vs 1.00, P = 0.03, respectively). Graft loss at 1 month and 1 year was similar between groups (O:E = 0.65 vs 1.00, P = 0.11 and O:E = 0.79 vs 1.00, P = 0.15, respectively). Ratios for mortality and graft loss were similar between VA centers and their respective academic affiliates. Additionally, a subgroup analysis for graft loss and mortality at 3 years (study period January 1, 2009–December 31, 2013) demonstrated no significant differences between VA centers, VA-affiliates, and all non-VA centers.

Conclusions:
Despite low clinical volume, VA centers offer excellent outcomes in kidney transplantation. Veteran referral to civilian hospitals should weigh the benefit of geographic convenience and patient preference with center outcomes.
Portable Automated Surveillance of Surgical Site Infections Using Natural Language Processing
Authors: Bucher Brian T. , Shi Jianlin , Ferraro Jeffrey P. , Skarda David E. , Samore Matthew H. , Hurdle John F. , Gundlapalli Adi V. , Chapman Wendy W. , Finlayson Samuel R. G. 
Published: August 2020

Objectives:
We present the development and validation of a portable NLP approach for automated surveillance of SSIs.

Summary of Background Data:
The surveillance of SSIs is labor-intensive limiting the generalizability and scalability of surgical quality surveillance programs.

Methods:
We abstracted patient clinical text notes after surgical procedures from 2 independent healthcare systems using different electronic healthcare records. An SSI detected as part of the American College of Surgeons’ National Surgical Quality Improvement Program was used as the reference standard. We developed a rules-based NLP system (Easy Clinical Information Extractor [CIE]-SSI) for operative event-level detection of SSIs using an training cohort (4574 operative events) from 1 healthcare system and then conducted internal validation on a blind cohort from the same healthcare system (1850 operative events) and external validation on a blind cohort from the second healthcare system (15,360 operative events). EasyCIE-SSI performance was measured using sensitivity, specificity, and area under the receiver-operating-curve (AUC).

Results:
The prevalence of SSI was 4% and 5% in the internal and external validation corpora. In internal validation, EasyCIE-SSI had a sensitivity, specificity, AUC of 94%, 88%, 0.912 for the detection of SSI, respectively. In external validation, EasyCIE-SSI had sensitivity, specificity, AUC of 79%, 92%, 0.852 for the detection of SSI, respectively. The sensitivity of EasyCIE-SSI decreased in clean, skin/subcutaneous, and outpatient procedures in the external validation compared to internal validation.

Conclusion:
Automated surveillance of SSIs can be achieved using NLP of clinical notes with high sensitivity and specificity.
A statistically rigorous deep neural network approach to predict mortality in trauma patients admitted to the intensive care unit
Authors: Ahmed Fahad Shabbir , Ali Liaqat , Joseph Bellal A. , Ikram Asad , Ul Mustafa Raza , Bukhari Syed Ahmad Chan 
Published: August 2020

BACKGROUND
Trauma patients admitted to critical care are at high risk of mortality because of their injuries. Our aim was to develop a machine learning-based model to predict mortality using Fahad-Liaqat-Ahmad Intensive Machine (FLAIM) framework. We hypothesized machine learning could be applied to critically ill patients and would outperform currently used mortality scores.

METHODS
The current Deep-FLAIM model evaluates the statistically significant risk factors and then supply these risk factors to deep neural network to predict mortality in trauma patients admitted to the intensive care unit (ICU). We analyzed adult patients (≥18 years) admitted to the trauma ICU in the publicly available database Medical Information Mart for Intensive Care III version 1.4. The first phase selection of risk factor was done using Cox-regression univariate and multivariate analyses. In the second phase, we applied deep neural network and other traditional machine learning models like Linear Discriminant Analysis, Gaussian Naïve Bayes, Decision Tree Model, and k-nearest neighbor models.

RESULTS
We identified a total of 3,041 trauma patients admitted to the trauma surgery ICU. We observed that several clinical and laboratory-based variables were statistically significant for both univariate and multivariate analyses while others were not. With most significant being serum anion gap (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.94–3.11), sodium (HR, 2.11; 95% CI, 1.61–2.77), and chloride (HR, 2.11; 95% CI, 1.69–2.64) abnormalities on laboratories, while clinical variables included the diagnosis of sepsis (HR, 2.03; 95% CI, 1.23–3.37), Quick Sequential Organ Failure Assessment score (HR, 1.52; 95% CI, 1.32–3.76). And Systemic Inflammatory Response Syndrome criteria (HR. 1.41; 95% CI, 1.24–1.26). After we used these clinically significant variables and applied various machine learning models to the data, we found out that our proposed DNN outperformed all the other methods with test set accuracy of 92.25%, sensitivity of 79.13%, and specificity of 94.16%; positive predictive value, 66.42%; negative predictive value, 96.87%; and area under the curve of the receiver-operator curve of 0.91 (1.45–1.29).

CONCLUSION
Our novel Deep-FLAIM model outperformed all other machine learning models. The model is easy to implement, user friendly and with high accuracy.

LEVEL OF EVIDENCE
Prognostic study, level II.
The elusive promise of myostatin inhibition for muscular dystrophy
Authors: Wagner Kathryn R. 
Published: August 2020

Purpose of reviewRecent terminations of clinical trials of myostatin inhibitors in muscular dystrophy have raised questions about the predictiveness of mouse models for this therapeutic strategy.Recent findingsA variety of myostatin inhibitors have been developed for preclinical and clinical studies. These inhibitors have ameliorated the phenotype of many but not all mouse models of muscular dystrophy. However, randomized double-blinded placebo controlled trials in both pediatric and adult muscular dystrophies have, as of yet, not demonstrated functional improvement.SummaryThe present article will review the preclinical promise of myostatin inhibitors, the clinical trial experience to date of these inhibitors in muscular dystrophy, and the potential reasons for the lack of observed translation.
The role of the microbiome in host evolution
Authors: Kolodny Oren , Callahan Benjamin J. , Douglas Angela E. 
Published: August 2020

In the last decade, we have witnessed a major paradigm shift in the life sciences: the recognition that the microbiome, i.e. the set of microorganisms associated with healthy animals (including humans) and plants, plays a crucial role in the sustained health and fitness of its host. Enabled by rapid advances in sequencing technologies and analytical methods, substantial advances have been achieved in both identifying the microbial taxa and understanding the relationship between microbiome composition and host phenotype. These breakthroughs are leading to novel strategies for improved human and animal health, enhanced crop yield and nutritional quality, and the control of various pests and disease agents.
This article is part of the theme issue ‘The role of the microbiome in host evolution'.
Symbiosis and stress: how plant microbiomes affect host evolution
Authors: Hawkes Christine V. , Bull James J. , Lau Jennifer A. 
Published: August 2020

Existing paradigms for plant microevolution rarely acknowledge the potential impacts of diverse microbiomes on evolutionary processes. Many plant-associated microorganisms benefit the host via access to resources, protection from pathogens, or amelioration of abiotic stress. In doing so, they alter the plant's perception of the environment, potentially reducing the strength of selection acting on plant stress tolerance or defence traits or altering the traits that are the target of selection. We posit that the microbiome can affect plant microevolution via (1) manipulation of plant phenotypes in ways that increase plant fitness under stress and (2) direct microbial responses to the environment that benefit the plant. Both mechanisms might favour plant genotypes that attract or stimulate growth of the most responsive microbial populations or communities. We provide support for these scenarios using infectious disease and quantitative genetics models. Finally, we discuss how beneficial plant–microbiome associations can evolve if traditional mechanisms maintaining cooperation in pairwise symbioses, namely partner fidelity, partner choice and fitness alignment, also apply to the interactions between plants and diverse foliar and soil microbiomes. To understand the role of the plant microbiome in host evolution will require a broad ecological understanding of plant–microbe interactions across both space and time.
This article is part of the theme issue ‘The role of the microbiome in host evolution'.
Optimal integration between host physiology and functions of the gut microbiome
Authors: Fontaine Samantha S. , Kohl Kevin D. 
Published: August 2020

Host-associated microbial communities have profound impacts on animal physiological function, especially nutrition and metabolism. The hypothesis of ‘symmorphosis’, which posits that the physiological systems of animals are regulated precisely to meet, but not exceed, their imposed functional demands, has been used to understand the integration of physiological systems across levels of biological organization. Although this idea has been criticized, it is recognized as having important heuristic value, even as a null hypothesis, and may, therefore, be a useful tool in understanding how hosts evolve in response to the function of their microbiota. Here, through a hologenomic lens, we discuss how the idea of symmorphosis may be applied to host-microbe interactions. Specifically, we consider scenarios in which host physiology may have evolved to collaborate with the microbiota to perform important functions, and, on the other hand, situations in which services have been completely outsourced to the microbiota, resulting in relaxed selection on host pathways. Following this theoretical discussion, we finally suggest strategies by which these currently speculative ideas may be explicitly tested to further our understanding of host evolution in response to their associated microbial communities.This article is part of the theme issue ‘The role of the microbiome in host evolution’.
Symbiotic magnetic sensing: raising evidence and beyond
Authors: Natan Eviatar , Fitak Robert Rodgers , Werber Yuval , Vortman Yoni 
Published: August 2020

The identity of a magnetic sensor in animals remains enigmatic. Although the use of the geomagnetic field for orientation and navigation in animals across a broad taxonomic range has been well established over the past five decades, the identity of the magnetic-sensing organ and its structure and/or apparatus within such animals remains elusive—‘a sense without a receptor’. Recently, we proposed that symbiotic magnetotactic bacteria (MTB) may serve as the underlying mechanism behind a magnetic sense in animals—‘the symbiotic magnetic-sensing hypothesis'. Since we first presented this hypothesis, both criticism and support have been raised accordingly. Here we address the primary criticisms and discuss the plausibility of such a symbiosis, supported by preliminary findings demonstrating the ubiquity of MTB DNA in general, and specifically in animal samples. We also refer to new supporting findings, and discuss host adaptations that could be driven by such a symbiosis. Finally, we suggest the future research directions required to confirm or refute the possibility of symbiotic magnetic-sensing.This article is part of the theme issue ‘The role of the microbiome in host evolution’.
Contemporary and historical selection in Tasmanian devils (Sarcophilus harrisii) support novel, polygenic response to transmissible cancer
Authors: Stahlke Amanda R. , Epstein Brendan , Barbosa Soraia , Margres Mark J. , Patton Austin , Hendricks Sarah A. , Veillet Anne , Fraik Alexandra K , Schönfeld Barbara , McCallum Hamish I. , Hamede Rodrigo , Jones Menna E. , Storfer Andrew , Hohenlohe Paul A. 
Published: August 2020

AbstractTasmanian devils (Sarcophilus harrisii) are evolving in response to a unique transmissible cancer, devil facial tumour disease (DFTD), first described in 1996. Persistence of wild populations and the recent emergence of a second independently evolved transmissible cancer suggest that transmissible cancers may be a recurrent feature in devils. Here we compared signatures of selection across temporal scales to determine whether genes or gene pathways under contemporary selection (6-8 generations) have also been subject to historical selection (65-85 million years), and test for recurrent selection in devils. First, we used a targeted sequencing approach, RAD-capture, to identify genomic regions subject to rapid evolution in approximately 2,500 devils in six populations as DFTD spread across the species range. We documented genome-wide contemporary evolution, including 186 candidate genes related to cell cycling and immune response. Then we used a molecular evolution approach to identify historical positive selection in devils compared to other marsupials and found evidence of selection in 1,773 genes. However, we found limited overlap across time scales, with historical selection detected in only 16 contemporary candidate genes, and no overlap in enriched functional gene sets. Our results are consistent with a novel, multi-locus evolutionary response of devils to DFTD. Our results can inform management actions to conserve adaptive potential of devils by identifying high priority targets for genetic monitoring and maintenance of functional diversity in managed populations.