bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretic and Evidence-Based Laparotomy Closure with Sutures and Meshes
Authors: Mioton Lauren M. , Dumanian Gregory A.
Published: August 2018

The ultimate tensile strength of newly apposed tissue is the sum of the strength of the physical construct holding the tissues and the strength of biologic healing. For successful incisional hernia repair, the total strength of the repair must remain greater than the forces applied. While much work has been done to understand the science of wound healing—the ability of an open defect to contract and close—far less has been done to understand the healing of 2 newly approximated previously nonwounded surfaces held together with sutures or other implants. In this article, the elements of ultimate tensile strength on laparotomy closure as well as their progression over time will be related to clinical studies of abdominal wall closure.
Reconstruction of the Abdominal Wall after Oncologic Resection: Defect Classification and Management Strategies
Authors: Mericli Alexander F. , Baumann Donald P. , Butler Charles E.
Published: August 2018

Compared with conventional ventral hernia repair, there are several additional considerations germane to the oncologic abdominal wall reconstruction, including the management of radiation soft-tissue injury, the management of bacterial contamination, and the location and extent of the defect. Herein, we review some of the unique challenges associated with oncologic abdominal wall reconstruction and introduce a new classification schema to assist the reconstructive surgeon in performing these complex cases.
Building a Multidisciplinary Hospital-Based Abdominal Wall Reconstruction Program: Nuts and Bolts
Authors: Schlosser Kathryn A. , Arnold Michael R. , Kao Angela M. , Augenstein Vedra A. , Heniford B. Todd
Published: August 2018

Background:

A nationwide trend toward “centers of excellence” for medical and surgical care has led to development and scrutiny of high-volume surgical specialty centers. The prevalence of hernias and the complexity of successful repair have led to the establishment of specialty practices. Herein we review and discuss the components of the successful establishment of a tertiary hernia referral center.

Methods:

Literature on establishment and impact of hernia specialty centers was reviewed, including the authors’ own practice. Factors and outcomes concerning the coordination, development, funding, and staffing of a hernia center were discussed and tabulated.

Results:

After establishment of a tertiary hernia center or center of excellence, institutions have reported an increase in surgical case volume, hernia complexity, patient comorbidity, and the area from which patients will travel. Driving factors for this practice development are varied and include team development, improvement in patient preoperative factors, and surgical outcomes assessment, among others.

Conclusions:

Establishment of a successful tertiary hernia referral center often includes institution participation, surgical expertise, interdisciplinary collaboration, and ongoing evaluation of outcomes. Success may be marked by increased case volume and tertiary referrals, but it is most evidenced by improved patient outcomes.
Patient Safety Culture, Health Information Technology Implementation, and Medical Office Problems That Could Lead to Diagnostic Error
Authors: Campione Joanne R. , Mardon Russell E. , McDonald Kathryn M.
Published: August 2018

Background

Diagnostic errors may cause harm to patients by preventing or delaying appropriate treatment or by leading to unnecessary or harmful treatment.

Objectives

The aim of the study was to investigate the relationship between patient safety culture, health information technology (IT) implementation, and the frequency of problems that could lead to diagnostic errors in the medical office setting, such as unavailable test results, unavailable medical records, or unpursued abnormal results.

Methods

We used survey data from 925 medical offices nationwide that voluntarily submitted results to the 2012 Agency for Healthcare Research and Quality Medical Office Surveys on Patient Safety Culture database. At the office level, we ran a multivariate regression model to estimate the effect of culture on problem frequency while controlling for office-reported implementation levels of health IT, office characteristics such as the number of locations, and survey characteristics such as the percent of respondents that were physicians.

Results

The most frequent problem was “results from a lab or imaging test were not available when needed”; across 925 offices, the average was 15% reporting that it happened daily or weekly. Higher overall culture scores were significantly associated with fewer occurrences of each problem assessed. Compared with offices with completed health IT implementation, offices in the process of health IT implementation had higher frequency of problems.

Conclusions

This study offers insight into how patient safety culture and health IT implementation in medical offices can influence the frequency of breakdowns in processes of care, thereby identifying potential vulnerabilities that can increase diagnostic errors.
Colorectal Cancer Among Gout Patients Undergoing Colonoscopy
Authors: Slobodnick Anastasia , Krasnokutsky Svetlana , Lehmann Robert A. , Keenan Robert T. , Quach Jonathan , Francois Fritz , Pillinger Michael H.
Published: August 2018

Background/Objective

The connection between gout and various cancers remains unclear. We assessed the relationship between gout and colorectal cancer in a population of veterans.

Methods

We reviewed the Computerized Patient Record System of the VA New York Harbor Health Care System to assess the 10-year occurrence of colorectal cancer in patients with gout undergoing colonoscopy, versus patients with osteoarthritis but no gout.

Results

Gout and osteoarthritis subjects were similar in age, ethnicity, body mass index, and smoking history. Among 581 gout and 598 osteoarthritis subjects with documented colonoscopies, the 10-year prevalence of colorectal cancer was significantly lower in gout (0.8%) versus osteoarthritis (3.7%) (p = 0.0008) patients. Differences in colorectal cancer rates remained significant after stratifying for nonsteroidal anti-inflammatory drug use. Among gout subjects, use of colchicine and/or allopurinol, as well as the presence/absence of concomitant osteoarthritis, did not influence colorectal cancer occurrence. On subanalysis, differences in colorectal cancer occurrence between gout and osteoarthritis subjects persisted among those who underwent diagnostic (0.5% in gout vs 4.6% in osteoarthritis subjects, p < 0.001) but not screening (0.9% in gout subjects vs 1% in osteoarthritis subjects, p = 1.0) colonoscopy. There was no significant difference in nonmalignant colorectal polyp occurrence between gout and osteoarthritis subjects.

Conclusions

Subjects with gout had decreased colonoscopy-documented occurrence of colorectal cancer compared with osteoarthritis subjects, suggesting a possible protective effect.
Association of Serum Lipid Profile With Coronary Computed Tomographic Angiography–derived Morphologic and Functional Quantitative Plaque Markers
Authors: Baumann Stefan , Kryeziu Philipp , Tesche Christian , Shuler Darby C. , Becher Tobias , Rutsch Marlon , Behnes Michael , Stach Ksenija , Jacobs Brian E. , Renker Matthias , Henzler Thomas , Haubenreisser Holger , Schoenberg Stefan O. , Weiss Christel , Borggrefe Martin , Schwemmer Chris , Schoepf U. Joseph , Akin Ibrahim , Lossnitzer Dirk
Published: August 2018

Purpose:

Recent advances in image quality of coronary computed tomographic angiography (cCTA) have enabled improved characterization of coronary plaques. Thus, we investigated the association between quantitative morphological plaque markers obtained by cCTA and serum lipid levels in patients with suspected or known coronary artery disease.

Materials and Methods:

We retrospectively analyzed data of 119 statin-naive patients (55±14 y, 66% men) who underwent clinically indicated cCTA between January 2013 and February 2017. Patients were subdivided into a plaque and a no-plaque group. Quantitative and morphologic plaque markers, such as segment involvement score, segment stenosis score, remodeling index, napkin-ring sign, total plaque volume, calcified plaque volume, and noncalcified plaque volume (NCPV) and plaque composition, were analyzed using a semiautomated plaque software prototype. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, low-density lipoprotein/high-density lipoprotein ratio, and triglycerides were determine in both groups.

Results:

Higher age (61±11 y vs. 52±14 y, P<0.0001) and a higher likelihood of male gender (77% vs. 56%, P<0.0001) were observed in the plaque group. Differences in lipid levels were neither observed for differentiation between plaque presence or absence, nor after subcategorization for plaque composition. LDL serum levels >160 mg/dL correlated with higher NCPV compared with patients with LDL between 100 and 160 mg/dL (112 vs. 27 mm3, P=0.037). Other markers were comparable between the different groups.

Conclusion:

Statin-naive patients with known or suspected coronary artery disease did not show differences in lipid levels related to plaque composition by cCTA. Patients with plaques tended to be men and were significantly older. High LDL levels correlated with high NCPV.
Augmenter of Liver Regeneration Protects Against Acetaminophen-Induced Acute Liver Injury in Mice by Promoting Autophagy
Authors: Hu Ting , Sun Hang , Deng Wan-Yan , Huang Wen-Qi , Liu Qi
Published: August 2018

Most cases of acute liver failure are caused by acetaminophen (APAP) overdose. Oxidative stress is a key factor in APAP toxicity. Although augmenter of liver regeneration (ALR) has both antioxidative and antiapoptotic effects, its therapeutic potential in APAP hepatotoxicity remains unknown. The current study assessed the protective effects and associated mechanisms of ALR against APAP-induced acute liver injury in female BALB/c mice. We found that serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, intrahepatic hemorrhage and necrosis were increased at 3, 6, 12, 24, 48, and 72 h after 600 mg/kg APAP i.p. injection. During the early stages (before 12 h) of acute liver injury, ALR levels increased significantly, followed by a decrease to control level at 24 h after APAP administration. ALR treatment increased autophagosomes, promoted the conversion of LC3 I to LC3 II, and the degradation of p62. ALR attenuated APAP-stimulated increases in ALT, AST, myeloperoxidase (MPO), malondialdehyde (MDA), and reactive oxidative species (ROS) levels; intrahepatic hemorrhage; and necrosis as well as superoxide dismutase (SOD) and Glutathione (GSH) depletion. We found that APAP caused release of the mitochondrial intermembrane proteins apoptosis-inducing factor (AIF) and cytochrome c and that ALR inhibited this change. Meanwhile, ALR decreased expression of cleaved-caspase 3 and apoptotic cells. Subsequently, we investigated the significance of autophagy in APAP-induced acute liver injury by treatment with 3-methyladenine (3-MA), which were classical pharmaceuticals for suppressing autophagy. ALR directly induced autophagy flux; and the inhibition of autophagy reversed the beneficial effects of ALR on hepatotoxicity. Our findings suggest that ALR protects against APAP hepatotoxicity by activating the autophagy pathway.
Association of Immune Cell Subtypes and Phenotype With Subsequent Invasive Candidiasis in Patients With Abdominal Sepsis
Authors: Arens Christoph , Kramm Timo , Decker Sebastian , Spannenberger Jens , Brenner Thorsten , Richter Daniel Christoph , Weigand Markus Alexander , Uhle Florian , Lichtenstern Christoph
Published: August 2018

Background:

In nonneutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis.

Methods:

The presented explorative, noninterventional diagnosis study recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis. Over 5 days, we determined white blood cell count, 1,3-β-d-glucan, and HLA-DR expression; the amount of Th1, Th17, regulatory T, T helper, and cytotoxic T cells; Dectin-1 and TLR2-expression; the amount of T, B, and NK cells; the ex vivo secretion of IL-8 upon stimulation with LPS, flagellin, and zymosan; and the distribution of distinct T-cell cytokines in a daily manner. On day 21, patients’ Candida infection status was stratified in no colonization or IC, colonization or IC.

Results:

A total of 26 patients were included. On day 21, five patients showed no colonization or IC, in 13 patients a colonization was detected, and eight patients were diagnosed with IC. On study inclusion, the stratification groups showed comparable values in standard laboratory parameters and morbidity scores. Decreased B and NK cell counts, as well as reduced IL-8 secretion after ex vivo stimulation with LPS or flagellin seemed to be associated with a higher risk of subsequent Candida colonization. Even lower values could distinguish the therapy-relevant difference between prospective IC from colonization alone.

Conclusions:

We were able to show distinct immune system impairments in early abdominal sepsis by specific immune-based measurements. A possible association of these impairments with a subsequent Candida affection is shown.
Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model
Authors: Vemuri Chandu , Upadhya Gundumi A. , Arif Batool , Jia Jianluo , Lin Yiing , Gaut Joseph P. , Fazal Jawad , Pan Hua , Wickline Samuel A. , Chapman William C.
Published: August 2018

Background

Over 100 000 patients await renal transplantation and 4000 die per year. Compounding this mismatch between supply and demand is delayed graft function which contributes to short-term and long-term graft failures. Previously, we reported that thrombin-targeted perfluorocarbon nanoparticles (PFC-NP) protect kidneys from ischemic renal injury after transient arterial occlusion. Here we hypothesize that perfusion of renal allografts with PFC-NP similarly can protect graft function after an ischemic interval.

Methods

After 60 minutes of warm ischemia, male Lewis rats underwent left renal explantation followed by renal perfusion with 5 mL of standard perfusate alone (N = 3) or with 0.3 mL of untargeted PFC-NP (N = 5) or 0.3 mL thrombin-targeted of PFC NP functionalized with phenylalanine-proline-arginine-chloromethylketone (PPACK) (PFC-PPACK), an irreversible thrombin inhibitor (N = 5). Kidneys underwent 6 hours of cold storage, followed by transplantation into recipients and native nephrectomy. Animals were euthanized at 24 hours for tissue collection or at 48 hours for blood and renal tissue collection. A survival experiment was performed using the same protocol with saline control (N = 3), PFC-NP (N = 3) or PFC-PPACK (N = 6).

Results

Serum creatinine was improved for the PFC-PPACK groups as compared with control groups (P < 0.04). Kaplan-Meier survival curves also indicated increased longevity (P < 0.05). Blinded histologic scoring revealed markedly attenuated renal damage in the PFC-PPACK group compared to untreated animals (2.75 ± 1.60 versus 0.83 ± 3.89; P = 0.0001) and greater preservation of renal vasculature.

Conclusions

These results validate an NP-based approach to improve renal graft function as antithrombin NPs improved allograft function, decreased renal damage, protected vasculature, and improved longevity.
Identification and Validation of the Predictive Capacity of Risk Factors and Models in Liver Transplantation Over Time
Authors: Blok Joris J. , Putter Hein , Metselaar Herold J. , Porte Robert J. , Gonella Federica , de Jonge Jeroen , van den Berg Aad P. , van der Zande Josephine , de Boer Jacob D. , van Hoek Bart , Braat Andries E.
Published: August 2018

Background

Outcome after liver transplantation (LT) is determined by donor, transplant and recipient risk factors. These factors may have different impact on either patient or graft survival (outcome type). In the literature, there is wide variation in the use of outcome types and points in time (short term or long term). Objective of this study is to analyze the predictive capacity of risk factors and risk models in LT and how they vary over time and per outcome type.

Methods

All LTs performed in the Netherlands from January 1, 2002, to December 31, 2011, were analyzed with multivariate analyses at 3-month, 1-year, and 5-year for patient and (non-)death-censored graft survival. The predictive capacity of the investigated risk models was compared with concordance indices.

Results

Recipient age, model for end-stage liver disease sodium, ventilatory support, diabetes mellitus, hepatocellular carcinoma, previous malignancy, hepatitis C virus antibody, hepatitis B virus antibody, perfusion fluid, and Eurotransplant donor risk index (ET-DRI) had significant impact on outcome (graft or patient survival) at 1 or multiple points in time. Significant factors at 3-month patient survival (recipient age, model for end-stage liver disease sodium, ventilatory support) were used to compose a concept model. This model, had a higher c-index than the balance-of-risk score, DRI, ET-DRI, donor-recipient model and simplified recipient risk index for long-term patient and non–death-censored graft survival.

Conclusions

In this study, the effects of recipient risk factors and models on different outcome types and time points were shown. Short-term patient survival mainly depends on recipient risk factors, long-term graft survival on donor risk factors and is more difficult to predict. Next to the concept model, the donor-recipient model has a higher predictive capacity to other risk models for (long-term) patient and non–death-censored graft survival. The DRI and ET-DRI best predicted death-censored graft survival. Knowledge about risk factors and models is critical when using these for waitlist management and/or help in organ allocation and decision-making.
Anti-HLA Donor-Specific IgG Subclasses and C1q-binding Evolution in Posttransplant Monitoring
Authors: Ponsirenas Renata von Glehn , Cazarote Helena B. , Araújo Stanley de Almeida , Wanderley David Campos , Shimakura Silvia , Valdameri Joana S. , Contieri Fabiana L. C. , von Glehn Cristina C. Q. C. , Susin Michelle F. , Sotomaior Vanessa Santos
Published: August 2018

Background

The identification of low-level antibodies by single-antigen bead methodology has brought advancements to risk evaluation of kidney transplant recipients. However, the use of mean fluorescence intensity (MFI) to quantify antibodies and to guide therapy is not enough. Notably, immunoglobulin G (IgG) subclass switching is hypothesized to follow a programmed sequence after an emergency signal from the germinal center. In transplantation this process is not clear yet. In the present study, we sequentially evaluate anti-HLA donor specific antibody (DSA) subclasses, their profile changes, and C1q-binding ability and the influence of those characteristics on antibody mediated rejection (AMR) occurrence and allograft function.

Methods

A total of 30 DSA-positive patients were tested for IgG subclass content and C1q-binding in sequential serum samples.

Results

Twenty-one patients were DSA-positive before transplant; patients sensitized only by transfusion or pregnancies had IgG1 and/or IgG3, and patients sensitized by both transfusion and pregnancies or previous transplant showed a broader range of IgG subclasses. C1q binding was detected in high MFI made up of IgG1 or multiple IgG subclasses. Only 4 patients were positive for C1q posttransplantation and 3 of these showed an increase in MFI, changes in subclasses patterns, AMR, and allograft dysfunction.

Conclusions

Posttransplant evaluation of DSA subclasses and the ability to bind C1q may be informative for both AMR occurrence and allograft dysfunction. Monitoring these events may help to better define risk and interventional time points.
Determining the replication kinetics and cellular tropism of the ruminant-associated Influenza D virus on primary human airway epithelial cells
Authors: Holwerda Melle , Laloli Laura , Stuermer Isabel , Portmann Jasmine , Stalder Hanspeter , Dijkman Ronald
Published: August 2018

Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of diseased swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed many similarities to the human-associated Influenza C virus, including the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock.
Uneven missing data skews phylogenomic relationships within the lories and lorikeets
Authors: Smith Brian Tilston , Mauck William M. , Benz Brett , Andersen Michael J.
Published: August 2018

The resolution of the Tree of Life has accelerated with advances in DNA sequencing technology. To achieve dense sampling, it is often necessary to obtain DNA from historical museum specimens to supplement modern genetic samples. However, DNA from historical material is generally degraded and fragmented, which presents various challenges. In this study, we evaluated how the coverage at variant sites and missing data among historical and modern sample types impacts phylogenomic inference. We explored these patterns in the brush-tongued parrots (lories and lorikeets) of Australasia by sampling ultraconserved elements in 105 taxa. Trees estimated with low coverage sites had several clades where historical or modern samples clustered together, which were not observed in trees with more stringent filtering. To assess if the aberrant relationships were affected by missing data, we performed a targeted outlier analysis of sites and loci and a more general data reduction approach where we excluded sites based on a percentage of data completeness. The outlier analyses showed that 6.6% of total sites were driving the topological differences among trees built with and without low coverage sites, and at these sites, historical samples had 7.5x more missing data than modern ones. An examination of subclades identified loci biased by missing data, and the exclusion of these loci shifted phylogenetic relationships. Predictive modeling found that outlier analysis scores were not correlated with summary statistics of locus alignments, indicating that outlier loci do not have characteristics differing from other loci. Excluding missing data by percentage completeness indicated that sites with 70% completeness were necessary to avoid spurious relationships, but more stringent conditions of data completeness produced less-resolved trees. After accounting for biased loci and understanding the stability of relationships, we inferred a more robust phylogenetic hypothesis for lories and lorikeets.
Group Based Trajectory Analysis of Cognitive Outcomes in Children with Perinatal HIV
Authors: Patel Payal B. , Apornpong Tanakorn , Kerr Stephen J. , Puthanakit Thanyawee , Thongpibul K. , Kosalaraksa P. , Ounchanum P. , Kanjanavanit S. , Ngampiyaskul C. , Luesomboon W. , Penhusun L. , Chettra K. , Mellins Claude , Malee Kay , Spudich Serena , Ananworanich Jintanat , Paul Robert ,   On behalf of the PREDICT/Resilience Study Group
Published: August 2018

Background

Cognitive impairment is common in children with perinatally-acquired HIV (pHIV). It is not known whether exposure to HIV-related neuropathogenic mechanisms during vulnerable periods of neurodevelopment may produce distinct long-term cognitive phenotypes as children age. We used group based trajectory modeling to identify clusters of children with pHIV following a unique developmental trajectory across age and predictors of belonging to select cognitive trajectory groups.

Methods

Participants included children aged 1 to 17 enrolled in the PREDICT resilience study, a cohort study of children with pHIV in Thailand and Cambodia. Cognitive testing was conducted semi-annually over three years. Group based trajectory analyses determined subgroups of children with differing cognitive trajectories using maximum likelihood estimates and Bayesian statistics. Multiple logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group.

Results

Three distinct cognitive phenotypes were identified for each neurocognitive test categorized as high, medium and low scoring groups. A subgroup of children demonstrated normal developmental patterns for Color Trails Test 1 and 2. Children in the low trajectory group were more likely to present at an older age (>8 years, OR: 2.72; p 0.01) and report lower household income level (OR: 0.33-0.42; p<0.005). Neither CD4 nadir nor treatment arm was associated with cognitive trajectory status.

Conclusion

Our study reflects the benefit of using group based trajectory modeling to classify the heterogeneity in cognitive outcomes of children with pHIV. Children were described as belonging to three distinct subgroups determined at study onset alluding to the fact that cognitive outcomes are likely to be determined at an early age with little variability over time in children with pHIV. Demographic variables, including older age at presentation and household income, were associated with low scoring cognitive trajectories, whereas HIV related variables were not. These findings mirror other studies and demonstrate the impact of socioeconomic factors on cognitive development in children with pHIV.
Immune genes are hotspots of shared positive selection across birds and mammals
Authors: Shultz Allison J. , Sackton Timothy B.
Published: August 2018

Consistent patterns of positive selection in functionally similar genes can suggest a common selective pressure across a group of species. We use alignments of orthologous protein-coding genes from 39 species of birds to estimate parameters related to positive selection for 11,000 genes conserved across birds. We show that functional pathways related to the immune system, recombination, lipid metabolism, and phototransduction are enriched for positively selected genes. By comparing our results with mammalian data, we find a significant enrichment for positively selected genes shared between taxa, and that these shared selected genes are enriched for viral immune pathways. Using pathogen-challenge transcriptome data, we show that genes up-regulated in response to pathogens are also enriched for positively selected genes. Together, our results suggest that pathogens, particularly viruses, consistently target the same genes across divergent clades, and that these genes are hotspots of host-pathogen conflict over deep evolutionary time.
Shared behavioral mechanisms underlieC. elegansaggregation and swarming
Authors: Ding S Serena , Schumacher Linus J. , Javer Avelino E. , Endres Robert G. , Brown André EX
Published: August 2018

In complex biological systems, simple individual-level behavioral rules can give rise to emergent group-level behavior. While such collective behavior has been well studied in cells and larger organisms, the mesoscopic scale is less understood, as it is unclear which sensory inputs and physical processes mattera priori. Here, we investigate collective feeding in the roundwormC. elegansat this intermediate scale, using quantitative phenotyping and agent-based modeling to identify behavioral rules underlying both aggregation and swarming—a dynamic phenotype only observed at longer timescales. Using fluorescent multi-worm tracking, we quantify aggregation behavior in terms of individual dynamics and population-level statistics. Based on our quantification, we use agent-based simulations and approximate Bayesian inference to identify three key behavioral rules that give rise to aggregation: cluster-edge reversals, a density-dependent switch between crawling speeds, and taxis towards neighboring worms. Our simulations suggest that swarming is simply driven by local food depletion but otherwise employs the same behavioral mechanisms as the initial aggregation. Hence, mesoscopicC. elegansuses mechanisms familiar from microscopic systems for aggregation, but implemented via more complex behaviors characteristic of macroscopic organisms.
Isolated individuals and groups show opposite preferences toward humidity
Authors: Martín Mariano Calvo , Nicolis Stamatios C. , Planas-Sitjà Isaac , de Biseau Jean-Christophe , Deneubourg Jean-Louis
Published: August 2018

Cockroaches, like most social arthropods, are led to choose collectively among different alternative resting places. These decisions are modulated by different factors, such as environmental conditions (temperature, relative humidity) and sociality (groups size, nature of communications). The aim of this study is to establish the interplay between environmental conditions and the modulation of the interactions between individuals within a group leading to an inversion of preferences. We show that the preferences of isolated cockroaches and groups of 16 individuals, on the selection of the relative humidity of a shelter are inversed and shed light on the mechanisms involved. We suggest that the relative humidity has a multi-level influence on cockroaches, manifested as an attractant effect at the individual level and as a negative effect at the group level, modulating the interactions.
Sex-specific migration strategies of ospreys (Pandion haliaetus) from Germany
Authors: Meyburg Bernd-Ulrich , Roepke Dietrich , Meyburg Christiane , van Wijk Rien E.
Published: August 2018

Birds exhibit a wide variety of migration strategies, not only between species, but also within species. Populations might migrate to specific sites outside of the breeding season, but individuals within populations may also exhibit different migration strategies. Young, unexperienced birds may take different routes, visit different sites, and time their annual cycle differently than adults. In turn, within groups of adult birds, there may be a division between the sexes whereby males and females migrate to different sites or, more commonly, at different times. We investigated differences in the migration strategies of male and female ospreys (Pandion haliaetus) from a breeding population in northeastern Germany. An important difference between the sexes was the much earlier leaving of the breeding place by the females compared to the males. The difference in the timing of departure was much more pronounced compared to most other raptor species. The other main difference between the male and female ospreys was the distance that the birds accumulated over the annual cycle, with males generally moving more while at the breeding ground compared with the non-breeding grounds, and the opposite in females. An exception to this observation was two males that migrated to the Iberian Peninsula, that covered longer distances during the non-breeding season. Consequently, individuals accumulated the same distances over the course of an annual cycle, regardless of sex or migration strategy. Unexpectedly, a difference in the timing of the annual cycle between the sexes occurred at the breeding grounds with females leaving 2 to 3 months before the males, long before the young had fledged. Because males migrated much faster and, unlike the females, did not make prolonged stops, their arrival times at the non-breeding grounds were not different. Return migration to the breeding grounds was very similar between the sexes, and even the two males that spent the non-breeding season on the Iberian Peninsula did not arrive before any of the other birds. Thus, a shorter migration distance is not necessarily associated with an advantage with respect to a timely return to the breeding grounds.
Which osteoarthritic gait features recover following Total Knee Replacement surgery?
Authors: Biggs Paul Robert , Whatling Gemma Marie , Wilson Chris , Metcalfe Andrew John , Holt Cathy Avril
Published: August 2018

Background

Gait analysis can be used to measure variations in joint function in patients with knee osteoarthritis (OA), and is useful when observing longitudinal biomechanical changes following Total Knee Replacement (TKR) surgery. The Cardiff Classifier is an objective classification tool applied previously to examine the extent of biomechanical recovery following TKR. In this study, it is further developed to reveal the salient features that contribute to recovery towards healthy function.

Methods

Gait analysis was performed on 30 patients before and after TKR surgery, and 30 healthy controls. Median TKR follow-up time was 13 months. The combined application of principal component analysis (PCA) and the Cardiff Classifier defined 18 biomechanical features that discriminated OA from healthy gait. Statistical analysis tested whether these features were affected by TKR surgery and, if so, whether they recovered to values found for the controls.

Results

The Cardiff Classifier successfully discriminated between OA and healthy gait in all 60 cases. Of the 18 discriminatory features, only six (33%) were significantly affected by surgery, including features in all three planes of the ground reaction force (p<0.001), ankle dorsiflexion moment (p<0.001), hip adduction moment (p=0.003), and transverse hip angle (p=0.007). All but two (89%) of these features remained significantly different to those of the control group after surgery.

Conclusions

This approach was able to discriminate gait biomechanics associated with knee OA. The ground reaction force provided the strongest discriminatory features. Despite increased gait velocity and improvements in self-reported pain and function, which would normally be clinical indicators of recovery, the majority of features were not affected by TKR surgery. This TKR cohort retained pre-operative gait patterns; reduced sagittal hip and knee moments, decreased knee flexion, increased hip flexion, and reduced hip adduction. The changes that were associated with surgery were predominantly found at the ankle and hip, rather than at the knee.
Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment
Authors: Bezler Alexandra , Braukmann Fabian , West Sean , Duplan Arthur , Conconi Raffaella , Schütz Frédéric , Gönczy Pierre , Piano Fabio , Gunsalus Kristin , Miska Eric A. , Keller Laurent
Published: August 2018

Background

RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter-and trans-generational inheritance. In the nematodeCaenorhabditis elegansenvironmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive.

Results

Here we use high-throughput sequencing of dissected gonads to quantify sex-specific endogenous piRNAs, miRNAs and siRNAs in theC. elegansgermline and the somatic gonad. We identify genes with exceptionally high levels of 22G RNAs that are associated with low mRNA expression, a signature compatible with silencing. We further demonstrate that contrary to the hermaphrodite germline, the male germline, but not male soma, is resistant to environmental RNAi triggers provided by feeding. This sex-difference in silencing efficacy is associated with lower levels of gonadal RNAi amplification products. Moreover, this tissue-and sex-specific RNAi resistance is regulated by the germline, since mutant males with a feminized germline are RNAi sensitive.

Conclusion

This study provides important sex-and tissue-specific expression data of miRNA, piRNA and siRNA as well as mechanistic insights into sex-differences of gene regulation in response to environmental cues.
PAVOOC: Designing CRISPR sgRNAs using 3D protein structures and functional domain annotation
Authors: Schaefer Moritz , Clevert Dr. Djork-Arné , Weiss Dr. Bertram , Steffen Dr. Andreas
Published: August 2018

Summary: sgRNAs targeting the same gene can significantly vary in terms of efficacy and specificity. PAVOOC (Prediction And Visualization of On- and Off-targets for CRISPR) is a web-based CRISPR sgRNA design tool that employs state-of-the art machine learning models to prioritize most effective candidate sgRNAs. In contrast to other tools, it maps sgRNAs to functional domains and protein structures and visualizes cut sites on corresponding protein crystal structures. Furthermore, PAVOOC supports HDR template generation for gene editing experiments and the visualization of the mutated amino acids in 3D.

Availability and Implementation: PAVOOC is available under https://pavooc.me and accessible using current browsers (Chrome/Chromium recommended). The source code is hosted at github.com/moritzschaefer/pavooc under the MIT License. The backend, including data processing steps, and the frontend is implemented in Python 3 and ReactJS respectively. All components run in a simple Docker environment.

Contact: mail@moritzs.de
Molecular memory of periodic thermal stimulation in an immune complex
Authors: Stan Razvan C. , de Camargo Maristela M.
Published: August 2018

Proteins search their vast conformational space in order to attain the native fold and bind productively to relevant biological partners. In particular, most proteins must be able to alternate between at least one active conformational state and back to an inactive conformer, especially for the macromolecules that perform work and need to optimize energy usage. This property may be invoked by a physical stimulus (temperature, radiation) or by a chemical ligand, and may occur through mapping of the protein external environment onto a subset of protein conformers. We have stimulated with temperature cycles two partners of an immune complex before and after assembly, and revealed that properties of the external stimulus (period, phase) are also found in the characteristics of the immune complex (i.e. periodic variations in the binding affinity). These results are important for delineating the bases of molecular memory ex vivo and could serve in the optimization of protein based sensors.
Data quality reporting: good practice for transparent estimates from forest and land cover surveys
Authors: Birigazzi Luca , Gregoire Timothy G. , Finegold Yelena , Cóndor Golec Rocίo D. , Sandker Marieke , Donegan Emily , Gamarra Javier G. P.
Published: August 2018

The need to provide transparent and reliable Greenhouse Gas (GHG) emission estimates is strongly emphasized in the context of international reporting under the United Nations Framework Convention on Climate Change (UN-FCCC) and the Paris Agreement. Yet it is difficult to find specific guidance about what information is really needed to evaluate the quality of the emission factors or activity data used for GHG emission estimates. The most commonly used indicator of the reliability of an estimation procedure (and one of the few indicators explicitly mentioned in the 2006 IPCC guidelines) is the so-called confidence interval, usually at a confidence level of 90% or 95%. This interval, however, is unlikely to be a meaningful indicator of the quality of the estimate, if not associated with additional information about the estimation and survey procedures (such as on the sampling design, measurement protocols or quality control routines, among others). We provide a review of the main sources of error that can have an impact on the precision and accuracy of the estimation of both emission factors and activity data and a list of the essential survey features that should be reported to properly evaluate the quality of a GHG emission estimate. Such list is also applicable to the reporting of national forest inventories and of area estimation of activity data, and includes the case in which confidence intervals are obtained using error propagation techniques.
Integrative pathway enrichment analysis of multivariate omics data
Authors: Paczkowska Marta , Barenboim Jonathan , Sintupisut Nardnisa , Fox Natalie C. , Zhu Helen , Abd-Rabbo Diala ,   PCAWG Network and Pathway Analysis Group, Boutros Paul C. , Reimand Jüri
Published: August 2018

Multi-omics datasets quantify complementary aspects of molecular biology and thus pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple omics datasets using a statistical data fusion approach, rationalizes contributing evidence and highlights associated genes. We demonstrate its utility by analyzing coding and non-coding mutations from 2,583 whole cancer genomes, revealing frequently mutated hallmark pathways and a long tail of known and putative cancer driver genes. We also studied prognostic molecular pathways in breast cancer subtypes by integrating genomic and transcriptomic features of tumors and tumor-adjacent cells and found significant associations with immune response processes and anti-apoptotic signaling pathways. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
EndoC-βH1 multi-genomic profiling defines gene regulatory programs governing human pancreatic β cell identity and function
Authors: Lawlor Nathan , Márquez Eladio J. , Orchard Peter , Narisu Narisu , Shamim Muhammad Saad , Thibodeau Asa , Varshney Arushi , Kursawe Romy , Erdos Michael R. , Kanke Matt , Gu Huiya , Pak Evgenia , Dutra Amalia , Russell Sheikh , Li Xingwang , Piecuch Emaly , Luo Oscar , Chines Peter S. , Fuchbserger Christian ,   NIH Intramural Sequencing Center, Sethupathy Praveen , Aiden Aviva Presser , Ruan Yijun , Aiden Erez Lieberman , Collins Francis S. , Ucar Duygu , Parker Stephen C.J. , Stitzel Michael L.
Published: August 2018

EndoC-βH1 is emerging as a critical human beta cell model to study the genetic and environmental etiologies of beta cell function, especially in the context of diabetes. Comprehensive knowledge of its molecular landscape is lacking yet required to fully take advantage of this model. Here, we report extensive chromosomal (spectral karyotyping), genetic (genotyping), epigenetic (ChIP-seq, ATAC-seq), chromatin interaction (Hi-C, Pol2 ChIA-PET), and transcriptomic (RNA-seq, miRNA-seq) maps of this cell model. Integrated analyses of these maps define known (e.g.,PDX1, ISL1) and putative (e.g.,PCSK1, mir-375) beta cell-specific chromatin interactions and transcriptionalcis-regulatory networks, and identify allelic effects oncis-regulatory element use and expression.

Importantly, comparative analyses with maps generated in primary human islets/beta cells indicate substantial preservation of chromatin looping, but also highlight chromosomal heterogeneity and fetal genomic signatures in EndoC-βH1. Together, these maps, and an interactive web application we have created for their exploration, provide important tools for the broad community in the design and success of experiments to probe and manipulate the genetic programs governing beta cell identity and (dys)function in diabetes.
Beyond stability constraints: a biophysical model of enzyme evolution with selection for stability and activity
Authors: Echave Julian
Published: August 2018

Proteins trace trajectories in sequence space as their amino acids become substituted by other amino acids. The number of substitutions per unit time, the rate of evolution, varies among sites because of biophysical constraints. Several properties that characterize sites’ local environments have been proposed as biophysical determinants of site-specific evolutionary rates. Thus, rate increases with increasing solvent exposure, increasing flexibility, and decreasing local packing density. For enzymes, rate increases also with increasing distance from the protein’s active residues, presumably due to functional constraints. The dependence of rates on solvent accessibility, packing density, and flexibility has been mechanistically explained in terms of selection for stability. However, as I show here, a stability-based model fails to reproduce the observed rate-distance dependence, overestimating rates close to the active residues and underestimating rates of distant sites. Here, I pose a new biophysical model of enzyme evolution with selection for stability and activity (MSA) and compare it with a stability-based counterpart (MS). Testing these models on a structurally and functionally diverse dataset of monomeric enzymes, I found that MSA fits observed rates better than MS for most proteins. While both models reproduce the observed dependence of rates on solvent accessibility, packing, and flexibility, MSA fits these dependencies somewhat better. Importantly, while MS fails to reproduce the dependence of rates on distance from the active residues, MSA accounts for the rate-distance dependence quantitatively. Thus, the variation of evolutionary rate among enzyme sites is mechanistically underpinned by natural selection for both stability and activity.
Hippocampal neurogenesis promotes preference for future rewards
Authors: Seib Désirée R. , Espinueva Delane , Princz-Lebel Oren , Chahley Erin , Floresco Stan B. , Snyder Jason S.
Published: August 2018

Adult hippocampal neurogenesis is implicated in a number of disorders where reward processes are disrupted but whether new neurons regulate specific reward behaviors remains unknown. We find that blocking neurogenesis in rats reduces activation of the ventral dentate gyrus and causes a profound aversion for delayed rewards. Delay-based decision-making restructured dendrites and spines in adult-born neurons, consistent with activity-dependent neuronal recruitment. These findings identify a novel role for neurogenesis in decisions about future rewards, which is compromised in disorders where short-sighted gains are preferred at the expense of long-term health.
Improved charge transfer multiplet method to simulateM- andL-edge X-ray absorption spectra of metal-centered excited states
Authors: Zhang Kaili , Girolami Gregory S. , Vura-Weis Josh
Published: August 2018

Charge transfer multiplet (CTM) theory is a computationally undemanding and highly mature method for simulating the soft X-ray spectra of first-row transition metal complexes. However, CTM theory has seldom been applied to the simulation of excited-state spectra. In this article, theCTM4XASsoftware package is extended to simulateM2,3- andL2,3-edge spectra for the excited states of first-row transition metals and also interpret CTM eigenfunctions in terms of Russell–Saunders term symbols. These new programs are used to reinterpret the recently reported excited-stateM2,3-edge difference spectra of photogenerated ferrocenium cations and to propose alternative assignments for the electronic state of these cations responsible for the spectroscopic features. These new programs were also used to model theL2,3-edge spectra of FeIIcompounds during nuclear relaxation following photoinduced spin crossover and to propose spectroscopic signatures for their vibrationally hot states.