bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelvic floor disorders in women with gynecologic malignancy
Authors: Hall Evelyn , Robison Katina , Wohlrab Kyle
Published: October 2018

Purpose of review

This article serves as an update on issues relating to the intersection of pelvic floor disorders and gynecology oncology.

Recent findings

Gynecologic cancer survivors experience pelvic floor disorders (PFDs) at a higher rate than their age-matched peers, often because of shared risk factors and as sequelae of cancer treatment. Concomitant pelvic floor and oncologic surgery can serve as a method to promote quality of life. Studies have demonstrated concomitant surgery to be well tolerated in appropriately selected patients, but only about 2% of oncologic surgeries are coordinated to include the treatment of PFDs. Conversely, women undergoing surgery for PFD have a low, but real risk of occult malignancy. Therefore, preoperative counseling is warranted in select populations. This article will discuss the management of concurrent PFDs and gynecologic malignancies.

Healthcare providers should be familiar with screening, management and referral of women with pelvic floor disorders in the gynecologic oncology population.
Ergonomics in gynecologic surgery
Authors: Catanzarite Tatiana , Tan-Kim Jasmine , Menefee Shawn Adam
Published: October 2018

Purpose of review

Work-related musculoskeletal disorders (WMSDs) are prevalent among surgeons and result in significant disability. We aimed to review the English-language literature regarding ergonomic risk, prevalence of WMSDs, and unique ergonomic considerations of gynecologic surgery.

Recent findings

Surgeon WMSDs are prevalent, with rates ranging from 66 to 94% for open surgery, 73–100% for conventional laparoscopy, 54–87% for vaginal surgery, and 23–80% for robotic-assisted surgery. Risk factors for injury in open surgery include use of loupes, headlamps, and microscopes. Unique risks in laparoscopic surgery include table and monitor position, long-shafted instruments, and poor instrument handle design. In vaginal surgery, improper table height and twisted trunk position create injury risk. Although robotic surgery offers some advantages in neck and shoulder strain, it remains associated with trunk, wrist, and finger strain.

WMSDs are prevalent among surgeons but have received little attention because of under-reporting of injury and logistical constraints of studying surgical ergonomics. Future research must aim to develop objective surgical ergonomics instruments and guidelines and to correlate ergonomics assessments with pain and tissue-level damage in surgeons with WMSDs. Ergonomics training should be developed and implemented in order to protect surgeons from preventable, potentially career-altering injuries.
Respiratory Microbiota Predicts Clinical Disease Course of Acute Otorrhea in Children With Tympanostomy Tubes
Authors: Man Wing Ho , van Dongen Thijs M.A. , Venekamp Roderick P. , Pluimakers Vincent G. , Chu Mei Ling J.N. , van Houten Marlies A. , Sanders Elisabeth A.M. , Schilder Anne G. M. , Bogaert Debby
Published: October 2018

Background:

Acute otitis media (AOM) is one of the most common childhood infections, generally thought to be caused by ascension of bacteria from the nasopharynx (NP) to the middle ear. Using 16S ribosomal RNA–based sequencing, we evaluated the relationship between the NP and middle ear fluid (MEF) microbiota in children with AOM with tympanostomy tubes (AOMT) as a proxy for AOM and explored whether microbiota profiling predicts natural disease course.

Methods:

Microbiota profiles of paired NP and MEF samples of 94 children below 5 years of age with uncomplicated AOMT were determined.

Results:

Local diversity (P < 0.001) and overall microbiota composition (P < 0.001) of NP and MEF samples differed significantly, although paired NP and MEF samples were much more similar than unpaired samples (P < 0.001). High qualitative agreement between the presence of individual bacteria in both niches was observed. Abundances of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Turicella otitidis, Klebsiella pneumoniae and Haemophilus spp. were strongly correlated between the 2 niches. Additionally, P. aeruginosa, S. aureus, T. otitidis and Streptococcus pneumoniae abundance in NP were predictive of the presence of a range of oral types of bacteria in MEF. Interestingly, there was no association between Moraxella catarrhalis in NP and MEF samples, which was highly present in NP but virtually absent in MEF. Finally, the NP microbiota composition could predict duration of AOMT, even better than MEF microbiota.

Conclusions:

We observed substantial correlations between paired NP and MEF microbiota in children with AOMT. Our data also suggest that NP microbiota profiling deserves further exploration as tool for future treatment decisions.
Recognition of Insufficient Competence—Nurses’ Experiences in Direct Involvement With Adolescent Children of Cancer Patients
Authors: Tafjord Trine
Published: October 2018

Background

A parent’s cancer may have disruptive impact on his/her adolescent children. Currently, nurses have been regarded as central actors in direct involvement with patients’ minor children. Development of an extended nursing role has become a pertinent issue.

Objective

Adolescents’ needs tend to be overlooked by nurses because of inexperience with this population. The aim of this study was to explore nurses’ experiences of direct involvement with these adolescents, to get a deeper understanding about this phenomenon.

Methods

Using a constructivist grounded theory approach, 12 interviews were conducted among Norwegian nurses within the cancer care context. The category insufficient competence was explored through analyzing participants’ experiences of direct involvements with adolescents.

Results

The recognition of insufficient competence became visible as nurses experienced being involved with a population about whom they held inadequate and limited knowledge. Adolescents were perceived as unpredictable and rejecting nurses’ approaches. Consequently, nurses feared involvement and experienced failing on their assignments. After completing more or less failed attempts to establish good relationships with adolescents, the nurses request for more knowledge and experience in order to support this group.

Conclusions

Nurses are recognizing insufficient competence in direct involvement with adolescents, which calls for extended competence. Because nurses are not the only responsible actors performing in this field, building competence requires a broadened attention at both an individual and organizational level, across several healthcare disciplines, as well as through user participation.

Implications for Practice

Competence building should be considered in light of organizational frameworks, collective learning possibilities across disciplines, and opportunities for involving adolescents/young adults as user participants.
Does the Oral Administration of Ginger Reduce Chemotherapy-Induced Nausea and Vomiting?
Authors: Chang Wen P. , Peng Yu X.
Published: October 2018

Background

Preclinical tests in animals have shown that ginger extract can be used to treat chemotherapy-induced nausea and vomiting (CINV); however, research findings in clinical trials have not been conclusive.

Objective

Through this meta-analysis, we aimed to determine whether ginger could be used to treat CINV, which was interpreted using the PICOS (patient, problem/population, intervention, comparison, outcome, study) framework, with P being patients who underwent chemotherapy; I being 0.5 to 2.0 g/d of Zingiberaceae, Zintoma, dry ginger, ginger capsules, powdered ginger root, Zingiber officinale Roscoe, ginger extract, powdered ginger, 6-gingerol, or shogalos; C being placebo or standard care; and O being the relief, reduction, or improvement of CINV.

Method

Via systematic literature review, we searched for studies in English from 2000 to 2017 in databases. We conducted a meta-analysis using Comprehensive Meta-analysis 2 on a total of 10 studies with complete data.

Results

The odds ratio (OR) of ginger in controlling CINV was 0.71 (95% confidence interval [CI], 0.54–0.94; P = .015). Heterogeneity existed among the samples; therefore, we proceeded with a subgroup analysis and divided nausea and vomiting into acute or delayed. The results revealed that ginger could only reduce acute CINV in patients (OR, 0.60; 95% CI, 0.42–0.86; P = .006), particularly acute vomiting (OR, 0.58; 95% CI, 0.37–0.94; P = .025).

Conclusions

Ginger displayed significant efficacy with regard to controlling CINV in the experimental groups.

Implications for Practice

Our results could provide a reference for antiemetic methods to treat CINV and facilitate support for more clinical trials in the future to establish relevant guidelines.
Daily Stress Processes as Contributors to and Targets for Promoting Cognitive Health in Later Life
Authors: Stawski Robert S. , Cerino Eric S. , Witzel Dakota D. , MacDonald Stuart W.S.
Published: October 2018

Objective

The aim of this study was to test the hypothesis that daily stress processes, including exposure and emotional reactivity to daily stressors, are associated with response time inconsistency (RTI), an indicator of processing efficiency and cognitive health. Furthermore, we considered daily stress–cognitive health associations at the level of individual differences and within-persons over time.

Methods

Participants were 111 older adults (mean = 80 years, range = 66–95 years) enrolled in a measurement burst study where assessments of response time–based cognitive performance, stressful experiences, and affect were administered on each of 6 days for a 2-week period. This protocol was repeated every 6 months for 2.5 years. Multilevel modeling was used to examine frequency of stressor exposure, nonstressor affect, and affect reactivity to daily stressors as individual difference and time-varying predictors of RTI.

Results

Between-persons, higher levels of nonstressor negative affect (b = 0.41, 95% confidence interval [CI] = −0.01 to 0.83, p = .055) and negative affect reactivity (b = 0.80, 95% CI = 0.18 to 1.42, p = .012) were associated with greater RTI. Within-persons over time, higher levels of negative affect (b = 0.20, 95% CI = 0.06 to 0.34, p = .006) and negative affect reactivity (b = 0.13, 95% CI = 0.02 to 0.24, p = .018) were associated with increased RTI among the oldest portion of the sample, whereas higher levels of positive affect (b = −0.11, 95% CI = −0.21 to −0.02, p = .019) were associated with reduced RTI.

Conclusions

Negative affect reactions to daily stressors are associated with compromised RTI both between and within-persons. Findings suggest that emotional reactions to daily stressors contribute to compromise older adults' cognitive health, whereas increased positive affect may be beneficial.
How to optimize antibiotic pharmacokinetic/pharmacodynamics for Gram-negative infections in critically ill patients
Authors: Heffernan Aaron J. , Sime Fekade B. , Taccone Fabio S. , Roberts Jason A.
Published: October 2018

Purpose of review

Optimized antibiotic dosing regimens improve survival rates in critically ill patients. However, dose optimization is challenging because of fluctuating antibiotic pharmacokinetics both between patients and within a single patient. This study reviews the pharmacokinetic changes that occur in critically ill patients, along with the pharmacodynamics and toxicodynamics of antibiotics commonly used for the treatment of Gram-negative bacterial infections to formulate a recommendation for antibiotic dosing at the bedside.

Recent findings

Recent studies highlight that critically ill patients do not achieve therapeutic antibiotic exposures with standard antibiotic dosing. Although dose increases are required, the method of administration, such as the use of β-lactam antibiotic continuous infusions and nebulized aminoglycoside administration, may improve efficacy and limit toxicity. In addition, the increased availability of therapeutic drug monitoring and antibiotic dosing software allow the formulation of individualized dosing regimens at the bedside.

When prescribing antibiotic doses, the clinician should consider antibiotic pharmacokinetic and pharmacodynamic principles. Before initiating high-dose antibiotic therapy, therapeutic drug monitoring may be considered to assist the clinician to optimize antibiotic treatment and minimize potential toxicity.
Combination versus monotherapy for the treatment of infections due to carbapenem-resistant Enterobacteriaceae
Authors: Carrara Elena , Bragantini Damiano , Tacconelli Evelina
Published: October 2018

Purpose of review

Combination therapy is a common strategy for treatment of multidrug resistant infections. Despite the strong twin rationales of improving efficacy and reducing resistance development, the evidence supporting this strategy remains controversial. The aims of this review are to assess the most recent studies supporting the use of combination therapy for treating infections because of carbapenem-resistant Enterobacteriaceae (CRE) and to highlight relevant areas for further research.

Recent findings

Evidence supporting the use of combination therapy for the treatment of CRE remains limited to in-vitro experiments and observational studies with considerable risk of bias. Very few antibiotic combinations have been tested in well designed randomized controlled trials, making it difficult to draw general conclusions for clinical practice.

Further studies are urgently needed to test the most promising synergistic combinations. New drugs potentially active against CRE should also to be tested in studies with adequate sample size and truly representative of the general patient population.
Neuraminidase inhibitor resistance in influenza: a clinical perspective
Authors: Lee Nelson , Hurt Aeron C.
Published: October 2018

Purpose of review

Neuraminidase inhibitors (NAIs), including oseltamivir, zanamivir, and peramivir, is the main class of antiviral available for clinical use. As such, development of resistance toward these agents is of great clinical and public health concern.

Recent findings

At present, NAI resistance remains uncommon among the circulating viruses (oseltamivir <3.5%, zanamivir <1%). Resistance risk is slightly higher in A(H1N1) than A(H3N2) and B viruses. Resistance may emerge during drug exposure, particularly among young children (<5 years), the immunocompromised, and individuals receiving prophylactic regimens. H275Y A(H1N1) variant, showing high-level oseltamivir resistance, is capable of causing outbreaks. R294K A(H7N9) variant shows reduced inhibition across NAIs. Multi-NAI resistance has been reported in the immunocompromised.

These findings highlight the importance of continuous surveillance, and assessment of viral fitness and transmissibility of resistant virus strains. Detection can be challenging, especially in a mix of resistant and wild-type viruses. Recent advances in molecular techniques (e.g. targeted mutation PCR, iART, ddPCR, pyrosequencing, next-generation sequencing) have improved detection and our understanding of viral dynamics. Treatment options available for oseltamivir-resistant viruses are limited, and susceptibility testing of other NAIs may be required, but non-NAI antivirals (e.g. polymerase inhibitors) that are active against these resistant viruses are in late-stage clinical development.
Hepatitis B virus and hepatitis C virus infection in immunocompromised patients
Authors: Hwang Jessica P. , Torres Harrys A.
Published: October 2018

Purpose of review

To provide an update on recent studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis on viral reactivation after cancer treatment, new antiviral therapies, and safety concerns.

Recent findings

The diagnostic criteria for HBV reactivation in patients receiving cancer therapy were revised in 2018. HBV reactivation in these patients is preventable, even with the use of new cancer therapies. HCV reactivation also has been reported in cancer patients, particularly those with hematologic malignancies, and is not a virologic condition usually associated with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended because therapy with direct-acting antivirals eradicates the infection in the majority of cancer patients.

Cancer patients with HBV or HCV infection are at risk for viral reactivation, with many similarities between these two infections. Patients at high risk for reactivation will benefit significantly from taking oral antivirals, which will reduce the risk of HBV reactivation or prevent development of HCV reactivation following its virologic cure.
Inter-comparison and assessment of gridded climate products over tropical forests during the 2015/2016 El Niño
Authors: Burton C. , Rifai S. , Malhi Y.
Published: October 2018

To understand the impacts of extreme climate events, it is first necessary to understand the spatio-temporal characteristics of the event. Gridded climate products are frequently used to describe climate patterns but have been shown to perform poorly over data-sparse regions such as tropical forests. Often, they are uncritically employed in a wide range of studies linking tropical forest processes to large-scale climate variability. Here, we conduct an inter-comparison and assessment of near-surface air temperature fields supplied by four state-of-the-art reanalysis products, along with precipitation estimates supplied by four merged satellite-gauge rainfall products. Firstly, spatio-temporal patterns of temperature and precipitation anomalies during the 2015–2016 El Niño are shown for each product to characterize the impact of the El Niño on the tropical forest biomes of Equatorial Africa, Southeast Asia and South America. Using meteorological station data, a two-stage assessment is then conducted to determine which products most reliably model tropical climates during the 2015–2016 El Niño, and which perform best over the longer-term satellite observation period (1980–2016). Results suggest that eastern Amazonia, parts of the Congo Basin and mainland Southeast Asia all experienced significant monthly mean temperature anomalies during the El Niño, while northeastern Amazonia, eastern Borneo and southern New Guinea experienced significant precipitation deficits. Our results suggest ERA-Interim and MERRA2 are the most reliable air temperature datasets, while TRMM 3B42 V7 and CHIRPS v2.0 are the best-performing rainfall datasets.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
The impact of the 2015/2016 El Niño on global photosynthesis using satellite remote sensing
Authors: Luo Xiangzhong , Keenan Trevor F. , Fisher Joshua B. , Jiménez-Muñoz Juan-Carlos , Chen Jing M. , Jiang Chongya , Ju Weimin , Perakalapudi Naga-Vineet , Ryu Youngryel , Tadić Jovan M.
Published: October 2018

The El Niño-Southern Oscillation exerts a large influence on global climate regimes and on the global carbon cycle. Although El Niño is known to be associated with a reduction of the global total land carbon sink, results based on prognostic models or measurements disagree over the relative contribution of photosynthesis to the reduced sink. Here, we provide an independent remote sensing-based analysis on the impact of the 2015–2016 El Niño on global photosynthesis using six global satellite-based photosynthesis products and a global solar-induced fluorescence (SIF) dataset. An ensemble of satellite-based photosynthesis products showed a negative anomaly of −0.7 ± 1.2 PgC in 2015, but a slight positive anomaly of 0.05 ± 0.89 PgC in 2016, which when combined with observations of the growth rate of atmospheric carbon dioxide concentrations suggests that the reduction of the land residual sink was likely dominated by photosynthesis in 2015 but by respiration in 2016. The six satellite-based products unanimously identified a major photosynthesis reduction of −1.1 ± 0.52 PgC from savannahs in 2015 and 2016, followed by a highly uncertain reduction of −0.22 ± 0.98 PgC from rainforests. Vegetation in the Northern Hemisphere enhanced photosynthesis before and after the peak El Niño, especially in grasslands (0.33 ± 0.13 PgC). The patterns of satellite-based photosynthesis ensemble mean were corroborated by SIF, except in rainforests and South America, where the anomalies of satellite-based photosynthesis products also diverged the most. We found the inter-model variation of photosynthesis estimates was strongly related to the discrepancy between moisture forcings for models. These results highlight the importance of considering multiple photosynthesis proxies when assessing responses to climatic anomalies.

This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.
Quasi-universality in single-cell sequencing data
Authors: Aparicio Luis , Bordyuh Mykola , Blumberg Andrew J. , Rabadan Raul
Published: October 2018

The development of single-cell technologies provides the opportunity to identify new cellular states and reconstruct novel cell-to-cell relationships. Applications range from understanding the transcriptional and epigenetic processes involved in metazoan development to characterizing distinct cells types in heterogeneous populations like cancers or immune cells. However, analysis of the data is impeded by its unknown intrinsic biological and technical variability together with its sparseness; these factors complicate the identification of true biological signals amidst artifact and noise. Here we show that, across technologies, roughly 95% of the eigenvalues derived from each single-cell data set can be described by universal distributions predicted by Random Matrix Theory. Interestingly, 5% of the spectrum shows deviations from these distributions and present a phenomenon known as eigenvector localization, where information tightly concentrates in groups of cells. Some of the localized eigenvectors reflect underlying biological signal, and some are simply a consequence of the sparsity of single cell data; roughly 3% is artifactual. Based on the universal distributions and a technique for detecting sparsity induced localization, we present a strategy to identify the residual 2% of directions that encode biological information and thereby denoise single-cell data. We demonstrate the effectiveness of this approach by comparing with standard single-cell data analysis techniques in a variety of examples with marked cell populations.
DNA analysis of a large collection of shark fins from a US retail shop: species composition, global extent of trade and conservation - a Technical Report from the Monterey Bay Aquarium
Authors: Palumbi Stephen R. , Robinson Kristin M. , Van Houtan Kyle S. , Jorgensen Salvador J.
Published: October 2018

We identified shark fins sampled across the entirety of a shark fin shop that had operated on the west coast of the United States until 2014. From these specimens we obtained 963 species identifications with Cytochrome oxidase (COI) sequencing and 1,720 identifications with control region (CR) sequences. We found 36-39 distinct species with COI and 38-41 with CR. Of the species identified, 16-23 are currently listed as Endangered or Vulnerable on the IUCN Red List, an additional 2 are considered data deficient, and 7 currently listed under CITES Appendix II. Of the 2.5 tonnes of fins from this collection, we estimated 56-66% (CR or COI, respectively) come from CITES-listed species or those the IUCN considers threatened or data deficient. Most of these species occur outside of the United States EEZ, comprising a global set of species that is common in most fin surveys. The principal target shark fishery in the United States (spiny dogfish; Squalus acanthias) has no fins in our collection. Fins seen abundantly in our collection include pelagic species such as thresher, mako, oceanic whitetip, silky, blue and hammerhead sharks, as in previous samples of the shark fin supply chain. However, in addition, we see a large flood of blacktip, dusky, sandbar, and smalltail sharks that are common in shallow coastal waters. This may indicate that the global market for shark fins takes sharks from nearshore coastal zones, all over the world. Abundant species in the fin shop included globally-distributed species such as scalloped hammerheads and shortfin mako sharks, but also regionally-restricted species such as finetooth, blacknose, and Caribbean Reef sharks found only in the western Atlantic or Caribbean. Specimens identified from rare species of particular conservation concern included the wedgefish genus Rhyncobatus and the white shark. Both molecular markers performed well in identifying most fins, achieving a similar degree of taxonomic certainty. The universal primers for COI regularly amplified bacteria in wet fin samples, but the CR primers were able to return shark sequences even from these degraded samples. However, the CR primers amplified a second gene, likely a pseudogene, in some important and abundant species, and seriously underestimated some species of high conversation concern such as the thresher sharks.
Detection of a novel insect specific flavivirus across ecologically diverse populations of Aedes aegypti on the Caribbean Island of Saint Lucia
Authors: Jeffries C.L. , White M. , Wilson L. , Yakob L. , Walker T.
Published: October 2018

Outbreaks of mosquito-borne arboviral diseases including dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV) and chikungunya virus (CHIKV) have recently occurred in the Caribbean. The geographical range of the principle vectors responsible for transmission, Aedes (Ae.) aegypti and Ae. albopictus is increasing and greater mosquito surveillance is needed in the Caribbean given international tourism is so prominent. The island of Saint Lucia has seen outbreaks of DENV and CHIKV in the past five years but vector surveillance has been limited with the last studies dating back to the late 1970s. Natural disasters have changed the landscape of Saint Lucia and the island has gone through significant urbanisation. In this study, we conducted an entomological survey of Ae. aegypti and Ae. albopictus distribution across the island and analysed environmental parameters associated with the presence of these species. Although we collected Ae. aegypti across a range of sites across the island, no Ae. albopictus were collected despite traps being placed in diverse ecological settings. The number of Ae. aegypti collected was significantly associated with higher elevation and semi-urban settings yielded female mosquito counts per trap-day that were 5-fold lower than urban settings. Screening for arboviruses revealed a high prevalence of a novel insect-specific flavivirus closely related to cell fusing agent virus (CFAV). We discuss the implications that natural disasters, water storage and lack of mosquito surveillance have on arboviral outbreaks in Saint Lucia and implications for insect only flaviviruses on surveillance and detection of pathogenic flaviviruses.
KCC2 regulates neuronal excitability and hippocampal activity via interaction with Task-3 channels
Authors: Goutierre Marie , Awabdh Sana Al , François Emeline , Gomez-Dominguez Daniel , Irinopoulou Theano , de la Prida Liset Menendez , Poncer Jean Christophe
Published: October 2018

The K+/Cl− co-transporter KCC2 (SLC12A5) regulates neuronal transmembrane chloride gradients and thereby controls GABA signaling in the brain. KCC2 downregulation is observed in several neurological and psychiatric disorders including epilepsy, neuropathic pain and autism spectrum disorders. Paradoxical, excitatory GABA signaling is usually assumed to contribute to abnormal network activity underlying the pathology. We tested this hypothesis and explored the functional impact of chronic KCC2 downregulation in the rat dentate gyrus. Although the reversal potential of GABAA receptor currents was depolarized in KCC2 knockdown neurons, this shift was fully compensated by depolarization of their resting membrane potential. This effect was due to downregulation of Task-3 leak potassium channels that we show require KCC2 for membrane trafficking. Increased neuronal excitability upon KCC2 suppression altered dentate gyrus rhythmogenesis that could be normalized by chemogenetic hyperpolarization. Our data reveal KCC2 downregulation engages complex synaptic and cellular alterations beyond GABA signaling that concur to perturb network activity, thus offering novel targets for therapeutic intervention.
Quantitative proteomics of the 2016 WHONeisseria gonorrhoeaereference strains surveys vaccine candidates and antimicrobial resistance determinants
Authors: El-Rami Fadi E. , Zielke Ryszard A. , Wi Teodora , Sikora Aleksandra E. , Unemo Magnus
Published: October 2018

The sexually transmitted disease gonorrhea (causative agent:Neisseria gonorrhoeae) remains an urgent public health threat globally due to the repercussions on reproductive health, high incidence, widespread antimicrobial resistance (AMR), and absence of a vaccine. To mine gonorrhea antigens and enhance our understanding of gonococcal AMR at the proteome level, we performed the first large-scale proteomic profiling of a diverse panel (n=15) of gonococcal strains, including the 2016 World Health Organization (WHO) reference strains. These strains show all existing AMR profiles, previously described in regard to phenotypic and reference genome characteristics, and are intended for quality assurance in laboratory investigations. Herein, these isolates were subjected to subcellular fractionation and labeling with tandem mass tags coupled to mass spectrometry and multi-combinatorial bioinformatics. Our analyses detected 901 and 723 common proteins in cell envelope and cytoplasmic subproteomes, respectively. We identified nine novel gonorrhea vaccine candidates. Expression and conservation of new and previously selected antigens were investigated. In addition, established gonococcal AMR determinants were evaluated for the first time using quantitative proteomics. Six new proteins, WHO_F_00238, WHO_F_00635, WHO_F_00745, WHO_F_01139, WHO_F_01144, and WHO_F_01226, were differentially expressed in all strains, suggesting that they represent global proteomic AMR markers, indicate a predisposition toward developing or compensating gonococcal AMR, and/or act as new antimicrobial targets. Finally, phenotypic clustering based on the isolates’ defined antibiograms and common differentially expressed proteins yielded seven matching clusters between established and proteome-derived AMR signatures. Together, our investigations provide a reference proteomics databank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.
Improving on hash-based probabilistic sequence classification using multiple spaced seeds and multi-index Bloom filters
Authors: Chu Justin , Mohamadi Hamid , Erhan Emre , Tse Jeffery , Chiu Readman , Yeo Sarah , Birol Inanc
Published: October 2018

Alignment-free classification of sequences against collections of sequences has enabled high-throughput processing of sequencing data in many bioinformatics analysis pipelines. Originally hash-table based, much work has been done to improve and reduce the memory requirement of indexing ofk-mer sequences with probabilistic indexing strategies. These efforts have led to lower memory highly efficient indexes, but often lack sensitivity in the face of sequencing errors or polymorphism because they arek-mer based. To address this, we designed a new memory efficient data structure that can tolerate mismatches using multiple spaced seeds, called a multi-index Bloom Filter. Implemented as part of BioBloom Tools, we demonstrate our algorithm in two applications, read binning for targeted assembly and taxonomic read assignment. Our tool shows a higher sensitivity and specificity for read-binning than BWA MEM at an order of magnitude less time. For taxonomic classification, we show higher sensitivity than CLARK-S at an order of magnitude less time while using half the memory.
Alpha diversity metrics for noisy OTUs
Authors: Edgar Robert C. , Flyvbjerg Henrik
Published: October 2018

Next-generation sequencing (NGS) of marker genes such as 16S ribosomal RNA is widely used to survey microbial communities. The in-sample (alpha) diversity of Operational Taxonomic Units (OTUs) is often summarized by metrics such as richness or entropy which are calculated from observed abundances, or by estimators such as Chao1 which extrapolate to unobserved OTUs. Most such measures are adopted from traditional biodiversity studies, where observational error can often be neglected. However, errors introduced by next-generation amplicon sequencing tend to induce spurious OTUs and spurious counts in OTU tables, both of which are especially prevalent at low abundances. In consequence, traditional metrics may be grossly inaccurate if they are naively applied to NGS OTU tables. In this work, we describe two novel alpha diversity estimators which are calculated from OTU abundances above a specified threshold. The singleton-free estimator (SFE) is a non-parametric estimator which is derived from a similar approach to Chao1 but extrapolates using doublet and triplet abundances rather than singletons and doublets. The octave estimator (OE) fits a log-normal distribution to non-singleton bars of an octave plot. We show that these estimators are effective under suitable conditions, but these conditions rarely apply in practice. We conclude that extrapolating to unobserved OTUs remains an open problem which is unlikely to be solved in the near future.
Rapid growth and defence evolution following multiple introductions
Authors: van Boheemen Lotte A. , Bou-Assi Sarah , Uesugi Akane , Hodgins Kathryn A.
Published: October 2018

Rapid adaptation can aid invasive populations in their competitive success. Resource-allocation trade-off hypotheses predict higher resource availability or the lack of natural enemies in introduced ranges allow for increased growth and reproduction, thus contributing to invasive success. Evidence for such hypotheses are however equivocal and tests among multiple ranges over productivity gradients are required to provide a better understanding of the general applicability of these theories.

Using common gardens, we investigated the adaptive divergence of various constitutive and inducible defence-related traits between the native North American and introduced European and Australian ranges, whilst controlling for divergence due to latitudinal trait clines, individual resource budgets and population differentiation, using >11,000 SNPs.

Rapid, repeated clinal adaptation in defence-related traits was apparent despite distinct demographic histories. We also identified divergence among ranges in some defence-related traits, although differences in energy budgets among ranges may explain some, but not all, defence-related trait divergence. We do not identify a general reduction in defence in concert with an increase in growth among the multiple introduced ranges as predicted trade-off hypotheses.

Synthesis: The rapid spread of invasive species is affected by a multitude of factors, likely including adaptation to climate and escape from natural enemies. Unravelling the mechanisms underlying invasives’ success enhances understanding of eco-evolutionary theory and is essential to inform management strategies in the face of ongoing climate change.
A machine learning approach for the spatiotemporal forecasting of ecological phenomena using dates of species occurrence records
Authors: Capinha César
Published: October 2018

Spatiotemporal forecasts of ecological phenomena are highly useful and significant in scientific and socio-economic applications. Nevertheless, developing the correlative models to make these forecasts is often stalled by the inadequate availability of the ecological time-series data. On the contrary, considerable amounts of temporally discrete biological records are being stored in public databases, and often include the sites and dates of the observation. While these data are reasonably suitable for the development of spatiotemporal forecast models, this possibility remains mostly untested.

In this paper, we test an approach to develop spatiotemporal forecasts based on the dates and locations found in species occurrence records. This approach is based on ‘time-series classification’, a field of machine learning, and involves the application of a machine-learning algorithm to classify between time-series representing the environmental conditions that precede the occurrence records and time-series representing other environmental conditions, such as those that generally occur in the sites of the records. We employed this framework to predict the timing of emergence of fruiting bodies of two mushroom species (Boletus edulis and Macrolepiota procera) in countries of Europe, from 2009 to 2015. We compared the predictions from this approach with those from a ‘null’ model, based on the calendar dates of the records.

Forecasts made from the environmental-based approach were consistently superior to those drawn from the date-based approach, averaging an area under the receiver operating characteristic curve (AUC) of 0.9 for B. edulis and 0.88 for M. procera, compared to an average AUC of 0.83 achieved by the null models for both species. Prediction errors were distributed across the study area and along the years, lending support to the spatiotemporal representativeness of the values of accuracy measured.

Our approach, based on species occurrence records, was able to provide useful forecasts of the timing of emergence of two mushroom species across Europe. Given the increased availability and information contained in this type of records, particularly those supplemented with photographs, the range of events that could be possible to forecast is vast.
Use of a filter cartridge combined with intra-cartridge bead beating improves detection of microbial DNA from water samples
Authors: Ushio Masayuki
Published: October 2018

Microbial communities play an important role in driving the dynamics of aquatic ecosystems. As difficulties in DNA sequencing faced by microbial ecologists are continuously being reduced, sample collection methods and the choice of DNA extraction protocols are becoming more critical to the outcome of any sequencing study. In the present study, I added a manual, intra-cartridge, bead-beating step in the protocol using a DNeasy® Blood & Tissue kit for DNA extraction from a filter cartridge (Sterivex™ filter cartridge) with-out breaking the cartridge unit (“Beads” method), and compared its performance with those of two other protocols that used the filter cartridge (“NoBeads” method, which was similar to the Beads method but without the bead-beating step, and “PowerSoil” method, which followed the manual of the DNeasy® PowerSoil DNA extraction kit after breaking apart the filter cartridge). Water samples were collected from lake, river, pond and coastal ecosystems in Japan, and DNA was extracted using the three protocols. Then, the V4 region of prokaryotic 16S rRNA genes was amplified. In addition, internal standard DNAs were included in the DNA library preparation process to estimate the number of 16S rRNA gene copies. The DNA library was sequenced using Illumina MiSeq, and sequences were analyzed using the amplicon sequence variant (ASV) approach implemented in the DADA2 pipeline. I found that, 1) the total prokaryotic DNA yields were highest with the Beads method, 2) the number of ASVs (a proxy for species richness) was also highest with the Beads method, 3) overall community compositions were significantly different among the three methods, and 4) the number of method-specific ASVs was highest with the Beads method. These results were generally robust across samples from all aquatic ecosystems examined. In conclusion, the inclusion of a bead-beating step performed inside the filter cartridge increased the DNA yield as well as the number of prokaryotic ASVs detected compared with the other two methods. Performing the bead-beating step inside the filter cartridge causes no dramatic increase in either handling time or processing cost and it can reduce the potential contamination risk from the ambient air and/or other samples. Therefore, this method has the potential to become one of the major choices when one aims to extract aquatic microbial DNAs.
Quasi-periodic patterns of brain activity in individuals with Attention-Deficit/Hyperactivity Disorder
Authors: Abbas Anzar , Bassil Yasmine , Keilholz Shella
Published: October 2018

Individuals with attention-deficit/hyperactivity disorder have been shown to have disrupted functional connectivity in the default mode and task positive networks. Traditional fMRI analysis techniques that focus on static changes in functional connectivity have been successful in identifying differences between healthy controls and individuals with ADHD. However, such analyses are unable to explain the mechanisms behind the functional connectivity differences observed. Here, we study dynamic changes in functional connectivity in individuals with ADHD through investigation of quasi-periodic patterns (QPPs). QPPs are reliably recurring low-frequency spatiotemporal patterns in the brain linked to infra-slow electrical activity. They have been shown to contribute to functional connectivity observed through static analysis techniques. We find that QPPs contribute to functional connectivity specifically in regions that are disrupted during ADHD. Individuals with ADHD also show differences in the spatiotemporal pattern observed within the QPPs. This difference results in a weaker contribution of QPPs to functional connectivity in the default mode and task positive networks. We conclude that quasi-periodic patterns provide insight into the mechanisms behind functional connectivity differences seen in individuals with ADHD. This allows for a better understanding of the etiology of the disorder and development of effective treatments.
Starless bias and parameter-estimation bias in the likelihood-based phylogenetic method
Authors: Xia Xuhua
Published: October 2018

I analyzed various site pattern combinations in a 4-OTU case to identify sources of starless bias and parameter-estimation bias in likelihood-based phylogenetic methods, and reported three significant contributions. First, the likelihood method is odd in that it may not generate a star tree with sequences that are equidistant from each other. This behaviour, dubbed starless bias, happens in a 4-OTU tree when there is an excess (i.e., more than expected from a star tree and a substitution model) of conflicting phylogenetic signals supporting the three resolved topologies equally. Special site pattern combinations leading to rejection of a star tree, when sequences are equidistant from each other, were identified. Second, fitting gamma distribution to model rate heterogeneity over sites is strongly confounded with tree topology, especially in conjunction with the starless bias. I present examples to show dramatic differences in the estimated shape parameter α between a star tree and a resolved tree. There may be no rate heterogeneity over sites (with the estimated α > 10000) when a star tree is imposed, but α < 1 (suggesting strong rate heterogeneity over sites) when an (incorrect) resolved tree is imposed. Thus, the dependence of “rate heterogeneity” on tree topology implies that “rate heterogeneity” is not a sequence-specific feature, cautioning against interpreting a small α to mean that some sites are under strong purifying selection and others not. Thirdly, because there is no existing (and working) likelihood method for evaluating a star tree with continuous gamma-distributed rate, I have implemented the method for JC69 in a self-contained R script for a four-OTU tree (star or resolved), in addition to another R script assuming a constant rate over sites. These R scripts should be useful for teaching and exploring likelihood methods in phylogenetics.
Variable Effects on Growth and Defence Traits for Plant Ecotypic Differentiation and Phenotypic Plasticity along Elevation Gradients
Authors: Bakhtiari Moe , Formenti Ludovico , Caggía Veronica , Glauser Gaëtan , Rasmann Sergio
Published: October 2018

Along ecological gradients, ecotypes generally evolve as the result of local adaptation to a specific environment to maximize organisms’ fitness. Alongside ecotypic differentiation, phenotypic plasticity, as the ability of a single genotype to produce different phenotypes under different environmental conditions, can also evolve for favouring increased organisms’ performance in different environments. Currently, there is a lack in our understanding of how varying habitats may contribute to the differential contribution of ecotypic differentiation and plasticity in growth versus defence traits. Using reciprocal transplant-common gardens along steep elevation gradients, we evaluated patterns of ecotypic differentiation and phenotypic plasticity of two coexisting but unrelated plant species,Cardamine pratensisandPlantago major. For both species, we observed ecotypic differentiation accompanied by plasticity in growth related traits. Plants grew faster and produced more biomass when placed at low elevation. In contrast, we observed fixed ecotypic differentiation for defence and resistance traits. Generally, low elevation ecotypes produced higher chemical defences regardless of the growing elevation. Yet, some plasticity was observed for specific compounds, such as indole glucosinolates. We speculate that ecotypic differentiation in defence traits is maintained by costs of chemical defence production, while plasticity in growth traits is regulated by temperature driven growth response maximization.
Interference with HIV infection of the first cell is essential for viral clearance in a pre-exposure prophylaxis model
Authors: De Las Muelas Ana Moyano , Lustig Gila , Rodel Hylton E. , Antal Tibor , Sigal Alex
Published: October 2018

Pre-exposure prophylaxis (PrEP) uses relatively weak HIV inhibition to reduce transmission between individuals. Why this approach is successful is unclear. Here we derive and experimentally validate a mathematical model for predicting infection clearance with PrEP based on the measured effect of a drug on the HIV replication ratio and number of initial infected cells. We tested the model by inhibiting low dose HIV infection with tenofovir, which reduces infection frequency per cell, and atazanavir, which reduces the cellular burst size of viable virions. Both drugs were at concentrations which allowed similar HIV replication. Reducing infection frequency dramatically increased infection clearance, while reducing burst size did not. This indicates that initial infection is vulnerable to inhibition before it infects the first cell, but not thereafter. Our model explains why PrEP is potent at drug concentrations which are ineffective against established infection, and provides a framework to test drug effectiveness for PrEP.