bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploiting Genetic Diversity for Blast Disease Resistance Sources in Finger Millet (Eleusine coracana)
Authors: Manyasa Eric O. , Tongoona Pangirayi , Shanahan Paul , Githiri Stephen , Ojulong Henry , Njoroge Samuel M. C.
Published: August 2019

Finger millet blast, caused by Magnaporthe grisea, is the most important disease of finger millet in East Africa. Diseased plants are significantly less productive, and most cultivars grown by farmers are susceptible to the disease. Fungicide application is an option for disease management; however, smallholder farmers cannot afford the cost. Host plant resistance is therefore the most viable option for managing the disease. Eighty-one finger millet germplasm accessions from East Africa were evaluated for resistance to blast disease, in natural and inoculated trials. Three accessions (G18, G43, and G67) were identified as resistant to all the three progressive stages of blast: leaf, neck, and panicle. However, one (G3) and four (G15, G16, G60, and G70) accessions were only resistant to leaf and neck blast, respectively. Two resistant (G39 and G43) and 12 moderately resistant (G3, G7, G11, G20, G23, G27, G31, G33, G36, G66, G74, and G81) accessions to blast attained grain yields >2.0 t/ha. These accessions varied in time to maturity, plant height, and grain color, which will enable farmers to select accessions appropriate to their target agro-ecological zones and desired end uses. East African finger millet germplasm has high potential as a source of blast-resistant accessions that could be evaluated for direct production and/or for blast-resistance breeding.
Biomechanics of Periprosthetic Fixation: Plates, Nails, Cables, and Allografts
Authors: Gausden Elizabeth B. , Wellman David S.
Published: August 2019

Periprosthetic fractures (PPFs) present unique challenges to orthopaedic surgeons in terms of limited cortical fixation options, poor bone quality, cement mantles, and stress risers introduced from the prosthesis. Various fixation strategies have been used in PPFs including the use of intramedullary nails, locked plates, unicortical locking screws, cerclage wires and cables, double-plating techniques, and allograft struts. Here, we will review the biomechanics of various fixation strategies used in PPFs.
High Satisfaction in Adolescent Idiopathic Scoliosis Patients on Enhanced Discharge Pathway
Authors: Yang Joshua , Skaggs David L. , Chan Priscella , Villamor Gabriela A. , Choi Paul D. , Tolo Vernon T. , Kissinger Catherine , Lehman Alison , Andras Lindsay M.
Published: August 2019

Background:

Recently, there have been several reports of using an enhanced discharge pathway following posterior spinal fusion (PSF) in patients with adolescent idiopathic scoliosis (AIS). No previous studies have prospectively examined patient satisfaction of patients with AIS using an enhanced discharge pathway. The purpose of this study was to evaluate patient satisfaction with an enhanced discharge pathway for PSF and whether patients felt that their length of stay was appropriate.

Methods:

Patients with AIS undergoing PSF were prospectively enrolled. At their first postoperative clinic visit, patients were administered a survey regarding their experience.

Results:

Of the 46 patients enrolled (mean age, 14 y), 1 was discharged on postoperative day (POD) 2, 33 were discharged on POD 3, 9 were discharged on POD 4, and 3 were discharged on POD 5. Eighty (37/46) of patients felt that they were discharged at an appropriate time, whereas 20% (9/46) felt they were discharged too early. Patients who felt they were discharged at an appropriate time (mean, 3.2 d) had a trend toward shorter stays than those who felt they were discharged too early (mean, 3.7 d). Overall patient satisfaction of hospital stay was high with a mean of 9 on a 10-point scale (range, 1 to 10). There was no correlation between length of stay and patient satisfaction (P=0.723). Patients who felt they were discharged early had a significantly higher mean FACES pain scores than those who felt they were discharged about right both as inpatients (mean, 4.8 vs. 3.4; P=0.0319) and at their first postoperative clinic visit (5.4 vs. 2.9; P=0.004).

Conclusions:

Eighty percent of patients with AIS who underwent PSF felt that the time of discharge was appropriate with an enhanced discharge pathway. There was no correlation between patient satisfaction and length of stay.

Level of Evidence:

Level II.
Bibliometric Analysis of the 100 Most Cited Articles on Intervertebral Disk Research
Authors: Yang Ge , Li Zhuoyang , Ye Weihua , Huang Shengxiang , Liu Shaohua , Liu Kun , Tan Qian
Published: August 2019

Study Design:

A bibliometric review of the literature.

Object:

To analyze and quantify the most frequently cited papers in intervertebral disk research.

Summary of Background Data:

The number of citations that a paper has received reflects its impact in related research area. In the field of disk research, however, it remains unknown which papers are most cited. By searching related literature databases, we identified the most cited 100 articles that advanced the understanding of the intervertebral disk to provide a historic view of scientific research of the disk.

Materials and Methods:

Intervertebral disk original research-related publications from January 1, 1900 to December 31, 2017 were retrieved from the Web of Science database. Each retrieved article was analyzed using the Cited Reference Search tool to identify the most cited articles. The number of citations, year of publication, publishing journal, authorship, country of publication, and the knowledge maps of keywords were gathered and generated.

Results:

The number of citations of the 100 selected articles ranges from 209 to 1269, and they were published from 1953 to 2009. Basic research is the most common type of study (n=60), followed by epidemiological study (n=40). Spine published 57 of the most cited 100 papers. The greatest contribution came from the United States of America (n=41), followed by the United Kingdom (n=18) and Japan (n=9). Frequently appearing keywords classified into 3 clusters: “biological study,” “clinical study,” and “imageological study.” The keyword “degeneration” was mentioned the most, 51 items, and the word “development” was the latest hot spot in the most cited articles.

Conclusions:

In the field of disk research, some papers were heavily cited more than 100 times, suggesting these studies have substantially contributed to the body of knowledge of the intervertebral disk and findings were widely accepted by related clinicians and scientists.
PREOPERATIVE AND POSTOPERATIVE MACULAR SENSITIVITY ASSESSMENT USING MICROPERIMETRY IN EYES UNDERGOING SILICONE OIL REMOVAL
Authors: Nagpal Manish , Khandelwal Jayesh , Eltayib Ahmed , Mehrotra Navneet , Juneja Rakesh
Published: August 2019

Purpose:

To evaluate the functional changes on the macula, before and after silicone oil removal (SOR) using microperimetry (MP3) in patients originally operated for macula-off rhegmatogenous retinal detachments.

Methods:

Prospective interventional study, N = 20. All cases underwent complete ophthalmic examination, including determination of Snellen best-corrected visual acuity, indirect ophthalmoscopy, and MP3 for measuring retinal sensitivity. Primary outcome measure was to describe the alterations in the retinal sensitivity on the macula after SOR.

Results:

Mean retinal sensitivity increased in 100% patients (20/20) after SOR with a mean value of 97.44 dB. Best-corrected visual acuity after SOR remained unchanged in 90% (18/20) and improved by 2 lines in only 10% patients (2/20). Median retinal sensitivity of central 6° of the macula was 766.95 ± 173.29 dB before SOR and 863.8 ± 181.08 dB after SOR, P < 0.0001. Mean best-corrected visual acuity was 20/40 before SOR (range, 20/30–20/60) (logarithm of the minimum angle of resolution 0.314 ± 0.169) and 20/40 after SOR (range 20/30–20/80) (logarithm of the minimum angle of resolution 0.315 ± 0.159), P = 0.1628.

Conclusion:

MP3 was found to be a highly sensitive tool in detecting increased retinal sensitivity after SOR, particularly in central 6° of the macula without significant change in best-corrected visual acuity. Hence, MP3 is an important qualitative indicator of visual function.
Clostridium difficile Infection in the Emergency Department
Authors: Garg Sushil K. , Obaitan Itegbemie , Sarvepalli Shashank , Anugwom Chimaobi M. , Pardi Darrell S. , Khanna Sahil
Published: August 2019

Introduction:

Clostridioides difficile infection (CDI) is associated with substantial emergency department (ED) and inpatient burden. To date, few studies have evaluated the ED burden of CDI. Using the Nationwide Emergency Department Sample, we evaluated trends in ED use, ED and inpatient charges, admission and mortality rates, length of stay, and independent risk factors for hospital admission and mortality after an ED visit.

Methods:

Using Nationwide Emergency Department Sample for 2006 through 2014, we identified all patients with the primary diagnosis of CDI (using diagnostic codes). We determined the trends in ED visits and used survey logistic regression analysis to identify factors associated with hospital admission.

Results:

Overall, 909,236 ED visits for CDI resulted in 817,935 admissions (90%) to the hospital. The number of visits increased from 76,709 in 2006 to 106,869 in 2014, and the admission rate decreased from 92.4% to 84.4%. ED charges adjusted for inflation went up from US$1433.0 to 2900, a significant rise even accounting for inflation. The overall length of hospital stay decreased from 7 to 5.8 days. Independent predictors of admission after ED visits included smoking, use of alcohol, and presence of multiple comorbidities. Independent risk factors for mortality in admitted patients include increasing age and presence of comorbidities.

Conclusions:

Although ED use for CDI increased, rates of hospital admission decreased over 9 years. Identification of predictors of admission and in-hospital mortality will help guide policies and interventions to reduce the burden on health care resources.
Microbial Contamination, Infection, and Antimicrobial Use During Total Pancreatectomy With Islet Autotransplantation
Authors: Trisler Michael J. , Kruer Rachel M. , Jarrell Andrew S. , Faghih Mahya , Walsh Christi M. , Singh Vikesh K. , Hall Erica , Kalyani Rita R. , Makary Martin A. , Hatfield Laura A.
Published: August 2019

Objectives

Total pancreatectomy with islet autotransplantation can relieve pain associated with chronic pancreatitis while preserving islet function. Islet preparations are often contaminated by enteric flora. We assessed the impact of contaminated islet preparations on the prevalence of postoperative infection.

Methods

Electronic health records for patients who underwent total pancreatectomy with islet autotransplantation from August 1, 2011, to November 15, 2017 were retrospectively reviewed to compare the prevalence of postoperative infection in patients with a positive islet culture and islet culture negative patients.

Results

Sixty-one patients were included. Twenty-nine patients (47.5%) had a positive islet culture, and 23 (79.3%) of these patients received antimicrobial prophylaxis. The prevalence of postoperative infection did not differ between the islet culture positive and islet culture negative groups (41% vs 34%, P = 0.57). No infections occurred in the 6 islet culture positive patients who did not receive prophylaxis. No difference in intensive care unit or hospital length of stay or in 30-day or 90-day readmission rates were observed.

Conclusions

Despite the common use of postoperative systemic antimicrobials, we observed no difference in the prevalence of postoperative infection, length of stay, or hospital readmission in patients receiving a contaminated islet preparation. If prophylactic antimicrobials are used, the duration should be minimized.
Instrument Development for Evaluation of Gerontological Nurse Specialists Core Competencies in China
Authors: Chen Hongxiu , Pu Lihui , Chen Qian , Xu Xiaofeng , Bai Chunlan , Hu Xiuying
Published: August 2019

Purpose:

This study aimed to determine the core competencies of Chinese gerontological nurse specialists and test the psychometric properties of a core competency self-evaluation instrument.

Methods:

This study consisted of 2 stages. A literature review, theoretical analysis, and the Delphi methods involving 28 experts were performed to identify the core competencies required of gerontological nurse specialists in China. Then, a self-evaluation instrument developed based on the results of stage I was tested among 225 certified gerontological nurse specialists. An exploratory factor analysis was applied to test the construct validity, and the content validity and reliability were also evaluated.

Results:

The core competencies of gerontological nurse specialists comprised 3 first-level domains, 9 second-level dimensions, and 69 third-level items. The average scale-level content validity, overall instrument’s Cronbach’s α, and test-retest reliability were 0.963, 0.983, and 0.834, respectively. The results of the exploratory factor analysis indicated that the factors in the 3 first-level domains (attitude, skill, and knowledge) explained 68.579%, 69.599%, and 75.872% of the variance, respectively.

Conclusion:

The results showed that the core competencies of Chinese gerontological nurse specialists were reliable and that gerontological nurse specialists could use this self-evaluation instrument to assess their core competencies.
Clinical Nurse Specialist Preceptor Protocol
Authors: Bloomingdale Rosina , Darmody Julie V.
Published: August 2019

Purpose:

Develop an evidence-based clinical nurse specialist (CNS) preceptor protocol to enhance preceptor’s skills and effectiveness and strengthen the preceptor-preceptee relationship and outcomes.

Description:

An effective CNS preceptor is a key variable to quality, timely, and fiscally responsible CNS transition and retention. Most preceptors receive no formal education or skill development. Literature searched from the previous 10 years explored CNS preceptor, preceptee, and preceptorship process.

Outcomes:

Protocol key components are development of the mutual collaborative relationship, shared meaning, understanding, goal setting, timelines, and evaluations. The planning phase of the protocol includes face-to-face meeting to identify overarching goals and establish a trusting collaborative relationship. The mutual iterative learning and growing phase includes identification of learning needs, goals, and strategies such as debriefing, reflective journaling, and mutual ongoing evaluation. The concluding phase includes formal evaluation. The outcome phase includes safe autonomous CNS practice, along with mutual growth and satisfaction.

Conclusions:

The literature informed the CNS preceptor protocol development. The protocol may be evaluated within a preceptor-preceptee relationship across multiple settings. Higher levels of CNS research are vital to identify evidence-based CNS preceptorship strategies. As CNSs are integrated into advanced practice roles, a structured preceptor protocol and education program is critical to provide quality outcomes.
Mapping of Lymph Node Metastasis From Esophagogastric Junction Tumors
Authors: Kurokawa Yukinori , Takeuchi Hiroya , Doki Yuichiro , Mine Shinji , Terashima Masanori , Yasuda Takushi , Yoshida Kazuhiro , Daiko Hiroyuki , Sakuramoto Shinichi , Yoshikawa Takaki , Kunisaki Chikara , Seto Yasuyuki , Tamura Shigeyuki , Shimokawa Toshio , Sano Takeshi , Kitagawa Yuko
Published: August 2019

Objective:

The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study.

Background:

Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized.

Methods:

Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%.

Results:

Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1.

Conclusion:

The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection.
Health-related Quality of Life Following Hybrid Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer, Analysis of a Multicenter, Open-label, Randomized Phase III Controlled Trial
Authors: Mariette Christophe , Markar Sheraz , Dabakuyo-Yonli Tienhan Sandrine , Meunier Bernard , Pezet Denis , Collet Denis , D’Journo Xavier Benoit , Brigand Cécile , Perniceni Thierry , Carrere Nicolas , Mabrut Jean Yves , Msika Simon , Peschaud Frédérique , Prudhomme Michel , Bonnetain Franck , Piessen Guillaume
Published: August 2019

Background:

Hybrid minimally invasive esophagectomy (HMIE) has been shown to reduce major postoperative complications compared with open esophagectomy (OE) for esophageal cancer.

Objectives:

The aim of this study was to compare short- and long-term health-related quality of life (HRQOL) following HMIE and OE within a randomized controlled trial.

Methods:

We performed a multicenter, open-label, randomized controlled trial at 13 study centers between 2009 and 2012. Patients aged 18 to 75 years with resectable cancers of the middle or lower third of the esophagus were randomized to undergo either transthoracic OE or HMIE. Patients were followed-up every 6 months for 3 years postoperatively and global health assessed with EORTC-QLQC30 and esophageal symptoms assessed with EORTC-OES18.

Results:

The short-term reduction in global HRQOL at 30 days specifically role functioning [−33.33 (HMIE) vs −46.3 (OE); P = 0.0407] and social functioning [−16.88 (HMIE) vs −35.74 (OE); P = 0.0003] was less substantial in the HMIE group. At 2 years, social functioning had improved following HMIE to beyond baseline (+5.37) but remained reduced in the OE group (−8.33) (P = 0.0303). At 2 years, increases in pain were similarly reduced in the HMIE compared with the OE group [+6.94 (HMIE) vs +14.05 (OE); P = 0.018]. Postoperative complications in multivariate analysis were associated with role functioning, pain, and dysphagia.

Conclusions:

Esophagectomy has substantial effects upon short-term HRQOL. These effects for some specific parameters are, however, reduced with HMIE, with persistent differences up to 2 years, and maybe mediated by a reduction in postoperative complications.
Long-term wildlife mortality surveillance in northern Congo: a model for the detection of Ebola virus disease epizootics
Authors: Kuisma Eeva , Olson Sarah H. , Cameron Kenneth N. , Reed Patricia E. , Karesh William B. , Ondzie Alain I. , Akongo Marc-Joël , Kaba Serge D. , Fischer Robert J. , Seifert Stephanie N. , Muñoz-Fontela César , Becker-Ziaja Beate , Escudero-Pérez Beatriz , Goma-Nkoua Cynthia , Munster Vincent J. , Mombouli Jean-Vivien
Published: August 2019

Ebolavirus (EBOV) has caused disease outbreaks taking thousands of lives, costing billions of dollars in control efforts and threatening great ape populations. EBOV ecology is not fully understood but infected wildlife and consumption of animal carcasses have been linked to human outbreaks, especially in the Congo Basin. Partnering with the Congolese Ministry of Health, we conducted wildlife mortality surveillance and educational outreach in the northern Republic of Congo (RoC). Designed for EBOV detection and to alert public health authorities, we established a low-cost wildlife mortality reporting network covering 50 000 km
2
. Simultaneously, we delivered educational outreach promoting behavioural change to over 6600 people in rural northern RoC. We achieved specimen collection by training project staff on a safe sampling protocol and equipping geographically distributed bases with sampling kits. We established in-country diagnostics for EBOV testing, reducing diagnostic turnaround time to 3 days and demonstrated the absence of EBOV in 58 carcasses. Central Africa remains a high-risk EBOV region, but RoC, home to the largest remaining populations of great apes, has not had an epidemic since 2005. This effort continues to function as an untested early warning system in RoC, where people and great apes have died from past Ebola virus disease outbreaks.

This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Ecological interventions to prevent and manage zoonotic pathogen spillover
Authors: Sokolow Susanne H. , Nova Nicole , Pepin Kim M. , Peel Alison J. , Pulliam Juliet R. C. , Manlove Kezia , Cross Paul C. , Becker Daniel J. , Plowright Raina K. , McCallum Hamish , De Leo Giulio A.
Published: August 2019

Spillover of a pathogen from a wildlife reservoir into a human or livestock host requires the pathogen to overcome a hierarchical series of barriers. Interventions aimed at one or more of these barriers may be able to prevent the occurrence of spillover. Here, we demonstrate how interventions that target the ecological context in which spillover occurs (i.e. ecological interventions) can complement conventional approaches like vaccination, treatment, disinfection and chemical control. Accelerating spillover owing to environmental change requires effective, affordable, durable and scalable solutions that fully harness the complex processes involved in cross-species pathogen spillover.

This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Epidemic growth rates and host movement patterns shape management performance for pathogen spillover at the wildlife–livestock interface
Authors: Manlove Kezia R. , Sampson Laura M. , Borremans Benny , Cassirer E. Frances , Miller Ryan S. , Pepin Kim M. , Besser Thomas E. , Cross Paul C.
Published: August 2019

Managing pathogen spillover at the wildlife–livestock interface is a key step towards improving global animal health, food security and wildlife conservation. However, predicting the effectiveness of management actions across host–pathogen systems with different life histories is an on-going challenge since data on intervention effectiveness are expensive to collect and results are system-specific. We developed a simulation model to explore how the efficacies of different management strategies vary according to host movement patterns and epidemic growth rates. The model suggested that fast-growing, fast-moving epidemics like avian influenza were best-managed with actions like biosecurity or containment, which limited and localized overall spillover risk. For fast-growing, slower-moving diseases like foot-and-mouth disease, depopulation or prophylactic vaccination were competitive management options. Many actions performed competitively when epidemics grew slowly and host movements were limited, and how management efficacy related to epidemic growth rate or host movement propensity depended on what objective was used to evaluate management performance. This framework offers one means of classifying and prioritizing responses to novel pathogen spillover threats, and evaluating current management actions for pathogens emerging at the wildlife–livestock interface.

This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Onward transmission of viruses: how do viruses emerge to cause epidemics after spillover?
Authors: Wasik Brian R. , de Wit Emmie , Munster Vincent , Lloyd-Smith James O. , Martinez-Sobrido Luis , Parrish Colin R.
Published: August 2019

The critical step in the emergence of a new epidemic or pandemic viral pathogen occurs after it infects the initial spillover host and then is successfully transmitted onwards, causing an outbreak chain of transmission within that new host population. Crossing these choke points sets a pathogen on the pathway to epidemic emergence. While many viruses spill over to infect new or alternative hosts, only a few accomplish this transition—and the reasons for the success of those pathogens are still unclear. Here, we consider this issue related to the emergence of animal viruses, where factors involved likely include the ability to efficiently infect the new animal host, the demographic features of the initial population that favour onward transmission, the level of shedding and degree of susceptibility of individuals of that population, along with pathogen evolution favouring increased replication and more efficient transmission among the new host individuals. A related form of emergence involves mutations that increased spread or virulence of an already-known virus within its usual host. In all of these cases, emergence may be due to altered viral properties, changes in the size or structure of the host populations, ease of transport, climate change or, in the case of arboviruses, to the expansion of the arthropod vectors. Here, we focus on three examples of viruses that have gained efficient onward transmission after spillover: influenza A viruses that are respiratory transmitted, HIV, a retrovirus, that is mostly blood or mucosal transmitted, and canine parvovirus that is faecal:oral transmitted. We describe our current understanding of the changes in the viruses that allowed them to overcome the barriers that prevented efficient replication and spread in their new hosts. We also briefly outline how we could gain a better understanding of the mechanisms and variability in order to better anticipate these events in the future.

This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Host phylogenetic distance drives trends in virus virulence and transmissibility across the animal–human interface
Authors: Guth Sarah , Visher Elisa , Boots Mike , Brook Cara E.
Published: August 2019

Historically, efforts to assess ‘zoonotic risk’ have focused mainly on quantifying the potential for cross-species emergence of viruses from animal hosts. However, viruses clearly differ in relative burden, both in terms of morbidity and mortality (virulence) incurred and the capacity for sustained human-to-human transmission. Extending previously published databases, we delineated host and viral traits predictive of human mortality associated with viral spillover, viral capacity to transmit between humans following spillover and the probability of a given virus being zoonotic. We demonstrate that increasing host phylogenetic distance from humans positively correlates with human mortality but negatively correlates with human transmissibility, suggesting that the virulence induced by viruses emerging from hosts at high phylogenetic distance may limit capacity for human transmission. Our key result is that hosts most closely related to humans harbour zoonoses of lower impact in terms of morbidity and mortality, while the most distantly related hosts—in particular, order Chiroptera (bats)—harbour highly virulent zoonoses with a lower capacity for endemic establishment in human hosts. As a whole, our results emphasize the importance of understanding how zoonoses manifest in the human population and also highlight potential risks associated with multi-host transmission chains in spillover.

This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Design of Epitope Based Peptide Vaccine Against Pseudomonas Aeruginosa Fructose Bisphosphate Aldolase Protein using Immunoinformatics
Authors: Elhag Mustafa , Alaagib Ruaa Mohamed , Ahmed Nagla Mohamed , Abubaker Mustafa , Haroun Esraa Musa , Obi Sahar , Hassan Mohammed A.
Published: August 2019

Pseudomonas aeruginosais common pathogen that is responsible of serious illnesses hospital acquired infection as ventilator associated pneumonia and various sepsis syndrome. Also it is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistant mechanisms. generally affects the immuonocompromised but can also infect the immunocompetent as in hot tub folliculitis. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against Fructose bisphosphate aladolase (FBA) ofPseudomonas aeruginosausing immunoinformatics tools. The sequences were obtained from NCBI and prediction tests took place to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility and hydrophilicity tests. Six MHC I epitopes were the most promising, while four from MHC II. Nineteen epitopes were shared between MHC I and II. For the population coverage, the epitopes covered 95.62% of the alleles worldwide excluding certain MHC II alleles. We recommend invivo and invitro studies to prove it’s effectiveness.
Olfactory receptor subgenome and expression in a highly olfactory procellariiform seabird
Authors: Sin Simon Yung Wa , Cloutier Alison , Nevitt Gabrielle , Edwards Scott V.
Published: August 2019

Procellariiform seabirds are known for their well-developed olfactory capabilities, reflected by their large olfactory bulb to brain ratio and olfactory-mediated behaviors. Many species in this clade use olfactory cues for foraging and navigation, and some species can recognize individual-specific odors. Their genomes and transcriptomes may yield important clues about how the olfactory receptor (OR) subgenome was shaped by natural and sexual selection. In this study, we assembled a high-quality Leach’s storm petrel (Oceanodroma leucorhoa) genome to facilitate characterization of the OR repertoire. We also surveyed expressed OR genes through transcriptome analysis of the olfactory epithelium - to our knowledge, the first avian study to interrogate OR diversity in this way. We detected a large number (∼61) of intact OR genes, and identified OR genes under positive selection. In addition, we estimated that this species has the lowest proportion (∼60%) of pseudogenes compared to other waterbirds studied thus far. We show that the traditional annotation-based genome mining method underestimates OR gene number (214) as compared to copy number analysis using depth-of-coverage analysis, which estimated a total of 492 OR genes. By examining OR expression pattern in this species, we identified highly expressed OR genes, and OR genes that were differentially expressed between age groups, providing valuable insight into the development of olfactory capabilities in this and other avian species. Our genomic evidence is consistent with the Leach’s storm petrel’s well-developed olfactory sense, a key sensory foundation for its pelagic lifestyle and behavioral ecology.
It takes two vanilloid ligand bindings per channel to transduce painful capsaicin stimuli
Authors: Liu Ting-Yi , Chu Ying , Mei Hao-Ruei , Chang Dennis S. , Chuang Huai-Hu
Published: August 2019

The capsaicin receptor TRPV1 in mammals evolved the capability of integrating pain arising from combinations of noxious temperature or chemical irritants. Four-fold repetition of TRPV1 subunits makes an ion channel endowed with excellent sensitivity for pain detection, assisting this ionotropic receptor to differentiate graded injuries. We manipulated the stoichiometry and relative steric coordination of capsaicin binding at the molecular level, explicating rules with which a receptor codes pain within a broad range of intensity. The first ligand binding delivers small but clear initiation of channel activation. Maximal agonist action has already been reached in a receptor-in-tandem containing two or three wild-type receptor units, displaying activity comparable to the full liganded all-wild-type tandem tetramers. When the binding sites outnumbered ligands, independent action dominates in each channel. The non-vanilloid agonist 2-APB differs from capsaicin by adopting a distinct open mechanism since it does not demand a vanilloid group to activate. The sharing of the same pore greatly simplifies synergism to transduce relevant inputs by summation for pain signaling. And questions the need to explore deeper into other aspects of nociception.
A prospective role for the rumen in generating antibiotic resistance
Authors: Strachan Cameron R. , Mueller Anna J. , Ghanbari Mahdi , Neubauer Viktoria , Zwirzitz Benjamin , Thalguter Sarah , Dziecol Monika , Wetzels Stefanie U. , Zanghellini Jürgen , Wagner Martin , Schmitz-Esser Stephan , Mann Evelyne
Published: August 2019

Antibiotics were a revolutionary discovery of the 20th century, but the ability of bacteria to spread the genetic determinants of resistance via horizontal gene transfer (HGT) has quickly endangered their use1. Indeed, there is a global network of microbial gene exchange, the analysis of which has revealed particularly frequent transfer of resistance determinants between farm animals and human-associated bacteria2. Here, we leverage the recent release of a rumen microbial genome reference set and show that the wide-spread resistance gene cluster aadE-sat4-aphA-3 is harboured in ruminal Bacteroidetes. While this cluster appears to have been recently transferred between commensal bacteria in the rumen and many diverse animal and human pathogens, comparative analysis suggests that the cluster stabilized in the pathogens. Then, focusing on streptomycin resistance, it was found that homologues from the rumen span much of the known diversity of aminoglycoside O-nucleotidyltransferases (AadEs) and that distinct variants of the enzyme are present in a single rumen bacterial genome. Notably, a second variant of AadE has also been recently transferred, albeit more often as a single gene, throughout a different set of animal and human associated bacteria. By examining the synteny of AadE orthologues in various bacterial genomes and analyzing corresponding gene trees in an environmental context, we speculate that the ruminant associated microbiome has a salient role in the emergence of specific resistance variants and clusters. In light of the recent literature on the evolutionary origin of antibiotic resistance, we further suggest that the rumen provides a possible route of dissemination of resistance genes from soil resistomes, throughout the farm, and to human pathogens3.
Systematic search for schizophrenia pathways sensitive to perturbation by immune activation
Authors: Gao Yue , Liang Xiaozhen , Ren Zhonglu , Li Yanjun , Yang Xinping
Published: August 2019

Immune activation has been recently found to play a large part in the development of schizophrenia, but the underlying mechanism remains largely unknown. Here, we report the construction of a high-quality protein interaction network for schizophrenia (SCZ Network) using a “neighborhood walking” approach to searching across human interactome network for disease-related neighborhoods. The spatiotemporal expression pattern of the immune genes in the SCZ Network demonstrates that this disease network is sensitive to the perturbation of immune activation during mid- to late fetal development and adolescence. The immune genes in the network are involved in pathways regulating the formation, structure and function of synapses and neural connections. Using single-cell transcriptome sequencing on the brains of immune-activated mice, we found that immune activation disturbed the SCZ network in the major brain cell types and the dysregulated pathways were also involved in synapse regulation, demonstrating that our “neighborhood walking” approach enables biological discovery in complex disorders.
LIBR Methamphetamine and Opioid Cue Database (LIBR MOCD): Development and Validation
Authors: Ekhtiari Hamed , Kuplicki Rayus , Pruthi Asheema , Paulus Martin
Published: August 2019

Introduction

Drug cue reactivity (DCR) is widely used in experimental settings for both assessment and intervention. There is no validated database of pictorial cues available for methamphetamine and opioids.

Methods

360 images in three-groups (methamphetamine, opioid and neutral (control)) matched for their content (objects, hands, faces and actions) were selected in an initial development phase. 28 participants with a history of both methamphetamine and opioid use (37.1 ± 8.11 years old, 12 female) with over six months of abstinence were asked to rate images for craving, valence, arousal, typicality and relatedness.

Results

All drug images were differentiated from neutral images. Drug related images received higher arousal and lower valence ratings compared to neutral images (craving (0-100) for neutral (11.5±21.9), opioid (87.7±18.5), and methamphetamine (88±18), arousal (1-9) for neutral (2.4±1.9), opioid (4.6±2.7), and methamphetamine (4.6±2.6), and valence (1-9) for neutral (4.8±1.3), opioid (4.4±1.9), and methamphetamine (4.4±1.8)). There is no difference between methamphetamine and opioid images in craving, arousal and valence. There is a significant positive relationship between the amount of time that participants spent on drug-related images and the craving they reported for the image. Every 10 points of craving were associated with an increased response time of 383millisecond. Three image sets were automatically selected for equivalent fMRI tasks (methamphetamine and opioids) from the database (tasks are available at github).

Conclusion

LIBR MOCD provides a resource of validated images/tasks for future DCR studies. Additionally, researchers can select several sets of unique but equivalent images based-on their psychological/physical characteristics for multiple assessments/interventions.
Methodological Challenges in Translational Drug Response Modeling in Cancer
Authors: Schätzle Lisa-Katrin , Esfahani Ali Hadizadeh , Schuppert Andreas
Published: August 2019

Translational models directly relating drug response-specific processes observed in vitro to their in vivo role in cancer patients constitute a crucial part of the development of personalized medication. Unfortunately, ongoing research is often confined by the irreproducibility of the results in other contexts. While the inconsistency of pharmacological data has received great attention recently, the computational aspect of this crisis still deserves closer examination. Notably, studies often focus only on isolated model characteristics instead of examining the overall workflow and the interplay of individual model components. Here, we present a systematic investigation of translational models using the R-package FORESEE. Our findings confirm that with the current exploitation of the available data and the prevailing trend of optimizing methods to only one specific use case, modeling solutions will continue to suffer from non-transferability. Instead, the conduct of developing translational approaches urgently needs to change to retrieve clinical relevance in the future.
openTSNE: a modular Python library for t-SNE dimensionality reduction and embedding
Authors: Poličar Pavlin G. , Stražar Martin , Zupan Blaž
Published: August 2019

Point-based visualisations of large, multi-dimensional data from molecular biology can reveal meaningful clusters. One of the most popular techniques to construct such visualisations is t-distributed stochastic neighbor embedding (t-SNE), for which a number of extensions have recently been proposed to address issues of scalability and the quality of the resulting visualisations. We introduce openTSNE, a modular Python library that implements the core t-SNE algorithm and its extensions. The library is orders of magnitude faster than existing popular implementations, including those from scikit-learn. Unique to openTSNE is also the mapping of new data to existing embeddings, which can surprisingly assist in solving batch effects.

Availability

openTSNE is available at https://github.com/pavlin-policar/openTSNE.

Contact

pavlin.policar@fri.uni-lj.si, blaz.zupan@fri.uni-lj.si
Cytosine but not adenine base editor generates mutations in mice
Authors: Lee Hye Kyung , Smith Harold E. , Liu Chengyu , Willi Michaela , Hennighausen Lothar
Published: August 2019

Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms and its ultimate success therapeutically depends on its accuracy. Here we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editor (ABE) in mouse embryos using unbiased whole genome sequencing of a family-based trio cohort. We demonstrate that BE4-edited mice carry an excess of single-nucleotide variants and deletions compared to ABE-edited mice and controls.
The structure ofMycobacterium tuberculosisheme-degrading protein, MhuD, in complex with product
Authors: Chao Alex , Burley Kalistyn H. , Sieminski Paul J. , Mobley David L. , Goulding Celia W.
Published: August 2019

Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis, requires iron for survival. In Mtb, MhuD is the cytosolic protein that degrades imported heme. MhuD is distinct, both in sequence and structure, from canonical heme oxygenases (HOs) but homologous with IsdG-type proteins. Canonical HO is found mainly in eukaryotes, while IsdG-type proteins are predominantly found in prokaryotes including pathogens. While there are several published structures of MhuD and other IsdG-type proteins in complex with heme substrate, no structures have been reported of IsdG-type proteins in complex with product, unlike HOs. We recently showed that the Mtb variant MhuD-R26S produces biliverdin IXα (αBV) rather than the wild-type (WT) mycobilin isomers as product. Given that mycobilin and other IsdG-type protein products like staphylobilin are difficult to isolate in quantities sufficient for structure determination, here we use the MhuD-R26S variant and its product αBV as a proxy to study the IsdG-type protein/product complex. First we show that αBV has nanomolar affinity for MhuD and the R26S variant. Second we determined the MhuD-R26S-αBV complex structure to 2.5 Å, which reveals two notable features (1) two αBV molecules bound per active site and (2) a new α-helix (α3) as compared with the MhuD-heme structure. Finally, by molecular dynamics simulations we show that α3 is stable with the proximal αBV alone. MhuD’s high affinity for its product and structural and electrostatic changes that accompany substrate turnover suggest that there is an unidentified protein that is responsible for product extraction from MhuD and other IsdG-type proteins.
Can individual and integrated water, sanitation, and handwashing interventions reduce fecal contamination in the household environment? Evidence from the WASH Benefits cluster-randomized trial in rural Kenya
Authors: Pickering Amy J. , Swarthout Jenna , Mureithi MaryAnne , Mboya John , Arnold Benjamin F. , Wolfe Marlene , Dentz Holly N. , Lin Audrie , Arnold Charles D. , Rao Gouthami , Stewart Christine P. , Ram Pavani K. , Clasen Thomas , Colford John M. , Null Clair
Published: August 2019

Combined water, sanitation, and handwashing (WSH) interventions have the potential to reduce fecal pathogens along more transmission pathways than single interventions alone. We measuredEscherichia colilevels in 3909 drinking water samples, 2691 child hand rinses, and 2422 toy ball rinses collected from households enrolled in a two-year cluster-randomized controlled trial evaluating single and combined WSH interventions. Water treatment alone reducedE. coliin drinking water, while a combined WSH intervention improved water quality by the same magnitude but did not affect levels of fecal indicator bacteria on child hands or toy balls. The failure of the WSH interventions to reduceE. colialong important child exposure pathways is consistent with the lack of a protective effect from the interventions on child diarrhea or child growth during the trial. Our results have important implications for WSH program design; the sanitation and handwashing interventions implemented in this trial should not be expected to reduce child exposure to fecal contamination in other similar settings.
The role of a priori-identified addiction and smoking gene sets in smoking behaviors
Authors: Evans Luke M. , Johnson Emma C. , Melroy-Grief Whitney E. , Hewitt John K. , Hoeffer Charles A. , Keller Matthew C. , Saba Laura M. , Stitzel Jerry A. , Ehringer Marissa A.
Published: August 2019

Introduction

Smoking is a leading cause of death, and genetic variation contributes to smoking behaviors. Identifying genes and sets of genes that contribute to risk for addiction is necessary to prioritize targets for functional characterization and for personalized medicine.

Methods

We performed a gene set-based association and heritable enrichment study of two addiction-related gene sets, those on the Smokescreen Genotyping Array and the nicotinic acetylcholine receptors, using the largest available GWAS summary statistics. We assessed smoking initiation, cigarettes per day, smoking cessation, and age of smoking initiation.

Results

Individual genes within each gene set were significantly associated with smoking behaviors. Both sets of genes were significantly associated with cigarettes per day, smoking initiation, and smoking cessation. Age of initiation was only associated with the Smokescreen gene set. While both sets of genes were enriched for trait heritability, each accounts for only a small proportion of the SNP-based heritability (2-12%).

Conclusions

These two gene sets are associated with smoking behaviors, but collectively account for a limited amount of the genetic and phenotypic variation of these complex traits, consistent with high polygenicity.

Implications

We evaluated evidence for association and heritable contribution of expert-curated and bioinformatically identified sets of genes related to smoking. Although they impact smoking behaviors, these specifically targeted genes do not account for much of the heritability in smoking and will be of limited use for predictive purposes. Advanced genome-wide approaches and integration of other ‘omics data will be needed to fully account for the genetic variation in smoking phenotypes.