bluuebunny/crossref_metadata_2025 huggingface dataset:
CHOROIDAL THICKNESS, VASCULAR FACTORS, AND AGE-RELATED MACULAR DEGENERATION
Authors: Gattoussi Sarra , Cougnard-Grégoire Audrey , Korobelnik Jean-François , Rougier Marie-Bénédicte , Delyfer Marie-Noëlle , Schweitzer Cédric , Le Goff Mélanie , Merle Bénédicte M.J. , Dartigues Jean-François , Delcourt Cécile
Published: July 2018

Purpose:

To study the associations of subfoveal choroidal thickness with vascular risk factors and age-related macular degeneration.

Methods:

Two hundred sixty-one participants of the Alienor study had gradable enhanced-depth imaging optical coherence tomography scans of the macula and available data on vascular and genetic risk factors (assessed through face-to-face interview and fasting blood samples) and age-related macular degeneration status (assessed from retinal photographs and optical coherence tomography). Subfoveal choroidal thickness was measured manually on one horizontal scan passing through the fovea.

Results:

In a multivariate mixed linear model, subfoveal choroidal thickness was independently associated with age greater than 80 years (−21.77 μm, P = 0.02), axial length (−21.77 μm, P < 0.0001), heavy smoking (≥20 pack-years: −24.89 μm, P = 0.05), fasting blood glucose higher than 7 mmol/L (−53.17 μm, P = 0.02), and lipid-lowering treatment (+18.23, P = 0.047). After multivariate adjustment for age, sex, axial length, and vascular and genetic risk factors, subfoveal choroidal thickness was thinner in eyes with central hyperpigmentation (−45.39 μm, P = 0.006), central hypopigmentation (−44.99 μm, P = 0.001), and central pigmentary abnormalities (−44.50 μm, P = 0.001), but not in eyes with late age-related macular degeneration (−18.05 μm, P = 0.33) or soft drusen.

Conclusion:

These findings indicate a relationship between vascular risk factors and choroidal thinning and suggest an early involvement of the choroid in the pathogenesis of age-related macular degeneration.
MACULAR HOLE ASSOCIATED WITH TOXOPLASMOSIS: A SURGICAL CASE SERIES
Authors: Sousa David Cordeiro , Andrade Gabriel Costa de , Nascimento Heloísa , Maia André , Muccioli Cristina
Published: July 2018

Purpose:

There are currently limited data addressing the surgical outcomes of pars plana vitrectomy (PPV) in toxoplasmosis-related macular hole (tMH). We aim to report and discuss safety and efficacy of PPV for tMH.

Methods:

Surgical case series (n = 11), with minimum postoperative follow-up time of 6 months. Consecutive patients who underwent PPV for tMH from 2013 to 2016 were included. Indications for surgery were: visual acuity ≥ 0.6 logarithm of the minimum angle of resolution (Snellen 20/80 or less), no intraocular inflammation for more than 6 months, extrafoveal toxoplasmosis scar, elevated tMH borders on optical coherence tomography, and patient agreement with surgery. Surgery was performed—PPV with epiretinal (if present) and internal limiting membrane peeling. Safety and efficacy of PPV for tMH were addressed by evaluating: 1) surgery-related complications and 2) visual acuity improvement.

Results:

A total of 11 patients (6 male), with a mean age of 33.2 ± 11.0 years were studied. Mean preoperative best-corrected visual acuity significantly improved from 1.10 ± 0.24 (Snellen 20/252) to 0.43 ± 0.18 logarithm of the minimum angle of resolution (Snellen 20/54) at last follow-up visit (P < 0.01). The rate of visual acuity improvement (i.e., a gain of at least three lines) and tMH closure was 100% for both. The only reported surgery-related complication was cataract in one case.

Conclusion:

Our results suggest that PPV is a safe and effective option in tMH cases. A controlled, longitudinal study would contribute to confirm these findings.
A Novel Approach for Therapeutic Delivery to the Rodent Pancreas Via Its Arterial Blood Supply
Authors: Choi Jeff , Wang Jing , Ren Gang , Thakor Avnesh S.
Published: July 2018

Objectives

Endovascular techniques can now access the arterial blood supply of the pancreas in humans to enable therapeutics to reach the gland in high concentrations while concurrently avoiding issues related to non-targeted delivery. However, there is no way to replicate this in small animals. In a rat model, we therefore developed a novel non-terminal technique to deliver therapeutics to different regions of the pancreas, via its arterial blood supply.

Methods

In female Wistar rats, selective branches of the celiac artery were temporarily ligated, depending on the region of the pancreas being targeted. Trypan blue dye was then administered as a surrogate marker for a therapeutic agent, via the celiac artery, and its staining/distribution throughout the pancreas determined. Postoperatively, animals were monitored daily, and serum was evaluated for markers of pancreatitis, liver, and metabolic function.

Results

Using this technique, we could selectively target the head, body/tail, or entire gland of the pancreas, via its arterial blood supply, with minimal nontarget staining. Following the procedure, all animals recovered with no evidence of pancreatitis or liver/metabolic dysfunction.

Conclusions

Our study demonstrates a novel technique that can be used to selectively deliver therapeutics directly to the rat pancreas in a safe manner with full recovery of the animal.
Medication Administration Errors
Authors: Salami Ibrahim , Subih Maha , Darwish Rima , Al-Jbarat Muntaha , Saleh Zyad , Maharmeh Mahmoud , Alasad Jafar , Al-Amer Rasmieh
Published: July 2018

Background:

Medication administration errors (MAEs) have short- and long-term implications on patients' health as well as on hospitals' accreditation and financial status.

Purpose:

The purpose was to explore Jordanian nurses' perceptions about MAEs.

Methods:

A cross-sectional design was used with a convenience sample of 470 nurses.

Results:

The most common types of MAEs were wrong time (32.6%) and wrong patient (30.5%). In addition, night shifts accounted for 42.9% of MAEs; the factor that contributed the most to MAEs was workload.

Conclusion:

Developing effective quality assurance programs in relation to medications and medication administration in all Jordanian health care settings is vital to ensure patient safety. Nursing educators in clinical and academic settings need to reinforce the importance of medication rights as well as medication calculation. A distraction-free zone should be created and reinforced in all medication rooms.
Quality of Pediatric Emergency Care as Assessed by Children and Their Parents
Authors: Janhunen Katja , Kankkunen Päivi , Kvist Tarja
Published: July 2018

Background:

Pediatric patients comprise a large user group for emergency services. However, few studies have concerned the views of children and parents on emergency care.

Purpose:

To describe and compare assessments of the quality of pediatric emergency care by children and their parents.

Methods:

Ninety-eight children and their parents from 4 emergency departments participated in the survey. Data were analyzed using descriptive methods and logistic regression analysis.

Results:

Participants considered emergency care of high quality. Although children and parents gave similar assessments, children gave lower scores than parents on children's ability to participate in care and private discussions with emergency staff. The predicting factors for children's and their parents' satisfaction with emergency department care were the parents' vocational degree and fewer visits of the child to the emergency department within the current year.

Conclusions:

Pediatric emergency care should focus on innovative ways of improving children's involvement in their care.
Implementation Strategies to Improve Evidence-Based Bathing Practices in a Neuro ICU
Authors: Reynolds Staci Sue , Sova Chris , McNalty Bridget , Lambert Suzanne , Granger Bradi
Published: July 2018

Background:

Evidence supports daily bathing using chlorhexidine gluconate (CHG) cloths to decrease preventable hospital-acquired central line–associated bloodstream infections (CLABSIs). However, implementation of this practice is inconsistent. Using multifaceted strategies to promote implementation is supported in the literature, yet there is a gap in knowing which strategies are most successful.

Purpose:

Using the Grol and Wensing Model of Implementation as a guide, the purpose of this study was to determine whether using tailored, multifaceted strategies would improve implementation of daily CHG bathing and decrease CLABSIs in a large neuro ICU.

Methods:

An observational pre-/postdesign was used.

Results:

Following implementation, infection rates decreased (P = .031). Statistically significant improvements were also seen across all process measures: bathing documentation, nursing knowledge, and perceived importance of CHG bathing.

Conclusions:

This study assists in closing the research-practice gap by using tailored, multifaceted implementation strategies to increase use of evidence-based nursing care for infection prevention practices.
Attachment Patterns Affect Spiritual Coping in Palliative Care
Authors: Kunsmann-Leutiger Elke , Loetz Cécile , Frick Eckhard , Petersen Yvonne , Müller Jakob Johann
Published: July 2018

Research has shown that spiritual coping is essential for palliative care patients in enhancing quality of life and that attachment patterns affect the emotional well-being of the terminally ill. This is the first study evaluating how spiritual coping and attachment are associated in palliative care patients. Four different attachment patterns—secure, dismissive, preoccupied, and unresolved—were examined, as well as how they relate to three different spiritual coping strategies—search, trust, and reflection. In a cross-sectional, correlative design, 80 patients were recruited from German palliative care wards and hospices. Attachment patterns were determined using the Adult Attachment Projective System and spiritual coping strategies by SpREUK questionnaire, measuring spiritual and religious attitudes in dealing with illness. The results indicate that there is an association between attachment style and spiritual coping. Preoccupied patients had the lowest score in spiritual coping, with the strategy “reflection” being significantly lowest (t = 2.389, P = .019). Securely and dismissively attached patients presented equally high scores, raising the question of what mechanisms underlie spiritual coping. Furthermore, the unresolved group scored high in spiritual coping. Heightening awareness for ways in which attachment styles influence spiritual coping can contribute significantly to the quality of life in terminally ill patients, enabling health care professionals to tailor to individual needs in this vulnerable stage of life.
Palliative Care Consultation Policy Change and Its Effect on Nurses' Moral Distress in an Academic Medical Center
Authors: Bosshardt Maribeth H. , Coyne Patrick J. , Marsden Justin , Su Zemin , Melvin Cathy L.
Published: July 2018

Moral distress affects workplace environment, burnout, employee retention, and patient safety. Palliative care is frequently involved in complex care for patients that may cause moral distress among staff. The goal of this study was to measure change in moral distress among nurses after implementation of a policy that allows nurses to consult palliative care. Before the policy change, data were gathered via email using the Moral Distress Scale-Revised. The scale was redistributed 6 months after implementation of the consult policy. Pre and post Moral Distress Scale-Revised results were analyzed. Qualitative thematic analyses of the nurses' comments were conducted.

A significantly lower percentage of nurses reported providing care for a hopelessly ill patient frequently or very frequently (34.6% vs 23.1%, P = .0397) after the policy change. However, a significantly higher percentage of nurses postpolicy reported frequently or very frequently providing less-than-optimal care because of pressures from administrators/insurers (14.4% vs 21.1%, P = .0378), caring for patients they did not feel qualified to care for (5.3% vs 14.8%, P = .0055), and working with providers who were not competent to care for the patient (13.9% vs 26.9%, P = .0059). Themes from nurses' comments were inadequate staffing, communication, ethical concerns, and lack of education.
Embedding Palliative Care Into Healthy Aging
Authors: Thiamwong Ladda , Pungchompoo Wanicha
Published: July 2018

This article provides a conceptual framework for understanding the relationship between palliative care and healthy aging using a narrative case study from Thailand. The Thai context is used to clarify two concepts: healthy aging and good death. This case study describes a Thai female older adult's perspective and her drive to stay physically, cognitively, and socially active for as long as possible—strong indicators of healthy aging until the end of life. Family support is a vital part of helping older adults stay active and achieve a good death. The Thai healthy aging model explains a lifelong process of how to be a healthy ager in the Thai context. The model is closely related to a palliative care philosophy, which focuses on dying without unnecessary suffering and promotes closeness to family. This model supports the inclusion of palliative care in healthy aging strategies to maximize quality of life and well-being, particularly in older adults experiencing multimorbidity and health inequalities. Improved healthy aging is integrally related to the provision of high-quality palliative care. The earlier systems and providers can promote healthy aging across contexts, the more effectively interventions can be targeted to encourage and improve the experience of care at the end of life.
Poorly Differentiated Nonkeratinizing Squamous Cell Carcinoma of the Thymus
Authors: Suster David , Pihan German , Mackinnon Alexander C. , Suster Saul
Published: July 2018

Thymic carcinoma represents a rare and poorly understood type of thymic epithelial neoplasm that has been the subject of much controversy. Poorly differentiated nonkeratinizing squamous cell carcinoma, also known as lymphoepithelioma-like thymic carcinoma, is a rare variant of thymic carcinoma that has not been adequately characterized in the literature. The clinicopathologic, immunohistochemical, ultrastructural, and molecular features of 25 cases are reported. The patients were 19 men and 6 women, ranging in age from 20 to 85 years (mean: 60 y). The tumors presented clinically as anterior mediastinal masses with chest pain and shortness of breath or were found incidentally on imaging studies. Tumor size ranged from 2.0 to 13.5 cm in greatest diameter. Most of the tumors were small, well-circumscribed and confined to the mediastinum. Five cases presented with large, bulky, and infiltrative masses. Histologically, the hallmark of these tumors was a neoplastic proliferation of large, round to oval cells with vesicular nuclei, prominent eosinophilic nucleoli, and scant cytoplasm. Two histologic growth patterns were identified: tumors with a heavy lymphoplasmacytic stroma (lymphoepithelioma-like pattern), and tumors showing abundant desmoplastic stroma (desmoplastic pattern). Immunohistochemical stains showed strong positivity of the tumor cells for cytokeratin AE1/AE3, CK5/6, CK18, MOC31, p16, p40, and p63. MIB-1 showed on average 35% nuclear positivity. CD117 was positive in 21/25 cases and CD5 in 20/25 cases. Epstein-Barr encoded RNA in situ hybridization was positive in only 1 case. Electron microscopy in 4 cases showed primitive round to oval cells with prominent nucleoli, scant cytoplasm and immature cell junctions. Molecular features were studied by next-generation sequencing using high quality sequence data obtained from 18 patients. Variants with allele frequency between 5% and 45% and quality scores >50 were classified as somatic. A total of 16/18 cases had one or more somatic variants of unknown significance. One case showed an IDH1 p. R132C mutation, also of unknown significance. No “actionable” genes amenable to currently available targeted therapies were identified in this cohort. Clinical follow-up was obtained in 20 patients; 14 patients were alive and well with no evidence of disease between 1.5 and 16 years after diagnosis (median survival: 4 y; mean: 5.5 y). Most survivors had relatively small tumors (<5 cm. diameter), were in stage I and II at diagnosis and showed clear surgical margins. Five patients died of their tumors with metastases to bone, brain, chest wall, lungs and lymph nodes; all were in advanced stages and showed positive margins. Prognosis for these tumors appears to be correlated with the staging and status of the margins at the time of initial surgery.
Frequent GNAQ and GNA14 Mutations in Hepatic Small Vessel Neoplasm
Authors: Joseph Nancy M. , Brunt Elizabeth M. , Marginean Celia , Nalbantoglu ILKe , Snover Dale C. , Thung Swan N. , Yeh Matthew M. , Umetsu Sarah E. , Ferrell Linda D. , Gill Ryan M.
Published: July 2018

Hepatic small vessel neoplasm (HSVN) is a recently described infiltrative vascular neoplasm of the liver, composed of small vessels. Although the infiltrative nature can mimic angiosarcoma, HSVN are thought to be benign or low-grade neoplasms because they lack cytologic atypia and increased proliferation. To characterize the molecular pathogenesis of HSVN, we performed both targeted panel sequencing and exome sequencing on 18 benign or low-grade vascular neoplasms in the liver including 8 HSVN, 6 classic cavernous hemangioma (CH), and 4 variant lesions (VL) with overlapping features between HSVN and CH. All 18 lesions had simple genomes without copy number alterations. In total, 75% (6/8) of HSVN demonstrated known activating hotspot mutations in GNAQ (2/8, p.Q209H) or GNA14 (4/8, p.Q205L), and the remaining 2 had the same missense mutation in GNAQ, p.G48L, which has not been previously described. 25% (1/4) of VL had a hotspot GNAQ p.Q209H mutation and another VL had a GNAQ p.G48L mutation. Known pathogenic mutations were not identified in any of the 6 CH. These data suggest that HSVN share a similar molecular biology to several other vascular lesions (congenital hemangioma, tufted angioma, anastomosing hemangioma, lobular capillary hemangioma, and kaposiform hemangioendothelioma) recently reported to have GNAQ, GNA11, or GNA14 mutations.
Pyloric Gland Adenoma (PGA) of the Gallbladder
Authors: He Cong , Fukumura Yuki , Toriyama Akane , Ogura Kanako , Sasahara Noriko , Mitani Keiko , Yao Takashi
Published: July 2018

Twenty-four surgically resected, gallbladder pyloric gland adenomas (GB-PGAs) were examined and their features were compared with the reported features of stomach, duodenum, and pancreatic PGAs to better understand GB-PGAs. Clinical information on background gallbladder lesions and histologic data, including tumor grade, existence of squamoid morules, intratumoral cholesterosis, and intracytoplasmic mucins were collected. Immunohistochemical staining for MUC2, MUC5AC, MUC6, CDX2, pepsinogen I, p53, and MIB-1/nuclear β-catenin were evaluated. Targeted mutational analyses of KRAS exon2, GNAS exon 7, and CTNNB1 exon 3 were conducted. We found that 29.2% of the GB-PGAs were histologically high-grade dysplasias/carcinomas; 70.8% were low grade; and 20.8% and 33.3% contained squamoid morules and intratumoral cholesterosis, respectively. In addition, 45.8% and 54.2% of GB-PGAs were mucin-rich and mucin-poor types, respectively. Immunohistochemically, MUC6 was diffusely positive in all GB-PGAs; MUC2, MUC5AC, and CDX2 were only focally positive, and no pepsinogen-I positive cells were observed. Nuclear β-catenin accumulation was observed in all cases; however, the ratio varied among cases. Mucin-poor types were significantly associated with high histologic grade dysplasias/carcinomas and high nuclear β-catenin labeling indices. Mutational analyses identified CTNNB1 mutations in 100% of GB-PGAs (21/21), KRAS in 4.2% (1/23), and GNAS in 0% (0/22). The present study clarified the unique histologic features, phenotypic differentiation, and molecular statuses frequently associated with GB-PGAs. Altogether, our data suggest that tumorigenesis of GB-PGA is distinct from that of stomach, duodenum, and pancreatic PGAs.
Local Health Departments' Engagement in Addressing Health Disparities: The Effect of Health Informatics
Authors: Shah Gulzar H. , Mase William A. , Waterfield Kristie C.
Published: July 2018

Context:

Health disparities and health inequities can lead to poor health outcomes. However, health disparities continue to persist in communities across the United States, presenting a crucial public health challenge. Persisting budget cuts and workforce challenges tend to hinder local health departments' (LHDs') ability to assess and address health disparities.

Objectives:

To examine the extent to which LHDs' use of informatics effects their engagement in strategies and activities addressing health disparities.

Methods:

Data from the 2016 Profile of LHDs were used in examining the association of informatics with 9 activities addressing health disparities/inequities.

Results:

Fifty-nine percent of LHDs used data and described health disparities in their jurisdiction, and 12% conducted original research to link health disparities to differences in social or environmental conditions. Less than 40% of LHDs prioritized resources for the reduction of health disparities. LHDs that implemented information systems had increased odds of describing the disparities in their jurisdiction (P < .01) and having prioritized resources for the reduction of disparities (P < .01). Per capita expenditures, participation in a national accreditation program process, and a larger LHD population were also positively associated with 7 of 9 activities for addressing health disparities/inequities.

Conclusions:

As LHDs advance efforts to reduce health disparities and inequities, leadership will find informatics a useful strategy. National initiatives aimed to boost LHDs' engagement in the reduction of disparities might benefit from our findings, positing a positive influence of informatics.
Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis
Authors: Liu Lijun , Liu Shengyun , Wang Cong , Guan Wenjuan , Zhang Yinli , Hu Wenlu , Zhang Lei , He Yujie , Lu Jiameng , Li Tianfang , Liu Xiaojun , Xuan Yiyi , Wang Peisong
Published: July 2018

Objective

To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential.

Methods

We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us.

Results

Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]).

Conclusion

Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.
Lessons Learned From a Faulty Transoral Endoscopic Thyroidectomy Vestibular Approach
Authors: Zhang Daqi , Wu Che-Wei , Inversini Davide , Kim Hoon Yub , Anuwong Angkoon , Bacuzzi Alessandro , Dionigi Gianlorenzo
Published: July 2018

Background:

Transoral endoscopic thyroidectomy via vestibular approach (TOETVA) is currently considered the most promisingly scarless approach to the thyroid and has gained more acceptance.

Materials and Methods:

We described a case of faulty TOETVA.

Results:

The faulty TOETVA resulted in pneumomediastinum, diffuse subcutaneous emphysema, prolonged surgery, and anesthesia.

Conclusions:

The important technical considerations during TOETVA, including the use of external retraction, the identification of the subplatysmal plane of dissection, CO2 insufflation settings, the learning curve, and patient selection, were described and discussed.
How We Approach Combination Antifungal Therapy for Invasive Aspergillosis and Mucormycosis in Transplant Recipients
Authors: Haidar Ghady , Singh Nina
Published: July 2018

Invasive aspergillosis and mucormycosis are life-threatening infections in solid organ and hematopoietic cell transplant recipients. Despite medical advancements in the care of these patients and the availability of new mold-active drugs, the outcomes remain suboptimal. Therefore, there has been increased interest in the use of combination antifungal therapy, in hopes that leveraging the possible in vitro synergy of these agents will improve the prognosis of invasive mold disease. However, there has been a large disconnect between the results of experimental and clinical investigations, as clinical studies have not unequivocally demonstrated the superiority of combination therapy over monotherapy. This is particularly true for mucormycosis, where the rarity of the condition has made it nearly impossible to prospectively study novel therapeutic strategies. We review the current standard of antifungal therapy and the preclinical and clinical data addressing the merit of combination therapy, and we provide guidance to optimize the management of these mycoses.
A powerful framework for an integrative study with heterogeneous omics data: from univariate statistics to multi-block analysis
Authors: Duruflé Harold , Selmani Merwann , Ranocha Philippe , Jamet Elisabeth , Dunand Christophe , Déjean Sébastien
Published: July 2018

The high-throughput data generated by new biotechnologies used in biological studies require specific and adapted statistical treatments. In this work, we propose a novel and powerful framework to manage and analyse multi-omics heterogeneous data to carry out an integrative analysis. We illustrate it using the package mixOmics for the R software as it specifically addresses data integration issues. Our work also aims at confronting the most recent functionalities of mixOmics to real data sets because, even if multi-block integrative methodologies exist, they still have to be used to enlarge our know-how and to provide an operational framework to biologists. Natural populations of the model plantArabidopsis thalianaare employed in this work but the framework proposed is not limited to this plant and can be deployed whatever the organisms of interest and the biological question. Four omics data sets (phenomics, metabolomics, cell wall proteomics and transcriptomics) have been collected, analysed and integrated in order to study the cell wall plasticity of plants exposed to sub-optimal temperature growth conditions. The methodologies presented start from basic univariate statistics and lead to multi-block integration analysis, and we highlight the fact that each method is associated to one biological issue. Using this powerful framework led us to novel biological conclusions that could not have been reached using standard statistical approaches.
Phylogeographic analysis and identification of factors impacting the diffusion of Foot-and-Mouth disease virus in Africa
Authors: Duchatel Florian , Bronsvoort Mark , Lycett Samantha
Published: July 2018

Foot and mouth disease (FMD) is endemic in sub-Saharan Africa and can lead to important and continuous economic losses for affected countries. Due to the complexity of the disease epidemiology and the lack of data there is a need to use inferential computational approaches to fill the gaps in our understanding of the circulation of FMD virus on this continent. Using a phylogeographic approach we reconstructed the circulation of FMD virus serotypes A, O and SAT2 in Africa and evaluated the influence of potential environmental and anthropological predictors of virus diffusion. Our results show that over the last hundred year the continental circulation of the tree serotypes was mainly driven by livestock trade. Whilst our analyses show that the serotypes A and O were introduced in Africa trough livestock trades, the SAT2 serotype probably originates from African wildlife population. The circulation of serotype O in eastern Africa is impacted by both indirect transmission through persistence in the environment and anthropological activities such as cattle movements.
Interspecific variation of olfactory preferences in flies, mice, and humans
Authors: Manoel Diogo , Makhlouf Melanie , Scialdone Antonio , Saraiva Luis R.
Published: July 2018

Aiming to unravel interspecific differences in olfactory preferences, we performed comparative studies of odor valence in flies, mice, and humans. Our analysis revealed that odor preferences of flies correlate positively with the ones of mice and negatively with the ones of humans, but found no evidence supporting the hypothesis that humans and mice prefer the same odors. We further find that odorants eliciting the highest and lowest preferences are often advertising critical biological sources (e.g., food or oviposition sites), suggesting that evolutionary pressures reflecting the ecological needs of each species shape olfactory preferences.
microRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis
Authors: Moro Albertomaria , Discroll Tristan , Armero William , Boraas Liana C. , Kasper Dionna M. , Baeyens Nicolas , Jouy Charlene , Mallikarjun Venkatesh , Swift Joe , Ahn Sang Joon , Lee Donghoon , Zhang Jing , Gu Mengting , Gerstein Mark , Schwart Martin , Nicoli Stefania
Published: July 2018

The mechanical properties of tissues, which are determined primarily by their extracellular matrix (ECM), are largely stable over time despite continual turnover of ECM constituents1,2. These observations imply active homeostasis, where cells sense and adjust rates of matrix synthesis, assembly and degradation to keep matrix and tissue properties within the optimal range. However, the regulatory pathways that mediate this process are essentially unknown3. Genome-wide analyses of endothelial cells revealed abundant microRNA-mediated regulation of cytoskeletal, adhesive and extracellular matrix (CAM) mRNAs. High-throughput assays showed co-transcriptional regulation of microRNA and CAM genes on stiff substrates, which buffers CAM expression. Disruption of global or individual microRNA-dependent suppression of CAM genes induced hyper-adhesive, hyper-contractile phenotypes in multiple systemsin vitro,and increased tissue stiffness in the zebrafish fin-fold during homeostasis and regenerationin vivo.Thus, a network of microRNAs and CAM mRNAs mediate tissue mechanical homeostasis.
ZetaHunter: a reproducible taxonomic classification tool for tracking the ecology of the Zetaproteobacteria and other poorly-resolved taxa
Authors: McAllister Sean M. , Moore Ryan M. , Chan Clara S
Published: July 2018

Like many taxa, the Zetaproteobacteria lack well-defined taxonomic divisions, 32 making it difficult to compare between studies. We designed ZetaHunter to reproducibly 33 assign 16S rRNA gene sequences to previously-described OTUs based on a curated 34 database. While ZetaHunter can use any given database, we include a curated 35 classification of publically-available Zetaproteobacteria.
phylostratr: A framework for phylostratigraphy
Authors: Arendsee Zebulun , Li Jing , Singh Urminder , Seetharam Arun , Dorman Karin , Wurtele Eve Syrkin
Published: July 2018

Motivation

The goal of phylostratigraphy is to infer the evolutionary origin of each gene in an organism. Currently, there are no general pipelines for this task. We present an R package, phylostratr, to fill this gap, making high-quality phylostratigraphic analysis accessible to non-specialists.

Results

Phylostratigraphic analysis entails searching for homologs within increasingly broad clades. The highest clade that contains all homologs of a gene is that gene’s phylostratum. We have created a general R-based framework, phylostratr, for estimating the phylostratum of every gene in a species. The program can fully automate an analysis: select species for a balanced representation of each strata, retrieve the sequences from UniProt, build BLAST databases, run BLAST, infer homologs for each gene against each subject species, determine phylostrata, and return summaries and diagnostics. phylostratr allows extensive customization. A user may: modify the automatically-generated clade tree or use their own tree; provide custom sequences in place of those automatically retrieved from UniProt; replace BLAST with an alternative algorithm; or tailor the method and sensitivity of the homology inference classifier. phylostratr also offers proteome quality assessments, false-positive diagnostics, and checks for missing organelle genomes. We show the utility of phylostratr through case studies in Arabidopsis thaliana and Saccharomyces cerevisiae.

Availability

phylostratr source code and vignettes are available on GitHub at https://github.com/arendsee/phylostratr

Contact

evewurtele@gmail.com
Nuclear and mitochondrial genomic resources for the meltwater stonefly,Lednia tumanaRicker, 1952 (Plecoptera: Nemouridae)
Authors: Hotaling Scott , Kelley Joanna L. , Weisrock David W.
Published: July 2018

With more than 3,700 described species, stoneflies (Order Plecoptera) are an important component of global aquatic biodiversity. The meltwater stoneflyLednia tumana(Ricker, 1952; Family Nemouridae) is endemic to alpine streams of Glacier National Park and has been petitioned for listing under the U.S. Endangered Species Act (ESA) due to climate change-induced loss of alpine glaciers and snowfields. Here, we presentde novoassemblies of the nuclear (~520 million base pairs [bp]) and mitochondrial (15,014-bp) genomes forL. tumana. TheL. tumananuclear genome is the most complete stonefly genome reported to date, with ~71% of genes present in complete form and more than 4,600 contigs longer than 10-kilobases (kb). TheL. tumanamitochondrial genome is the second for the family Nemouridae and the first from North America. Together, both genomes represent important foundational resources, setting the stage for future efforts to understand the evolution ofL. tumana, stoneflies, and aquatic insects worldwide.
Temperature-mediated inhibition of a bumble bee parasite by an intestinal symbiont
Authors: Palmer-Young Evan C , Raffel Thomas R , McFrederick Quinn S
Published: July 2018

Competition between organisms is often mediated by environmental factors including temperature. In animal intestines, nonpathogenic symbionts compete physically and chemically against pathogens, with consequences for host infection. We used metabolic theory-based models to characterize differential responses to temperature of a bacterial symbiont and a co-occurring trypanosomatid parasite of bumble bees, which regulate body temperature during flight and incubation. We hypothesized that inhibition of parasites by bacterial symbionts would increase with temperature, due to symbionts having higher optimal growth temperatures than parasites.

We found that a temperature increase over the range measured in bumble bee colonies would favor symbionts over parasites. As predicted by our hypothesis, symbionts reduced the optimal growth temperature for parasites, both in direct competition and when parasites were exposed to symbiont spent medium. Inhibitory effects of the symbiont increased with temperature, reflecting accelerated growth and acid production by symbionts. Our results indicate that high temperatures, whether due to host endothermy or environmental factors, can enhance the inhibitory effects of symbionts on parasites. Temperature-modulated manipulation of microbiota could be one explanation for fever- and heat-induced reductions of infection in animals, with consequences for diseases of medical and conservation concern.
Risk of disease spillover from dogs to wild carnivores in Kanha Tiger Reserve, India
Authors: Chaudhary V. , Rajput N. , Shrivastav A. B. , Tonkyn D. W.
Published: July 2018

Many mammalian carnivore species have been reduced to small, isolated populations by habitat destruction, fragmentation, poaching, and human conflict. Their limited genetic variability and increased exposure to domestic animals such as dogs place them at risk of further losses from infectious diseases. In India, domestic and feral dogs are associated with villages in and around protected areas, and may serve as reservoirs of pathogens to the carnivores within. India’s Kanha Tiger Reserve (KTR) is home to a number of threatened and endangered mammalian carnivores including tiger (Panthera tigris), leopard (Panthera pardus), wolf (Canis lupus), and dhole (Cuon alpinus). It also has more than 150 villages with associated dog populations. We found that dog populations ranged from 14 to 45/village (3.7 to 23.7/km2), and did not vary with village area, human population size, or distance from the KTR’s core area, though they all increased between summer 2014 and winter 2015, primarily through reproduction. No dog tested positive for rabies but seroprevalence levels to three other generalist viral pathogens were high in summer (N=67) and decreased somewhat by winter (N=168): canine parvovirus (83.6% to 68.4%), canine distemper virus (50.7% to 30.4%) and canine adenovirus (41.8% to 30.9%). The declines in seroprevalence were primarily due to new recruitments by birth and these were not yet exposed to the viruses. Wild carnivores frequently entered the villages, as shown by tracks, scats, kills and other indicators, and the dogs are known to leave the villages so that encounters between dogs and wild carnivores may be common. We conclude that there is a large population of unvaccinated dogs in and around Kanha Tiger Reserve, with high levels of seroprevalence to pathogens with broad host ranges and these dogs which interact with wild carnivores, therefore posing a high risk of disease spillover to the wild carnivores.
Candida albicansgenetic background influences mean and heterogeneity of drug responses and genome stability during evolution to fluconazole
Authors: Gerstein Aleeza C. , Berman Judith
Published: July 2018

The importance of within-species diversity in determining the evolutionary potential of a population to evolve drug resistance or tolerance is not well understood, including in eukaryotic pathogens. To examine the influence of genetic background, we evolved replicates of twenty different clinical isolates ofCandida albicans,a human fungal pathogen, in fluconazole, the commonly used antifungal drug. The isolates hailed from the majorC. albicansclades and had different initial levels of drug resistance and tolerance to the drug. The majority of replicates rapidly increased in fitness in the evolutionary environment, with the degree of improvement inversely correlated with ancestral strain fitness in the drug. Improvement was largely restricted to up to the evolutionary level of drug: only 4% of the evolved replicates increased resistance (MIC) above the evolutionary level of drug. Prevalent changes were altered levels of drug tolerance (slow growth of a subpopulation of cells at drug concentrations above the MIC) and increased diversity of genome size. The prevalence and predominant direction of these changes differed in a strain-specific manner but neither correlated directly with ancestral fitness or improvement in fitness. Rather, low ancestral strain fitness was correlated with high levels of heterogeneity in fitness, tolerance, and genome size among evolved replicates. Thus, ancestral strain background is an important determinant in mean improvement to the evolutionary environment as well as the diversity of evolved phenotypes, and the range of possible responses of a pathogen to an antimicrobial drug cannot be captured by in-depth study of a single strain background.

Importance

Antimicrobial resistance is an evolutionary phenomenon with clinical implications. We tested how replicates from diverse strains ofCandida albicans, a prevalent human fungal pathogen, evolve in the commonly-prescribed antifungal drug fluconazole. Replicates on average increased in fitness in the level of drug they were evolved to, with the least fit ancestral strains improving the most. Very few replicates increased resistance above the drug level they were evolved in. Notably, many replicates increased in genome size and changed in drug tolerance (a drug response where a subpopulation of cells grow slowly in high levels of drug) and variability among replicates in fitness, tolerance and genome size was higher in strains that initially were more sensitive to the drug. Genetic background influenced the average degree of adaptation and the evolved variability of many phenotypes, highlighting that different strains from the same species may respond and adapt very differently during adaptation.
Modelling genotypes in their microenvironment to predict single- and multi-cellular behaviour
Authors: Voukantsis Dimitrios , Kahn Kenneth , Hadley Martin , Wilson Rowan , Buffa Francesca M.
Published: July 2018

A cell’s phenotype is the set of observable characteristics resulting from the interaction of the genotype with the surrounding environment, determining cell behaviour. Deciphering genotype-phenotype relationships has been crucial to understand normal and disease biology. Analysis of molecular pathways has provided an invaluable tool to such understanding; however, it does typically not consider the physical microenvironment, which is a key determinant of phenotype.

In this study, we present a novel modelling framework that enables to study the link between genotype, signalling networks and cell behaviour in a 3D microenvironment. To achieve this we bring together Agent Based Modelling, a powerful computational modelling technique, and gene networks. This combination allows biological hypotheses to be tested in a controlled stepwise fashion, and it lends itself naturally to model a heterogeneous population of cells acting and evolving in a dynamic microenvironment, which is needed to predict the evolution of complex multi-cellular dynamics. Importantly, this enables modelling co-occurring intrinsic perturbations, such as mutations, and extrinsic perturbations, such as nutrients availability, and their interactions.

Using cancer as a model system, we illustrate the how this framework delivers a unique opportunity to identify determinants of single-cell behaviour, while uncovering emerging properties of multi-cellular growth.

Availability and Implementation

Freely available on the web athttp://www.microc.org. Research Resource Identification Initiative ID (https://scicrunch.org/): SCR 016672
Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders
Authors: de Lange Siemon C. , Scholtens Lianne H. , van den Berg Leonard H. , Boks Marco P. , Bozzali Marco , Cahn Wiepke , Dannlowski Udo , Durston Sarah , Geuze Elbert , van Haren Neeltje E.M. , Hillegers Manon H.J. , Koch Kathrin , Jurado María Ángeles , Mancini Matteo , Marqués-Iturria Idoia , Meinert Susanne , Ophoff Roel A. , Reess Tim J. , Repple Jonathan , Kahn René S. , van den Heuvel Martijn P. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2018

Macroscale white matter pathways form the infrastructure for large-scale communication in the human brain, a prerequisite for healthy brain function. Conversely, disruptions in the brain’s connectivity architecture are thought to play an important role in a wide range of psychiatric and neurological brain disorders. Here we show that especially connections important for global communication and network integration are involved in a wide range of brain disorders. We report on a meta-analytic connectome study comprising in total 895 patients and 1,016 controls across twelve neurological and psychiatric disorders. We extracted disorder connectome fingerprints for each of these twelve disorders, which were then combined into a cross-disorder disconnectivity involvement map, representing the involvement of each brain pathway across brain disorders. Our findings show connections central to the brain’s infrastructure are disproportionally involved across a wide range of disorders. Connections critical for global network communication and integration display high disturbance across disorders, suggesting a general cross-disorder involvement and importance of these pathways in normal function. Taken together, our cross-disorder study suggests a convergence of disconnectivity across disorders to a partially shared disconnectivity substrate of central connections.