bluuebunny/crossref_metadata_2025 huggingface dataset:
A High-Quality Reference Genome Assembly of the Saltwater Crocodile, Crocodylus porosus, Reveals Patterns of Selection in Crocodylidae
Authors: Ghosh Arnab , Johnson Matthew G , Osmanski Austin B , Louha Swarnali , Bayona-Vásquez Natalia J , Glenn Travis C , Gongora Jaime , Green Richard E , Isberg Sally , Stevens Richard D , Ray David A
Published: December 2019

Crocodilians are an economically, culturally, and biologically important group. To improve researchers’ ability to study genome structure, evolution, and gene regulation in the clade, we generated a high-quality de novo genome assembly of the saltwater crocodile, Crocodylus porosus, from Illumina short read data from genomic libraries and in vitro proximity-ligation libraries. The assembled genome is 2,123.5 Mb, with N50 scaffold size of 17.7 Mb and N90 scaffold size of 3.8 Mb. We then annotated this new assembly, increasing the number of annotated genes by 74%. In total, 96% of 23,242 annotated genes were associated with a functional protein domain. Furthermore, multiple noncoding functional regions and mappable genetic markers were identified. Upon analysis and overlapping the results of branch length estimation and site selection tests for detecting potential selection, we found 16 putative genes under positive selection in crocodilians, 10 in C. porosus and 6 in Alligator mississippiensis. The annotated C. porosus genome will serve as an important platform for osmoregulatory, physiological, and sex determination studies, as well as an important reference in investigating the phylogenetic relationships of crocodilians, birds, and other tetrapods.
Alterations in Diffusion Measures of White Matter Integrity Associated with Healthy Aging
Authors: Molloy Ciara J , Nugent Sinead , Bokde Arun L W
Published: December 2019

This study aimed to characterize age-related white matter changes by evaluating patterns of overlap between the linear association of age with fractional anisotropy (FA) with mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Specifically, we assessed patterns of overlap between diffusion measures of normal appearing white matter by covarying for white matter hyperintensity (WMH) load, as WMHs are thought to increase with age and impact diffusion measures. Seventy-nine healthy adults aged between 18 and 75 years took part in the study. Diffusion tensor imaging (DTI) data were based on 61 directions acquired with a b-value of 2,000. We found five main patterns of overlap: FA alone (15.95%); FA and RD (31.90%); FA and AD (12.99%); FA, RD, and AD (27.93%); and FA, RD, and MD (8.79%). We showed that cognitively healthy aging adults had low WMH load, which subsequently had minimal effect on diffusion measures. We discuss how patterns of overlap may reflect underlying biological changes observed with aging such as loss of myelination, axonal damage, as well as mild microstructural and chronic white matter impairments. This study contributes to understanding the underlying causes of degeneration in specific regions of the brain and highlights the importance of considering the impact of WMHs in aging studies of white matter.
Prediction of the salmon lice infestation pressure in a Norwegian fjord
Authors: Sandvik Anne D , Johnsen Ingrid A , Myksvoll Mari S , Sævik Pål N , Skogen Morten D
Published: December 2019

A further growth in the Norwegian aquaculture industry might potentially be hampered by the conclusion that it is not environmentally sustainable. As direct measurements of the lice induced mortality on wild salmonids are impossible, the management is based on a set of high-quality and well-documented sustainability indicators. These indicators combine observations from the national Norwegian salmon lice monitoring programme with salmon lice models. Here, we have documented the quality of one of these models used to identify areas where the impact from farmed to wild salmonids is over the prescribed limit. The Hardangerfjord area has been used as a test area, but the model is general and, therefore, suitable for the rest of the coast. It is shown that the model system is robust and also can be used to test whether new knowledge gained from laboratory experiments improves the model. New findings on salmon lice behaviour at low salinities have been incorporated and the new model, consisting of a high-resolution hydrodynamic model coupled with an individual-based salmon lice model and forced with realistic input of salmon lice larvae from aquaculture farms, represents the best realization of the local potential infestation pressure on wild fish.
Birth Registration in Crisis: Exploring a Rights-Based Approach to Birth Registration through the Experience of Syrian Refugees
Authors: Elmolla Jazmine Hesham
Published: December 2019

The right to birth registration is protected under international human rights law. While this protection clearly confers an obligation on States to register births, it is less clear how this birth registration process should be carried out in order to ensure that individuals can realize numerous other human rights. For example, how should States register the births of children born to refugees or asylum seekers in order to give effect to the right to a nationality? The question is particularly relevant given the increasing number of people who are fleeing the many contemporary conflicts. The article investigates this question, along with the precise meaning and requirements of the right to birth registration under the International Covenant on Civil and Political Rights and the Convention on the Rights of the Child. It argues that the birth registration frameworks established by States often fail to protect the human rights of the child. Using Syrian refugees in Lebanon as a case study, the conclusion reached is that there is an urgent need for States to adopt a rights-based approach to birth registration that reflects the relationship between birth registration and other human rights.
The Brauer Group of the Universal Moduli Space of Vector Bundles Over Smooth Curves
Authors: Fringuelli Roberto , Pirisi Roberto
Published: December 2019

We compute the Brauer group of the universal moduli stack of vector bundles on (possibly marked) smooth curves of genus at least three over the complex numbers. As consequence, we obtain an explicit description of the Brauer group of the smooth locus of the associated moduli space of semistable vector bundles, when the genus is at least four.
Spatial Distribution of Lycorma delicatula (Hemiptera: Fulgoridae) Egg Masses on Tree-of-Heaven, Black Walnut, and Siberian Elm in North America
Authors: Liu Houping , Hartlieb Richard J
Published: December 2019

The spatial distribution of Lycorma delicatula (White) egg masses on three species of trees were studied in Pennsylvania. Five tree-of-heaven, five black walnut, and one Siberian elm trees were felled in early spring 2019 to sample for egg masses. Each egg mass was marked for its cardinal direction, position in the tree, height above ground, and spread from the bole. A total of 214 egg masses were found on tree-of-heaven and black walnut, with 38.3, 29.4, 22.0, and 10.3% on the north, west, south, and east quadrant, respectively. No significant difference in cardinal direction was found for either species. Equal number of egg masses were found on branches and boles on tree-of-heaven. However, significantly more egg masses were found on branches (96.5%) compared to boles (3.5%) on black walnut. Egg masses were laid at 0.30–12.92 and 0.70–17.00 m above ground, with most on boles/higher branches and middle/lower branches for tree-of-heaven and black walnut, respectively. Significant effect of height above ground was found for black walnut, with more egg masses found at 4–6 m compared to 0–2, 12–14, and 14–16 m. Significant effect of spread from the bole was found for tree-of-heaven, with more egg masses found at 0–2 m compared to 2–4 and 4–6 m. The 24 egg masses on the Siberian elm were mostly found on east quadrant branches 0–2 m above ground and within 2 m from the bole. Variation in tree branching patterns and difference in egg mass distribution of other forest pests were discussed.
Too Proud to Stop: Regret in Dynamic Decisions
Authors: Strack Philipp , Viefers Paul
Published: December 2019

Regret and its anticipation affect a wide range of decisions. Job-seekers reject offers while waiting for an offer to match their best past offer; investors hold on to badly performing stocks; and managers throw good money after bad projects. We analyze behavior of a decision maker with regret preferences in a dynamic context and show that regret agents have a disposition to gamble until they receive a payoff matching the best past offer. Results from a lab experiment confirm that many subjects exhibit such behavior and are reluctant to stop below the past peak.
An HBV-encoded miRNA activates innate immunity to restrict HBV replication
Authors: Zhao Xiaoqing , Sun Lu , Mu Ting , Yi Jianying , Ma Chaoqun , Xie Hong , Liu Min , Tang Hua
Published: December 2019

We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immune response after HBV infection. We found that HBV-miR-3 expression gradually increased in a dose- and time-dependent manner in HBV-infected HepG2-NTCP cells. HBV-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes, thereby enhancing the IFN-induced anti-HBV effect. In addition, HBV-miR-3 in exosomes facilitated the M1 polarization of macrophages. Furthermore, exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of EGFR. In short, these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways, which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection.
Transcriptional and biochemical analyses of gibberellin expression and content in germinated barley grain
Authors: Betts Natalie S , Dockter Christoph , Berkowitz Oliver , Collins Helen M , Hooi Michelle , Lu Qiongxian , Burton Rachel A , Bulone Vincent , Skadhauge Birgitte , Whelan James , Fincher Geoffrey B
Published: December 2019

Mobilization of reserves in germinated cereal grains is critical for early seedling vigour, global crop productivity, and hence food security. Gibberellins (GAs) are central to this process. We have developed a spatio-temporal model that describes the multifaceted mechanisms of GA regulation in germinated barley grain. The model was generated using RNA sequencing transcript data from tissues dissected from intact, germinated grain, which closely match measurements of GA hormones and their metabolites in those tissues. The data show that successful grain germination is underpinned by high concentrations of GA precursors in ungerminated grain, the use of independent metabolic pathways for the synthesis of several bioactive GAs during germination, and a capacity to abort bioactive GA biosynthesis. The most abundant bioactive form is GA1, which is synthesized in the scutellum as a glycosyl conjugate that diffuses to the aleurone, where it stimulates de novo synthesis of a GA3 conjugate and GA4. Synthesis of bioactive GAs in the aleurone provides a mechanism that ensures the hormonal signal is relayed from the scutellum to the distal tip of the grain. The transcript data set of 33 421 genes used to define GA metabolism is available as a resource to analyse other physiological processes in germinated grain.
Morphological and stage-specific transcriptome analyses reveal distinct regulatory programs underlying yam (Dioscorea alata L.) bulbil growth
Authors: Wu Zhi-Gang , Jiang Wu , Tao Zheng-Ming , Pan Xiao-Jun , Yu Wen-Hui , Huang Hui-Lian
Published: December 2019

In yam (Dioscorea spp) species, bulbils at leaf axils are the most striking species-specific axillary structure and exhibit important ecological niches. Genetic regulation underlying bulbil growth remains largely unclear so far. Here, we characterize yam (Dioscorea alata L.) bulbil development using histological analysis, and perform full transcriptional profiling on key developmental stages together with phytohormone analyses. Using the stage-specific scoring algorithm, we have identified 3451 stage-specifically expressed genes that exhibit a tight link between major transcriptional changes and stages. Co-expressed gene clusters revealed an obvious over-representation of genes associated with cell division and expansion at the initiation stage of bulbils (T1). Transcriptional changes of hormone-related genes highly coincided with hormone levels, indicating that bulbil initiation and growth are coordinately controlled by multiple phytohormones. In particular, localized auxin is transiently required to trigger bulbil initiation, and be further depleted or exported from bulbils to promote growth by up-regulation of genes involved in auxinconjugation and efflux. The sharp increase in supply of sucrose and an enhanced trehalose-6-phophate pathway at T1 were observed, suggesting that sucrose probably functions as a key signal and promotes bulbil initiation. Analysis of the expression of transcription factors (TFs) predicated 149 TFs as stage-specifically expressed; several T1-specific TFs (from Aux/IAA, E2F, MYB, and bHLH families) have been shown to play key roles in triggering bulbil formation. Together, our work provides a crucial angle for in-depth understanding of the molecular programs underlying yam’s unique bulbil development processes. Stage-specific gene sets can be queried to obtain key candidates regulating bulbil growth, serving as valuable resources for further functional research.
International Commercial Surrogacy as a New Head of Tortious Damage: XX v Whittington Hospital NHS Trust [2018] EWCA Civ 2832
Authors: Taylor John Lucas M
Published: December 2019

In XX v Whittington Hospital NHS Trust [2018] EWCA Civ 2832, the Court of Appeal recognised commercial surrogacy in California as a permissible head of damage in a case of negligently inflicted infertility. Due to changing public policies and judicial opinion regarding the practice, and by incorporating the three-part test of illegality developed for civil claims by the Supreme Court in Patel v Mirza [2016] UKSC 42 into tort law, the Court of Appeal held that the principle of restorative justice required a departure from the precedent established in Briody v St Helens and Knowsley AHA [2001] EWCA Civ 1010.
18F-Fluciclovine PET to distinguish treatment-related effects from disease progression in recurrent glioblastoma: PET fusion with MRI guides neurosurgical sampling
Authors: Henderson Fraser , Brem Steven , O’Rourke Donald M , Nasrallah MacLean , Buch Vivek P , Young Anthony J , Doot Robert K , Pantel Austin , Desai Arati , Bagley Stephen J , Nabavizadeh S Ali
Published: December 2019

Differentiation of true tumor progression from treatment-related effects remains a major unmet need in caring for patients with glioblastoma. Here, we report how the intraoperative combination of MRI with18F-fluciclovine PET guided surgical sampling in 2 patients with recurrent glioblastoma.18F-Fluciclovine PET is FDA approved for use in prostate cancer and carries an orphan drug designation in glioma. To investigate its utility in recurrent glioblastoma, we fused PET and MRI images using 2 different surgical navigation systems and performed targeted stereotactic biopsies from the areas of high (“hot”) and low (“cold”) radiotracer uptake. Concordant histopathologic and imaging findings suggest that a combined18F-fluciclovine PET-MRI–guided approach can guide neurosurgical resection of viable recurrent glioblastoma in the background of treatment-related effects, which can otherwise look similar on MRI.
Importance of Laterality in Cervical Spinal Cord Stimulation for Facial Pain: Case Report and Anatomic Review
Authors: Jones Michael R , Rosenow Joshua M
Published: December 2019

BACKGROUND AND IMPORTANCE

Chronic neuropathic facial pain is a debilitating disease that can be approached with multiple different treatment modalities. Cervical spinal cord stimulation has been demonstrated to be effective for patients suffering from neuropathic facial pain. Consensus does not exist in the literature regarding technique for placement.

CLINICAL PRESENTATION

A 49-yr-old female presented with chronic intractable neuropathic facial pain. She underwent a successful percutaneous spinal cord stimulation trial, followed by placement of a paddle electrode for permanent implantation. The paddle electrode failed to duplicate the pain relief of her trial. Measurement of the width of the paddle demonstrated that it was 2 mm smaller than the separation of the percutaneous trial electrodes. Electrodes with wider interelectrode distance were then placed with satisfactory pain relief.

CONCLUSION

Although conventional spinal cord stimulation targets the dorsal columns, cervical spinal cord stimulation for facial pain targets the spinal trigeminal nucleus. The effectiveness of stimulation may be increased with a more laterally positioned electrode in order to recruit the more laterally positioned spinal trigeminal nucleus. This case report illustrates the importance of this anatomic consideration.
Posterior C2-6 Laminoplasty for Resection of Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: December 2019

Large extramedullary-intramedullary arteriovenous malformations (AVMs) within the spinal cord provide a unique management opportunity, compared with the cranial counterpart, in that the surgical morbidity can be minimized and surgical cure can still be achieved by resecting the extramedullary segment and leaving the intramedullary segment without invading the parenchyma. This management strategy minimizes morbidity and provides an excellent chance of surgical cure. This patient had a history of longstanding left hemiparesis since birth that progressed, prompting imaging evaluation that demonstrated a large cervical AVM with bilateral vertebral artery, anterior spinal artery, and left thyrocervical trunk feeding vessels. The AVM had both extramedullary and intramedullary components, making this a challenging lesion for microsurgical obliteration and preservation of neurological function. Preoperative embolization was utilized through the right vertebral artery pedicle. Microdissection was performed to isolate the extramedullary from the intramedullary component. Surgical cure was attempted for this patient by removing the extramedullary component and leaving the intramedullary segment. Indocyanine green fluoroscopy was used to isolate the feeding pedicle and guide surgical resection. Postoperative imaging demonstrated a small residual from the thyrocervical injection, which was obliterated with embolization. The patient improved neurologically within the postoperative period and regained ambulatory status during long-term follow-up. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Surgical Management of a Ruptured Dissecting Anterior Cerebral Artery (A2) Aneurysm Utilizing Contralateral Frontopolar for Reconstruction: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: December 2019

Dissecting aneurysms can pose an immense surgical challenge, and intervention often involves high risk for rerupture because of the volatile nature of the fibrin thrombus overlying the rupture site. This patient presented following rupture of a dissecting aneurysm along the A2 segment of the anterior cerebral artery (ACA). The patient underwent a right orbitozygomatic craniotomy, and the aneurysm was approached within the interhemispheric fissure. Manipulation of the aneurysm dome resulted in intraoperative rerupture of the aneurysm, which was controlled by the application of a temporary clip on the parent A2 proximally and distally. Aneurysmectomy of the thin diseased vessel wall was performed. The defect was filled by transecting the frontopolar branch of the ACA and sewing the frontopolar branch onto the aneurysmectomy defect. This provided a suitable patch for the ACA defect. Postprocedural indocyanine green angiography demonstrated patency of the A2 and the anastomosed frontopolar branch. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
DNA methylome study of human cerebellar tissues identified genes and pathways possibly involved in essential tremor
Authors: Paul Jennifer L , Dashtipour Khashayar , Chen Zhong , Wang Charles
Published: December 2019

Background

Essential tremor (ET) is a neurological syndrome of unknown origin with poorly understood etiology and pathogenesis. It is suggested that the cerebellum and its tracts may be involved in the pathophysiology of ET. DNA methylome interrogation of cerebellar tissue may help shine some light on the understanding of the mechanism of the development of ET. Our study used postmortem human cerebellum tissue samples collected from 12 ET patients and 11 matched non-ET controls for DNA methylome study to identify differentially methylated genes in ET.

Results

Using Nugen’s Ovation reduced representation bisulfite sequencing (RRBS), we identified 753 genes encompassing 938 CpG sites with significant differences in DNA methylation between the ET and the control group. Identified genes were further analyzed with Ingenuity Pathway Analysis (IPA) by which we identified certain significant pathways, upstream regulators, diseases and functions, and networks associated with ET.

Conclusions

Our study provides evidence that there are significant differences in DNA methylation patterns between the ET and control samples, suggesting that the methylation alteration of certain genes in the cerebellum may be associated with ET pathogenesis. The identified genes allude to the GABAergic hypothesis which supports the notation that ET is a neurodegenerative disease, particularly involving the cerebellum.
AT HIGH BACKGROUND RADIATION AREAS THE RELATIONSHIP BETWEEN IN SITU INDOOR GAMMA DOSE RATES AND BUILDING MATERIALS: A CASE STUDY FROM ARIKLI VILLAGE (AYVACIK/ÇANAKKALE/TURKEY)
Authors: Top Gülcan , Örgün Yüksel , Karahan Gürsel , Özcan Orkan , Horvath Mark , Kampfl Györgyi
Published: December 2019

This study measured in situ indoor gamma dose rates in Arıklı village situated near a uranium mineralisation region, evaluated the risks of radiological health hazards and established a hypothetical relationship between these values and building materials using statistical tools. Eberline brand portable type ESP-2 model Na (I) scintillation probe connected detector was used for the measurements in 45 dwellings. Statistics revealed two groups. The first group consists of the dwellings made of bricks or mixed materials both plastered by cement, while the second group represented the dwellings made of Arıklı tuff plastered with soil (modified Arıklı tuff) or cement. For the first and second groups, respectively, the medians of the indoor gamma dose rates were 188.79 and 261.87 nGy/h; for indoor Annual Effective Dose Equivalents (AEDEin) they were 0.93 and 1.28 mSv/h; and for Excess Lifetime Cancer Risks (ELCRin) they were 3.69 and 5.12, respectively. All the values were higher than those of the world averages.
Compensatory Interventions for Cognitive Impairments in Psychosis: A Systematic Review and Meta-Analysis
Authors: Allott Kelly , van-der-EL Kristi , Bryce Shayden , Parrish Emma M , McGurk Susan R , Hetrick Sarah , Bowie Christopher R , Kidd Sean , Hamilton Matthew , Killackey Eoin , Velligan Dawn
Published: December 2019

Objective

Cognitive compensatory interventions aim to alleviate psychosocial disability by targeting functioning directly using aids and strategies, thereby minimizing the impact of cognitive impairment. The aim was to conduct a systematic review and meta-analysis of cognitive compensatory interventions for psychosis by examining the effects on functioning and symptoms, and exploring whether intervention factors, study design, and age influenced effect sizes.

Methods

Electronic databases (Ovid Medline, PsychINFO) were searched up to October 2018. Records obtained through electronic and manual searches were screened independently by two reviewers according to selection criteria. Data were extracted to calculate estimated effects (Hedge’s g) of treatment on functioning and symptoms at post-intervention and follow-up. Study quality was assessed using Cochrane Collaboration’s risk of bias tool.

Results

Twenty-six studies, from 25 independent randomized controlled trials (RCTs) were included in the meta-analysis (1654 participants, mean age = 38.9 years, 64% male). Meta-analysis revealed a medium effect of compensatory interventions on functioning compared to control conditions (Hedge’s g = 0.46, 95% CI = 0.33, 0.60, P < .001), with evidence of relative durability at follow-up (Hedge’s g = 0.36, 95% CI = 0.19, 0.54, P < .001). Analysis also revealed small significant effects of cognitive compensatory treatment on negative, positive, and general psychiatric symptoms, but not depressive symptoms. Estimated effects did not significantly vary according to treatment factors (ie, compensatory approach, dosage), delivery method (ie, individual/group), age, or risk of bias. Longer treatment length was associated with larger effect sizes for functioning outcomes. No evidence of publication bias was identified.

Conclusion

Cognitive compensatory interventions are associated with robust, durable improvements in functioning in people with psychotic illnesses.
Radical Self-Care for Social Workers in the Global Climate Crisis
Authors: Powers Meredith C F , Engstrom Sandra
Published: December 2019

Gradual environmental degradation, more extreme climate change events, and related environmental injustices affect individuals and communities every day. Social work entities around the world are increasingly highlighting professional responsibilities for addressing the global climate crisis. Often, social workers experience vicarious trauma from work with those immediately affected. Working within the context of the global climate crisis brings further risk. Social workers may be personally affected, or experiencing their own challenges, such as climate anxiety and eco-grief. Thus, radical self-care is a dire need as social workers promote sustainable communities and environments and seek ecological justice for all. This article discusses the health and mental health impacts of the compounding factors of the climate crisis, modern technology, and current political contexts. Activism for change and ecotherapeutic strategies are presented as radical self-care for social workers, in both academic and practice-based settings. These strategies are essential for recognizing, legitimizing, and addressing the need for radical self-care practices in the global climate crisis.
The Effect of Age on Daily Positive Emotions and Work Behaviors
Authors: Dello Russo Silvia , Antino Mirko , Zaniboni Sara , Caetano Antonio , Truxillo Donald
Published: December 2019

This study draws on socioemotional selectivity and person–job fit theories to investigate the emotional bases for age-related differences in daily task crafting and in-role performance. We tested a mediation model in which age is related to positive emotions that in turn predict task crafting and in-role performance. A total of 256 people working in multiple organizations participated in a 5-day diary study. Multilevel modeling showed that, at the person level of analysis, age is significantly and positively related to positive emotions and task crafting and, via crafting, to in-role performance. No significant mediation of high- and low-arousal positive emotions was found between age and task crafting. However, at the day level of analysis, high-arousal positive emotions are positively related to task crafting, and this in turn is positively related to in-role performance. These findings make important theoretical contributions to understanding within-person processes associated with employee age in addition to more traditional between-person factors. They also have implications for managing an age-diverse workforce by means of job crafting.
A DeoR-Type Transcription Regulator Is Required for Sugar-Induced Expression of Type III Secretion-Encoding Genes in Pseudomonas syringae pv. tomato DC3000
Authors: Turner Sydney E. , Pang Yin-Yuin , O’Malley Megan R. , Weisberg Alexandra J. , Fraser Valerie N. , Yan Qing , Chang Jeff H. , Anderson Jeffrey C.
Published: December 2019

The type III secretion system (T3SS) of plant-pathogenic Pseudomonas syringae is essential for virulence. Genes encoding the T3SS are not constitutively expressed and must be induced upon infection. Plant-derived metabolites, including sugars such as fructose and sucrose, are inducers of T3SS-encoding genes, yet the molecular mechanisms underlying perception of these host signals by P. syringae are unknown. Here, we report that sugar-induced expression of type III secretion A (setA), predicted to encode a DeoR-type transcription factor, is required for maximal sugar-induced expression of T3SS-associated genes in P. syringae DC3000. From a Tn5 transposon mutagenesis screen, we identified two independent mutants with insertions in setA. When both setA::Tn5 mutants were cultured in minimal medium containing fructose, genes encoding the T3SS master regulator HrpL and effector AvrRpm1 were expressed at lower levels relative to that of a wild-type strain. Decreased hrpL and avrRpm1 expression also occurred in a setA::Tn5 mutant in response to glucose, sucrose, galactose, and mannitol, demonstrating that setA is genetically required for T3SS induction by many different sugars. Expression of upstream regulators hrpR/S and rpoN was not altered in setA::Tn5, indicating that SetA positively regulates hrpL expression independently of increased transcription of these genes. In addition to decreased response to defined sugar signals, a setA::Tn5 mutant had decreased T3SS deployment during infection and was compromised in its ability to grow in planta and cause disease. These data suggest that SetA is necessary for P. syringae to effectively respond to T3SS-inducing sugar signals encountered during infection.
Pathogenic, Morphological, and Phylogenetic Characterization ofFusarium solanif. sp.cucurbitaeIsolates From Cucurbits in Almería Province, Spain
Authors: Pérez-Hernández Ana , Rocha Liliana O. , Porcel-Rodríguez Elena , Summerell Brett A. , Liew Edward C. Y. , Gómez-Vázquez Julio M.
Published: December 2019

Fusarium solani f. sp. cucurbitae (syn. Neocosmosporum cucurbitae) is one of the most devastating soilborne pathogens affecting the production of cucurbits worldwide. Since its first detection in Almería Province in Spain in the spring of 2007, it has become one of the main soilborne pathogens affecting zucchini production. It has also been reported on melon, watermelon, and squash rootstocks in Spain, representing a high risk of dissemination in the area. The objectives of this study were to investigate the incidence and distribution of this disease in southeastern Spain and characterize isolates collected over 5 years. These strains were characterized on the basis of greenhouse aggressiveness assays on a range of cucurbit hosts, morphological characteristics, and elongation factor 1-α and RNA polymerase II second largest subunit phylogenies. All pathogenic isolates were highly aggressive on zucchini plants, causing a high mortality rate a few weeks after inoculation. The rest of the cucurbit hosts showed differential susceptibility to the pathogen, with cucumber being the least susceptible. Plants belonging to other families remained asymptomatic. Morphological characterization revealed the formation of verticilate monophialides and chlamydospores forming long chains, characteristics not described for this forma specialis. Phylogenetic studies of both the individual loci and combined datasets revealed that all pathogenic isolates clustered together with strong monophyletic support, nested within clade 3 in the F. solani species complex.
Bacterial Brown Pit, a New Disease of Edible Mushrooms Caused by Mycetocola sp.
Authors: Hamidizade Mozhde , Taghavi S. Mohsen , Martins Samuel J. , Herschlag Rachel A. , Hockett Kevin L. , Bull Carolee T. , Osdaghi Ebrahim
Published: December 2019

From September to December 2018, commercial button mushroom (Agaricus bisporus) farms in central Iran were surveyed to monitor the causal agent(s) of browning and blotch symptoms on mushroom caps. In addition to dozens of pseudomonads (i.e., Pseudomonas tolaasii and Pseudomonas reactans), six slow-growing gram-positive bacterial strains were isolated from blotched mushroom caps. These bacteria presented as creamy white, circular, smooth, nonfluorescent, and shiny colonies with whole margins resembling members of Microbacteriaceae (Actinobacteria). All of the actinobacterial strains were aggressively pathogenic on cut cap surface of two edible mushrooms (i.e., A. bisporus and Pleurotus eryngii), inducing brown pit symptoms 48 h postinoculation. The strains did not induce symptoms on the vegetables tested (i.e., carrot, cucumber, and potato), and they did not affect the growth of mycelium of tested plant-pathogenic fungi (i.e., Acremonium sp., Fusarium spp., and Phytopythium sp.). Phylogeny of 16S ribosomal RNA and multilocus sequence analysis of six housekeeping genes (i.e., atpD, dnaK, gyrB, ppK, recA, and rpoB) revealed that the bacterial strains belong to the actinobacterial genus Mycetocola spp., whereas the species status of the strains remains undetermined. Mushroom-associated Mycetocola species were previously reported to be capable of detoxifying tolaasin, a toxin produced by P. tolaasii, whereas the strains isolated in this study did not show tolaasin detoxification activities. Altogether, this is the first report of a mushroom disease caused by an actinobacterial species, and “bacterial brown pit” was assigned as the common name of the disease.
High-Quality Genome Resource of Xanthomonas hyacinthi Generated via Long-Read Sequencing
Authors: Cohen Stephen P. , Luna Emily K. , Lang Jillian M. , Ziegle Janet , Chang Christine , Leach Jan E. , Le-Saux Marion Fischer , Portier Perrine , Koebnik Ralf , Jacobs Jonathan M.
Published: December 2019

The bacterial plant pathogen Xanthomonas hyacinthi is the causal agent of yellow disease of Hyacinthus and other ornamental plant genera. There is no available complete genome for X. hyacinthi, limiting basic research for this pathogen. Here, we release a high-quality complete genome sequence for the X. hyacinthi type strain, CFBP 1156. Single-molecule real-time (SMRT) sequencing with a mean coverage of 306× revealed two contigs of 4,918,645 and 44,381 bp in size. This was the first characterized plant-disease-causing species of Xanthomonas and this genome provides a resource to better understand the biology of yellow disease of hyacinth.
Pain Unstuck
Authors: Tabor Abby , Van Ryckeghem Dimitri M.L. , Hasenbring Monika I.
Published: December 2019

Background:

What is it that motivates our actions? As human beings, existing as part of complex societies, the actions we take are subject to multiple, often competing motives. Spanning non-conscious reflexes, cognitively derived choice as well as long- and short-term goals, our actions allow us to make sense of our environment. Pain disrupts action and hijacks our intentions. Whilst considered adaptive when temporary, pain that persists continues to interrupt and can threaten our ability to actively investigate a changing world.

Objective:

This work is a narrative review.

Results:

Drawing upon three complementary theoretical approaches to pain: an embodied framework, a motivational approach and the avoidance-endurance model, this review places the relationship between pain, motivation and action at its core, unpicking a dynamic process that can become stuck.

Conclusions:

In taking a wide view of pain and action, we expose the nuances within drive to goal behaviour in the presence of pain. This has implications for the clinic, specifically in relation to assessing the multifactorial influences that shape action in pain. But it also seeks to go further, considering the broader environment in which we make decisions and the influence that other professionals, outside of typical healthcare roles, may play a part in the maintenance and resolution of pain.
Endogenous Modulation of Pain
Authors: Vaegter Henrik B. , Fehrmann Elisabeth , Gajsar Hannah , Kreddig Nina
Published: December 2019

Background:

Pain is a complex and highly subjective phenomenon that can be modulated by several factors. On the basis of results from experimental and clinical studies, the existence of endogenous pain modulatory mechanisms that can increase or diminish the experience of pain is now accepted.

Methods:

In this narrative review, the pain modulatory effects of exercise, stress, and cognitions in humans are assessed.

Results:

Experimental studies on the effect of exercise have revealed that pain-free participants show a hypoalgesic response after exercise. However, in some patients with chronic pain, this response is reduced or even hyperalgesic in nature. These findings will be discussed from a mechanistic point of view. Stress is another modulator of the pain experience. Although acute stress may induce hypoalgesia, ongoing clinical stress has detrimental effects on pain in many patients with chronic pain conditions, which have implications for the understanding, assessment, and treatment of stress in patients with pain. Finally, cognitive strategies play differing roles in pain inhibition. Two intuitive strategies, thought suppression and focused distraction, will be reviewed as regards experimental, acute, and chronic pain.

Conclusion:

On the basis of current knowledge on the role of exercise, stress, and cognitive pain control strategies on the modulation of pain, implications for treatment will be discussed.
Pediatric Trauma Patient Intensive Care Resource Utilization in U.S. Military Operations in Iraq and Afghanistan
Authors: Gale Hannah L. , Borgman Matthew A. , April Michael D. , Schauer Steven G.
Published: December 2019

Objectives:

Children represent a unique patient population treated by military personnel during wartime, as seen in the recent conflicts in Iraq and Afghanistan. We sought to describe ICU resource utilization by U.S. military personnel treating pediatric trauma patients in Iraq and Afghanistan.

Design:

This is a retrospective review of prospectively collected data within Department of Defense Trauma Registry.

Setting:

We studied pediatric casualties treated in U.S. and coalition military hospitals in Iraq and Afghanistan between January 2007 and January 2016.

Patients:

We queried the Department of Defense Trauma Registry for patients less than 18 years with one documented day within an ICU.

Interventions:

We used descriptive statistics to analyze injuries patterns and interventions. We defined prolonged length of stay as ICU stay four days or greater. Regression methodology was utilized to identify factors associated with prolonged length of stay.

Measurements and Main Results:

There were 1955 (56.8%) pediatric patients that met our inclusion criteria. The most common mechanism of injury was explosive (45.2%) followed by gunshot wounds (20.8%). The median composite ISS was 14. The median length of stay was 3 days with 90.2% surviving to hospital discharge. Mechanical ventilation was the most frequent intervention (67.6%) followed by arterial access (21.8%). Prolonged length of stay was associated with all serious injuries, ventilator management, blood product administration, wound dressing, bronchoscopy, imaging, and central venous access.

Conclusions:

Pediatric casualties accounted for nearly one in 10 admissions with the majority requiring intensive care. The most commonly performed interventions were mechanical ventilation, vascular access, and imaging, each of which requires a specialized skill set to provide optimal patient management. All serious injuries by body region except facial were associated with a prolonged length of ICU stay, as well as blood product administration, ventilator management, intracranial pressure monitoring, wound care, bronchoscopy, imaging, and central venous access. The epidemiology of this unique population may be useful in planning future pre-deployment training and resource management in ICUs in deployed environments.
Optimizing Tele-ICU Operational Efficiency Through Workflow Process Modeling and Restructuring
Authors: Becker Christian D. , Yang Muer , Fusaro Mario , Fry Michael , Scurlock Corey S.
Published: December 2019

Objectives/Design:

Little is known on how to best prioritize various tele-ICU specific tasks and workflows to maximize operational efficiency. We set out to: 1) develop an operational model that accurately reflects tele-ICU workflows at baseline, 2) identify workflow changes that optimize operational efficiency through discrete-event simulation and multi-class priority queuing modeling, and 3) implement the predicted favorable workflow changes and validate the simulation model through prospective correlation of actual-to-predicted change in performance measures linked to patient outcomes.

Setting:

Tele-ICU of a large healthcare system in New York State covering nine ICUs across the spectrum of adult critical care.

Patients:

Seven-thousand three-hundred eighty-seven adult critically ill patients admitted to a system ICU (1,155 patients pre-intervention in 2016Q1 and 6,232 patients post-intervention 2016Q3 to 2017Q2)

Interventions:

Change in tele-ICU workflow process structure and hierarchical process priority based on discrete-event simulation.

Measurements and Main Results:

Our discrete-event simulation model accurately reflected the actual baseline average time to first video assessment by both the tele-ICU intensivist (simulated 132.8 ± 6.7 min vs 132 ± 12.2 min actual) and the tele-ICU nurse (simulated 128.4 ± 7.6 min vs 123 ± 9.8 min actual). For a simultaneous priority and process change, the model simulated a reduction in average TVFA to 51.3 ± 1.6 min (tele-ICU intensivist) and 50.7 ± 2.1 min (tele-ICU nurse), less than the added simulated reductions for each change alone, suggesting correlation of the changes to some degree. Subsequently implementing both changes simultaneously resulted in actual reductions in average time to first video assessment to values within the 95% CIs of the simulations (50 ± 5.5 min for tele-intensivists and 49 ± 3.9 min for tele-nurses).

Conclusions:

Discrete-event simulation can accurately predict the effects of contemplated multidisciplinary tele-ICU workflow changes. The value of workflow process and task priority modeling is likely to increase with increasing operational complexities and interdependencies.
Intermittent Hemodialysis for Managing Metabolic Acidosis During Resuscitation of Septic Shock: A Descriptive Study
Authors: Nogi Kazutaka , Shiraishi Atsushi , Yamamoto Ryohei , Sasano Mikio , Matsumoto Takashi , Karumai Toshiyuki , Hayashi Yoshiro
Published: December 2019

Objectives:

Septic shock is often complicated by severe metabolic acidosis, for which renal replacement therapy may be considered. However, little is known about the use of intermittent hemodialysis to manage this condition. The aim of this study was to compare physiologic and biochemical variables and vasopressor requirements before and after intermittent hemodialysis among patients who received intermittent hemodialysis to manage metabolic acidosis during resuscitation of septic shock.

Design:

This retrospective, cross-sectional study was conducted between April 2014 and September 2015.

Settings:

The ICU of a non-university-affiliated teaching hospital.

Patients:

Patients who were admitted to the ICU with septic shock and underwent intermittent hemodialysis to manage metabolic acidosis within 48 hours after the diagnosis of septic shock.

Measurements and Main Results:

The main outcomes were mean arterial pressure, minute ventilator volume, norepinephrine requirement, bicarbonate and pH before and after intermittent hemodialysis. Of 1,190 patients screened, 34 were included, and 33 accomplished a planned session of intermittent hemodialysis. After intermittent hemodialysis, an increased mean arterial pressure (+9.0 mm Hg; 95% CI, 6–13; p < 0.001), decreased minute ventilatory volume (–2.0 L/min; 95% CI, –3.3 to 0.8; p = 0.002), decreased norepinephrine requirement (–0.07 µg/kg/min; 95% CI, –0.12 to –0.02; p = 0.009), increased bicarbonate level (+7.2 mmol/L; 95% CI, 6.1–8.3; p < 0.001), and increased pH (+0.17; 95% CI, 0.13–0.21; p < 0.001) were observed in comparison to those before intermittent hemodialysis.

Conclusions:

In conclusion, intermittent hemodialysis appeared to be feasible and to stabilize hemodynamic and respiratory conditions in patients with septic shock complicated by metabolic acidosis during resuscitation.
Epigenetic Profiling in Severe Sepsis: A Pilot Study of DNA Methylation Profiles in Critical Illness*
Authors: Binnie Alexandra , Walsh Christopher J. , Hu Pingzhao , Dwivedi Dhruva J. , Fox-Robichaud Alison , Liaw Patricia C. , Tsang Jennifer L. Y. , Batt Jane , Carrasqueiro Gabriela , Gupta Sahil , Marshall John C. , Castelo-Branco Pedro , dos Santos Claudia C.
Published: December 2019

Objectives:

Epigenetic alterations are an important regulator of gene expression in health and disease; however, epigenetic data in sepsis are lacking. To demonstrate proof of concept and estimate effect size, we performed the first epigenome-wide methylation analysis of whole blood DNA samples from a cohort of septic and nonseptic critically ill patients.

Design:

A nested case-control study using genomic DNA isolated from whole blood from septic (n = 66) and nonseptic (n = 68) critically ill patients on “Day 1” of ICU admission. Methylation patterns were identified using Illumina 450K arrays with percent methylation expressed as β values. After quality control, 134 participants and 414,818 autosomal cytosine-phosphate-guanine sites were used for epigenome-wide methylation analyses.

Setting:

Tertiary care hospitals.

Subjects:

Critically ill septic and nonseptic patients.

Interventions:

Observational study.

Measurements and Main Results:

A total of 668 differentially methylated regions corresponding to 443 genes were identified. Known sepsis-associated genes included complement component 3; angiopoietin 2; myeloperoxidase; lactoperoxidase; major histocompatibility complex, class I, A; major histocompatibility complex, class II, isotype DR β I; major histocompatibility complex, class I, C; and major histocompatibility complex, class II, isotype DQ β I. When compared with whole blood gene expression data from seven external datasets containing septic and nonseptic patients, 81% of the differentially methylated region–associated genes were differentially expressed in one or more datasets and 31% in three or more datasets. Functional analysis showed enrichment for antigen processing and presentation, methyltransferase activity, cell adhesion, and cell junctions. Analysis by weighted gene coexpression network analysis revealed DNA comethylation modules that were associated with clinical traits including severity of illness, need for vasopressors, and length of stay.

Conclusions:

DNA methylation marks may provide important causal and potentially biomarker information in critically ill patients with sepsis.