bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing Victims of a Hidden Crime: Human Trafficking Victims in Your Pediatric Trauma Bay
Authors: Roney Linda Nancy , Villano Caitlin Elizabeth
Published: December 2019

Human trafficking is the second largest criminal industry in the United States and almost half of the victims are children. This crime against children is referred to as domestic minor human sex trafficking (DMHST). The majority DMHST victims access health care, often at an emergency department, at some point during their captivity. Trafficking of minors has been cited as the most underreported form of child abuse making education on this topic essential for all health care providers to help meet the needs of this population. A case study provides an illustration of a pediatric trauma patient who was a victim of DMHST and presented to an emergency department for care. As nurses who care for pediatric trauma patients in all settings strive to learn more about child abuse, topics in DMHST should also be included in these educational activities.
Preservation of Forensic Evidence by Nurses in a Prehospital Emergency Care Service in Brazil
Authors: Silva Juliana O. M. , Santos Luiz F. S. , dos Santos Suelen M. , da Silva Denison P. , Santos Victor S. , de Melo Claudia M.
Published: December 2019

Violence is a growing public health problem worldwide. Nurses increasingly must perform forensic procedures with the responsibility to collect, document, preserve, and store evidence that may be used in the investigation of a violent crime. However, few nurses receive education in forensic evidence collection as part of their training. This study aimed to evaluate the relationship between nurses' knowledge and performance of forensic evidence procedures. This is a descriptive survey study of nurses working in a prehospital emergency care service in Aracaju, Brazil. A 32-question survey related to forensic evidence knowledge and procedures was completed by 128 nurses. Descriptive statistics and Kendall's Tau-b were used to describe the sample and evaluate correlations. Results revealed an overall linear relationship between knowledge and performance of forensic evidence procedures (r = .69). The strongest correlation was between knowledge and documentation (r = .71). Weaker correlations were demonstrated between knowledge and evidence collection (r = .47), evidence preservation (r = .47), and overall evidence procedure execution (r = .53). Forensic nursing knowledge is related to forensic evidence procedure performance. Although the study showed that nurses agreed forensic evidence procedures are important for criminal investigations, most reported they were unprepared to carry out these procedures. The need for additional training and adherence to established institutional protocols are identified as contributing factors.
The impact of Ga-68 DOTATATE PET/CT imaging on management of patients with paragangliomas
Authors: Skoura Evangelia , Priftakis Dimitrios , Novruzov Fuad , Caplin Martyn E. , Gnanasegaran Gopinath , Navalkissoor Shaunak , Bomanji Jamshed
Published: December 2019

Objective

Paragangliomas are rare tumours of neural crest origin that express high levels of somatostatin receptor. Ga-68 DOTATATE PET/CT is a widely accepted method for imaging of neuroendocrine tumours. This study was performed to review a Ga-68 DOTATATE PET/CT patient database and to establish the impact of the modality on patient treatment.

Methods

Demographic data, imaging data and change in management after Ga-68 DOTATATE PET/CT were evaluated.

Results

Ga-68 DOTATATE PET/CT scans were performed in 21 patients in whom paragangliomas had been confirmed after biopsy or surgery and in one patient with suspected paraganglioma. In most patients, the primary site was the organ of Zuckerkandl (12/22). Of the 22 Ga-68 DOTATATE PET/CT scans completed, 19 (86.4%) were positive and three (13.6%) negative. In 12 of 14 recurrent cases (90.9%), the treatment plan was changed after the Ga-68 DOTATATE PET/CT scan owing to new, unexpected findings, while it remained unchanged in two (9.1%). Regarding the change in treatment plan, in most instances the new treatment comprised peptide receptor radionuclide therapy (PRRT).

Conclusion

Ga-68 DOTATATE PET/CT findings led to a change in the scheduled treatment plan in 90.9% of patients with suspected recurrence. The most frequent change consisted in initiation of PRRT due to disease recurrence or progression or detection of multiple metastases.
When is parenteral nutrition indicated in the hospitalized, acutely ill patient?
Authors: Fragkos Konstantinos C. , Sebepos-Rogers Gregory , Rahman Farooq
Published: December 2019

Purpose of review

The current review discusses current practices regarding appropriate indications for parenteral nutrition in acutely ill hospitalized patients. We address-specific indications for parenteral nutrition in the perioperative period, and in inflammatory bowel disease, oncology, hepatobiliary, critical care and end-stage renal disease patients.

Recent findings

Acutely ill hospitalized patients can develop intestinal failure requiring parenteral nutrition. Recent studies have provided insight into the main indications. The most common indications for inpatient parenteral nutrition include postsurgical complications, including prolonged ileus, sepsis, fistula and leaks, and bowel obstruction, predominantly malignant. Severe or complicated inflammatory bowel disease and cancer treatment-related mucosal enteropathies (mucositis, enterocolitis, gut graft-versus-host disease) are the next commonest indications. Less frequent indications are primary motility disorders and inability to secure enteral access for enteral nutrition. Gastrointestinal failure of the intensive care patient is a separate entity resulting from multiple mechanisms, including an enteropathy and dysmotility.

Despite the wider availability of nutrition support teams, use of parenteral nutrition is not without risk. The risks and benefits of parenteral nutrition in the acute setting need to be carefully considered even when it is indicated.
Management of the penile squamous cell carcinoma patient after node positive radical inguinal lymph node dissection: current evidence and future prospects
Authors: de Vries Hielke M. , Ottenhof Sarah R. , van der Heijden Michiel S. , Pos Floris J. , Horenblas Simon , Brouwer Oscar R.
Published: December 2019

Purpose of review

The level of evidence for current (adjuvant) treatment strategies after node positive inguinal lymphadenectomy is relatively low because of a paucity of prospective studies and controversy exist between the two major guidelines. The present review aims to provide a review of current literature on the available treatment options of patients after a tumor positive inguinal lymph node dissection.

Recent findings

Patients without inguinal extranodal extension or less than two tumor positive inguinal nodes are at low risk of ipsilateral pelvic nodal disease. Patients with pN1 disease are unlikely to benefit from adjuvant treatment, whereas patients with pN2 disease might benefit from adjuvant radiotherapy. For patients with high risk of pelvic nodal disease, prophylactic pelvic lymph node dissection (PLND) is advised by current guidelines. The InPACT study investigates whether adjuvant chemoradiotherapy could be used instead of prophylactic PLND. Subgroup analyses of retrospective cohorts suggest that patients with pN3 disease based on tumor positive pelvic nodes may benefit from adjuvant radiotherapy or chemotherapy. Given the weak level of evidence and substantial toxicity associated with current regimens, adjuvant chemotherapy cannot be generally recommended.

Despite current treatment strategies, patients with pN2–pN3 disease still have a poor prognosis. Prospective international multicenter studies are necessary to identify the best treatment options for patients with advanced node positive penile squamous cell carcinoma.
The Role of Anti-Neutrophil Antibodies in the Etiologic Classification of Childhood Neutropenia: A Cross-Sectional Study in a Tertiary Center
Authors: Karakilic-Ozturan Esin , Karaman Serap , Soguksu Pinar , Mese Sevim , Agacfidan Ali , Mutlu Umit D. , Karakas Zeynep , Tugcu Deniz , Karagenc-Ozkan Ayse , Devecioglu Omer
Published: December 2019

Infections, drugs, malignancies, immunodeficiency, and autoimmunity may cause neutropenia. In primary autoimmune neutropenia, anti-neutrophil antibodies (ANeuA) bind to membrane antigens of neutrophils, which give rise to peripheral destruction of neutrophils. However, it is not always easy to detect these antibodies. This study aims to investigate the etiology of neutropenia, and at the same time to evaluate the immune mechanisms by ANeuA testing using granulocyte indirect immunofluorescence test. In our study, 310 neutropenic patients who were between 3 months and 18 years of age were evaluated. ANeuA screening tests were performed in 108 neutropenic patients (group 1), and these patients were divided into 2 subgroups as persistent neutropenia (group 1P, n=12) and recovered neutropenia (group 1R, n=96). Besides, a control group in the same age range was formed, consisting of 39 non-neutropenic children (group 2). ANeuA serum levels were also checked in these groups, and no statistically significant difference could be found between groups 1 and 2, or between groups 1P and 1R, regarding ANeuA levels. As a conclusion, our study was the first comprehensive research in Turkey investigating the large-scale etiology of neutropenia. Moreover, while ANeuA screening tests did not provide sufficient insight for immune neutropenia, we argue that it is not necessary for routine use and that further research in the etiology of neutropenia is required.
Priorities for Cancer Research From the Viewpoints of Cancer Nurses and Cancer Patients
Authors: Cadorin Lucia , Bressan Valentina , Truccolo Ivana , Suter Nicoletta
Published: December 2019

Background

Setting priorities in oncology is a useful way to produce a robust set of research questions that researchers can address.

Objective

The aim of this review was to describe cancer nurses and patients' main research priorities and describe their development over time.

Methods

A mixed-method systematic review was conducted for the period from 2000 to 2018 through a search of multiple databases. The methodological quality of the studies included was assessed using the Mixed-Methods Appraisal Tool, and the process of setting the health research priorities was assessed using Viergever's tool. Each study's top research priorities were extracted and summarized in categories.

Results

Fifteen studies were included: 13 addressed nurses' research priorities, and 2 focused on those of patients. The majority were Delphi and quantitative studies that were conducted in the United States and United Kingdom. The quality criteria score and the quality of the process were considered sufficiently good. The most important research priorities were categorized as disease control and management, patient-related issues, and professional dimensions and issues. Management of symptoms and pain, education, information, and communication were research priorities always present in the articles during the study period.

Conclusion

Priorities change over time and depend on several factors; however, some have remained consistent for the last 18 years. Although there is increasing emphasis on including patients in establishing research priorities that inform cancer care, this involvement is still lacking.

Implications for Practice

Future studies should describe the primary cancer research priorities of nurses in collaboration with patients.
Observation and Imitation of Social Emotions Are Essential for Improving Cognitive and Affective Theory of Mind in Schizophrenia
Authors: Yeh Pin-Yang , Yu Lifa , Guo Nai-Wen , Lin Wei-Che , Wu Ching-Kuan
Published: December 2019

People with schizophrenia often demonstrate deficits in theory of mind (ToM), which may be addressed via social cognition training that includes observation and imitation of social emotions. We examined the effect of observation and imitation on ToM and whether computerized cognitive training (CCT) can improve ToM. Among 14 controlled trials, 264 of 494 people with schizophrenia received treatment. Observation and imitation of social emotions improved cognitive (g = 0.53; 95% confidence interval [CI], 0.29–0.76) and affective ToM (g = 0.54; 95% CI, 0.34–0.73), versus treatment as usual or cognitive rehabilitation alone. CCT did not significantly enhance affective ToM (p = 0.42); however, cognitive ToM improvements without CCT (g = 1.20; 95% CI, 0.78–1.61) were superior to those with CCT (g = 0.33; 95% CI, 0.02–0.64; p < 0.01). Observation and imitation of social emotions are essential for improving ToM in schizophrenia, but CCT may not improve ToM.
Pharmacogenomic Testing in Psychiatry
Authors: Rakesh Gopalkumar , Sumner Calvin R. , Alexander Jeanne Leventhal , Gross Lawrence S. , Pine Janet , Slaby Andrew , Garakani Amir , Baron David
Published: December 2019

Pharmacogenomic testing in clinical psychiatry has grown at an accelerated pace in the last few years and is poised to grow even further. Despite robust evidence lacking regarding efficacy in clinical use, there continues to be growing interest to use it to make treatment decisions. We intend this article to be a primer for a clinician wishing to understand the biological bases, evidence for benefits, and pitfalls in clinical decision-making. Using clinical vignettes, we elucidate these headings in addition to providing a perspective on current relevance, what can be communicated to patients, and future research directions. Overall, the evidence for pharmacogenomic testing in psychiatry demonstrates strong analytical validity, modest clinical validity, and virtually no evidence to support clinical use. There is definitely a need for more double-blinded randomized controlled trials to assess the use of pharmacogenomic testing in clinical decision-making and care, and until this is done, they could perhaps have an adjunct role in clinical decision-making but minimal use in leading the initial treatment plan.
Principal Diagnoses in Psychiatric Outpatients With Posttraumatic Stress Disorder
Authors: Kiefer Reina , Chelminski Iwona , Dalrymple Kristy , Zimmerman Mark
Published: December 2019

In this study, we examined the prevalence of posttraumatic stress disorder (PTSD) in 3800 psychiatric outpatients with different principal diagnoses. For all disorders identified as a principal diagnosis, we compared patients' odds ratios of PTSD to all other patients in the sample. Approximately one-sixth of the sample (n = 663, 17.4%) was diagnosed with PTSD, including 417 patients with current PTSD and 246 with PTSD in partial remission. Patients with principal bipolar disorder and major depressive disorder (MDD) demonstrated higher rates of PTSD compared with those without principal bipolar and MDD. For most psychiatric outpatients with PTSD, the principal diagnosis for which they seek treatment is not PTSD, but rather a mood disorder. This highlights the importance of screening for PTSD, particularly in patients with a principal diagnosis for which the prevalence of PTSD is relatively high, namely, MDD, bipolar disorder, panic disorder, and borderline personality disorder.
Anti–Jo-1 Syndrome Often Misdiagnosed as Rheumatoid Arthritis (for Many Years)
Authors: Kumar Rajiv Ranjan , Jha Saket , Dhooria Aadhaar , Naidu G.S.R.S.N.K , Minz Ranzana W. , Kumar Susheel , Sharma Shefali Khanna , Sharma Aman , Jain Sanjay , Dhir Varun
Published: December 2019

Background

Antisynthetase syndrome is characterized by a triad of myositis, arthritis, and interstitial lung disease. Anti–Jo-1 is the most common associated autoantibody. This study planned to look at the presentation of anti–Jo-1 antisynthetase syndrome in a single Indian center.

Methods and Materials

This was a medical records review single-center study that included patients with anti–Jo-1 antisynthetase syndrome over 10 years.

Results

This study included 27 patients with anti–Jo-1 antisynthetase syndrome, with mean age of 40 ± 9.2 years and female preponderance (female-to-male ratio, 4:1). At presentation, the characteristic triad was present in only 4 patients. A majority presented with the incomplete form, with 2 clinical features (of triad) in 11 and single feature (of triad) being present in 12 patients at initial presentation. Seven presented only with polyarthritis, out of which 6 had been earlier diagnosed as rheumatoid arthritis. Time gap from diagnosis of “rheumatoid arthritis” to antisynthetase syndrome ranged from 3 to 20 years. In patients who had only arthritis in the beginning, there was a significantly longer delay to diagnosis of antisynthetase syndrome, higher frequency of rheumatoid factor, and lower frequency of anti–Ro-52. Overall, outcome was good, with Eastern Cooperative Oncology Group class 1 or 2 in most except 2 patients.

Conclusions

Anti–Jo-1 antisynthetase syndrome commonly presented as incomplete (not a triad) and often only with arthritis. These patients are diagnosed and treated as rheumatoid arthritis for many years, before a diagnosis of antisynthetase syndrome is made. Being aware of this presentation may help in earlier diagnosis by actively searching for subtle clues.
Measuring Serum Sclerostin in Egyptian Patients With Systemic Lupus Erythematosus and Evaluating Its Effect on Disease Activity
Authors: Fayed Ahmed , Soliman Ahmed , Elgohary Rasmia
Published: December 2019

Objective

Sclerostin is an osteocyte-secreted protein that downregulates bone formation by blocking the Wnt/β-catenin signaling pathway. Sclerostin can be induced by inflammation, and high levels have been reported in patients with proteinuria and renal impairment. Studies evaluating the role of sclerostin in systemic lupus erythematosus (SLE) patients are scarce. This study aims to measure serum sclerostin in SLE patients and correlate its level with bone biomarkers and disease activity, particularly in lupus nephritis and arthritis. Finally, we evaluated factors that may predict sclerostin concentrations.

Methods

This cross-sectional, case-control study was conducted from May 2017 to April 2018. Serum sclerostin was measured by enzyme-linked immunosorbent assay in 100 SLE patients, including 50 patients with current lupus nephritis and 27 patients with current arthritis, as well as in 50 healthy controls. Correlation analysis of serum sclerostin with demography, bone biomarkers, and disease activity in SLE patients was carried out.

Results

Sclerostin levels were significantly elevated in SLE patients, particularly those with lupus nephritis, compared with healthy controls. Higher levels were identified in patients without arthritis compared with those with; however, the former group had more proteinuria and renal impairment. Significant correlations were observed between sclerostin levels and serum creatinine, proteinuria, consumed C3 and C4 complement, and corrected Ca. Using multiple linear regression, proteinuria was the only significant predictor for serum sclerostin in SLE patients.

Conclusions

This study is the first to report that serum sclerostin is associated with proteinuria in SLE patients and could be used as a valuable biomarker for lupus nephritis.
Online interventions to address body image distress in cancer
Authors: Esplen Mary Jane , Trachtenberg Lianne
Published: December 2019

Purpose of review

Body image is a critical psychosocial issue for patients with cancer, because of the profound effects the disease and its treatment can have on appearance and bodily functioning. Adverse psychological effects of body image changes associated with cancer include debilitating levels of anxiety, social avoidance, depression, problems with intimacy and impaired sexuality, and feelings of shame/inadequacy. The construct of body image is increasingly recognized as complex and multifaceted from an embodied lens, creating more meaningful and efficacious interventions. Although there is some evidence now for in-person interventions, more research is needed in online and in-person interventions, particularly beyond what has been demonstrated in breast cancer. There is also need to address concerns around the practical and psychosocial barriers that can diminish access to, and participation in such individual or group interventions. Internet-based interventions offer opportunity for greater access to tailored psychosocial care.

Recent findings

An emerging conceptualization of body image for cancer patients is discussed. Internet-delivered interventions targeting body image are outlined; the majority are pilot trials and those developed for breast cancer patients. Challenges found in online interventions are also discussed.

Internet-delivered body image interventions would benefit from a broader conceptualization of body image, greater methodological rigor, and investigations focused on a broader range of cancer populations, beyond patients with breast cancer. Future research is needed to develop, test, and identify who can benefit from online interventions within cancer care.
The Use of Cannabis as a Treatment for Epilepsy in Adult Patients: Are Side Effects a Limitation of Use?
Authors: Téllez-Zenteno Jose F. , Ladino Lady D. , Hernández-Ronquillo Lizbeth
Published: December 2019

Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties areCannabis sativaandCannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.
The role of motile cilia in the development and physiology of the nervous system
Authors: Ringers Christa , Olstad Emilie W. , Jurisch-Yaksi Nathalie
Published: December 2019

Motile cilia are miniature, whip-like organelles whose beating generates a directional fluid flow. The flow generated by ciliated epithelia is a subject of great interest, as defective ciliary motility results in severe human diseases called motile ciliopathies. Despite the abundance of motile cilia in diverse organs including the nervous system, their role in organ development and homeostasis remains poorly understood. Recently, much progress has been made regarding the identity of motile ciliated cells and the role of motile-cilia-mediated flow in the development and physiology of the nervous system. In this review, we will discuss these recent advances from sensory organs, specifically the nose and the ear, to the spinal cord and brain ventricles.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Simulations of particle tracking in the oligociliated mouse node and implications for left–right symmetry-breaking mechanics
Authors: Gallagher M. T. , Montenegro-Johnson T. D. , Smith D. J.
Published: December 2019

The concept of internal anatomical asymmetry is familiar–usually in humans the heart is on the left and the liver is on the right; however, how does the developing embryo know to produce this consistent laterality? Symmetry-breaking initiates with left–right asymmetric cilia-driven fluid mechanics in a small fluid-filled structure called the ventral node in mice. However, the question of what converts this flow into left–right asymmetric development remains unanswered. A leading hypothesis is that flow transports morphogen-containing vesicles within the node, the absorption of which results in asymmetrical gene expression. To investigate how vesicle transport might result in the situs patterns observe in wild-type and mutant experiments, we extend the open-source Stokes flow package, NEAREST, to consider the hydrodynamic and Brownian motion of particles in a mouse model with flow driven by one, two and 112 beating cilia. Three models for morphogen-containing particle released are simulated to assess their compatibility with observed results in oligociliated and wild-type mouse embryos: uniformly random release, localized cilium stress-induced release and localized release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localized release model resulting in significant transport in the oligociliated embryo.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Cilia in the developing zebrafish ear
Authors: Whitfield Tanya T.
Published: December 2019

The inner ear, which mediates the senses of hearing and balance, derives from a simple ectodermal vesicle in the vertebrate embryo. In the zebrafish, the otic placode and vesicle express a whole suite of genes required for ciliogenesis and ciliary motility. Every cell of the otic epithelium is ciliated at early stages; at least three different ciliary subtypes can be distinguished on the basis of length, motility, genetic requirements and function. In the early otic vesicle, most cilia are short and immotile. Long, immotile kinocilia on the first sensory hair cells tether the otoliths, biomineralized aggregates of calcium carbonate and protein. Small numbers of motile cilia at the poles of the otic vesicle contribute to the accuracy of otolith tethering, but neither the presence of cilia nor ciliary motility is absolutely required for this process. Instead, otolith tethering is dependent on the presence of hair cells and the function of the glycoprotein Otogelin. Otic cilia or ciliary proteins also mediate sensitivity to ototoxins and coordinate responses to extracellular signals. Other studies are beginning to unravel the role of ciliary proteins in cellular compartments other than the kinocilium, where they are important for the integrity and survival of the sensory hair cell.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
The unity and diversity of the ciliary central apparatus
Authors: Zhao Lei , Hou Yuqing , McNeill Nathan A. , Witman George B.
Published: December 2019

Nearly all motile cilia and flagella (terms here used interchangeably) have a ‘9+2’ axoneme containing nine outer doublet microtubules and two central microtubules. The central pair of microtubules plus associated projections, termed the central apparatus (CA), is involved in the control of flagellar motility and is essential for the normal movement of ‘9+2’ cilia. Research using the green algaChlamydomonas reinhardtii, an important model system for studying cilia, has provided most of our knowledge of the protein composition of the CA, and recent work using this organism has expanded the number of known and candidate CA proteins nearly threefold. Here we take advantage of this enhanced proteome to examine the genomes of a wide range of eukaryotic organisms, representing all of the major phylogenetic groups, to identify predicted orthologues of theC. reinhardtiiCA proteins and explore how widely the proteins are conserved and whether there are patterns to this conservation. We also discuss in detail two contrasting groups of CA proteins—the ASH-domain proteins, which are broadly conserved, and the PAS proteins, which are restricted primarily to the volvocalean algae.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Reorganization of complex ciliary flows around regeneratingStentor coeruleus
Authors: Wan Kirsty Y. , Hürlimann Sylvia K. , Fenix Aidan M. , McGillivary Rebecca M. , Makushok Tatyana , Burns Evan , Sheung Janet Y. , Marshall Wallace F.
Published: December 2019

The phenomenon of ciliary coordination has garnered increasing attention in recent decades and multiple theories have been proposed to explain its occurrence in different biological systems. While hydrodynamic interactions are thought to dictate the large-scale coordinated activity of epithelial cilia for fluid transport, it is rather basal coupling that accounts for synchronous swimming gaits in model microeukaryotes such asChlamydomonas.Unicellular ciliates present a fascinating yet understudied context in which coordination is found to persist in ciliary arrays positioned across millimetre scales on the same cell. Here, we focus on the ciliateStentor coeruleus, chosen for its large size, complex ciliary organization, and capacity for cellular regeneration. These large protists exhibit ciliary differentiation between cortical rows of short body cilia used for swimming, and an anterior ring of longer, fused cilia called the membranellar band (MB). The oral cilia in the MB beat metachronously to produce strong feeding currents. Remarkably, upon injury, the MB can be shed and regenerated de novo. Here, we follow and track this developmental sequence in its entirety to elucidate the emergence of coordinated ciliary beating: from band formation, elongation, curling and final migration towards the cell anterior. We reveal a complex interplay between hydrodynamics and ciliary restructuring inStentor, and highlight for the first time the importance of a ring-like topology for achieving long-range metachronism in ciliated structures.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Diversity of cilia-based mechanosensory systems and their functions in marine animal behaviour
Authors: Bezares-Calderón Luis Alberto , Berger Jürgen , Jékely Gáspár
Published: December 2019

Sensory cells that detect mechanical forces usually have one or more specialized cilia. These mechanosensory cells underlie hearing, proprioception or gravity sensation. To date, it is unclear how cilia contribute to detecting mechanical forces and what is the relationship between mechanosensory ciliated cells in different animal groups and sensory systems. Here, we review examples of ciliated sensory cells with a focus on marine invertebrate animals. We discuss how various ciliated cells mediate mechanosensory responses during feeding, tactic responses or predator–prey interactions. We also highlight some of these systems as interesting and accessible models for future in-depth behavioural, functional and molecular studies. We envisage that embracing a broader diversity of organisms could lead to a more complete view of cilia-based mechanosensation.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Synchrony and symmetry-breaking in active flagellar coordination
Authors: Wan Kirsty Y.
Published: December 2019

Living creatures exhibit a remarkable diversity of locomotion mechanisms, evolving structures specialized for interacting with their environment. In the vast majority of cases, locomotor behaviours such as flying, crawling and running are orchestrated by nervous systems. Surprisingly, microorganisms can enact analogous movement gaits for swimming using multiple, fast-moving cellular protrusions called cilia and flagella. Here, I demonstrate intermittency, reversible rhythmogenesis and gait mechanosensitivity in algal flagella, to reveal the active nature of locomotor patterning. In addition to maintaining free-swimming gaits, I show that the algal flagellar apparatus functions as a central pattern generator that encodes the beating of each flagellum in a network in adistinguishablemanner. The latter provides a novel symmetry-breaking mechanism for cell reorientation. These findings imply that the capacity to generate and coordinate complex locomotor patterns does not require neural circuitry but rather the minimal ingredients are present in simple unicellular organisms.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Chemosensing versus mechanosensing in nodal and Kupffer's vesicle cilia and in other left–right organizer organs
Authors: Cartwright Julyan H. E. , Piro Oreste , Tuval Idan
Published: December 2019

How is sensing carried out by cilia in the mouse node, zebrafish Kupffer's vesicle and similar left–right (LR) organizer organs in other species? Two possibilities have been put forward. In the former, cilia would detect some chemical species in the fluid; in the latter, they would detect fluid flow. In either case, the hypothesis is that an imbalance would be detected between this signalling coming from cilia on the left and right sides of the organizer, which would initiate a cascade of signals leading ultimately to the breaking of LR symmetry in the developing body plan of the organism. We review the evidence for both hypotheses.

This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations
Authors: Ali Hebah , Puccio Ignazio , Akarca Ayse U , Bob Roshanak , Pomplun Sabine , Wong Wai Keong , Gupta Rajeev , Sekhar Mallika , Lambert Jonathan , Al-Masri Hytham , Stein Harald , Marafioti Teresa
Published: December 2019

The discovery of mutated Calreticulin (CALR) in myeloproliferative neoplasms (MPN) has provided proof of clonality, diagnostic importance, and influence on prognosis of this pathology. The identification of this MPN-associated driver mutation -currently based on molecular assays- is represented as a major diagnostic criterion for essential thrombocythaemia (ET), pre-fibrotic myelofibrosis and primary myelofibrosis (PMF) in the updated World Health Organization (WHO) 2008 classification. In the present study, we validated by immunohistochemistry the diagnostic usefulness of the monoclonal CAL2 antibody. Cases of acute myeloid leukaemia (AML) and myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) have been also investigated to assess the specificity of CAL2 antibody. For this purpose, the result of the CAL2 immunostaining was compared with the result of molecular assays. Additionally, we investigated by double staining whether expression of mutated CALR can also be demonstrated on cells of the erythroid and myeloid lineage. We confirmed the usefulness of the CAL2 monoclonal antibody in successfully detecting mutant CALR in bone marrow biopsies. We showed that the immune-reactivity of CAL2 was absolutely restricted to the presence of CALR mutations, which were seen only in ET and MDS/MPN biopsies, but not in AML biopsies (14/14). There was 100% concordance in biopsy specimens with the concomitant molecular results. We applied double staining technique and confirmed that a subpopulation of granulopoietic and erythropoietic cells express mutated CALR as demonstrated with the CAL2 antibody in cases of MPNs. This supports the suggestion that the CALR mutations occur in a multipotent progenitor capable of generating both myeloid and erythroid progeny with preferential expansion of megakaryocytic cell lineage as a result of CALR mutation in an immature hematopoietic stem cell.
Emergence of mcr-9.1 in ESBL-producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome and Mobilome
Authors: Sekyere John Osei , Maningi Nontuthuko E. , Modipane Lesedi , Mbelle Nontombi Marylucy
Published: December 2019

Background

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with little therapeutic options.

Methods

Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analysed to determine their resistome, mobilome, and evolutionary relationship to global strains. The global phylogenomics of mcr-9.1-bearing genomes were further analysed.

Results & conclusion

Ten isolates were ESBL positive. The isolates were multidrug-resistant and phylogenetically related to global clones, but distant from local strains. Multiple resistance genes, including blaCTX-M-15blaTEM-1 and mcr-9.1 were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed blaCTX-M-15 and blaTEM-1. Common plasmid types included IncF, IncH and ColRNAI. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A-F), with those of this study belonging to clade B. Enterobacter sp. and Salmonella sp. are the main hosts of mcr-9.1 globally, albeit diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices.
Diabetes mellitus, glycemic traits, and cerebrovascular disease: a Mendelian randomization study
Authors: Georgakis Marios K. , Harshfield Eric L , Malik Rainer , Franceschini Nora , Langenberg Claudia , Wareham Nicholas J. , Markus Hugh S. , Dichgans Martin
Published: December 2019

Rationale

Type 2 diabetes mellitus (T2D) is an established risk factor for cerebrovascular disease but the mechanisms underlying this association remain elusive. Disentangling the causal effects of T2D, hyperglycemia, and pre-diabetic phenotypes (insulin resistance, β-cell dysfunction) on major etiological stroke subtypes (ischemic stroke, intracerebral hemorrhage, ischemic stroke subtypes) could inform the development of preventive strategies.

Objective

We employed Mendelian randomization (MR) to explore the effects of genetic predisposition to T2D, hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes.

Methods and Results

We selected instruments for genetic predisposition to T2D, HbA1c levels, fasting glucose levels, insulin resistance, and β-cell dysfunction (proxied by pro-insulin levels) based on published genome-wide association studies (up to 898,130 individuals). Applying two-sample MR, we examined associations with ischemic stroke, intracerebral hemorrhage, and ischemic stroke subtypes (large artery, cardioembolic, small vessel stroke; up to 60,341 cases and 454,450 controls). We further explored associations with the related phenotypes of carotid atherosclerosis, imaging markers of cerebral white matter integrity, and brain atrophy. Genetic predisposition to T2D and elevated HbA1c levels in the pre-diabetic range were associated with higher risk of any ischemic stroke, large artery stroke, carotid plaque and small vessel stroke. Independently of HbA1c levels, we further found genetic predisposition to insulin resistance to be associated with large artery and small vessel stroke, whereas predisposition to β-cell dysfunction was associated with small vessel stroke. Predisposition to β-cell dysfunction was further associated with intracerebral hemorrhage, lower grey matter volume, and total brain volume.

Conclusions

This study supports causal effects of T2D and hyperglycemia on large artery and small vessel stroke. We show differential effects of genetically determined insulin resistance and β-cell dysfunction on large artery and small vessel stroke that might have implications for anti-diabetic treatments targeting these mechanisms.
Efficient data management infrastructure for the integration of imaging and omics data in life science research
Authors: Cuellar Luis Kuhn , Friedrich Andreas , Gabernet Gisela , de la Garza Luis , Fillinger Sven , Seyboldt Adrian , Oven-Krockhaus Sven zur , Wanke Friederike , Richter Sandra , Thaiss Wolfgang M. , Horger Marius , Malek Nisar , Harter Klaus , Bitzer Michael , Nahnsen Sven
Published: December 2019

As technical developments in omics and biomedical imaging drive the increase in quality, modality, and throughput of data generation in life sciences, the need for information systems capable of integrative, long-term storage and management of these heterogeneous digital assets is also increasing. Here, we propose an approach based on principles of Service Oriented Architecture design, to allow the integrated management and analysis of multi-omics and biomedical imaging data. The proposed architecture introduces an interoperable image management system, the OMERO server, into the backend of qPortal, a FAIR-compliant web-based platform for omics data management. The implementation of an integrated metadata model, the development of software components to enable the communication with the OMERO server, and an extension to the data management operations of established software, allows for FAIR management of heterogeneous omics and biomedical imaging data within an integrated system, which facilitates metadata queries from web-based scientific applications. The applicability of the proposed architecture is demonstrated in two prototypical use cases, a plant biology study using confocal scanning microscopy, and a clinical study on hepatocellular carcinoma, with data from a variety of medical imaging and omics modalities. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, as the joint analysis of omics and imaging data becomes not only desirable but necessary to derive novel insights into biological processes. In particular for powerful machine learning applications where the availability of large datasets with high quality phenotypic annotations is a requirement.
Dual role of auxin in regulating plant defense and bacterial virulence gene expression duringPseudomonas syringae PtoDC3000 pathogenesis
Authors: Djami-Tchatchou Arnaud T. , Harrison Gregory A. , Harper Chris P. , Wang Renhou , Prigge Michael J. , Estelle Mark , Kunkel Barbara N.
Published: December 2019

Modification of host hormone biology is a common strategy used by plant pathogens to promote disease. For example, the bacterial pathogenPseudomonas syringaestrainPtoDC3000 produces the plant hormone auxin (Indole-3-acetic acid, or IAA) to promotePtoDC3000 growth in plant tissue. Previous studies suggest that auxin may promotePtoDC3000 pathogenesis through multiple mechanisms, including both suppression of salicylic acid (SA)-mediated host defenses and via an unknown mechanism that appears to be independent of SA. To test if host auxin signaling is important during pathogenesis, we took advantage ofArabidopsis thalianalines impaired in either auxin signaling or perception. We found that disruption of auxin signaling in plants expressing an inducible dominantaxr2-1mutation resulted in decreased bacterial growth, demonstrating that host auxin signaling is required for normal susceptibility toPtoDC3000, and this phenotype was dependent on SA-mediated defenses. However, despite exhibiting decreased auxin perception,tir1 afb1 afb4 afb5quadruple mutant plants lacking four of the six known auxin co-receptors supported increased levels of bacterial growth. This mutant also exhibited elevated IAA levels, suggesting that the increased IAA in these plants may promotePtoDC3000 growth independent of host auxin signaling, perhaps through a direct effect on the pathogen. In support of this, we found that IAA directly impacted the pathogen, by modulating expression of bacterial virulence genes, both in liquid culture and in planta. Thus, in addition to suppressing host defenses, IAA acts as a microbial signaling molecule that regulates bacterial virulence gene expression.
Vulnerability and life-history traits correlate with the load of deleterious mutations in fish
Authors: Rolland Jonathan , Romiguier Jonathan
Published: December 2019

Understanding why some species accumulate more deleterious substitutions than others is an important question relevant in evolutionary biology and conservation sciences. Previous studies conducted in terrestrial taxa suggest that life history traits correlate with the efficiency of purifying selection and accumulation of deleterious mutations. Using a large genome dataset of 76 species of fishes, we show that the rate of deleterious mutation accumulation (measured via dN/dS,i.e.non-synonymous over synonymous substitution rate) is associated to the vulnerability, the life-history strategies, and the latitude of species. Our results, focusing on a large clade of aquatic species, generalizes previous patterns found so far in few clades of terrestrial vertebrates. These results also suggest that vulnerable species accumulate more deleterious substitutions than non-threatened ones, which give insights in how life-history traits, populations sizes and genetic risk of extinction can be tightly interconnected.
Human walking in the real world: Interactions between terrain type, gait parameters, and energy expenditure
Authors: Kowalsky DB , Rebula JR , Ojeda LV , Adamczyk PG , Kuo AD
Published: December 2019

Humans often traverse real-world environments with a variety of surface irregularities and inconsistencies, which can disrupt steady gait and require additional effort. Such effects have, however, scarcely been demonstrated quantitatively, because few laboratory biomechanical measures apply outdoors. Walking can nevertheless be quantified by other means. In particular, the foot’s trajectory in space can be reconstructed from foot-mounted inertial measurement units (IMUs), to yield measures of stride and associated variabilities. But it remains unknown whether such measures are related to metabolic energy expenditure. We therefore quantified the effect of five different outdoor terrains on foot motion (from IMUs) and net metabolic rate (from oxygen consumption) in healthy adults (N = 10; walking at 1.25 m/s). Energy expenditure increased significantly (P < 0.05) in the order Sidewalk, Dirt, Gravel, Grass, and Woodchips, with Woodchips about 27% costlier than Sidewalk. Terrain type also affected measures, particularly stride variability and virtual foot clearance (swing foot’s lowest height above consecutive footfalls). In combination, such measures can also roughly predict metabolic cost (adjustedR2= 0.52, partial least squares regression), and even discriminate between terrain types (10% reclassification error). Body-worn sensors can characterize how uneven terrain affects gait, gait variability, and metabolic cost in the real world.
Highly heterogeneous long-range interactions explain chromosome compartmentalization
Authors: Eidelman Y.A. , Salnikov I.V. , Slanina S.V. , Andreev S.G.
Published: December 2019

The explanation for the compartmentalization of the chromosome contact maps observed by Hi-C method is still an unsolved mystery. The most natural and generally accepted explanation is that blocks of frequent/rare contacts on the entire map are associated with the existence of blocks of homogeneous elements along the chromosome that interact in 3D so that elements of the same type interact frequently and those of different types rarely. We study the polymer model of the chromosome, in which there are neither blocks of homogeneous elements nor homogeneous interactions and all the interaction energies are different. We demonstrate that such a heteropolymer model is able to describe chromosomal maps with high accuracy. The differences from compartment polymer models of chromosomes, which actually reflect the mechanism of microphase separation in polymers, are discussed further.