bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended Treatment With Mesenchymal Stromal Cells-Frankfurt am Main in a Pediatric Patient With Steroid-refractory Acute Gastrointestinal Graft-Versus-Host Disease: Case Report and Review of the Literature
Authors: Gruhn Bernd , Brodt Grit , Ernst Jana
Published: March 2020

In acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation, there are various options available after the failure of initial steroid therapy. Since the publication of the first study in 2008, mesenchymal stromal cells (MSCs) have also been used with increasing frequency, including in pediatric patients with steroid-refractory aGVHD, and the manufacturing process has undergone further development. MSC-Frankfurt am Main (MSC-FFM, Obnitix), which is manufactured from pooled mononuclear bone marrow cells from 8 donors using a standardized process, resulted in a response rate of 84% in children with steroid-refractory aGVHD. We report on a 13-year-old female patient with acute myeloid leukemia who received Obnitix as a third-line treatment for gastrointestinal (GI) aGVHD in a life-threatening situation. The patient was initially given a total of 4 Obnitix infusions as per the regulatory approval, with her symptoms improving from day 9 after the first infusion. The second cycle of 4 Obnitix infusions followed due to persistent severe protein-losing enteropathy and resulted in complete remission. A systematic review of the literature on MSC in pediatric patients with steroid-refractory aGVHD confirms that MSC treatment beyond 4 weeks is employed in accordance with treatment protocols or on a case-by-case basis. To summarize, aGVHD activity can be checked endoscopically in patients with persistent GI symptoms and a second Obnitix cycle can then be administered if appropriate, with the goal of achieving complete remission. Future studies should also investigate the potential influence of tissue repair properties as an element in MSCs’ efficacy in GI aGVHD.
Primary IgA-mediated Autoimmune Hemolytic Anemia in an Infant Successfully Treated With Rituximab
Authors: van den Akker Machiel , Smolders David , Mahieu Sarah , Bonouvrie Kimberley , van der Werf Ten Bosch Jutte
Published: March 2020

Autoimmune hemolytic anemia (AIHA) is uncommon in the pediatric population and is often associated with an infectious etiology or postvaccination. Mostly, the child presents with a positive direct antiglobulin test. The diagnosis can be challenging, as in our case with an immunoglobulin A–mediated AIHA. In addition to supportive therapy, such as a red blood cell transfusion, steroids are the first choice of treatment. Rituximab, as second-line treatment, can be given in conjunction. We report the first case of immunoglobulin A–mediated AIHA treated with rituximab in the literature.
Insulinoma-associated Protein 1 (INSM1) Is a Better Marker for the Diagnosis and Prognosis Estimation of Small Cell Lung Carcinoma Than Neuroendocrine Phenotype Markers Such as Chromogranin A, Synaptophysin, and CD56
Authors: Sakakibara Rie , Kobayashi Maki , Takahashi Naoko , Inamura Kentaro , Ninomiya Hironori , Wakejima Ryo , Kitazono Satoru , Yanagitani Noriko , Horiike Atsushi , Ichinose Junji , Matsuura Yosuke , Nakao Masayuki , Mun Mingyon , Nishio Makoto , Okumura Sakae , Motoi Noriko , Ito Takaaki , Miyazaki Yasunari , Inase Naohiko , Ishikawa Yuichi
Published: March 2020

To diagnose small cell lung carcinoma (SCLC), neuroendocrine (NE) phenotype markers such as chromogranin A, synaptophysin, and CD56 are helpful. However, because they are dispensable, SCLCs occur without apparent NE phenotypes. Insulinoma-associated protein 1 (INSM1) is a transcription factor for NE differentiation and has emerged as a single practical marker for SCLC. Using the surgical samples of 141 pulmonary NE tumors (78 SCLCs, 44 large cell NE carcinomas, and 19 carcinoids), and 246 non-NE carcinomas, we examined the immunohistochemical expression and prognostic relevance of INSM1 in association with NE phenotype markers. We evaluated its sensitivity and specificity for SCLC diagnosis, as well as its usefulness to diagnose SCLC without NE marker expression and to estimate the prognosis. INSM1 was expressed in SCLCs (92%, 72/78), large cell NE carcinomas (68%, 30/44), and carcinoids (95%, 18/19). In addition, among SCLCs with no expression of NE phenotype markers (n=12), 9 (75%) were positive for INSM1. These data suggest the superiority of INSM1 to the phenotype markers. Only 7% of adenocarcinomas (9/134) and 4% of squamous cell carcinomas (4/112) were positive for INSM1. SCLC with low-INSM1 expression (n=28) had a significantly better prognosis (P=0.040) than the high-INSM1 group (n=50). Our study revealed that INSM1 is highly sensitive and specific to detect SCLC and can estimate prognosis. INSM1 will be a promising marker for SCLC.
Comparative Study of Micro-Bone Window and Conventional Bone Window Microsurgery for Hypertensive Intracerebral Hemorrhage
Authors: Shao Xuefei , Wang Qifu , Shen Jun , Liu Jiaqiang , Chen Sansong , Jiang Xiaochun
Published: March 2020

Objective:

To compare and analyze the efficacy and safety of traditional craniotomy and small bone window craniotomy in the treatment of hypertensive cerebral hemorrhage (HICH).

Patients and Methods:

Fifty-four patients with HICH treated with traditional craniotomy and small bone window craniotomy were retrospectively analyzed. The operation time, hospitalization time, preoperative, and postoperative CT analysis, Glasgow coma scale (GCS) score and Glasgow outcome scale (GOS) scores were analyzed.

Results:

There were no significant differences in gender, age, hematoma volume, GCS score and pre-operative time between the 2 groups (P 
> 0.05). The operation time and hospitalization time of the micro-bone window group were shorter than those of the traditional operation group (P 
< 0.05). The GCS and GOS scores of the small bone window group after 3 days and 6 months were higher than those of the traditional operation group (P 
< 0.05). However, there was no significant difference in hematoma clearance rate, re-bleeding rate and infection rate between the two groups (P 
> 0.05).

Conclusion:

For patients with GCS 8–12 HICH, micro-bone window not only has the same effect as traditional bone window, but also has the advantages of shorter operation time and less trauma.
Airway Obstruction Management With Mandibular Distraction and Matthews Device in Pruzansky III Craniofacial Microsomia
Authors: Shih Linden , Davis Matthew J. , Sequitin Jeromie , Abu-Ghname Amjed , Dempsey Robert F. , Truong Tuan A. , Buchanan Edward P.
Published: March 2020

Patients with craniofacial microsomia (CFM) may present with severely malformed mandibles resulting in secondary tongue-based airway obstruction. While surgical management of clinically significant airway obstruction in these patients often involves mandibular distraction osteogenesis (MDO), patients with Pruzansky III CFM typically require additional costochondral bone grafting. In this report, the authors present the successful surgical management of airway obstruction and severe obstructive sleep apnea using a cranio-mandibular fixator (Matthews device) combined with MDO in a 4-year-old female patient with Goldenhar syndrome and associated Pruzansky III CFM. The patient tolerated the procedure without complications and experienced a significant improvement in airway obstruction. With this approach, a severely deformed mandible can be successfully distracted while avoiding tracheostomy and disruption of native TMJ anatomy.
Augmented Reality Microsurgery
Authors: Ropelato Sandro , Menozzi Marino , Michel Dominique , Siegrist Michael
Published: March 2020

Introduction

Current methods of training microsurgical interventions have various limitations, including limited transferability to the human model, economic demands, and ethical concerns. In this article, we show how surgery simulations can overcome these issues and how, combined with the application of an intelligent tutoring system (ITS), they can be used to train tasks in ophthalmic surgery more efficiently.

Methods

We investigated physician trainee efficiency of learning microsurgical skills using our purpose-built microsurgery simulator that tracks a micromanipulator and displays a three-dimensional representation of the interior of a human eye in an augmented reality (AR) headset. The expertise of ophthalmic surgeons helped define five subtasks corresponding to the steps of internal limiting membrane peeling. Using our AR surgery simulation, 50 participants underwent two training sessions, one using the ITS that dynamically adapts the task sequence to the participant's progress and one using a fixed task sequence.

Results

We found significant improvement in micromanipulation performance in the first training session with both the ITS and classic training. In the second session, however, only the participants training with the ITS had further improvements in performance.

Conclusions

Results of this study demonstrate the usability of AR simulation in training micromanipulation skills and support the claim that simulators can be used in ophthalmic surgery training. This study also extends the existing literature by demonstrating an application of ITS for surgical training. The potential of this method is further analyzed in ongoing studies and discussions with experts in ophthalmic surgery.
Clinical Utility of the Risk Analysis Index as a Prospective Frailty Screening Tool within a Multi-practice, Multi-hospital Integrated Healthcare System
Authors: Varley Patrick R. , Borrebach Jeffrey D. , Arya Shipra , Massarweh Nader N. , Bilderback Andrew L. , Wisniewski Mary Kay , Nelson Joel B. , Johnson Jonas T. , Johanning Jason M. , Hall Daniel E.
Published: March 2020

Objective:

The goal of this project was to first address barriers to implementation of the Risk Analysis Index (RAI) within a large, multi-hospital, integrated healthcare delivery system, and to subsequently demonstrate its utility for identifying at-risk surgical patients.

Background:

Prior studies demonstrate the validity of the RAI for evaluating preoperative frailty, but they have not demonstrated the feasibility of its implementation within routine clinical practice.

Methods:

Implementation of the RAI as a frailty screening instrument began as a quality improvement initiative at the University of Pittsburgh Medical Center in July 2016. RAI scores were collected within a REDCap survey instrument integrated into the outpatient electronic health record and then linked to information from additional clinical datasets. NSQIP-eligible procedures were queried within 90 days following the RAI, and the association between RAI and postoperative mortality was evaluated using logistic regression and Cox proportional hazards models. Secondary outcomes such as inpatient length of stay and readmissions were also assessed.

Results:

RAI assessments were completed on 36,261 unique patients presenting to surgical clinics across five hospitals from July 1 to December 31, 2016, and 8,172 of these underwent NSQIP-eligible surgical procedures. The mean RAI score was 23.6 (SD 11.2), the overall 30-day and 180-day mortality after surgery was 0.7% and 2.6%, respectively, and the median time required to collect the RAI was 33 [IQR 23–53] seconds. Overall clinic compliance with the recommendation for RAI assessment increased from 58% in the first month of the study period to 84% in the sixth and final month. RAI score was significantly associated with risk of death (HR=1.099 [95% C.I.: 1.091 – 1.106], p < 0.001). At an RAI cutoff of ≥37, the positive predictive values for 30- and 90-day readmission were 14.8% and 26.2%, respectively, and negative predictive values were 91.6% and 86.4%, respectively.

Conclusions:

The RAI frailty screening tool can be efficiently implemented within multi-specialty, multi-hospital healthcare systems. In the context of our findings and given the value of the RAI in predicting adverse postoperative outcomes, health systems should consider implementing frailty screening within surgical clinics.
Evaluation of sepsis using compensatory reserve measurement: A prospective clinical trial
Authors: Benov Avi , Brand Anat , Rozenblat Tal , Antebi Ben , Ben-Ari Anat , Amir-Keret Rotem , Nadler Roy , Chen Jacob , Chung Kevin K. , Convertino Victor A. , Paran Haim
Published: March 2020

BACKGROUND

Sepsis, a leading cause of morbidity and mortality worldwide, characterized by metabolic and hemodynamic changes that can lead to multiorgan failure and death. The evaluation of a patient's condition is routinely performed by several objective criteria. The compensatory reserve measurement (CRM) represents a new paradigm that measures the total of all physiological compensatory mechanisms, using noninvasive photoplethysmography to read changes in arterial waveforms. The present study's aim was to evaluate the applicability and the predictive value of the CRM during sepsis.

METHODS

Data were prospectively collected from patients hospitalized in the department of surgery because of different inflammatory illnesses. All subjects were evaluated with hemodynamic, laboratory measurements and CRM throughout hospitalization.

RESULTS

Of 100 subjects enrolled, 84 patients were not septic. The remaining 16 patients were in sepsis (Sequential Organ Failure Assessment [SOFA] score, >2), 6 of whom were in septic shock and 4 died. When nonseptic patients were compared with septic patients, statistical differences were found in C-reactive protein level (p < 0.0005), SOFA score (p < 0.0005), and CRM (p < 0.0001). Other parameters did not show any difference between groups. The area under the receiver operating characteristic curve for CRM was 1, significantly higher than the area under the receiver operating characteristic for heart rate (0.78), systolic blood pressure (0.67), quick SOFA (0.81), and respiratory rate (0.56).

CONCLUSION

Clinical criteria, imaging, and laboratory features used to identify a septic patient are suboptimal. This demonstrates the need for a monitoring device capable of detecting rapidly, constantly, and simply the sum condition of the ill patient. We have shown that CRM was able to distinguish between severe septic and nonseptic patients early in the course of hospitalization and was significantly more sensitive than the conventional diagnostic tools. Such capability to assess the septic patients or even to triage these patients will surely aid treatment of sepsis.

LEVEL OF EVIDENCE

Care management, level II.
Combat medic testing of a novel monitoring capability for early detection of hemorrhage
Authors: Koons Natalie J. , Owens Gregory A. , Parsons Donald L. , Schauer Steven G. , Buller Jerome L. , Convertino Victor A.
Published: March 2020

BACKGROUND

Current out-of-hospital protocols to determine hemorrhagic shock in civilian trauma systems rely on standard vital signs with military guidelines relying on heart rate and strength of the radial pulse on palpation, all of which have proven to provide little forewarning for the need to implement early intervention prior to decompensation. We tested the hypothesis that addition of a real-time decision-assist machine-learning algorithm, the compensatory reserve measurement (CRM), used by combat medics could shorten the time required to identify the need for intervention in an unstable patient during a hemorrhage profile as compared with vital signs alone.

METHODS

We randomized combat medics from the Army Medical Department Center and School Health Readiness Center of Excellence into three groups: group 1 viewed a display of no simulated hemorrhage and unchanging vital signs as a control (n = 24), group 2 viewed a display of simulated hemorrhage and changing vital signs alone (hemorrhage; n = 31), and group 3 viewed a display of changing vital signs with the addition of the CRM (hemorrhage + CRM; n = 22). Participants were asked to push a computer key when they believed the patient was becoming unstable and needed medical intervention.

RESULTS

The average time of 11.0 minutes (95% confidence interval, 8.7–13.3 minutes) required by the hemorrhage + CRM group to identify an unstable patient (i.e., stop the video sequence) was less by more than 40% (p < 0.01) compared with 18.9 minutes (95% confidence interval, 17.2–20.5 minutes) in the hemorrhage group.

CONCLUSION

The use of a machine-learning monitoring technology designed to measure the capacity to compensate for central blood volume loss resulted in reduced time required by combat medics to identify impending hemodynamic instability.

LEVEL OF EVIDENCE

Diagnostic, level IV.
Monitoring Electroconvulsive Therapy–Related Anxiety
Authors: Obbels Jasmien , Vanbrabant Koen , Verwijk Esmée , Bouckaert Filip , Vansteelandt Kristof , Sienaert Pascal
Published: March 2020

Objectives

A reliable questionnaire designed to measure electroconvulsive therapy (ECT)–related anxiety is currently not available. We report the development and evaluation of the ECT-Related Anxiety Questionnaire (ERAQ), a questionnaire that measures anxiety with respect to ECT in clinical practice.

Methods

Patients 18 years or older who were about to start with or were having an ECT course were asked to complete a self-designed 17-item ECT-related anxiety questionnaire. We investigated the psychometric properties of the ERAQ through the use of an exploratory and confirmatory factor analysis and Item Response Theory analysis.

Results

One hundred eighty-three patients were included. From the exploratory factor analysis, we conclude that the scale is unidimensional. The confirmatory factor analysis model did not fit well to the data. The Item Response Theory analysis showed that the slope estimates ranged from 1.23 to 2.95 and that location parameters reflected a sizable underlying anxiety for ECT.

Conclusions

The ERAQ is a questionnaire that assesses ECT-related anxiety. It offers a measure of global severity and differentiates between various topics of anxiety. The ERAQ thus informs the clinician about the specific aspects of an ECT course that could trigger a patient's anxiety and can guide clinicians in how to discuss ECT-related anxieties with patients.
Spectrally efficient optical orthogonal frequency division multiplexing
Authors: Lowery Arthur James
Published: March 2020

This paper charts the development of spectrally efficient forms of optical orthogonal frequency division multiplexing (OFDM) that are suited for intensity-modulated direct detection systems, such as wireless optical communications. The journey begins with systems using a DC-bias to ensure that no parts of the signal that modulates the optical source are negative in value, as negative optical intensity is unphysical. As the DC-part of the optical signal carries no information, it is wasteful in energy; thus asymmetrically clipped optical OFDM was developed, removing any negative-going peaks below the mean. Unfortunately, the clipping causes second-order distortion and intermodulation, so some subcarriers appear to be unusable, halving spectral efficiency; this is similar for unipolar and flipped optical OFDM. Thus, a considerable effort has been made to regain spectral efficiency, using layered techniques where the clipping distortion is mostly cancelled at the receiver, from a knowledge of one unpolluted layer, enabling one or more extra ‘layers/paths/depths’ to be received on the previously unusable subcarriers. Importantly, for a given optical power and high-order modulation, layered methods offer the best spectral efficiencies and need the lowest signal-to-noise ratios, especially if diversity combining is used. Thus, they could be important for high-bandwidth optical fibre systems. Efficient methods of generating all layers simultaneously, using fast Fourier transforms with their partial calculations extracted, are discussed, as are experimental demonstrations in both wireless and short-haul communications links. A musical analogy is also provided, which may point to how orchestral and rock music is deciphered in the brain.

This article is part of the theme issue ‘Optical wireless communication’.
Interference in multi-user optical wireless communications systems
Authors: Abdalla Iman , Rahaim Michael B. , Little Thomas D. C.
Published: March 2020

Visible light communications (VLC) (including LiFi) represent a subset of the broader field of optical wireless communications. Where narrow beams, typical of free space optical communications are largely free from interference. VLC encompasses use cases involving combined illumination and data access and supporting a wireless access point (AP) model. The use of many units provides scaling of spatial coverage for both lighting and data access. However, AP replication in close proximity creates many interference challenges that motivate the investigation embodied in this paper. In particular, we frame the interference challenge in the context of existing strategies for driving improvements in link performance and consider the impacts of multiple users, multiple sources and multiple cells. Lastly, we review the state of existing research in this area and recommend areas for further study.

This article is part of the theme issue ‘Optical wireless communication’.
Optical wireless communication
Authors: Haas Harald , Elmirghani Jaafar , White Ian
Published: March 2020

Optical wireless communication has attracted significant interest recently in industry and academia. This special issue features a collection of inter-related papers with the intention to cover all necessary multidisciplinary challenges to realize optical wireless networks. We hope that this special issue will serve as a comprehensive reference and that it will be a resource which fosters many more new ideas for this rapidly emerging field.

This article is part of the theme issue ‘Optical wireless communication’.
Roseovarius arcticus sp. nov., a bacterium isolated from Arctic marine sediment
Authors: Lu Lu , Zhang Yumin , Peng Xiaoya , Liu Jia , Qin Kun , Peng Fang
Published: March 2020

An aerobic, Gram-stain-negative, motile, rod or long-rod-shaped bacterial isolate, strain MK6-18T, was isolated from a marine sediment sample from Kongsfjorden, Arctic. The bacterium grew optimally at 20 °C, pH 7.0 and in the presence of 1.0–2.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MK6-18T belonged to the genus

Roseovarius

. Its closest phylogenetic neighbour was

Roseovarius nanhaiticus

NH52JT showing 96.97 % 16S rRNA gene sequence similarity. The genome of strain MK6-18T is 4.2 Mb long in size with a G+C content of 59.5 mol%. The average nucleotide identity value between the genomes of strain MK6-18T and

Roseovarius nanhaiticus

NH52JT, was 78.0 %. Similar to other species of the genus

Roseovarius

, strain MK6-18T had ubiquinone 10 as the predominant ubiquinone and C12 : 0, C16 : 0, summed feature 3 (C16 : 1ω7c/ω6c) and summed feature 8 (C18 : 1ω7c/ω6c) as the major fatty acids. The polar lipid pattern consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine; one unidentified polar lipid, one unidentified aminolipid and one unidentified lipid were also detected. This is the first time that a member of the genus

Roseovarius

has been isolated from the Arctic, which may promote the study of the distribution characteristics and environmental adaptability of this genus. On the basis of the data provided here, strain MK6-18T should be classed as representing a novel species of the genus

Roseovarius

, for which the name Roseovarius arcticus sp. nov. is proposed. The type strain is MK6-18T (=CCTCC AB 2018219T=KCTC 72187T).
Trends in Helicobacter pylori resistance to clarithromycin: from phenotypic to genomic approaches
Authors: Marques Andreia T. , Vítor Jorge M. B. , Santos Andrea , Oleastro Mónica , Vale Filipa F.
Published: March 2020

For a long time

Helicobacter pylori

infections have been treated using the macrolide antibiotic, clarithromycin. Clarithromycin resistance is increasing worldwide and is the most common cause of

H. pylori

treatment failure. Here we review the mechanisms of antibiotic resistance to clarithromycin, detailing the individual and combinations of point mutations found in the 23S rRNA gene associated with resistance. Additionally, we consider the methods used to detect clarithromycin resistance, emphasizing the use of high-throughput next-generation sequencing methods, which were applied to 17 newly sequenced pairs of

H. pylori

strains isolated from the antrum and corpus of a recent colonized paediatric population. This set of isolates was composed of six pairs of resistant strains whose phenotype was associated with two point mutations found in the 23S rRNA gene: A2142C and A2143G. Other point mutations were found simultaneously in the same gene, but, according to our results, it is unlikely that they contribute to resistance. Further, among susceptible isolates, genomic variations compatible with mutations previously associated with clarithromycin resistance were detected. Exposure to clarithromycin may select low-frequency variants, resulting in a progressive increase in the resistance rate due to selection pressure.
Using genomics to understand inter- and intra- outbreak diversity of Pasteurella multocida isolates associated with fowl cholera in meat chickens
Authors: Omaleki Lida , Blackall Patrick J. , Cuddihy Thom , Beatson Scott A. , Forde Brian M. , Turni Conny
Published: March 2020

Fowl cholera, caused by Pasteurella multocida, continues to be a challenge in meat-chicken-breeder operations and has emerged as a problem for free-range meat chickens. Here, using whole-genome sequencing (WGS) and phylogenomic analysis, we investigate isolate relatedness during outbreaks of fowl cholera on a free-range meat chicken farm over a 5-year period. Our genomic analysis revealed that while all outbreak isolates were sequence type (ST) 20, they could be separated into two distinct clades (clade 1 and clade 2) consistent with difference in their lipopolysaccharide (LPS) type. The isolates from the earlier outbreaks (clade 1) were carrying LPS type L3 while those from the more recent outbreaks (clade 2) were LPS type L1. Additionally, WGS data indicated high inter- and intra-chicken genetic diversity during a single outbreak. Furthermore, we demonstrate that while a killed autogenous vaccine carrying LPS type L3 had been successful in protecting against challenge from L3 isolates it might have driven the emergence of the closely related clade 2, against which the vaccine was ineffective. The genomic results also revealed a 14 bp deletion in the galactosyltransferase gene gatG in LPS type L3 isolates, which would result in producing a semi-truncated LPS in those isolates. In conclusion, our study clearly demonstrates the advantages of genomic analysis over the conventional PCR-based approaches in providing clear insights in terms of linkage of isolate within and between outbreaks. More importantly, it provides more detailed information than the multiplex PCR on the possible structure of outer LPS, which is very important in the case of strain selection for killed autogenous vaccines.
Transient enhanced cell division by blocking DNA synthesis in Escherichia coli
Authors: Martín Carmen Mata , Zaritsky Arieh , Fishov Itzhak , Guzmán Elena C.
Published: March 2020

Duplication of the bacterial nucleoid is necessary for cell division hence specific arrest of DNA replication inhibits divisions culminating in filamentation, nucleoid dispersion and appearance of a-nucleated cells. It is demonstrated here that during the first 10 min however,

Escherichia coli

enhanced residual divisions: the proportion of constricted cells doubled (to 40%), nucleoids contracted and cells remodelled dimensions: length decreased and width increased. The preliminary data provides further support to the existence of temporal and spatial couplings between the nucleoid/replisome and the sacculus/divisome, and is consistent with the idea that bacillary bacteria modulate width during the division process exclusively.
ZIKA VIRUS VERTICAL TRANSMISSION IN CHILDREN WITH CONFIRMED ANTENATAL EXPOSURE
Authors: Brasil Patrícia , Vasconcelos Zilton , Kerin Tara , Gabaglia Claudia Raja , Ribeiro Ieda P. , Bonaldo Myrna C. , Damasceno Luana , Pone Marcos V. , Pone Sheila , Zin Andrea , Tsui Irena , Adachi Kristina , Pereira Jose Paulo , Gaw Stephanie L. , Carvalho Liege , Cunha Denise C. , Guida Leticia , Rocha Mirza , Cherry James D. , Wang Lulan , Aliyari Saba , Cheng Genhong , Foo Suan-Sin , Chen Weiqiang , Jung Jae , Brickley Elizabeth , Moreira Maria Elisabeth L. , Nielsen-Saines Karin
Published: March 2020

Background

In utero transmission of Zika virus (ZIKV) can lead to adverse infant outcomes, but vertical transmission rates are unknown.

Methods

Antenatally ZIKV-exposed children were followed prospectively since the time of the Rio de Janeiro epidemic in 2015-16. Serum and urine specimens were collected from infants from birth throughout the first year of life. Specimens were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM antibody capture Zika MAC-ELISA. Infants had neurodevelopmental evaluations, brain imaging, eye examinations, and hearing assessments.

Results

Over time 130 in utero ZIKV-exposed (mothers PCR+) children were tested with 407 specimens evaluated: 161 sera were tested by PCR and IgM assays, 85 urines by PCR; 84 children (65%) were positive in at least one assay. Among 94 children tested within 3 months of age, 70% were positive (39% serum PCR, 48% urine PCR, 39% IgM). After 3 months, 33% were positive by any laboratory method. Five children were intermittently PCR+ beyond 200 days of life. Concordance between IgM and PCR results was 52%, sensitivity 65%, specificity 40% (with any positive PCR result as the gold standard); IgM and serum PCR were 61% concordant; serum and urine PCR 55%. Most children (65%) were clinically normal. Positive results were seen in 29 of 45 children (64%) with abnormal findings and 55 of 85 normal children (65%), p=0·98. Earlier maternal trimester of infection was associated with positive infant laboratory results but not infant clinical disease (p=0·04).

Conclusions

ZIKV has a high in utero transmission rate. Laboratory confirmed infection is not necessarily associated with abnormal infant findings.
Analysis on the Clinical Characteristics of 36 Cases of Novel Coronavirus Pneumonia in Kunming
Authors: Fu Haiyan , Li Hongjuan , Tang Xiaoqing , Li Xiang , Shen Jie , Zhou Yujun , Xu Bing , Luo Yu
Published: March 2020

Objective

To analyze the clinical characteristics of patients with novel coronavirus pneumonia in Kunming City, and to study the correlation between nutritional status and immune function.

Methods

Clinical data of 36 patients with novel coronavirus pneumonia in isolation area of Kunming Third People’s Hospital from January 31 to February 15, 2020 were collected, and the basic situation, clinical characteristics, laboratory examination and CT imaging characteristics were analyzed. Serum albumin (ALB), prealbumin (PAB), hypersensitive c-reactive protein (hs-crp), CD3T cells, CD4T cells, CD8T cells and normal control group were analyzed. A simple linear regression analysis of the relationship between proalbumin and T cell subpopulation counts in the blood of patients.

Results

(1) The patients with new coronavirus pneumonia in Kunming were mainly of common type. (2) 50% of the patients’ first symptoms were fever and cough; (3) The total number of white blood cells in peripheral blood was normal or decreased in 23 cases (79%), and the lymphocyte count decreased in 5 cases (13.89%), without anemia. Hypersensitive c-reactive protein increased in 19 (52.78%) cases, and procalcitonin increased in 1 case. Albumin decreased in 5 cases (13.89%), proalbumin decreased in 15 cases (41.67%), alanine transaminase increased slightly in 4 cases (11.11%), alanine transaminase increased slightly in 4 cases (11.11%), total bilirubin increased slightly in 11 cases (30.56%), and renal function and blood coagulation were normal. Absolute value of CD3+T cells is with a decrease in 21 cases (58.3%), CD4+T in 28 cases (77.8%), CD8+T in 17 cases (47.2%), and CD4+/ CD8+ inverse in 6 cases (16.7%). (4) The prealbumin, CD3 T cells, CD4 T cells and CD8 T cells in the new coronavirus pneumonia group were significantly lower than those in the normal control group, and the hypersensitive c-reactive protein was higher than that in the normal control group. (5) The levels of PAB in the serum of the patients were linearly correlated with hs-crp, CD3 T cells, CD4 T cells and CD8 T cells, and the correlation coefficients were −0.474, 0.558, 0.467 and 0.613, respectively, showing statistical differences.

Conclusion

The clinical characteristics of the novel coronavirus pneumonia in Kunming are different from those in Wuhan. The changes of serum proalbumin and T cell subsets are relatively obvious. Changes in serum proalbumin may contribute to the early warning of novel coronavirus pneumonia. The nutritional status of patients with common and mild pneumonia should be considered.
Genomic architecture and evolutionary conflict drive allele-specific expression in the social supergene of the red fire ant
Authors: Martinez-Ruiz Carlos , Pracana Rodrigo , Stolle Eckart , Paris Carolina I. , Nichols Richard A. , Wurm Yannick
Published: March 2020

Supergenes are genomic regions of suppressed recombination that underlie complex polymorphisms. Despite the importance of such regions, our empirical understanding of their early evolution is limited. The young “social” supergene of the fire ant Solenopsis invicta provides a powerful system for disentangling the roles of evolutionary conflict and the implications of suppressed recombination.

We used population genomics to identify genetic differences between supergene variants and gene expression analyses across different populations, castes and body parts to characterize allelic expression differences for the hundreds of genes in the supergene.

We find that the expression of most genes is independent of social form or supergene variant, in line with the young age of this system. Many of the genes with allelic expression differences, however, show a pattern consistent with gene degeneration due to suppressed recombination. In contrast, a small portion of the genes has the signature of evolutionary conflict between social forms.
Efficient rational modification of non-ribosomal peptides by adenylation domain substitution
Authors: Calcott Mark J. , Owen Jeremy G. , Ackerley David F.
Published: March 2020

Non-ribosomal peptide synthetase (NRPS) enzymes form modular assembly-lines, wherein each module typically governs the incorporation of a specific amino acid or related monomer into a short peptide product. Modules are comprised of one or more key domains, including adenylation (A) domains, which recognise and activate the monomer substrate; condensation (C) domains, which catalyse amide bond formation; and thiolation (T) domains, which shuttle reaction intermediates between catalytic domains.1This arrangement offers prospects for rational peptide modification via substitution of substrate-specifying domains within an assembly line.2,3For over 20 years, it has been considered that both A domains and C domains play key roles in selecting and “proof-reading” the substrate;4a presumption that has greatly complicated rational NRPS redesign.2,5Here we present evidence derived both from natural and directed evolution studies that C domains do not play a substrate-specifying role, and that novel non-ribosomal peptides can be generated by substitution of A domains alone. We identify permissive A domain recombination boundaries and show that these allow us to efficiently generate novel pyoverdine peptides at high yields. We further demonstrate the transferability of our approach in the PheATE-ProCAT model system originally used to infer C domain substrate specificity, generating novel dipeptide products at yields that should not be attainable according to existing dogma.
ConsHMM Atlas: conservation state annotations for major genomes and human genetic variation
Authors: Arneson Adriana , Felsheim Brooke , Chien Jennifer , Ernst Jason
Published: March 2020

ConsHMM is a method recently introduced to annotate genomes into conservation states, which are defined based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multi-species DNA sequence alignment. Previously, ConsHMM was only applied to a single genome for one multi-species sequence alignment. Here we apply ConsHMM to produce 22 additional genome annotations covering human and seven other organisms for a variety of multi-species alignments. Additionally, we have extended ConsHMM to generate allele specific annotations, which we used to produce conservation state annotations for every possible single nucleotide mutation in the human genome. Finally, we provide a web interface to interactively visualize parameters and annotation enrichments for ConsHMM models. These annotations and visualizations comprise the ConsHMM Atlas, which we expect will be a valuable resource for analyzing a variety of major genomes and genetic variation.
Kallikrein 13: a new player in coronaviral infections
Authors: Milewska Aleksandra , Falkowski Katherine , Kalinska Magdalena , Bielecka Ewa , Naskalska Antonina , Mak Pawel , Lesner Adam , Ochman Marek , Urlik Maciej , Potempa Jan , Kantyka Tomasz , Pyrc Krzysztof
Published: March 2020

Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, butin vitromodel for virus replication is lacking. Interaction between the coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host specificity, but virus entry is a complex process requiring a concerted action of multiple cellular elements. Here, we show that KLK13 is required for the infection of the human respiratory epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that protease distribution and specificity predetermines the tissue and cell specificity of the virus and may also regulate interspecies transmission. It is also of importance that presented data may be relevant for the emerging coronaviruses, including SARS-CoV-2 and may help to understand the differences in their zoonotic potential.
Standard Immunization of Mice, Rats, and Hamsters
Authors: Greenfield Edward A.
Published: March 2020

Mice, rats, or hamsters are immunized by giving biweekly injections of a purified antigen, cultured cells, or cDNA. For mice, if a pure, soluble protein antigen is being used and is abundant, a dose of 50–100 µg in adjuvant at each immunization is a sensible general recommendation; for rats and hamsters, a dose of 100–200 µg is sufficient. Lower doses can be used for antigens with higher immunogenicity. Adjuvants (Freund's, Ribi, Hunter's TiterMax, ImmunEasy, or Alum) should be mixed with the immunizing antigen for the first two immunizations only; Complete Freund's adjuvant is only used with the first immunization. Subsequent immunizations are performed in phosphate-buffered saline (PBS) or normal saline, with or without Incomplete Freund's adjuvant. The choice of adjuvant is dependent on the subclass of immunoglobulin required. Over the course of the 6-wk immunization schedule, each animal usually receives a total of six injections (three subcutaneous and three intraperitoneal). Once a good titer has developed against the antigen of interest, regular boosts and bleeds are performed to collect the maximum amount of serum. For rats and hamsters, boosts should be spaced every 2–3 wk, and serum samples of 400–500 µL should be collected 10–12 d after each boost. For mice, boosts should be spaced every 2–3 wk, and serum samples of 200–300 µL should be collected 10–12 d after each boost.
Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization
Authors: Mitropoulou Alkistis N. , Ceska Tom , Heads James T. , Beavil Andrew J. , Henry Alistair J. , McDonnell James M. , Sutton Brian J. , Davies Anna M.
Published: March 2020

Immunoglobulin E (IgE) plays a central role in the allergic response, in which cross-linking of allergen by Fc∊RI-bound IgE triggers mast cell and basophil degranulation and the release of inflammatory mediators. The high-affinity interaction between IgE and Fc∊RI is a long-standing target for therapeutic intervention in allergic disease. Omalizumab is a clinically approved anti-IgE monoclonal antibody that binds to free IgE, also with high affinity, preventing its interaction with Fc∊RI. All attempts to crystallize the pre-formed complex between the omalizumab Fab and the Fc region of IgE (IgE-Fc), to understand the structural basis for its mechanism of action, surprisingly failed. Instead, the Fab alone selectively crystallized in different crystal forms, but their structures revealed intermolecular Fab/Fab interactions that were clearly strong enough to disrupt the Fab/IgE-Fc complexes. Some of these interactions were common to other Fab crystal structures. Mutations were therefore designed to disrupt two recurring packing interactions observed in the omalizumab Fab crystal structures without interfering with the ability of the omalizumab Fab to recognize IgE-Fc; this led to the successful crystallization and subsequent structure determination of the Fab/IgE-Fc complex. The mutagenesis strategy adopted to achieve this result is applicable to other intractable Fab/antigen complexes or systems in which Fabs are used as crystallization chaperones.
Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions
Authors: Tanaka Miki , Hayakawa Kaori , Ogawa Nozomi , Kurokawa Tatsuki , Kitanishi Kenichi , Ite Kenji , Matsui Toshitaka , Mori Yasuo , Unno Masaki
Published: March 2020

TRPV1, a member of the transient receptor potential (TRP) channels family, has been found to be involved in redox sensing. The crystal structure of the human TRPV1 ankyrin-repeat domain (TRPV1-ARD) was determined at 4.5 Å resolution under nonreducing conditions. This is the first report of the crystal structure of a ligand-free form of TRPV1-ARD and in particular of the human homologue. The structure showed a unique conformation in finger loop 3 near Cys258, which is most likely to be involved in inter-subunit disulfide-bond formation. Also, in human TRPV1-ARD it was possible for solvent to access Cys258. This structural feature might be related to the high sensitivity of human TRPV1 to oxidants. ESI-MS revealed that Cys258 did not form an S–OH functionality even under nonreducing conditions.
Bridging the gap between corporate social responsibility performance and tax aggressiveness
Authors: Ortas Eduardo , Gallego-Álvarez Isabel
Published: March 2020

Purpose

This paper addresses the role of corporate social responsibility (CSR) performance as a potential mechanism for reducing firms' likelihood of engaging in tax aggressiveness (TAG). The paper also contributes to the existing literature by addressing the moderating effect of national cultures on the link between CSR performance and corporate TAG.

Design/methodology/approach

The focus is placed on an unbalanced panel of 2,696 companies distributed in 30 countries and seven economic sectors over the period of 2002–2014.

Findings

The results provide support for those companies achieving high corporate social performance (CSP), corporate environmental performance (CEP) and corporate governance performance (CGP) being less likely to engage in aggressive tax practices. Finally, the results identify some national cultural dimensions moderating the link between disaggregated measures of CSR performance and firms' TAG.

Research limitations/implications

The difficulty of accessing CSR and TAG data for non-listed companies could bias the data set towards a compliant company profile because of the higher visibility. In addition, the use of effective tax rates to examine firms' TAG should be interpreted with some caution.

Practical implications

The paper's findings provide unique and useful information for company stakeholders and managers aiming to address the factors that enhance firms' incentives to engage in aggressive tax practices.

Originality/value

This paper addresses the multidimensional nature of CSR performance by analysing the links between CSP, CEP and CGP and corporations' TAG. Furthermore, the research addresses the way in which national culture moderates the links between disaggregated measures of CSR performance and corporate TAG.
The impact of microfinance on Indonesian rural households' welfare
Authors: Santoso Danang Budi , Gan Christopher , Revindo Mohamad Dian , Massie Natanael Waraney Gerald
Published: March 2020

Purpose

This study investigates the welfare impact of microfinance on rural households in Indonesia. Its finding will bridge the gap in the Indonesian microfinance literature.

Design/methodology/approach

The research was conducted by collecting primary data and administering a structured questionnaire to rural households in Bantul District, Yogyakarta Province, Indonesia. We employed the logistic model to measure welfare impacts of microcredit borrowers.

Findings

The research finds that purpose of loan, monthly income, monthly expenditure, interest rates, loan amount, education and marital status have significant effects on the probability of increasing borrowers' welfare after accessing microcredit.

Practical implications

This study will propose some policy recommendations for Indonesian policymakers that may yield better strategies to help improve the impact of their microcredit programmes on the welfare of rural households.

Originality/value

The authors confirm that the article has not been submitted to peer review, nor is in the process of peer reviewing and nor has been accepted for publishing in another journal. The author(s) confirms that the research in their work is original, and that all the data given in the article are real and authentic.
Prevalence of antibiotic-resistantSalmonellain retail organic chicken
Authors: Guran Husnu Sahan , Ciftci Resat , Gursoy Nafia Canan , Ozekinci Tuncer , Alali Walid Q.
Published: March 2020

Purpose

The objective of this study was to determineSalmonellaprevalence, antimicrobial-resistant phenotypes, and their genetic relatedness in frozen organic chicken collected at retail level in Turkey.

Design/methodology/approach

Retail packs (n = 348) of cut-up chicken parts (breast, leg quarter and drumstick) and whole chicken carcasses were purchased from a central hypermarket in Diyarbakir (Southeast Anatolia Region in Turkey) and from a large online retailer in Turkey. The retail packs were paired by part type, brand, production date, and sell-by date. The chicken samples were analyzed for the presence ofSalmonellaspp., and then isolates were screened for antibiotic susceptibility, class I integron, and genetic similarity.

Findings

Salmonellaprevalence in retail frozen organic chicken samples was 6.3 percent; however, the prevalence by parts, leg quarter, drumstick, breast, and whole chicken was 2.1 percent, 10.4 percent, 10.4 percent, and 0 percent, respectively.Salmonellaprevalence was significantly higher in samples obtained from the hypermarket (9.2 percent) compared to online retailer (3.8 percent). All the isolates were serotype Infantis, genetically similar (highly clonal), and 68.2 percent harbored class I integron. All isolates were resistant to ciprofloxacin (drug of choice to treat salmonellosis in human), and 86.3 percent of the isolates were multidrug-resistant.

Originality/value

Salmonellaprevalence in organic chicken meat, regardless of the retail market source in Turkey, may pose a health risk to consumers especially with the high prevalence of multi-drug resistant phenotypes. Findings inform researchers and the public about the safety of organically produced chicken and the potential health risk to consumers.