bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019
Authors: Nickbakhsh Sema , Ho Antonia , Marques Diogo F P , McMenamin Jim , Gunson Rory N , Murcia Pablo R
Published: April 2020

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.
Keyboard-Based Protocol for Typing Algebraic Expressions
Authors: Fajardo-Flores Silvia , Pulido J R G , Andrade-Aréchiga María
Published: April 2020

Writing mathematical contents on digital format is more common every day. The usual method is to use WYSIWYG (What You See Is What You Get) equation editors included in mainstream text editors. However, this method requires a good deal of interaction with formula templates and the use of a pointing device. While this type of equation editors is accessible to users without visual disabilities, they present barriers for users with visual disability (UWVDs). Keyboard-based equation editors should promote not only inclusion but also an acceptable performance for sighted and non-sighted users. In this article, we analyze the efficiency of the typing protocol of the Algebra Editor, an accessible keyboard-based equation editor prototype, with sighted users. Results suggest that the protocol allows typing approximately 60 characters per minute. We also analyze the type and frequency of errors made by participants and suggest improvements to the protocol, derived from the findings. These results can be used as a reference to compare the efficiency of the protocol with non-sighted users and with other equation editors in future studies.
Ethyl Formate as a Methyl Bromide Alternative for Phytosanitary Disinfestation of Imported Banana in Korea With Logistical Considerations
Authors: Park Min-Goo , Park Chung-Gyoo , Yang Jeong-Oh , Kim Gil-Hah , Ren Yonglin , Lee Byung-Ho , Cha Dong H
Published: April 2020

Methyl bromide (MB) use for quarantine and phytosanitary purposes is being phased out. Several effective MB alternatives have been identified depending on the target system. Industry commitment for the shift to new technologies will depend not only on the efficacy of alternatives but also on their compatibility and integrability into existing operations. We compared the efficacy of MB and ethyl formate (EF) for disinfestation of Planococcus citri (Risso) (Hemiptera: Pseudococcidae) as a representative surface pest on banana and evaluated whether EF fumigation is compatible with the current packaging materials and loading ratio used by the South Korean banana import industry. Fumigation trials with P. citri adults and eggs showed that EF was at least as effective as MB at the EF and MB concentrations recommended under the current phytosanitary disinfestation guidelines. From a logistical standpoint, EF gas could not effectively penetrate plastic bagging typically used in banana cartons during commercial shipping. Also, EF sorption to bananas and packing materials (used as cushioning inside bagging) further lowered realized EF concentrations around bananas. These reductions in EF concentration translated into reduced mortality of P. citri eggs, indicating that despite similar efficacy of MB and EF for controlling P. citri, further consideration and optimization of other industry logistics such as packaging and loading ratio is necessary to enhance the adoption of this MB alternative.
Validation of the Health-Related Felt Stigma and Concealment Questionnaire
Authors: Laird Kelsey T , Smith Craig A , Hollon Steven D , Walker Lynn S
Published: April 2020

Objective

Stigma is associated with many health conditions, including chronic pain. Research on health-related stigma is limited by the lack of validated instruments that distinguish among various stigma-related constructs. We aimed to develop and validate such a measure for pediatric functional abdominal pain (FAP). Felt stigma (FS) was defined as comprising both perceived and internalized stigma. Stigma concealment (SC) was defined as efforts by stigmatized individuals to prevent others from learning of their condition.

Methods

Using a theory-driven approach, we adapted items from existing self-report measures of stigma to construct the health-related FS and Concealment Questionnaire (FSC-Q). Patients with FAP (N = 179, ages 11–17) completed the preliminary FSC-Q and health-related measures hypothesized to be associated with stigma. Cognitive interviewing and exploratory factor analysis (EFA) informed the final version of the measure.

Results

EFA identified a 2-factor model comprised of FS and SC. The FS and SC scales exhibited good internal consistency and construct validity. Consistent with study hypotheses, both factors were significantly associated with anxiety, depression, pain catastrophizing, pain threat, physical symptoms, and pain interference/disability. Higher FS was associated with higher mental healthcare utilization. The subset of participants meeting criteria for irritable bowel syndrome (IBS) reported higher FS and SC compared with those without IBS.

Conclusion

The FSC-Q may help advance research on health-related stigma in FAP and other chronic health conditions by allowing for assessment of distinct stigma-related constructs.
Update onCandida krusei, a potential multidrug-resistant pathogen
Authors: Jamiu A T , Albertyn J , Sebolai O M , Pohl C H
Published: April 2020

Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.
Multiphase outflows in post-starburst E+A galaxies - II. A direct connection between the neutral and ionized outflow phases
Authors: Baron Dalya , Netzer Hagai , Davies Ric I , Xavier Prochaska J
Published: April 2020

Post-starburst E+A galaxies are systems that hosted a powerful starburst that was quenched abruptly. Simulations suggest that these systems provide the missing link between major merger ULIRGs and red and dead ellipticals, where AGN feedback is responsible for the expulsion or destruction of the molecular gas. However, many details remain unresolved and little is known about AGN-driven winds in this short-lived phase. We present spatially resolved IFU spectroscopy with MUSE/VLT of SDSS J124754.95-033738.6, a post-starburst E+A galaxy with a recent starburst that started 70 Myr ago and ended 30 Myr ago, with a peak SFR of $\sim 150\, \mathrm{M_{\odot }\,yr^{ -1}}$. We detect disturbed gas throughout the entire field of view, suggesting triggering by a minor merger. We detect fast-moving multiphased gas clouds, embedded in a double-cone face-on outflow, which are traced by ionized emission lines and neutral NaID emission and absorption lines. We find remarkable similarities between the kinematics, spatial extents, and line luminosities of the ionized and neutral gas phases, and propose a model in which they are part of the same outflowing clouds, which are exposed to both stellar and AGN radiation. Our photoionization model provides consistent ionized line ratios, NaID absorption optical depths and EWs, and dust reddening. Using the model, we estimate, for the first time, the neutral-to-ionized gas mass ratio (about 20), the sodium neutral fraction, and the size of the outflowing clouds. This is one of the best ever observed direct connections between the neutral and ionized outflow phases in AGN.
A global view on the colliding-wind binary WR 147
Authors: Zhekov Svetozar A , Petrov Blagovest V , Tomov Toma V , Pessev Peter
Published: April 2020

We present results from a global view on the colliding-wind binary WR 147. We analysed new optical spectra of WR 147 obtained with the Gran Telescopio Canarias and archive spectra from the Hubble Space Telescope by making use of modern atmosphere models accounting for optically thin clumping. We adopted a grid-modelling approach to derive some basic physical characteristics of both stellar components in WR 147. For the currently accepted distance of 630 pc to WR 147, the values of mass-loss rate derived from modelling its optical spectra are in acceptable correspondence with that from modelling its X-ray emission. However, they give a lower radio flux than observed. A plausible solution for this problem could be the volume filling factor at large distances from the star (radio-formation region) being smaller than that close to the star (optical-formation region). Adopting this, the model can match well both optical and thermal radio emission from WR 147. The global view on the colliding-wind binary WR 147 thus shows that its observational properties in different spectral domains can be explained in a self-consistent physical picture.
A minimum reporting standard for multiple sequence alignments
Authors: Wong Thomas K F , Kalyaanamoorthy Subha , Meusemann Karen , Yeates David K , Misof Bernhard , Jermiin Lars S
Published: April 2020

Multiple sequence alignments (MSAs) play a pivotal role in studies of molecular sequence data, but nobody has developed a minimum reporting standard (MRS) to quantify the completeness of MSAs in terms of completely specified nucleotides or amino acids. We present an MRS that relies on four simple completeness metrics. The metrics are implemented in AliStat, a program developed to support the MRS. A survey of published MSAs illustrates the benefits and unprecedented transparency offered by the MRS.
A Primer on Human Brain Organoids for the Neurosurgeon
Authors: Blue Rachel , Miranda Stephen P , Gu Ben Jiahe , Chen H Isaac
Published: April 2020

Human brain organoids emerged in 2013 as a technology that, unlike prior in Vitro neural models, recapitulates brain development with a high degree of spatial and temporal fidelity. As the platform matured with more accurate reproduction of cerebral architecture, brain organoids became increasingly valuable for studying both normal cortical neurogenesis and a variety of congenital human brain disorders. While the majority of research utilizing human brain organoids has been in the realm of basic science, clinical applications are forthcoming. These present and future translational efforts have the potential to make a considerable impact on the field of neurosurgery. For example, glioma organoids are already being used to study tumor biology and drug responses, and adaptation for the investigation of other neurosurgery-relevant diseases is underway. Moreover, organoids are being explored as a structured neural substrate for repairing brain circuitry. Thus, we believe it is important for our field to be aware and have an accurate understanding of this emerging technology. In this review, we describe the key characteristics of human brain organoids, review their relevant translational applications, and discuss the ethical implications of their use through a neurosurgical lens.
Contralateral Interhemispheric Approach for Resection of A Meningioma: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: April 2020

The contralateral interhemispheric approach is utilized to provide the surgeon with a favorable trajectory for approaching lesions projecting contralaterally from the midline falcine dura. The contralateral approach also requires a less rigid retraction than other approaches, which is paramount when manipulating the eloquent cortex of the paracentral lobule. This patient had a large laterally projecting falcine meningioma. This case demonstrates well the effect that gravity has on the tumor, pulling the tumor medially into the surgeon's view and making the surgical approach ideal for this lesion. The lesion was removed en bloc with the falcine dura, and postoperative imaging demonstrated a gross total resection. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
From Written Record to Bureaucratic Mind: Imagining a Criminal Record*
Authors: McGlynn Margaret
Published: April 2020

In 1518 the chief justice of King’s Bench initiated an attempt to track successful claims of benefit of clergy on the assize circuits to ensure that laymen could make such claims only once, as mandated by a statute dating from 1490. By doing so he was the first to attempt to create a criminal record in England, where an individual felon’s crimes were recorded with the expectation that an earlier crime would have implications for the punishment of a subsequent one. Both this attempt and a later statutory attempt in 1543 were largely unsuccessful, however. They failed, not because of principled opposition or even inertia, but because the well-established bureaucratic structures of the early Tudor period struggled to keep up with the bureaucratic imagination of those who sought to reform or extend the reach of government. The failed attempt to construct a criminal record demonstrates that as the development of print changed information cultures, and the policies of the Tudors led to an intensification of governance, legal records remained profoundly limited by the intellectual and administrative structures within which they operated. Masters of the gathering of information, Tudor governors struggled to adapt old documents to new purposes or to manage information dynamically.
Interrater Reliability of Muscle Ultrasonography Image Acquisition by Physical Therapists in Patients Who Have or Who Survived Critical Illness
Authors: Mayer Kirby P , Dhar Sanjay , Cassity Evan , Denham Aaron , England Johnny , Morris Peter E , Dupont-Versteegden Esther E
Published: April 2020

Objective

Previous studies have demonstrated that muscle ultrasound (US) can be reliably performed at the patient bedside by novice assessors with minimal training. The primary objective of this study was to determine the interrater reliability of muscle US image acquisition by physical therapists and physical therapist students. Secondarily, this study was designed to elucidate the process for training physical therapists to perform peripheral skeletal muscle US.

Methods

This was a cross-sectional observational study. Four novices and 1 expert participated in the study. Novice sonographers engaged in a structured training program prior to implementation. US images were obtained on the biceps brachii, quadriceps femoris, and tibialis anterior muscles in 3 groups: patients in the intensive care unit, patients on the hospital ward, and participants in the outpatient gym who were healthy. Reliability of image acquisition was analyzed compared with the expert sonographer.

Results

Intraclass correlation coefficient values ranged from 0.76 to 0.97 with an average for all raters and all muscles of 0.903, indicating excellent reliability of image acquisition. In general, the experienced physical therapist had higher or similar intraclass correlation coefficient values compared with the physical therapist students in relation to the expert sonographer.

Conclusions

Excellent interrater reliability for US was observed regardless of the level of experience, severity of patient illness, or patient setting. These findings indicate that the use of muscle US by physical therapists can accurately capture reliable images in patients with a range of illness severity and different clinical practice settings across the continuum of care.

Impact

Physical therapists can utilize US to obtain images to assess muscle morphology.

Lay Summary

Physical therapists can use noninvasive US as an imaging tool to assess the size and quality of peripheral skeletal muscle. This study demonstrates that physical therapists can receive training to reliably obtain muscle images in patients admitted to the intensive care unit who may be at risk for muscle wasting and may benefit from early rehabilitation.
Unclear Signals, Uncertain Prospects: The Labor Market Consequences of Freelancing in the New Economy
Authors: Mai Quan D
Published: April 2020

The advent of various types of contingent jobs complicates selection criteria for full-time employment. While previous studies analyzed the penalties associated with other forms of contingent work, the labor market consequences of freelancing have been overlooked. I argue that freelancing works have features of both “good” and “bad” jobs, transcend the demarcation between “primary” and “secondary” sectors implied by segmentation theorists, and thus embed uncertainty around their categorization and meaning. Drawing on the “signal clarity” concept from management scholarship, I extend existing sociological works on employer perceptions of candidates by proposing a model to theorize how a history of freelancing affects workers’ prospects at the hiring stage. I present results from two interrelated studies. First, I use a field experiment that involves submitting nearly 12,000 fictitious resumes to analyze the causal effect of a freelancing work history on the likelihood of getting callbacks. The experiment reveals that freelancing decreases workers’ odds of securing full-time employment by about 30 percent. Second, I use data from 42 in-depth interviews with hiring officers to illustrate two mechanisms that could account for that observed effect. Interview data demonstrate that freelancing sends decidedly unclear competence signals: employers are hesitant to hire freelancers not because these candidates lack skills but because verifying these skills is difficult. Freelancing also sends clearer and negative commitment signals. This study sheds new lights on labor market segmentation theory and deepens our understanding of how nonstandard work operates as a vehicle for inequality in the new economy.
A Trio of Risk Factors for Childhood Sexual Abuse: Investigating Exposure to Parental Domestic Violence, Parental Addiction, and Parental Mental Illness as Correlates of Childhood Sexual Abuse
Authors: Fuller-Thomson Esme , Agbeyaka Senyo
Published: April 2020

Targeted screening for sexual abuse is needed for social workers to accurately identify those at risk. Drawing on a cumulative disadvantage framework, this study investigates how parental addictions, parental mental illness, and exposure to domestic violence, both individually and cumulatively, are associated with childhood sexual abuse (CSA). Two waves of regionally representative data were analyzed. Bivariate and logistic regression analyses were conducted using the 2010 Brief Risk Factor Surveillance Survey (BRFSS) (n = 9,241 men, n = 13,627 women) and replicated using the 2012 BRFSS (n = 11,656 men, n = 18,145 women). The 2010 data indicated that 8.5 percent of men who had endured all three childhood adversities reported that they had experienced CSA, compared with 0.6 percent of men who did not experience any of these adversities. Levels of CSA for women in 2010 were 28.7 percent for those experiencing all three risk indicators, and 2.1 percent for women with no risk indicators. Results were similar in the BRFSS 2012. Those with two or more risk factors had between five- and eightfold higher odds of CSA. Social workers may be able to decrease false positives if they screen for CSA based on the presence of two or more risk factors.
History Matters: Racialized Motherhoods and Neoliberalism
Authors: Toft Jessica
Published: April 2020

Neoliberal political reasoning is remaking the state’s democratic character and its governing rules to reflect those of the market. The most prominent legislative example, Temporary Assistance for Needy Families, dictates work requirements, time limits, and monitoring and sanctioning of clients. Through such policies, the primary aims of government assistance changed from aiding needy citizens to transforming individuals into paid workers, regardless of continued poverty or care obligations. Although scholarship of related policy and governance tools has grown, less study has centered on understanding the historic events and ways in which race-based, gendered, and poverty narratives facilitated adoption of such austere policies. This article compares circumstances of African American and White mothers in the United States from the Revolutionary War to the postwelfare era. It describes what neoliberalism is, discusses the role of ideological discourses in policy and governance, presents the history and historical racialized portrayals of White and African American motherhood during this period, and analyzes the differential impact of ideological discourses using a lens of intersectionality. The conclusion discusses how discriminatory discourses subvert a democratic ethos for all and suggests ways for social workers to contest the impacts of neoliberalism.
The Influence of High Flow Nasal Cannulae on the Outcomes of Severe Respiratory Disease in Children Admitted to a Regional Hospital in South Africa
Authors: Richards Mark , Le Roux David , Cooke Louise , Argent Andrew
Published: April 2020

In settings where access to paediatric intensive care unit (PICU) facilities is constrained and transfer capacity is limited, High Flow Nasal Cannulae (HFNC) might fill an important service gap. The aim of this study was to document the effect of HFNC on the outcomes of children admitted with severe respiratory disease at a regional hospital without a PICU in Cape Town, South Africa. It is a 4-year retrospective analysis documenting two periods of 2 years each, one before (2013–15) and one after (2016–18) the initiation of HFNC use. Patients were between the ages of 2 months and 13 years and had been admitted to a paediatric ward. Outcomes were defined by the need for transfer to a tertiary hospital, the need for invasive ventilation and death. There were 90 instances of HFNC use with a significant reduction in the number of children who were transferred (59 vs. 31), invasively ventilated (20 vs. 6, p ≤ 0.01) and who died (3 vs. 0, p = 0.02). Before HFNC implementation, there was also a significantly greater proportion of transferred children who remained on low flow nasal cannulae (15 vs. 2, p ≤ 0.001) at the tertiary hospital. Children who failed HFNC use tended to do this within a day of initiation (Median 11 vs. 60 h for success, p ≤ 0.001). There were no complications related to its use. We believe that in our setting the utilization of HFNC has helped to timeously and accurately identify children needing to be transferred and may mitigate against severe respiratory disease progression.
COVID-19: Financial Stress Test for Academic Medical Centers
Authors: Colenda Christopher C. , Applegate William B. , Reifler Burton V. , Blazer Dan G.
Published: April 2020

The coronavirus (COVID-19) pandemic is having profound effects on the lives and well-being of the world’s population. All levels of the nation’s public health and health care delivery systems are rapidly adjusting to secure the health infrastructure to manage the pandemic in the United States. As the nation’s safety net health care systems, academic medical centers (AMCs) are vital clinical and academic resources in managing the pandemic. COVID-19 may also risk the financial underpinnings of AMCs because their cost structures are high, and they may have incurred large amounts of debt over the last decade as they expanded their clinical operations and facilities. This Invited Commentary reviews existing data on AMC debt levels; summarizes relief provided in the Coronavirus Aid, Relief, and Economic Security Act; and suggests policy options to help mitigate risk.
An Introduction to Causal Diagrams for Anesthesiology Research
Authors: Gaskell Amy L. , Sleigh Jamie W.
Published: April 2020

Making good decisions in the era of Big Data requires a sophisticated approach to causality. We are acutely aware that association ≠ causation, yet untangling the two remains one of our greatest challenges. This realization has stimulated a Causal Revolution in epidemiology, and the lessons learned are highly relevant to anesthesia research. This article introduces readers to directed acyclic graphs; a cornerstone of modern causal inference techniques. These diagrams provide a robust framework to address sources of bias and discover causal effects. We use the topical question of whether anesthetic technique (total intravenous anesthesia vs. volatile) affects outcome after cancer surgery as a basis for a series of example directed acyclic graphs, which demonstrate how variables can be chosen to statistically control confounding and other sources of bias. We also illustrate how controlling for the wrong variables can introduce, rather than eliminate, bias; and how directed acyclic graphs can help us diagnose this problem.

This is a rapidly evolving field, and we cover only the most basic elements. The true promise of these techniques is that it may become possible to make robust statements about causation from observational studies—without the expense and artificiality of randomized controlled trials.
Serum Apelin and Asymmetric Dimethylarginine Levels in Patients With Exfoliation Syndrome or Exfoliative Glaucoma
Authors: Bezci Aygun Figen , Kocabeyoglu Sibel , Irkec Murat , Dikmen Zeliha Gunnur , Umaroglu M. Mutlu , Konstas Anastasios G.P.
Published: April 2020

Précis:

Apelin and asymmetric dimethylarginine (ADMA) concentrations, affecting the nitric oxide pathway, were different in the patient group compared with the control subjects. These 2 molecules may have potential effects in vascular pathologies and their possible role in predisposition to vascular comorbidities in exfoliation syndrome (XFS) or exfoliative glaucoma (XFG).

Purpose:

To evaluate apelin and ADMA levels in serum samples from patients with XFS or XFG compared with healthy control subjects.

Methods:

Serum ADMA and apelin concentrations were evaluated from 36 and 32 XFS patients; 27 and 24 XFG patients; and 34 and 30 healthy controls, respectively. Subjects without systemic disease (including diabetes mellitus, hypertension, coronary artery disease, obesity) were included in the study and body mass index was calculated in all participants. An enzyme-linked immunosorbent assay and high-performance liquid chromatography were used to determine serum apelin and ADMA concentrations. Independent sample t test, χ2 test, analysis of variance test, and Pearson test were used for statistical analysis.

Results:

Mean serum apelin levels of XFG, XFS, and control group were 1063.3±373.4, 1196.7±433.7, and 1343.3±405.1 ng/mL, respectively. Patients with XFG demonstrated significantly lower level of apelin versus controls (P=0.034). Mean serum ADMA concentration was significantly greater in XFS subjects (2.05±0.98 µmol/L) compared with normal controls (1.57±0.58 µmol/L) (P=0.042). No association was detected between ADMA and apelin concentrations and age, sex, and body mass index for both XFS and XFG groups.

Conclusions:

Significant alterations in serum levels of apelin and ADMA may suggest potential effects in vascular pathologies and a possible role in predisposition to vascular comorbidities in XFS/XFG.
Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology
Authors: Ambartsumyan Lusine , Khlevner Julie , Nurko Samuel , Rosen Rachel , Kaul Ajay , Pandolfino John E. , Ratcliffe Elyanne , Yacob Desale , Li B.U.K. , Punati Jaya , Sood Manu , Rao Satish S.C. , Levitt Marc A. , Cocjin Jose T. , Rodriguez Leonel , Flores Alejandro , Rosen John M. , Belkind‐Gerson Jaime , Saps Miguel , Garza Jose M. , Fortunato John E. , Schroedl Rose L. , Keefer Laurie A. , Friedlander Joel , Heuckeroth Robert O. , Rao Meenakshi , El‐Chammas Khalil , Vaz Karla , Chumpitazi Bruno P. , Sanghavi Rina , Matta Sravan K.R. , Danialifar Tanaz , Di Lorenzo Carlo , Darbari Anil
Published: April 2020

Objectives:

Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology – AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies.

Methods:

The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought‐provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment‐based approach.

Conclusions:

The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.
Hemophagocytic Lymphohistiocytosis and Graft Failure Following Unrelated Umbilical Cord Blood Transplantation in Children
Authors: Noguchi Maiko , Inagaki Jiro
Published: April 2020

Hemophagocytic lymphohistiocytosis (HLH) following hematopoietic stem cell transplantation is closely correlated with graft failure and poor prognosis. Because of its rarity, the incidence, risk factors, and optimal treatment strategy are unclear. We analyzed data from cases of HLH following umbilical cord blood transplantation (UCBT) performed for pediatric patients at our center. Among 66 UCBT recipients, 5 developed HLH and imminent graft failure. The median time of diagnosis of HLH was 22 (range, 19 to 30) days after UCBT, and the cumulative incidence of HLH was 7.6% (95% confidence interval, 2.8-15.7) at day 60. In univariate analysis, the cumulative incidence of HLH was significantly higher in patients with infused CD34+ cells <1.0×105/kg than in patients with higher CD34+ cells. Patients with preengraftment infection showed a trend toward higher incidence of HLH compared with patients without any infection. All 5 patients with HLH received corticosteroids and low-dose etoposide (VP-16), with or without high-dose intravenous immunoglobulin. Following these treatments, successful engraftment was observed in 2 patients. Corticosteroids and low-dose VP-16 may be worthy of a trial before attempting salvage hematopoietic stem cell transplantation. Further analyses are required to identify risk factors and to develop methods for prophylaxis, diagnosis, and treatment of HLH.
Tilt-table Echocardiography Unmasks Early Diastolic Dysfunction in Patients With Hemoglobinopathies
Authors: Mah Kandice , Bruce Aisha , Zahari Norazah , Venner Mary Anne , Chow Kelvin , Thompson Richard B. , Khoo Nee S. , Tham Edythe B.
Published: April 2020

Individuals with hemoglobinopathy (sickle cell anemia and thalassemia major) are at risk for cardiac complications such as heart failure and cardiomyopathy. Diastolic dysfunction is known to precede systolic dysfunction in many cardiac diseases. This study sought to determine whether changes in left atrial (LA) function during manipulation of cardiac preload by tilt-table echocardiography can unmask subclinical diastolic dysfunction in pediatric patients with hemoglobinopathies. Eleven sickle cell anemia, 9 transfusion-dependent thalassemia major, and 10 control subjects underwent tilt-table echocardiogram in the supine (loading) and 30-degree upright (unloading) positions and cardiac magnetic resonance imaging (MRI). Echocardiography assessed LA and left ventricular (LV) strain, strain rate, mitral inflow, and annular velocities. MRI assessed LV function, myocardial T1 and T2* for iron deposition. Both thalassemia major and sickle cell anemia patients had normal LV function and no evidence of cardiac iron deposition on MRI T2* measurements. During cardiac loading, controls appropriately increased LA conduit (P=0.002) and reservoir strain (P=0.002), mitral e’ velocity (P<0.0001) and medial e’ velocity (P=0.002), while the hemoglobinopathy patients showed no change in these parameters. In pediatric sickle cell anemia and thalassemia, tilt-table echocardiography unmasked a failure to augment LA function in response to loading, suggesting altered myocardial relaxation is present, before evidence of iron overload or systolic dysfunction.
Vitamin D Insufficiency is Not Associated With Pediatric and Adolescent Immune Thrombocytopenia: A Study in Conjunction With its Receptor Genetic Polymorphisms
Authors: Shaheen Iman Abdelmohsen , Aboukhalil Reham , Abulata Nelly , Abdel-Raouf Rasha , Meligy Bassant , Abdel-Dayem Omnia
Published: April 2020

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous immunologic disorder. Vitamin D has immune-modulatory effects. The pleiotropic effects of vitamin D are exerted via vitamin D receptor (VDR) and its genetic alterations could influence its functions. In our study, we measured the serum 25-hydroxyvitamin D levels in 98 Pediatric and Adolescent ITP patients, in addition to 100 apparently healthy controls. Genetic polymorphisms of the VDR gene FokI, BsmI, ApaI, and TaqI were tested using specific restriction enzymes for each polymorphism. Vitamin D deficiency in the studied Pediatric age was a dominant factor, but it was found not to be associated with Pediatric ITP. However, patients carrying the FokI CC genotype had statistically higher vitamin D levels compared with those carrying other genotypes (P=0.036). Patients who were carriers of the BsmI G allele had a nearly 2-fold higher risk of ITP (odds ratio: 2.203; 95% confidence interval: 1.467-3.309). Therefore, the BsmI polymorphism of VDR could be considered a molecular risk factor for ITP.
Advances in Hereditary Angioedema: The Prevention of Angioedema Attacks With Subcutaneous C1-Inhibitor Replacement Therapy
Authors: Lumry William , Templeton Teri , Omert Laurel , Levy Donald
Published: April 2020

Hereditary angioedema (HAE) is a debilitating condition caused by a functional C1-inhibitor (C1-INH) deficiency and characterized clinically by episodes of subcutaneous or submucosal swelling. C1-INH replacement is highly effective for preventing HAE attacks and can improve health-related quality of life. Once available only for intravenous use, C1-INH is now available as a subcutaneous formulation for self-administration, shown to provide sustained plasma levels of C1-INH and reducing the monthly median HAE attack rate by 95% versus placebo in the phase 3 COMPACT study. Subcutaneously administered C1-INH satisfies multiple unmet needs in the management of patients with HAE.
Protocol to Measure Hair Cortisol in Low Mass Samples From Very Preterm Infants
Authors: Nist Marliese Dion , Sullenbarger Brent A. , Harrison Tondi M. , Pickler Rita H.
Published: April 2020

Background

Hair cortisol is a measure of chronic or repeated hypothalamic–pituitary–adrenal axis activation in response to physical or psychological stressors. Hair cortisol has been successfully used as a measure of chronic stress in adults and children; however, its use as a valid measure in preterm infants has been limited by challenges in measuring cortisol in the low mass samples collectable from these infants.

Objectives

The purpose of this report is to present a novel protocol for the measurement of hair cortisol in very low mass hair samples.

Methods

Small changes were made to previously published protocols. After washing and pulverizing the hair samples, a double methanol cortisol extraction was performed. Samples were spiked with a known quantity of cortisol and analyzed in duplicate using an enzyme-linked immunosorbent assay.

Results

Hair cortisol was detectable in samples weighing between 0.4 and 10.9 mg. The mean cortisol level was 23.74 pg/mg hair (SD = 26.38).

Discussion

With small changes to previously published laboratory protocols, cortisol is quantifiable in low mass hair samples from preterm infants. This technical advance is an important step toward quantifying the stress experiences of hospitalized preterm infants.
Hepatocellular Carcinoma Score and Subclassification Into Aggressive Subtypes Using Immunohistochemical Expression of p53, β-Catenin, CD133, and Ki-67
Authors: Abdou Asmaa G. , Holah Nanis S. , Elazab Dina S. , El-Gendy Walaa G. , Badr Mohammed T. , Al-Sharaky Dalia R.
Published: April 2020

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy in adults. Several studies have classified HCC into molecular subtypes aiming at detecting aggressive subtypes. The aim of the present study was to investigate the role of p53, β-catenin, CD133, and Ki-67 in subclassification of HCC into different aggressive subtypes and the correlation between those markers and the clinicopathologic characteristics of HCC patients. This retrospective study was conducted on paraffin-embedded blocks of 114 HCC specimens. Tissue microarray was constructed and immunostaining for p53, β-catenin, CD133, and Ki-67 was performed and HCC score was formulated. P53 expression was associated with old age (P=0.028), large tumor size (P=0.019), poorly differentiated HCC (P=0.012), hepatitis B virus (HBV) positivity (P=0.032), and hepatitis C virus (HCV) negativity (P =0.046). β-catenin expression was associated with small sized tumors (P=0.005), HBV negativity (P=0.027), early-staged tumors (P=0.029), and prolonged recurrence-free survival (P=0.045). High percentage of CD133 expression was associated with old patients (P=0.035) and HBV positivity (P= 0.045). Ki-67 expression was associated with large tumor size (P= 0.049), vascular invasion (P= 0.05), old age (P=0.035), and previous treatment of HCV by direct acting antiviral agents (P=0.005). Cases with high HCC score showed significant association with old patients (P=0.002), previous treatment of HCV by direct acting antiviral agents (P<0.001), large tumor size (P<0.001), and poorly differentiated tumors (P= 0.009). The proposed HCC score can divide HCC patients into subtypes necessitating tailoring of treatment strategy according to this proposed score to target and optimally treat the aggressive subtypes. This score needs to be further validated on large number of patients with longer follow-up period.
Comparison of the Lymph2Cx Assay and Hans Algorithm in Determining the Cell-of-Origin of Diffuse Large B-Cell Lymphomas, Not Otherwise Specified
Authors: Cho Inju , Yoon Nara , Hyeon Jiyeon , Sim Jongmin , Yoo Hae Yong , Kim Seok Jin , Kim Won Seog , Ko Young Hyeh
Published: April 2020

In the era of precision medicine, accurate and reproducible assignment of cell-of-origin (COO) in diffuse large B-cell lymphoma patients has become important. The Lymph2Cx assay is accurately determining COO by analyzing RNA expression of 20 selected genes while the Hans algorithm based on immunohistochemistry is the most popular method for routine daily diagnosis. However, there are discrepancies between the 2 methods, which need to be evaluated for better correlation. We prospectively analyzed 156 cases of diffuse large B-cell lymphoma, not otherwise specified to analyze the characteristics of discrepancy groups of COO determined by Lymph2Cx and Hans algorithm. We investigated the pattern and cause of discrepancy of COO assigned by the 2 methods. Hans algorithm classified 50 cases (32%) as germinal-center B-cell-like (GCB) type and 106 cases (68%) as non-GCB type. Lymph2Cx assay assigned 43 cases (28%) as GCB type, 94 cases (60%) as activated B-cell-like type, and 19 cases (12%) as intermediate/unclassified type. The agreement rate was 86% after exclusion of unclassified type. With regard to the clinicopathologic factors related with discrepancy between Hans algorithm and Lymph2Cx assay, endoscopic biopsy of the gastrointestinal tract (4/11, 36%) showed higher discrepancy rate (P=0.052). Immunophenotypically, CD10−/BCL6+/MUM1− GCB type and CD10−/BCL6+/−/MUM1+ (=30%, low level expression) non-GCB type exhibited a significantly higher discrepancy rate (6/13, 46%; 4/13, 31%) (P=0.0001). Activated B-cell-like subgroup via Lymph2Cx assay predicted poor progression-free survival (mean survival duration 28.6 mo, P=0.049) compared with the GCB and unclassified type. Hans algorithm revealed no significant difference in progression-free survival and overall survival (P=0.122 and 0.121). These results suggest that when assigning COO via Hans algorithm, CD10−/BCL6+/MUM1− GCB type and CD10−/BCL6+/MUM1+ (=30%, low level) non-GCB type require careful interpretation, especially if the MUM1 staining is weak and heterogeneous in the biopsied specimen.
Risk factors for loss to follow-up from antiretroviral therapy programmes in low-income and middle-income countries
Authors: Frijters Elise M. , Hermans Lucas E. , Wensing Annemarie M.J. , Devillé Walter L.J.M. , Tempelman Hugo A. , De Wit John B.F.
Published: April 2020

Introduction:

Loss to follow-up (LTFU) rates from antiretroviral treatment (ART) programmes in low- and middle-income countries (LMIC) are high, leading to poor treatment outcomes and onward transmission of HIV. Knowledge of risk factors is required to address LTFU. In this systematic review, risk factors for LTFU are identified and meta-analyses performed.

Methods:

PubMed, Embase, Psycinfo and Cochrane were searched for studies that report on potential risk factors for LTFU in adults who initiated ART in LMICs. Meta-analysis was performed for risk factors evaluated by at least five studies. Pooled effect estimates and their 95% confidence intervals (95% CI) were calculated using random effect models with inverse variance weights. Risk of bias was assessed and sensitivity analyses performed.

Results:

Eighty studies were included describing a total of 1 605 320 patients of which 87.4% from sub-Saharan Africa. The following determinants were significantly associated with an increased risk of LTFU in meta-analysis: male sex, older age, being single, unemployment, lower educational status, advanced WHO stage, low weight, worse functional status, poor adherence, nondisclosure, not receiving cotrimoxazole prophylactic therapy when indicated, receiving care at secondary level and more recent year of initiation. No association was seen for CD4+ cell count, tuberculosis at baseline, regimen, and geographical setting.

Conclusion:

There are several sociodemographic, clinical, patient behaviour, treatment-related and system level risk factors for LTFU from ART programs. Knowledge of risk factors should be used to better target retention interventions and develop tools to identify high-risk patients.
HIV diagnostic algorithm requires confirmatory testing for initial indeterminate or positive screens in the first week of life
Authors: Ajibola Gbolahan , Moyo Sikhulile , Mohammed Terrence , Moseki Seretlogelwa , Jack Disaro , Sakoi Maureen , Batlang Oganne , Maswabi Kenneth , Bennett Kara , Hughes Michael D. , Lockman Shahin , Makhema Joseph M. , Lichterfeld Mathias , Kuritzkes Daniel R. , Shapiro Roger L.
Published: April 2020

Background:

Risk for nondiagnostic and false-positive HIV testing has not been quantified for neonates.

Methods:

From April 2015 to July 2018, we screened HIV-exposed infants in Botswana less than 96 h from birth by qualitative DNA PCR. Repeat blood draws for DNA and RNA PCR testing occurred for initial positive and indeterminate results to establish final diagnosis. We compared screening DNA PCR cycle threshold values with final HIV status of the child.

Results:

Of 10 622 HIV-exposed infants, 10 549 (99.3%) had no HIV DNA detected (negative), 42 (0.4%) had HIV DNA detected (positive), and 31 (0.3%) tested indeterminate at first HIV screen. Repeat testing identified 2 (5.0%) of 40 positive screens (2 declined additional testing) as false positives and confirmed 2 (6.5%) of 31 indeterminate screens as infected. Median cycle threshold value at screening was 28.1 (IQR 19.8--34.8) for children with final positive status, and 35.5 (IQR 32.8--41.4) for indeterminates who were ultimately negative. Six (15%) of 40 infants with final positive status had cycle threshold value greater than 33 at first screen, whereas 3 (9.7%) of 31 indeterminates with final negative status had cycle threshold value 33 or less at first screen. This threshold resulted in a negative predictive value of 82% and a positive predictive value of 92% for a single screen.

Conclusion:

Although a DNA PCR cycle threshold value of 33 was predictive of the final HIV status in newborns, overlap occurred for true positives, false positives, and initial indeterminates. Testing additional samples should be standard practice for positive and indeterminate HIV DNA PCR tests in the first week of life.