bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Clinical Validation of a Multiplex Gene Fusion Assay
Authors: García Rolando , Patel Nirav , Uddin Naseem , Park Jason Y
Published: February 2020

Objective

The detection of gene fusion events is important for the diagnosis and management of malignancies. In this study, we describe the validation of a next-generation sequencing assay for multiplex detection of gene fusions.

Methods

Based on previously described gene fusion events that occur in pediatric oncology, a custom anchored multiplex next-generation sequencing assay was designed to target 93 genes.

Results

A total of 24 previously characterized specimens were examined. Twenty specimens had 1 or more previously described fusion events, and 4 specimens were negative for fusion events. The accuracy across specimens was 100% (20 of 20 specimens). The analytical sensitivity and specificity were both 100%. Interday reproducibility for fusion events was 94%; in comparison, intraday reproducibility was 90%.

Conclusion

This multiple-gene fusion assay demonstrated appropriate sensitivity, specificity, and accuracy for clinical use. We anticipate that this assay will improve the diagnosis and management of patients with pediatric solid tumors.
Characterization of an immunogenic cellulase secreted by Cryptococcus pathogens
Authors: Midiri Angelina , Mancuso Giuseppe , Lentini Germana , Famà Agata , Galbo Roberta , Zummo Sebastiana , Giardina Miriam , De Gaetano Giuseppe Valerio , Teti Giuseppe , Beninati Concetta , Biondo Carmelo
Published: February 2020

Members of the C. neoformans/C. gattiii species complex are an important cause of serious humans infections, including meningoencephalitis. We describe here a 45 kDa extracellular cellulase purified from culture supernatants of C. neoformans var. neoformans. The N-terminal sequence obtained from the purified protein was used to isolate a clone containing the full-length coding sequence from a C. neoformans var. neoformans (strain B-3501A) cDNA library. Bioinformatics analysis indicated that this gene is present, with variable homology, in all sequenced genomes of the C. neoformans/C. gattii species complex. The cDNA clone was used to produce a recombinant 45 kDa protein in E. coli that displayed the ability to convert carboxymethyl cellulose and was therefore designated as NG-Case (standing for Neoformans Gattii Cellulase). To explore its potential use as a vaccine candidate, the recombinant protein was used to immunize mice and was found capable of inducing T helper type 1 responses and delayed-type hypersensitivity reactions, but not immune protection against a highly virulent C. neoformans var grubii strain. These data may be useful to better understand the mechanisms underlying the ability C. neoformans/C. gattii to colonize plant habitats and to interact with the human host during infection.
The embryonic linker histone dBigH1 alters the functional state of active chromatin
Authors: Climent-Cantó Paula , Carbonell Albert , Tatarski Milos , Reina Oscar , Bujosa Paula , Font-Mateu Jofre , Bernués Jordi , Beato Miguel , Azorín Fernando
Published: February 2020

Linker histones H1 are principal chromatin components, whose contribution to the epigenetic regulation of chromatin structure and function is not fully understood. In metazoa, specific linker histones are expressed in the germline, with female-specific H1s being normally retained in the early-embryo. Embryonic H1s are present while the zygotic genome is transcriptionally silent and they are replaced by somatic variants upon activation, suggesting a contribution to transcriptional silencing. Here we directly address this question by ectopically expressing dBigH1 in Drosophila S2 cells, which lack dBigH1. We show that dBigH1 binds across chromatin, replaces somatic dH1 and reduces nucleosome repeat length (NRL). Concomitantly, dBigH1 expression down-regulates gene expression by impairing RNApol II binding and histone acetylation. These effects depend on the acidic N-terminal ED-domain of dBigH1 since a truncated form lacking this domain binds across chromatin and replaces dH1 like full-length dBigH1, but it does not affect NRL either transcription. In vitro reconstitution experiments using Drosophila preblastodermic embryo extracts corroborate these results. Altogether these results suggest that the negatively charged N-terminal tail of dBigH1 alters the functional state of active chromatin compromising transcription.
Percutaneous Trigeminal Stimulation for Intractable Facial Pain: A Case Series
Authors: Texakalidis Pavlos , Tora Muhibullah S , McMahon J Tanner , Greven Alexander , Anthony Casey L , Nagarajan Purva , Campbell Melissa , Boulis Nicholas M
Published: February 2020

BACKGROUND

Facial pain syndromes can be refractory to medical management and often need neurosurgical interventions. Neuromodulation techniques, including percutaneous trigeminal ganglion (TG) stimulation, are reversible and have emerged as alternative treatment options for intractable facial pain.

OBJECTIVE

To report the complication rates and analgesic effects associated with TG stimulation and identify potential predictors for these outcomes.

METHODS

A retrospective chart review of 59 patients with refractory facial pain who underwent TG stimulation was conducted. Outcomes following trial period and permanent stimulation were analyzed. Patients with >50% pain relief during trial stimulation received permanent implantation of the stimulation system.

RESULTS

Successful trial stimulation was endorsed by 71.2% of patients. During the trial period, 1 TG lead erosion was identified. History of trauma (facial/head trauma and oral surgery) was the only predictor of a failed trial compared to pain of idiopathic etiology (odds ratio: 0.15; 95% CI: 0.03-0.66). Following permanent implantation, approximately 29.6% and 26.5% of patients were diagnosed with lead erosion and infection of the hardware, respectively. TG lead migrations occurred in 11.7% of the patients. The numeric rating scale score showed a statistically significant reduction of 2.49 (95% CI: 1.37-3.61; P = .0001) at an average of 10.8 mo following permanent implantation.

CONCLUSION

TG stimulation is a feasible neuromodulatory approach for the treatment of intractable facial pain. Facial/head trauma and oral surgery may predict a nonsuccessful trial stimulation. Future development of specifically designed electrodes for stimulation of the TG, and solutions to reduce lead contamination are needed to mitigate the relatively high complication rate.
Sensitivity and Specificity of On-Field Visible Signs of Concussion in the National Football League
Authors: Elbin Robert J , Zuckerman Scott L , Sills Allen K , Crandall Jeff R , Lessley David J , Solomon Gary S
Published: February 2020

BACKGROUND

On-field visible signs (VS) are used to help identify sport-related concussion (SRC) in the National Football League (NFL). However, the predictive utility of a VS checklist for SRC is unknown.

OBJECTIVE

To report the frequency, sensitivity, specificity, and predictive value of VS in a cohort of NFL athletes.

METHODS

On-field VS ratings from 2 experts who independently reviewed video footage of a cohort of 251 injury plays that resulted in an SRC diagnosis (n = 211) and no diagnosis (n = 40) from the 2017 NFL season were examined. The frequency, sensitivity, specificity, and a receiver operating characteristic (ROC) curve with area under the curve (AUC) were calculated for each VS.

RESULTS

Slow to get up (65.9%) and motor incoordination (28.4%) were the most frequent VS in concussed athletes, and slow to get up (60.0%) was the most common VS among nonconcussed athletes. The most sensitive VS was slow to get up (66%); the most specific signs in concussed NFL athletes were blank/vacant look and impact seizure (both 100%). Approximately 26% of concussed NFL players did not exhibit a VS, and the overall sensitivity and specificity for the VS checklist to detect SRC were 73% and 65%, respectively. The VS checklist demonstrated “poor” ability to discriminate between SRC and non-SRC groups (AUC = 0.66).

CONCLUSION

In the NFL, the diagnosis of concussion cannot be made from on-field VS alone. The VS checklist is one part of the comprehensive sideline/acute evaluation of concussion, and the diagnosis remains a multimodal clinical decision.
Global production networks and the evolution of industrial capabilities: does production sharing warp the product space?
Authors: Thomson Russell , Athukorala Prema-Chandra
Published: February 2020

Do production capabilities of countries evolve from existing capabilities or emerge de novo? The Product Space approach developed by Hidalgo, Klinger, Barabási and Hausmann postulates that a country’s existing industrial structure largely determines its opportunities for industrial upgrading. However, this is difficult to reconcile with the export dynamism of many developing countries such as Thailand, Malaysia, Costa Rica and Vietnam that transformed from primary commodity dependence to exporters of dynamic manufactured products. In each of these cases, global production sharing facilitated industrial transition. In this article, we advance the Product Space approach to accommodate the role of global production sharing. Using a newly constructed multi-country data set of manufacturing exports that distinguishes between trade within global production networks and traditional horizontal trade, we find that that existing industrial structure has a smaller impact, but trade openness has a greater impact, on industrial upgrading within vertically integrated global industries.
Financing Efficiency of Securities-Based Crowdfunding
Authors: Brown David C , Davies Shaun William
Published: February 2020

We analyze early-venture fundraising from dispersed, endogenously informed investors. An entrepreneur chooses a payoff-maximizing offering, and investors communicate their information by either contributing capital or abstaining. The entrepreneur uses the information conveyed by fundraising amounts to decide whether or not to undertake a risky venture. His decision threshold hedges investors against bad projects, creating a “loser’s blessing” that encourages contributing without information. Making the offering less attractive to investors mitigates the loser’s blessing but can give rise to a winner’s curse. Both tensions reduce financing efficiency.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
ORGAN EQUIVALENT DOSE AND LIFETIME ATTRIBUTABLE RISK OF CANCER INCIDENCE AND MORTALITY ASSOCIATED WITH CARDIAC CT ANGIOGRAPHY
Authors: Hosseini Nasab Seyed Mohammad Bagher , Deevband Mohammad Reza , Shabestani-Monfared Ali , Hoseini Amoli Seyed Ali , Fatehi Feyzabad Seyed Hasan
Published: February 2020

The aim of this study is the calculation of equivalent organ dose and estimation of lifetime attributable risk (LAR) of cancer incidence and mortality related to cardiac computed tomography angiography (CCTA) because the use of CT angiography as a noninvasive diagnostic method has increased. The organ dose has been calculated by ImPACT software based on the volumetric CT dose index (CTDIvol), and LAR of cancer risk incidence and mortality from CCTA has estimated according to the BEIR VII report. The median value of the effective dose was 13.78 ± 6.88 mSv for both genders. In all scanners, the highest median value for LAR of cancer incidence in males and females for lung cancer was 44.20 and 109.17 per 100 000, respectively. And in infants was 5.89 and 12 for lung cancer in males and breast cancer in females, respectively. Also, the median value of LAR of all cancer incidence from single CCTA in adult patients for males and females was 122 and 238 cases, respectively. Maximum LAR of cancer mortality in adults for lung cancer was 40.28 and 91.84 and in pediatrics was 5.69 and 8.50 in males and females, respectively. Despite many benefits of CTA in the heart disease evaluation, according to a high radiation dose in CCTA, to reduce the cancer risk: CCTA should be used cautiously, especially for pediatric and females.
RESEARCH ON DOSE MONITORING IN BACKSCATTERING NEUTRON HALL IN CHINA SPALLATION NEUTRON SOURCE
Authors: Wu Qingbiao , Zhuang Sixuan , Liu Qiongyao , Jing Hantao , Ye Rong , Li Lun , Wang Yufei , Wang Qingbin
Published: February 2020

The back-n project in China Spallation Neutron Source (CSNS) was launched primarily for nuclear data measurements. In the backscattering neutron hall, the neutron and gamma monitors were used for dose monitoring. Because of the dead time problem of monitors, performance of the monitors in such pulsed radiation field needs to be analyzed. In this research, experiments with dose monitors and personal dosemeters were conducted, and simulation by Monte Carlo code FLUKA was performed. Results showed that the values by monitors are smaller, and the larger the dose, the larger the difference. The reasons in term of energy response and dead time have been analyzed, and corrections were discussed. After corrections, the measured value can agree with the simulation results in the range of about a factor 3. Totally speaking, the values recorded by neutron and gamma monitors can be a reference for radiation safety management in CSNS.
The Relationship Between Dissociation and Symptoms of Psychosis: A Meta-analysis
Authors: Longden Eleanor , Branitsky Alison , Moskowitz Andrew , Berry Katherine , Bucci Sandra , Varese Filippo
Published: February 2020

Evidence suggests that dissociation is associated with psychotic experiences, particularly hallucinations, but also other symptoms. However, until now, symptom-specific relationships with dissociation have not been comprehensively synthesized. This is the first prospectively registered (CRD42017058214) meta-analysis to quantify the magnitude of association between dissociative experiences and all symptoms of psychosis. MEDLINE, PsycINFO, PubMed, and Scopus databases were searched using exhaustive terms denoting dissociation and psychotic symptoms. We included both nonclinical (58 studies; 16 557 participants) and clinical (46 studies; 3879 patient participants) samples and evaluated study quality. Ninety-three eligible articles considering 20 436 participants were retained for analysis. There was a robust association between dissociation and clinical and nonclinical positive psychotic symptoms (r = .437; 95%CI: .386 −.486), with the observed effect larger in nonclinical studies. Symptom-specific associations were also evident across clinical and nonclinical studies, and included significant summary effects for hallucinations (r = .461; 95%CI: .386 −.531), delusions (r = .418; 95%CI: .370 −.464), paranoia (r = .447; 95%CI: .393 −.499), and disorganization (r = .346; 95%CI: .249 −.436). Associations with negative symptoms were small and, in some cases, not significant. Overall, these findings confirm that dissociative phenomena are not only robustly related to hallucinations but also to multiple positive symptoms, and less robustly related to negative symptoms. Our findings are consistent with proposals that suggest certain psychotic symptoms might be better conceptualized as dissociative in nature and support the development of interventions targeting dissociation in formulating and treating psychotic experiences.
Perinatal antecedents of sleep disturbances in schoolchildren
Authors: Brockmann Pablo E , Poggi Helena , Martinez Alejandro , D’Apremont Ivonne , Moore Rosario , Smith Dale , Gozal David
Published: February 2020

Study Objectives

Prematurity has been associated with an increased risk for sleep apnea. However, sleep disturbances in children born preterm have not been extensively investigated. Considering that determinants of sleep may originate early in life, the potential impact of prematurity on sleep disturbances later in life could be important. To establish the role of prematurity on sleep disturbances in a cohort of schoolchildren that were born preterm and compare them with healthy controls.

Methods

A cohort of 147 schoolchildren, 45 born at term (≥37 weeks) and 102 very preterm (<32 weeks), was recruited and evaluated at school age (5–9 years). The Pediatric Sleep Questionnaire (PSQ) and the Sleep Disturbance Scale for Children (SDSC) were used to assess sleep disturbances in different domains.

Results

PSQ score was significantly higher in former preterm children (0.26 ± 0.18 vs. 0.18 ± 0.14 in controls; p = 0.004), and SDSC total score was also significantly different among groups (21.7 ± 11.6 vs. 14.1 ± 12.6; p < 0.001). Regression models showed significant mean differences in PSQ score, total SDSC score, and two SDSC subscale scores (i.e. sleep-wake transition disorders, sleep-breathing disorders, and sleep hyperhidrosis) even after adjustment for confounders. Maternal age and type of delivery were not significantly associated with total PSQ scores.

Conclusions

Sleep disturbances may originate early in life since children born preterm exhibit an increased risk for developing long-term sleep problems. These findings may have important implications for management of preterm children and for implementation of early interventions focused on optimizing sleep habits.
The effect of trichloroethylene metabolites on the hepatic vitamin B12-dependent methionine salvage pathway and its relevance to increased excretion of formic acid in the rat
Authors: Yaqoob Noreen , Bloch Katarzyna M , Evans Andrew R , Lock Edward A
Published: February 2020

The industrial solvent trichloroethylene (TCE) and its two major metabolites trichloroethanol (TCE-OH) and trichloroacetic acid (TCA) cause formic aciduria in male F344 rats. Prior treatment of male F344 rats with 1-aminobenzotriazole a cytochrome P450 inhibitor, followed by TCE (16mk/kg, po), completely prevented formic aciduria, but had no effect on formic acid excretion produced by TCA (8 or 16 mg/kg, po), suggesting TCA may be the proximate metabolite producing this response. Dow and Green reported an increase in the concentration of 5-methyltetrahydrofolate (5-MTHF) in the plasma of rats treated with TCE-OH, suggesting a block in the cycling of 5-MTHF to tetrahydrofolate (THF). This pathway is under the control of the vitamin B12-dependent methionine salvage pathway. We therefore treated rats with three daily doses of methylcobalamin (CH3Cbl) or hydroxocobalamin (OHCbl), a cofactor for methionine synthase, or L-methionine, followed by TCE (16 mg/kg) to determine if they could alleviate the formic aciduria. These pretreatments only partially reduced the excretion of formic acid in the urine. Although prior treatment with S-adenosyl-L-methionine had no effect on formic acid excretion. Consistent with these findings, the activity of methionine synthase in the liver of TCE-treated rats was not inhibited. Transcriptomic analysis of the liver-identified nine differential expressed genes, of note, was downregulation of Lmbrd1 involved in the conversion of vitamin B12 into CH3Cbl, a cofactor for methionine synthase. Our findings indicate that the formic aciduria produced by TCE-OH and TCA may be the result of a block in the recycling of 5-MTHF to THF, the effect on the methionine salvage pathway being a secondary response following acute exposure.
Suppression of LINC00460 mediated the sensitization of HCT116 cells to ionizing radiation by inhibiting epithelial–mesenchymal transition
Authors: Zhang Jiani , Ding Lixin , Sun Gaofeng , Ning Huacheng , Huang Ruixue
Published: February 2020

Radiation resistance is the most common challenge for improving radiotherapy. The mechanisms underlying the development of radioresistance remain poorly understood. This study aims to explore the role of LINC00460 in ionizing radiation-induced radioresistance as well as the mechanisms by which LINC00460 is regulated by radiation exposure. The expression of LINC00460 was measured. Cell proliferation and colony formation were measured in HCT116 cells after treatment by radiation. The development of epithelial–mesenchymal transition (EMT) was determined with or without knockdown LINC00460 expression using western blot analysis. Transcription activity was determined using a series of LINC00460-promoter luciferase reporter gene vectors. LINC00460 expression was significantly higher in HCT116 cells, relative to other cell types, with LINC00460 expression significantly affecting HCT116 cell proliferation. Suppression of LINC00460 inhibits EMT development in HCT116 cells via regulation of ZEB1 expression. Furthermore, LINC00460 expression was induced by irradiation via the activation of c-jun transcription factor-binding element located on the LINC00460 promoter. LINC00460 was shown to play a crucial role in EMT-associated progression of colorectal cancer, indicating that LINC00460 may be an indicator or new potential therapeutic target for colorectal cancer radiosensitization.
Genome Sequence Resources of Two ‘Candidatus Liberibacter asiaticus’ Strains from Pakistan
Authors: Liu Kehong , Atta Sagheer , Cui Xuejin , Zeng Chunhua , Chen Jianchi , Zhou Changyong , Wang Xuefeng
Published: February 2020

‘Candidatus Liberibacter asiaticus’ (CLas) is an unculturable, phloem-restricted αProteobacteria, associated with citrus Huanglongbing (HLB), which is one of the most destructive diseases in citrus production worldwide. Here, we present the genome sequences of CLas strains PA19 and PA20 from HLB-affected kinnow trees in Multan, Punjab Province, Pakistan. The CLas genomes of PA19 and PA20 comprise 1,224,156 bp and 1,226,225 bp, respectively, with an average GC content of 36.4%. Both harbored the Type 2 prophage. In this study, we report two CLas genomes from Pakistan, which extends the sequence database of CLas and will contribute to CLas biology and HLB management.
Inheritance and Characterization of Rph27: A Third Race-Specific Resistance Gene in the Barley Cultivar Quinn
Authors: Rothwell Christopher T. , Singh Davinder , Dracatos Peter M. , Park Robert F.
Published: February 2020

The barley cultivar Quinn was previously reported to carry two genes for resistance to Puccinia hordei, viz. Rph2 and Rph5. In this study, we characterized and mapped a third resistance gene (RphCRQ3) in cultivar Quinn. Multipathotype testing in the greenhouse on a panel of barley genotypes previously postulated to carry Rph2 revealed rare race specificity in four genotypes in response to P. hordei pathotype (pt.) 222 P+ (virulent on Rph2 and Rph5). This suggested either the presence of a race-specific allele variant of Rph2 or the presence of an independent uncharacterized leaf rust resistance locus. A test of allelism on 1,271 F2 Peruvian (Rph2)/Quinn (Rph2 + Rph5) derived seedlings with P. hordei pt. 220 P+ (avirulent on Rph2 and virulent on Rph5) revealed no susceptible segregants. To determine whether the race-specific resistance in Quinn was due to an allele of Rph2 on chromosome 5H or a third uncharacterized resistance gene, we tested the Peruvian/Quinn F3 population with 222 P+ and observed monogenic inheritance. Subsequent bulked segregant analysis indicated the presence of complete in-phase marker fixation near the telomere on the short arm of chromosome 4H, confirming the presence of a third resistance locus in Quinn in addition to Rph2 and Rph5. In accordance with the rules and numbering system of barley gene nomenclature, RphCRQ3 has been designated Rph27.
Perilous Politics: Morbidity and Mortality in the Pre-Roe Era
Authors: Rosenbaum L.
Published: February 2020

(N Engl J Med. 2019;381:893–895)

Before the Roe v. Wade Supreme Court decision, a significant number of women lost their lives due to injuries from illegal abortion attempts. As a result of 2 conservative Supreme Court justices being appointed, state legislatures are attempting to remove Roe’s safeguards and introduce laws to restrict abortion access in medical settings. These efforts will once again put the lives of many women at risk, especially poor and minority women with limited resources.
Prepregnancy Maternal Body Mass Index and Venous Thromboembolism: A Population-based Cohort Study
Authors: Butwick A.J. , Bentley J. , Leonard S.A. , Carmichael S.L. , El-Sayed Y.Y. , Stephansson O. , Guo N.
Published: February 2020

(BJOG. 2019;126:581–588)

Obesity is a risk factor for pregnancy-related venous thromboembolism (VTE), a leading cause of maternal death. Recommendations for VTE prevention specific to maternal body mass index (BMI) are limited and inconsistent across various organizations such as the Royal College of Obstetricians and Gynecologists and the American College of Obstetricians and Gynecologists. The aim of this study was to examine the association between maternal BMI and pregnancy-related VTE.
Cardiac Structure and Function in Morbidly Obese Parturients: An Echocardiographic Study
Authors: Buddeberg B.S. , Fernandes N.L. , Vorster A. , Cupido B.J. , Lombard C.J. , Swanevelder J.L. , Girard T. , Dyer R.A.
Published: February 2020

(Anesth Analg. 2019;129(2):444–449)

Obesity’s negative effects on cardiovascular health are well documented in the general adult population. However, little is known about the impact that obesity has on cardiovascular changes during pregnancy. The aim of this study was to compare cardiovascular health in morbidly obese pregnant women [body mass index (BMI) ≥40 kg/m2] versus pregnant women of normal body mass (BMI≤30 kg/m2).
Resting Hemodynamics and Response to Exercise Using the 6-Minute Walk Test in Late Pregnancy: An International Prospective Multicentre Study
Authors: Dennis A.T. , Salman M. , Paxton E. , Flint M. , Leeton L. , Roodt F. , Yentis S. , Dyer R.A.
Published: February 2020

(Anesth Analg. 2019;129(2):450–457)

The 6-Minute Walk Test (6MWT) is a validated tool that has been used to assess cardiorespiratory reserve in the nonpregnant population. Tools to identify pregnant women who have developed or are at risk of developing cardiac disease is lacking. Early recognition of cardiac disease and its risk in the pregnant population can reduce maternal morbidity and mortality as well as complications during and after birth. The aim of this study is to establish reference intervals for resting heart rate (HR) and the 6MWT in healthy women in late pregnancy, and to determine the expected and actual ratings of perceived exertion and breathlessness during exercise.
Nifedipine Alone or Combined With Sildenafil Citrate for Management of Threatened Preterm Labour: A Randomized Trial
Authors: Maher M.A. , Sayyed T.M. , El-khadry S.W.
Published: February 2020

(BJOG. 2019;126:729–735)

Threatened preterm labor (PTL) (between 20 and 37 wks’ gestation) can be postponed using tocolytic therapy to transfer the patient to a center with a neonatal intensive care unit (NICU) and/or administer corticosteroids for the prevention or management of respiratory morbidity. Nifedipine is a calcium channel blocker that has been shown to be more effective and safer than ritodrine for tocolytic therapy of threatened PTL. This study aimed to compare a combination of nifedipine and sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase-5, compared with nifedipine alone, in terms of tocolytic effects in PTL cases.
Association Between Apgar Scores of 7 to 9 and Neonatal Mortality and Morbidity: A Population-based Cohort Study of Term Infants in Sweden
Authors: Razaz N. , Cnattingius S. , Joseph K.S.
Published: February 2020

(BMJ. 2019;365:l1656)

While low Apgar scores (<7) have been associated with increased risk of poor neonatal outcomes including mortality and morbidity, there have not been any investigations into whether the risks of these outcomes vary between normal Apgar scores of 7, 8, and 9 compared with a score of 10. This information could be useful in predicting the risk of conditions such as neonatal infection, respiratory distress, and hypoxic-ischemic encephalopathy, which have been associated with worse neurodevelopmental status later in childhood compared with children without these conditions. This population-based Swedish study examined the risks of neonatal mortality and morbidity associated with Apgar scores of 7, 8, and 9 (vs. 10) at 1, 5, and 10 minutes.
The Effect of Labor Epidural Analgesia on Breastfeeding Outcomes: A Prospective Observational Cohort Study in a Mixed-parity Cohort
Authors: Orbach-Zinger S. , Landau R. , Davis A. , Oved O. , Caspi L. , Fireman S. , Fein S. , Ioscovich A. , Bracco D. , Hoshen M. , Eidelman L.A.
Published: February 2020

(Anesth Analg. 2019;129(3):784–791)

Breastfeeding is recommended by many international organizations and institutes because of its health benefits for the breastfed neonate as well as for the mother, and many efforts have been made to promote breastfeeding in the postnatal setting. Researchers have examined the relationship between labor epidural analgesia (LEA) and successful breastfeeding, but factors such as intent to breastfeed, past breastfeeding experience, and mothers’ working status have not been taken into account in prior studies. These investigators conducted this current study to investigate the influence of LEA on breastfeeding status at 6 weeks postpartum in a mixed parity cohort who delivered vaginally at an institution that encourages breastfeeding.
Preclinical Evaluation of Ropivacaine in 2 Liposomal Modified Systems
Authors: Rennó C.C. , Papini J.Z.B. , Cereda C.M.S. , Martinez E. , Montalli V.A. , de Paula E. , Pedrazzoli Júnior J. , Calafatti S.A. , Tofoli G.R.
Published: February 2020

(Anesth Analg. 2019;129(2):387–396)

Postoperative pain management is a challenge, with only 1 in 4 surgical patients in the United States reporting adequate pain relief. This can lead to unwanted consequences, such as excessive analgesic use. The authors of this study recently developed new liposomal delivery models for ropivacaine (RVC), and they sought to assess these formulations for postoperative pain control in animal models.
Connective tissue growth factor as an unfavorable prognostic marker promotes the proliferation, migration, and invasion of gliomas
Authors: Song Zi-Bin , Yang Hui-Ping , Xu An-Qi , Zhan Zheng-Ming , Song Ye , Li Zhi-Yong
Published: February 2020

Background

In consideration of the difficulty in diagnosing high heterogeneous glioma, valuable prognostic markers are urgent to be investigated. This study aimed to verify that connective tissue growth factor (CTGF) is associated with the clinical prognosis of glioma, also to analyze the effect of CTGF on the biological function.

Methods

In this study, glioma and non-tumor tissue samples were obtained in 2012 to 2014 from the Department of Neurosurgery of Nanfang Hospital of Southern Medical University, Guangzhou, China. Based on messenger RNA (mRNA) data from the Cancer Genome Atlas (TCGA) and CCGA dataset, combined with related clinical information, we detected the expression of CTGF mRNA in glioma and assessed its effect on the prognosis of glioma patients. High expression of CTGF mRNA and protein in glioma were verified by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blotting. The role of CTGF in the proliferation, migration, and invasion of gliomas were respectively identified by methylthiazoletetrazolium assay, Transwell and Boyden assay in vitro. The effect on glioma cell circle was assessed by flow cytometry. For higher expression of CTGF in glioblastoma (GBM), the biological function of CTGF in GBM was investigated by gene ontology (GO) analysis.

Results

In depth analysis of TCGA data revealed that CTGF mRNA was highly expressed in glioma (GBM, n = 163; lowly proliferative glioma [LGG], n = 518; non-tumor brain tissue, n = 207; LGG, t = 2.410, GBM, t = 2.364, P 
< 0.05). CTGF mRNA and protein expression in glioma (86%) was significantly higher than that in non-tumor tissues (18%) verified by collected samples. Glioma patients with higher expression of CTGF showed an obviously poorer overall survival (35.4 and 27.0 months compared to 63.3 and 55.1 months in TCGA and Chinese Glioma Genome Atlas (CGGA) databases separately, CGGA: χ
2 = 7.596, P = 0.0059; TCGA: χ
2 = 10.46, P = 0.0012). Inhibiting CTGF expression could significantly suppress the proliferation, migration, and invasion of gliomas. CTGF higher expression had been observed in GBM, and GO analysis demonstrated that the function of CTGF in GBM was mainly associated with metabolism and energy pathways (P < 0.001).

Conclusions

CTGF is highly expressed in glioma, especially GBM, as an unfavorable and independent prognostic marker for glioma patients and facilitates the progress of glioma.
Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for Visual Rehabilitation in Limbal Stem Cell Deficiency
Authors: Kim Kyeong Hwan , Deloss Karen S. , Hood Christopher T.
Published: February 2020

Objectives:

To evaluate the clinical outcomes of patients with limbal stem cell deficiency (LSCD) who were fitted with the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral device.

Methods:

In this retrospective, interventional case series, we reviewed the charts of 31 eyes of 19 consecutive patients clinically diagnosed with LSCD who were evaluated for the PROSE device. Clinical data were reviewed before PROSE evaluation and at the last available follow-up. The main outcomes measures were best-corrected distance visual acuity (CDVA) and modified ocular involvement score (OIS), graded using a previously described system for corneal findings.

Results:

Corrected distance visual acuity improved from 0.86±0.50 logarithm of the minimal angle of resolution (Snellen equivalent, 20/145) at baseline to 0.46±0.44 (Snellen equivalent, 20/58) with PROSE at the last follow-up (mean, 25.1±18.0 months; P<0.0001). In 27 eyes (87.1%) CDVA improved, with 22 eyes (71.0%) gaining 2 or more lines of Snellen acuity. When categorized by disease severity, CDVA improved in less severe eyes (stage 1) and more severe eyes (stage 2 or 3; P=0.049 and P=0.00009, respectively). Total OIS was not significantly different between baseline and last follow-up (P=0.754); however the epithelial defect score was significantly less (P=0.034). Twenty-four of 31 eyes (77.4%) continued wearing the PROSE device, with a mean daily wearing time of 10.0±4.6 hrs.

Conclusions:

In patients with LSCD, vision improved and the OIS remained stable with PROSE, suggesting that the device could be considered for visual rehabilitation in this population.
Ocular Surface Changes in Hashimoto's Thyroiditis Without Thyroid Ophthalmopathy
Authors: Altin Ekin Meryem , Karadeniz Ugurlu Seyda , Egrilmez Emine Deniz , Oruk Guzide Gonca
Published: February 2020

Objective:

We sought to evaluate ocular surface changes in patients with Hashimoto's thyroiditis without thyroid ophthalmopathy and elucidate the relationship between dry eye syndrome and meibomian gland dysfunction (MGD) in cases of Hashimoto's thyroiditis.

Methods:

This prospective study included 105 patients with Hashimoto's thyroiditis and 105 age- and sex-matched controls. The 12-item Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients. Both eyes affected by Hashimoto's thyroiditis and normal eyes were evaluated and compared with regard to the following parameters: Hertel exophthalmometry, palpebral fissure height, tear-film breakup time (TBUT), Schirmer 1 test, area and density scores for corneal fluorescein staining, eyelid abnormality, meibomian gland expression, meibography scores, and areas of meibomian gland loss.

Results:

The eyes affected by Hashimoto's thyroiditis demonstrated significantly lower TBUTs (P<0.001), Schirmer 1 test scores (P<0.001), and meibomian gland expression (P<0.05) and significantly higher OSDI scores (P<0.001), corneal fluorescein staining results (P<0.05), eyelid abnormality scores (P<0.05), meibography scores (P<0.05), and areas of meibomian gland loss (P<0.05). Ocular Surface Disease Index scores were significantly positively correlated with eyelid abnormality scores (P=0.025), meibography scores (P<0.05), and areas of meibomian gland loss (P<0.05) and negatively correlated with meibomian gland expression (P<0.05). The duration of Hashimoto's thyroiditis was significantly positively correlated with MGD (P<0.05).

Conclusion:

Dry eye syndrome and ocular discomfort symptoms are significantly more common among patients with Hashimoto's thyroiditis, even in the absence of thyroid ophthalmopathy. Dry eye syndrome in patients with Hashimoto's thyroiditis is believed to result from MGD and is correlated with the duration of the thyroid disease.
Potential Biomarkers for Allergic Conjunctival Diseases
Authors: Roy Neeta , Levanon Shir , Asbell Penny A.
Published: February 2020

Allergic conjunctival diseases (ACDs) are a group of ocular allergies that include allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Although a large body of information exists on the pathophysiology of ACDs, this has not yet lead to the development of clear recommendations and guidelines for the diagnosis of ACDs or development of conclusive and objective diagnostic tools. Identification of objectively measurable biomarkers that represent the molecular and cellular mechanisms associated with ACDs will be an important step toward achieving these aims. This is a comprehensive review of biological markers that have the potential to become “biomarker(s)” for ACDs and aid in the classification, diagnosis, and development of new therapeutic strategies for these group of allergic conditions.
Development of a Questionnaire for Detecting Changes in Dry Eye Disease–Related Symptoms
Authors: Pinto-Fraga José , Calonge Margarita , Enríquez-de-Salamanca Amalia , Fernández Itziar , González-García María J. , Steven Philipp
Published: February 2020

Objectives:

Determining the changes in symptomatology suffered by dry eye disease (DED) patients after an intervention is difficult because there is only one validated questionnaire specifically designed to measure these changes and it is somewhat complex. This work uses a simplified questionnaire to evaluate the changes in DED-related symptoms.

Methods:

A new questionnaire based on a global rating of change scale was designed. The Change in Dry Eye Symptoms Questionnaire (CDES-Q) consists of 2 questions: CDES-Q1 asks for the change in symptoms (“better,” “same,” or “worse”) relative to a determined previous time and CDES-Q2 quantifies this change (range: 0 to +100). To evaluate the CDES-Q, a prospective observational study was performed. At baseline (V1; day-0), DED-related symptoms were evaluated using the ocular surface disease index (OSDI). In the post-treatment visit (V2; day-90), OSDI, Symptoms Assessment Questionnaire in Dry Eye (SANDE) II, and CDES-Q were used. Also, clinical evaluations were performed in each visit.

Results:

Thirty-six patients were included. At V2, OSDI, SANDE II, and CDES-Q showed a significant reduction in symptoms (−7.17±12.73, P=0.0021; −11.29±20.95, P=0.0035; −25.28±42.28, P=0.0011, respectively). Patients who answered “better” in CDES-Q1 showed a significantly lower SANDE II than those who answered “same” or “worse,” while SANDE II did not discriminate between these groups.

Conclusions:

CDES-Q can be a useful tool for the evaluation of changes in DED-related symptoms. It is simple and better discriminates patients without changes from those who suffered a worsening than SANDE II.
Epidemiology and Etiology of Severe Childhood Encephalitis in The Netherlands
Authors: de Blauw Dirkje , Bruning Andrea H.L. , Busch C.B.E , Kolodziej Lisa M. , Jansen N.J.G. , van Woensel J.B.M. , Pajkrt Dasja ,   for the Dutch Pediatric Encephalitis Study Group
Published: February 2020

Background:

Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands.

Methods:

We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality.

Results:

We included 121 children with a median age of 4.6 years (IQR 1.3–9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral- and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77–5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72–14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08–0.78]). The detection of a bacterial (OR 9.4 [CI 2.18–40.46]) or viral (OR 3.7 [CI 1.16–11.73]) pathogen was associated with a higher mortality.

Conclusions:

In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality.
Physical Activity in Healthcare Workers With Low Back Pain
Authors: Bernardelli Giuseppina , Vigna Luisella , Nava Carlo , De Gennaro Colonna Vito , Andersen Lars L. , Consonni Dario , Riboldi Luciano
Published: February 2020

Objective:

To evaluate the effects of physical activity program in healthcare workers with low back pain (LBP).

Methods:

A group of healthcare workers participated voluntarily to a meeting about LBP and to be accepted, were randomly allocated to workplace program or to home-based exercises, illustrated in a booklet and in a video available on the company intranet website. Both programs consisted in 7 weeks of moderate intensity exercises adapted to LBP.

Results:

Most outcomes improved in both groups, however with larger improvement of the Oswestry Disability Index in the workplace group (P = 0.02).

Conclusions:

Regular physical exercise, at home or at the workplace among healthcare workers with LBP, represents a great opportunity to improve health and reduce disability.
Cardiovascular Disease Risk Factor Changes Over 5 Years Among Male and Female US Firefighters
Authors: Smith Denise L. , Graham Elliot , Stewart Donald , Mathias Kevin C.
Published: February 2020

Objective:

To examine changes in measures of cardiovascular health in male and female firefighters over 5 years.

Methods:

Anthropometrics and biomarkers of cardiovascular health from two occupational medical exams separated by 5 years (2009 to 2016) were examined from a cohort of US career firefighters in Virginia (males, n = 603; females, n = 69). Changes over time were tested using paired t-tests and McNemar's tests.

Results:

At baseline, 29% of males and 10% of females were obese. Body weight and body mass index significantly increased (P < 0.05) in males (2.5 ± 0.2 kg) (0.8 ± 0.1 kg·m–2) and females (2.5 ± 0.8 kg) (1.0 ± 0.3 kg·m–2) over the 5-year period. The prevalence of obesity, hypercholesterolemia, hypertensive medication usage, and high blood glucose significantly increased in males over the 5-year period.

Conclusions:

While improvements in blood pressure were observed, large percentages of firefighters, particularly males, had cardiovascular disease risk factors that increased over time.
The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis
Authors: Huang Juntao , Teh Bing Mei , Eikelboom Robert Henry , Han Liyuan , Xu Guodong , Yao Xu , Hu Yi , Zheng Minghao , Shen Yi
Published: February 2020

Objective:

To investigate the effectiveness of basic fibroblast growth factor (bFGF) versus placebo or no intervention in the treatment of tympanic membrane (TM) perforations from randomized controlled trials (RCTs), prospective and retrospective studies.

Data Sources:

PubMed, EMBASE, and Cochrane databases were screened from their inceptions to June 2019.

Study Selection:

Inclusion criteria: 1) English language; 2) observational (retrospective or prospective) or treatment (RCT) studies; 3) reported the outcomes on the application of bFGF in adult or pediatric population. Exclusion criteria: 1) studies without a control group; 2) animal studies, in vitro studies, review studies, and case reports.

Data Extraction:

Number of patients, cause of TM perforation, perforation size, treatment, mean age, follow-up time, sex, closure rate, healing time, mean air-bone gap improvement.

Data Synthesis:

A total of 14 studies were included, including seven RCTs and seven non-RCTs with a total of 1,072 participants. The odds ratio for closure rate of bFGF treatment was 7.33 (95% confidence interval [CI], 4.65 to 11.53; p < 0.01; I

2
 = 44%) and the standardized mean difference (SMD) for healing time was –5.89 (95% CI: –7.85 to –3.93, p < 0.01, I
2 = 98%), suggesting bFGF application has a significant effect on closure of TM perforations. However, no significant change in hearing (SMD: 0.08, 95% CI: –0.11 to 0.27, p = 0.39, I
2 = 0%) was seen as a result of bFGF treatment.

Conclusions:

Our meta-analysis has revealed that the application of bFGF can significantly enhance the closure rate as well as shorten the healing time for TM perforations. In terms of hearing, there is as yet no evidence that bFGF has a significant effect. Given its ease, availability, and safety, bFGF can be used effectively for TM repair.
Severity of Villous Atrophy at Diagnosis in Childhood Does Not Predict Long‐term Outcomes in Celiac Disease
Authors: Kröger Sofia , Kurppa Kalle , Repo Marleena , Huhtala Heini , Kaukinen Katri , Lindfors Katri , Arvola Taina , Kivelä Laura
Published: February 2020

Objectives:

Current pediatric guidelines allow noninvasive diagnosis of celiac disease in selected children. We investigated in a large cohort study whether the severity of villous atrophy at diagnosis is associated with clinical characteristics or long‐term health outcomes, thus having a prognostic significance.

Methods:

Comprehensive medical data on 906 children with celiac disease were analyzed. Long‐term health outcomes of 503 adult patients diagnosed in childhood were moreover assessed with a specific study questionnaire and validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well‐Being (PGWB) questionnaires. Patients were classified into 3 groups according to the severity of villous atrophy at diagnosis, and all variables were compared.

Results:

Altogether 34% of the patients had partial, 40% subtotal, and 26% total villous atrophy. Children with milder lesions were diagnosed more recently (median year 2007 vs 2006 vs 2001, respectively, P < 0.001), more often by screening (30% vs 25% vs 17%, P < 0.001) and they suffered less often from anemia (16% vs 21% vs 32%, P < 0.001) and growth disturbances (22% vs 36% vs 54%, P < 0.001) and had lower transglutaminase‐2 antibody levels (median 64 U/L vs 120 U/L vs 120 U/L, P < 0.001). There was no difference in other disease features.

Altogether 212 adults diagnosed in childhood completed the questionnaires. Severity of villous atrophy at childhood diagnosis did not predict presence of complications or comorbidities, persistent symptoms, and self‐perceived health, quality of life or adherence to a gluten‐free diet in adulthood.

Conclusion:

Presence of advanced villous atrophy at diagnosis is associated with more severe clinical characteristics but not with poorer long‐term health and treatment outcomes.