bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse
Authors: Hadji-Turdeghal Katra , Andreasen Laura , Hagen Christian M , Ahlberg Gustav , Ghouse Jonas , Bækvad-Hansen Marie , Bybjerg-Grauholm Jonas , Hougaard David M , Hedley Paula , Haunsø Stig , Svendsen Jesper H , Kanters Jørgen K , Jepps Thomas A , Skov Morten W , Christiansen Michael , Olesen Morten S
Published: April 2019

Aims

Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse.

Methods and results

We used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10–1.17, P = 5.8 × 10−15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15–1.46, P = 1.68 × 10−5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue.

Conclusion

We identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse.
Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults
Authors: Pérez Laura M , Hooshmand Babak , Mangialasche Francesca , Mecocci Patrizia , Smith A David , Refsum Helga , Inzitari Marco , Fratiglioni Laura , Rizzuto Debora , Calderón-Larrañaga Amaia
Published: April 2019

We aimed to investigate the association between baseline levels of total serum glutathione (tGSH) and rate of chronic disease accumulation over time. The study population (n = 2,596) was derived from a population-based longitudinal study on ≥60-year-olds living in Stockholm. Participants were clinically assessed at baseline, 3- and 6-year follow-ups. Multimorbidity was measured as the number of chronic conditions from a previously built list of 60 diseases. Linear mixed models were applied to analyze the association between baseline tGSH levels and the rate of multimorbidity development over 6 years. We found that at baseline, participants with ≥4 diseases had lower tGSH levels than participants with no chronic conditions (3.3 vs 3.6 µmol/L; p < .001). At follow-up, baseline levels of tGSH were inversely associated with the rate of multimorbidity development (β * time: −0.044, p < .001) after adjusting for age, sex, education, levels of serum creatinine, C-reactive protein, albumin, body mass index, smoking, and time of dropout or death. In conclusion, serum levels of tGSH are inversely associated with multimorbidity development; the association exists above and beyond the link between tGSH and specific chronic conditions. Our findings support the hypothesis that tGSH is a biomarker of multisystem dysregulation that eventually leads to multimorbidity.
Cultural Relevance Reduces the Enhanced Neural Processing of Positively Valenced Information in Older Adults
Authors: Gong Xianmin , Fung Helene H , Zeng Ginger Qinghong , Tse Chun-Yu
Published: April 2019

Objectives

This study investigated (a) whether the age-related enhancement in processing positive relative to negative emotional information happened at the early and/or late processing stages and (b) if the age-related positivity effect was modulated by cultural relevance using event-related brain potential (ERP).

Methods

Seventeen younger and 19 older Chinese adults judged the emotional valence of Chinese and Western pictures while electroencephalogram (EEG) was recorded and analyzed by temporospatial principal component analysis to dissociate the processing stages.

Results

(a) Larger N100 for negative than positive pictures was observed in younger, but not older adults, while older but not younger adults showed larger late anterior P300 for positive than negative pictures. (b) Older adults showed larger early posterior P300 for positive than negative Western pictures, but not culturally relevant Chinese pictures; such modulation effect by cultural relevance was absent in younger adults.

Discussion

These findings suggest an age-related decrease in sensitivity to negative information in the earlier stage and an age-related increase in sensitivity to positive information in the later stage of cognitive processing. This supports a dual-route model of the age-related positivity effect. Moreover, the age-related positivity effect is more evident for stimuli with less cultural relevance.
Imaging Features Associated With Failure of Nonoperative Management of Intraabdominal Abscesses in Crohn Disease
Authors: Perl Daniel , Waljee Akbar K , Bishu Shrinivas , Higgins Peter D R , Wasnik Ashish P , Stidham Ryan W
Published: April 2019

Management of Crohn’s-related intra-abdominal abscesses is challenging. In a retrospective study of patients undergoing non-operative intra-abdominal abscess management, radiographic factors including abscess size, pre-stenotic bowel dilation, and bowel wall thickening are associated with the need for future bowel resection.
Glycoengineering of HEK293 cells to produce high-mannose-type N-glycan structures
Authors: Ren Wei-Wei , Jin Ze-Cheng , Dong Weijie , Kitajima Toshihiko , Gao Xiao-Dong , Fujita Morihisa
Published: April 2019

Therapeutic proteins are a developing part of the modern biopharmaceutical industry, providing novel therapies to intractable diseases including cancers and autoimmune diseases. The human embryonic kidney 293 (HEK293) cell line has been widely used to produce recombinant proteins in both basic science and industry. The heterogeneity of glycan structures is one of the most challenging issues in the production of therapeutic proteins. Previously, we knocked out genes encoding α1,2-mannosidase-Is, MAN1A1, MAN1A2 and MAN1B1, in HEK293 cells, establishing a triple-knockout (T-KO) cell line, which produced recombinant protein with mainly high-mannose-type N-glycans. Here, we further knocked out MAN1C1 and MGAT1 encoding another Golgi α1,2-mannosidase-I and N-acetylglucosaminyltransferase-I, respectively, based on the T-KO cells. Two recombinant proteins, lysosomal acid lipase (LIPA) and immunoglobulin G1 (IgG1), were expressed in the quadruple-KO (QD-KO) and quintuple-KO (QT-KO) cell lines. Glycan structural analysis revealed that all the hybrid-type and complex-type N-glycans were eliminated, and only the high-mannose-type N-glycans were detected among the recombinant proteins prepared from the QD-KO and QT-KO cells. Overexpression of the oncogenes MYC and MYCN recovered the slow growth in QD-KO and QT-KO without changing the glycan structures. Our results suggest that these cell lines could be suitable platforms to produce homogeneous therapeutic proteins.
Emerging Cancer Survival Trends, Disparities, and Priorities in Adolescents and Young Adults: A California Cancer Registry-Based Study
Authors: Moke Diana J , Tsai Kaiya , Hamilton Ann S , Hwang Amie , Liu Lihua , Freyer David R , Deapen Dennis
Published: April 2019

Background

Although landmark studies in the 1990s demonstrated that adolescents and young adults (AYAs, ages 15–39 years) with cancer had lower survival improvement compared to other ages, therapeutic advances warrant reappraisal of those observations. We utilized more recent data to study site-specific AYA survival trends and disparities and gain a more contemporary understanding of this problem.

Methods

Using California Cancer Registry data from 1988 to 2014, we calculated 1) 5-year overall survival improvement for AYAs compared to other age groups; 2) hazard ratios (HRs) of death for AYAs comparing 2001–2014 with 1988–2000 stratified by site, stage, sex, age group, race and ethnicity, and socioeconomic status (SES); and 3) site-specific adjusted HRs (aHRs) for AYA risk groups and interaction analyses by time period.

Results

For all cancers combined, AYAs demonstrated survival improvement that exceeded all other age groups, largely due to reduced mortality in human immunodeficiency virus and acquired immunodeficiency syndrome-related cancers. The strongest predictor of death was cancer stage (aHR = 6.32 for distant vs localized, 95% confidence interval [CI] = 6.20 to 6.45). The aHR of death was statistically significantly higher for blacks (1.46, 95% CI = 1.42 to 1.50), Asian and Pacific Islanders (1.12, 95% CI = 1.09 to 1.15), and Latino whites (1.06, 95% CI = 1.04 to 1.08) compared to non-Latino whites, and was statistically significantly higher for low SES compared to high (1.31, 95% CI = 1.29 to 1.34). Survival disparities by stage, race and ethnicity, and SES worsened over time.

Conclusions

For AYAs in aggregate, the historical cancer survival improvement gap has been closed. However, the growing survival disparities in AYA subsets reported here, including advanced stage disease, racial and ethnic minorities, and low SES, highlight new priorities in need of increased attention, including inequities in cancer care and delivery within this vulnerable population.
Prospective Cohort Study of Next-Generation Sequencing as a Diagnostic Modality for Unexplained Encephalitis in Children
Authors: Haston Julia C , Rostad Christina A , Jerris Robert C , Milla Sarah S , McCracken Courtney , Pratt Catherine , Wiley Michael , Prieto Karla , Palacios Gustavo , Shane Andi L , McElroy Anita K
Published: April 2019

Background

Encephalitis is an inflammatory condition of the brain associated with long-term neurologic sequelae and even death in children. Although viruses are often implicated, an etiology is not identified in the majority of cases. Metagenomics-based next-generation sequencing (mNGS) is a high-throughput sequencing technique that can enhance the detection of novel or low-frequency pathogens.

Methods

Hospitalized immunocompetent children aged 6 months to 18 years with encephalitis of unidentified etiology were eligible for enrollment. Demographic, historical, and clinical information was obtained, and residual blood and cerebrospinal fluid (CSF) samples were subjected to mNGS. Pathogens were identified by querying the sequence data against the NCBI GenBank database.

Results

Twenty children were enrolled prospectively between 2013 and 2017. mNGS of CSF identified 7 nonhuman nucleic acid sequences of significant frequency in 6 patients, including that of Mycoplasma bovis, parvovirus B19, Neisseria meningitidis, and Balamuthia mandrillaris. mNGS also detected Cladophialophora species, tobacco mosaic virus, and human bocavirus, which were presumed to be contaminants or nonpathogenic organisms. One patient was found to have positive serology results for California encephalitis virus, but mNGS did not detect it. Patients for whom mNGS identified a diagnosis had a significantly higher CSF white blood cell count, a higher CSF protein concentration, and a lower CSF glucose level than patients for whom mNGS did not identify a diagnosis.

Conclusion

We describe here the results of a prospective cohort analysis to evaluate mNGS as a diagnostic tool for children with unexplained encephalitis. Although mNGS detected multiple nonpathogenic organisms, it also identified multiple pathogens successfully and was most useful in patients with a CSF abnormality.
Specific chromatin changes mark lateral organ founder cells in the Arabidopsis inflorescence meristem
Authors: Frerichs Anneke , Engelhorn Julia , Altmüller Janine , Gutierrez-Marcos Jose , Werr Wolfgang
Published: April 2019

Fluorescence-activated cell sorting (FACS) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were combined to analyse the chromatin state of lateral organ founder cells (LOFCs) in the peripheral zone of the Arabidopsis apetala1-1 cauliflower-1 double mutant inflorescence meristem. On a genome-wide level, we observed a striking correlation between transposase hypersensitive sites (THSs) detected by ATAC-seq and DNase I hypersensitive sites (DHSs). The mostly expanded DHSs were often substructured into several individual THSs, which correlated with phylogenetically conserved DNA sequences or enhancer elements. Comparing chromatin accessibility with available RNA-seq data, THS change configuration was reflected by gene activation or repression and chromatin regions acquired or lost transposase accessibility in direct correlation with gene expression levels in LOFCs. This was most pronounced immediately upstream of the transcription start, where genome-wide THSs were abundant in a complementary pattern to established H3K4me3 activation or H3K27me3 repression marks. At this resolution, the combined application of FACS/ATAC-seq is widely applicable to detect chromatin changes during cell-type specification and facilitates the detection of regulatory elements in plant promoters.
The initiation of bud burst in grapevine features dynamic regulation of the apoplastic pore size
Authors: Signorelli Santiago , Shaw Jeremy , Hermawaty Dina , Wang Zi , Verboven Pieter , Considine John A , Considine Michael J
Published: April 2019

Molecular modelling, histochemistry, and micro-computed tomography reveal that the apoplastic pore size is dynamically regulated during bud burst in grapevine, and associated with oxygenation of the meristematic core.
Cute Jews: Modernist Photographic Forms and Minor Aesthetic Categories in ‘Jüdische Kinder in Erez Israel. Ein Fotobuch’
Authors: Magilow Daniel H
Published: April 2019

Jüdische Kinder in Erez Israel was the last overtly Jewish-themed photobook published in Germany before the Holocaust. Although it consists only of a six-page introduction by the scholar-activist Bertha Badt-Strauß, one page of captions, and twenty-one photographs by photographer Nachum ‘Tim’ Gidal of adorable young children in Mandatory Palestine, its propaganda mission transcends its diminutive size and surface superficiality. This article interprets this photobook as an example of the photo essay, a modernist form that emerged from Weimar Germany’s unique media environment, in which photographs assumed rhetorical and argumentative functions generally associated with written language. To encourage German Jews and particularly German-Jewish women to emigrate, Jüdische Kinder in Erez Israel creates an allegory of the children’s vulnerability by eliciting responses associated with the minor aesthetic category of ‘cuteness’. To this end, it draws on two important photo essay genres of interwar Germany: photobooks and illustrated magazine photostories about cute children and about Palestine. By synthesizing these discourses, Gidal and Badt-Strauß create a cultural artifact that aims to establish positive, affective relationships between German-Jewish readers and Mandatory Palestine, and to convince the former to visualize and embrace the latter as they might imagine their own children. In this way, Jüdische Kinder in Erez Israel broadens our understandings of both the media constellation from which photo essays emerged, and how this form helped broaden the visual lexicon and aesthetic strategies central to the project of Jewish cultural and political regeneration.
Multimodal Therapy
Authors: Lazarus Clifford N. , Lazarus Arnold A.
Published: April 2019

Arnold Lazarus pioneered cognitive-behavior therapy but soon realized that it contained significant treatment omissions. He thus created multimodal therapy (MMT), a comprehensive, biopsychosocial approach to psychological assessment and technically eclectic psychotherapy. Unlike traditional cognitive-behavior therapy, in addition to focusing on behavior, cognition, and affect, MMT also thoroughly assesses imagery, sensations, interpersonal relationships, and biological factors, which results in a comprehensive diagnostic and treatment planning framework. This chapter features the foundations of MMT, its applicability and structure, its therapy relationship, and its key methods. The chapter concludes with case example, a review of outcome research, and several future directions.
Cognitive-Behavioral Assimilative Integration
Authors: Castonguay Louis G. , Newman Michelle G. , Holtforth Martin grosse
Published: April 2019

The integrative approach described in this chapter represents the authors’ efforts to improve the efficacy of cognitive-behavioral therapy (CBT) via a systematic and theoretically cohesive assimilation of treatment procedures typically associated with other psychotherapy orientations. The primary emphasis is on an integrative therapy for generalized anxiety disorder which, based on treatment and psychopathology research, has added interpersonal- and emotional-focused interventions to CBT techniques. Other assimilative treatments aimed at increasing the efficacy of CBT for a number of clinical problems are also briefly described. The chapter further illustrates how the integration of other contributions may be implemented clinically.
Cognitive Behavioral Analysis System of Psychotherapy for Chronic Depression
Authors: McCullough James P. , Schramm Elisabeth
Published: April 2019

The cognitive behavioral analysis system of psychotherapy (CBASP) is designed specifically for chronic depression and is based on Donald Kiesler’s interpersonal model, with the role of the psychotherapist being administered from a disciplined personal involvement perspective. To achieve its learning goals, CBASP has been operationalized such that the two major goals are learned in an acquisition learning manner criterion. Patients are taught throughout treatment that the lessons of CBASP are intended to be “lifelong” lessons that must be practiced daily to reduce psychopathology. This chapter reviews CBASP’s fundamental tenets, assessment, applicability, change processes, therapy relationship, and key methods. The chapter concludes with a detailed case example, outcome research, and future directions.
Integrative Psychotherapy with Culturally Diverse Clients
Authors: Harris Jeff E. , Shukla Natasha , Ivey Allen E.
Published: April 2019

When multiple cultural influences are acknowledged, all psychotherapy clients are recognized as culturally unique. Cultural assessment involves understanding the intersecting impact of race/ethnicity, gender, sexual orientation, socioeconomic status, disabilities, and other influences on clients. Case formulation often involves understanding the process of identity development related to important cultural identities. Processes of change include consciousness-raising, catharsis, choosing, and social justice. The therapy relationship can be adapted to the cultural expectations of clients, and differences can be discussed to reduce unintended therapy microaggressions and to repair ruptures. Four types of cultural methods and techniques are presented. In the integrative tradition, psychotherapists are encouraged to think about when to focus on group membership and when to explore the individual meaning of cultural influences.
Integrative Psychotherapy with Children
Authors: Drewes Athena A. , Seymour John W.
Published: April 2019

Children’s psychological disorders are complex and multidetermined, compounded by emerging cognitive styles, self-concepts, developmental trajectories, and environmental considerations that result in unique clinical demands. Consequently, child psychotherapy requires a broader conceptualization and individualized treatment. This chapter examines psychotherapy integration in working with children. The use of integrative treatments is central to children, although it is neither clearly identified nor well developed in research or practice. The authors examine assimilative, theoretical, and technical integration as well as common factors in treating children. A case example, a review of outcome research, and forecasts of future directions conclude the chapter.
Unprecedented Parallel Photosynthetic Losses in a Heterotrophic Orchid Genus
Authors: Barrett Craig F , Sinn Brandon T , Kennedy Aaron H
Published: April 2019

Heterotrophic plants are evolutionary experiments in genomic, morphological, and physiological change. Yet, genomic sampling gaps exist among independently derived heterotrophic lineages, leaving unanswered questions about the process of genome modification. Here, we have sequenced complete plastid genomes for all species of the leafless orchid genus Hexalectris, including multiple individuals for most, and leafy relatives Basiphyllaea and Bletia. Our objectives are to determine the number of independent losses of photosynthesis and to test hypotheses on the process of genome degradation as a result of relaxed selection. We demonstrate four to five independent losses of photosynthesis in Hexalectris based on degradation of the photosynthetic apparatus, with all but two species displaying evidence of losses, and variation in gene loss extending below the species level. Degradation in the atp complex is advanced in Hexalectris warnockii, whereas only minimal degradation (i.e., physical loss) has occurred among some “housekeeping” genes. We find genomic rearrangements, shifts in Inverted Repeat boundaries including complete loss in one accession of H. arizonica, and correlations among substitutional and genomic attributes. Our unprecedented finding of multiple, independent transitions to a fully mycoheterotrophic lifestyle in a single genus reveals that the number of such transitions among land plants is likely underestimated. This study underscores the importance of dense taxon sampling, which is highly informative for advancing models of genome evolution in heterotrophs. Mycoheterotrophs such as Hexalectris provide forward-genetic opportunities to study the consequences of radical genome evolution beyond what is possible with mutational studies in model organisms alone.
Protein convertase subtilisin/kexin type 9 biology in nephrotic syndrome: implications for use as therapy
Authors: Busuioc Ruxandra Mihaela , Covic Adrian , Kanbay Mehmet , Banach Maciej , Burlacu Alexandru , Mircescu Gabriel
Published: April 2019

Low-density lipoprotein cholesterol (LDL-C) levels almost constantly increased in patients with nephrotic syndrome (NS). Protein convertase subtilisin/kexin type 9 (PCSK9) [accelerates LDL-receptor (LDL-R) degradation] is overexpressed by liver cells in NS. Their levels, correlated inversely to LDL-R expression and directly to LDL-C, seem to play a central role in hypercholesterolaemia in NS. Hypersynthesis resulting from sterol regulatory element-binding protein dysfunction, hyperactivity induced by c-inhibitor of apoptosis protein expressed in response to stimulation by tumour necrosis factor-α produced by damaged podocytes and hypo-clearance are the main possible mechanisms. Increased LDL-C may damage all kidney cell populations (podocytes, mesangial and tubular cells) in a similar manner. Intracellular cholesterol accumulation produces oxidative stress, foam cell formation and apoptosis, all favoured by local inflammation. The cumulative effect of cellular lesions is worsened proteinuria and kidney function loss. Accordingly, NS patients should be considered high risk and treated by lowering LDL-C. However, there is still not enough evidence determining whether lipid-lowering agents are helpful in managing dyslipidaemia in NS. Based on good efficacy and safety proved in the general population, therapeutic modulation of PCSK9 via antibody therapy might be a reasonable solution. This article explores the established and forthcoming evidence implicating PCSK9 in LDL-C dysregulation in NS.
Styloidogenic Jugular Venous Compression Syndrome: Clinical Features and Case Series
Authors: Zhao Xiaochun , Cavallo Claudio , Hlubek Randall J , Mooney Michael A , Belykh Evgenii , Gandhi Sirin , Moreira Leandro Borba , Lei Ting , Albuquerque Felipe C , Preul Mark C , Nakaji Peter
Published: April 2019

BACKGROUND

Styloidogenic jugular venous compression syndrome (SJVCS) is a rare cause of idiopathic intracranial hypertension (IIH).

OBJECTIVE

To elucidate the pathophysiology and the hemodynamics of SJVCS.

METHODS

We conducted a retrospective review of medical records, clinical images, dynamic venography, and manometry for consecutive patients with SJVCS undergoing microsurgical decompression from April 2009 to October 2017. Patients with IIH with normal venography and manometry findings served as controls.

RESULTS

Data were analyzed for 10 patients with SJVCS who presented with headaches. Neck flexion exacerbated headaches in 7 patients. Eleven patients with IIH provided control data for normal intracranial venous pressure and styloid process anatomy. Patients with SJVCS had bilateral osseous compression of venous outflow. The styloid processes were significantly longer in patients with SJVCS than in those with IIH (mean [standard deviation (SD)] distance, 31.0 [10.6] vs 19.0 [14.1] mm; P < .01). The styloid process–C1 lateral tubercle distance was shorter in patients with SJVCS than in those with IIH (mean [SD] distance, 2.9 [1.0] vs 9.9 [2.8] mm; P < .01). Patients with SJVCS had significantly higher global venous pressure and a higher pressure gradient across the stenosis site than controls (mean [SD] pressure, 2.86 [2.61] vs 0.13 [1.09] cm H2O; P = .09). All 10 patients with SJVCS experienced venous pressure elevation during contralateral neck turning (mean [SD] pressure, 4.29 [2.50] cm H2O). All 10 patients with SJVCS underwent transcervical microsurgical decompression, and 9 experienced postoperative improvement or resolution of symptoms. One patient had transient postoperative dysphagia and facial drooping, and another patient reported jaw numbness.

CONCLUSION

SJVCS is a novel clinical entity causing IIH. Patients should be evaluated with dynamic venography with manometry. Surgical decompression with removal of osseous overgrowth is an effective treatment in select patients.
Paediatric health care access in community health centres is associated with survival for critically ill children who undergo inter-facility transport: A province-wide observational study
Authors: Tijssen Janice A , To Teresa , Morrison Laurie J , Alnaji Fuad , MacDonald Russell D , Cupido Cynthia , Lee Kyong-Soon , Parshuram Christopher S
Published: April 2019

Background

Diverse settlement makes inter-facility transport of critically ill children a necessary part of regionalized health care. There are few studies of outcomes and health care services use of this growing population.

Methods

A retrospective study evaluated the frequency of transports, health care services use, and outcomes of all critically ill children who underwent inter-facility transport to a paediatric intensive care unit (PICU) in Ontario from 2004 to 2012. The primary outcome was PICU mortality. Secondary outcomes were 24-hour and 6-month mortality, PICU and hospital lengths of stay, and use of therapies in the PICU.

Results

The 4,074 inter-facility transports were for children aged median (IQR) 1.6 (0.1 to 8.3) years. The rate of transports increased from 15 to 23 per 100,000 children. There were 233 (5.7%) deaths in PICU and an additional 78 deaths (1.9%) by 6 months. Length of stay was median (IQR) 2 (1 to 5) days in PICU and 7 (3 to 14) days in the receiving hospital. Lower PICU mortality was independently associated with prior acute care contact (odds ratio [OR]=0.3, 95% confidence interval [CI]: 0.2 to 0.6) and availability of paediatric expertise at the referral hospital (OR=0.7, 95% CI: 0.5 to 1.0).

Conclusions

We found that in Ontario, children undergoing inter-facility transport to PICUs are increasing in number, consume significant acute care resources, and have a high PICU mortality. Access to paediatric expertise is a potentially modifiable factor that can impact mortality and warrants further evaluation.
Effects of Thiosulfate as a Sulfur Source on Plant Growth, Metabolites Accumulation and Gene Expression in Arabidopsis and Rice
Authors: Nakajima Takatsugu , Kawano Yusuke , Ohtsu Iwao , Maruyuama-Nakashita Akiko , Allahham Alaa , Sato Muneo , Sawada Yuji , Hirai Masami Yokota , Yokoyama Tadashi , Ohkama-Ohtsu Naoko
Published: April 2019

Plants are considered to absorb sulfur from their roots in the form of sulfate. In bacteria like Escherichia coli, thiosulfate is a preferred sulfur source. It is converted into cysteine (Cys). This transformation consumes less NADPH and ATP than sulfate assimilation into Cys. In Saccharomyces cerevisiae, thiosulfate promoted growth more than sulfate. In the present study, the availability of thiosulfate, the metabolite transformations and gene expressions it induces were investigated in Arabidopsis and rice as model dicots and monocots, respectively. In Arabidopsis, the thiosulfate-amended plants had lower biomass than those receiving sulfate when sulfur concentrations in the hydroponic medium were above 300 μM. In contrast, rice biomass was similar for plants raised on thiosulfate and sulfate at 300 μM sulfur. Therefore, both plants can use thiosulfate but it is a better sulfur source for rice. In both plants, thiosulfate levels significantly increased in roots following thiosulfate application, indicating that the plants absorbed thiosulfate into their root cells. Thiosulfate is metabolized in plants by a different pathway from that used for sulfate metabolism. Thiosulfate increases plant sulfide and cysteine persulfide levels which means that plants are in a more reduced state with thiosulfate than with sulfate. The microarray analysis of Arabidopsis roots revealed that 13 genes encoding Cys-rich proteins were upregulated more with thiosulfate than with sulfate. These results together with those of the widely targeted metabolomics analysis were used to proposes a thiosulfate assimilation pathway in plants.
In Their Own Words: A Phenomenological Exploration of Student Mental Health and Success in College
Authors: Sherman Megan Callahan
Published: April 2019

National statistics suggest that an increasing number of students are exhibiting mental health symptoms while in college. Despite this alarming trend, limited research has been conducted for the purpose of better understanding the complex dynamics at play for individuals navigating these challenges. This phenomenological research study provides a descriptive analysis of the lived experience shared by successful college students dealing with a mental health condition. In adopting a strengths perspective that acknowledges achievement, this exploratory research serves as a platform for future studies and introduces several common elements of the phenomena. Five emerging essential themes are defined and discussed: meaning making, goal setting and purpose, spirituality, reciprocal relationships, and altruism. This investigation provides insight into the common factors that promote success for college students living with mental health issues. Study findings should be considered when developing intervention initiatives on college campuses for these historically marginalized students.
Migraine in adults
Authors: Vacca Vincent M.
Published: April 2019

Migraine is a chronic episodic disorder typically characterized by a debilitating headache. This article offers tools to identify potential triggers and prevent or reduce the occurrence of attacks.
Mechanical Performance of Posterior Spinal Instrumentation and Growing Rod Implants
Authors: Foltz Mary H. , Freeman Andrew L. , Loughran Galyna , Bechtold Joan E. , Barocas Victor H. , Ellingson Arin M. , Polly David W.
Published: April 2019

Study Design.

Experimental and computational study of posterior spinal instrumentation and growing rod constructs per ASTM F1717-15 vertebrectomy methodology for static compressive bending.

Objective.

Assess mechanical performance of standard fusion instrumentation and growing rod constructs.

Summary of Background Data.

Growing rod instrumentation utilizes fewer anchors and spans longer distances, increasing shared implant loads relative to fusion. There is a need to evaluate growing rod's mechanical performance. ASTM F1717-15 standard assesses performance of spinal instrumentation; however, effects of growing rods with side-by-side connectors have not been evaluated.

Methods.

Standard and growing rod constructs were tested per ASTM F1717-15 methodology; setup was modified for growing rod constructs to allow for connector offset. Three experimental groups (standard with active length 76 mm, and growing rods with active lengths 76 and 376 mm; n = 5/group) were tested; stiffness, yield load, and load at maximum displacement were calculated. Computational models were developed and used to locate stress concentrations.

Results.

For both constructs at 76 mm active length, growing rod stiffness (49 ± 0.8 N/mm) was significantly greater than standard (43 ± 0.4 N/mm); both were greater than growing rods at 376 mm (10 ± 0.3 N/mm). No significant difference in yield load was observed between growing rods (522 ± 12 N) and standard (457 ± 19 N) constructs of 76 mm. Growing rod constructs significantly decreased from 76 mm (522 ± 12 N) to 376 mm active length (200 ± 2 N). Maximum load of growing rods at 76 mm (1084 ± 11 N) was significantly greater than standard at 76 mm (1007 ± 7 N) and growing rods at 376 mm active length (392 ± 5 N). Simulations with active length of 76 mm were within 10% of experimental mechanical characteristics; stress concentrations were at the apex and cranial to connector–rod interaction for standard and growing rod models, respectively.

Conclusion.

Growing rod constructs are stronger and stiffer than spinal instrumentation constructs; with an increased length accompanied a decrease in strength. Growing rod construct stress concentration locations observed during computational simulation are consistent with clinically observed failure locations.

Level of Evidence: 5
Genetic Variants of ABO and SOX6 are Associated With Adolescent Idiopathic Scoliosis in Chinese Han Population
Authors: Wu Zhichong , Wang Yuwen , Dai Zhicheng , Qiu Yong , Xu Leilei , Zhu Zezhang
Published: April 2019

Study Design.

A genetic association study.

Objective.

The aim of this study was to determine whether variants of ABO, SOX6, and CDH13 are associated with the susceptibility of AIS in Chinese Han population.

Summary of Background Data.

A recent large-scale genome-wide association study reported three novel loci in CDH13, ABO, and SOX6 genes associated with adolescent idiopathic scoliosis (AIS) in Japanese population. However, the association of these three genes with AIS in other populations remains obscure.

Methods.

The SNPs rs4513093, rs687621, and rs1455114 were genotyped in 1208 female patients and 2498 healthy controls. Samples for the expression analysis in paraspinal muscles were collected from 49 AIS and 33 congenital scoliosis (CS) patients during surgical interventions. Chi-square analysis was used to assess the difference regarding genotype and allele frequency between cases and controls. Tissue expressions of ABO, CDH13, and SOX6 were compared between AIS and CS patients by the Student t test.

Results.

SNPs rs4513093 of CDH13 and rs687621 of ABO were found to be significantly associated with AIS with an odds ratio of 0.8691 and 1.203, respectively. There was no significant association of rs1455114 with AIS. Moreover, AIS patients were found to have significantly increased expression of ABO. As for expression of CDH13 and SOX6, no remarkable difference was found between the two groups.

Conclusion.

The association of CDH13 and ABO variants with AIS was successfully replicated in the Chinese Han population. More studies are warranted to explore the functional role of ABO in the development of AIS.

Level of Evidence: N/A
Association between coffee intake and the risk of oral cavity cancer: a meta-analysis of observational studies
Authors: He Tao , Guo Xiangyu , Li Xue , Liao Chunjuan , Yin Wei
Published: April 2019

The association between coffee intake and the risk of oral cavity cancer has been inconsistent in previous studies. Therefore, we conducted a meta-analysis to summarize the evidence regarding the strength of association between coffee intake and oral cavity cancer. PubMed, Embase, and Cochrane Library were searched to select studies on the relationship between coffee intake and oral cavity cancer conducted up to September 2018. Case–control or cohort studies and those that have reported about the effect estimates with 95% confidence intervals (CIs) of oral cavity cancer according to the different categories of coffee intake were included. The odds ratio (OR) and its corresponding 95% CI were calculated using the random-effects model. Fourteen case–control and five cohort studies that recruited 6456 patients with oral cavity cancer were included in the final quantitative meta-analysis. High versus low coffee intake was associated with a reduced risk of oral cavity cancer (OR: 0.68; 95% CI: 0.56–0.82; P < 0.001) in case–control studies (OR: 0.70; 95% CI: 0.55–0.90; P = 0.006) and cohort studies (OR: 0.65; 95% CI: 0.48–0.87; P = 0.004). Moreover, intermediate coffee intake was significantly associated with a reduced risk of oral cavity cancer (OR: 0.85; 95% CI: 0.77–0.94; P = 0.002), and such associations were mainly observed in case–control studies (OR: 0.86; 95% CI: 0.76–0.98; P = 0.021) but not in cohort studies (OR: 0.83; 95% CI: 0.67–1.02; P = 0.071). High or intermediate coffee intake might have protective effects against oral cavity cancer. However, the underlying mechanisms must be further evaluated in large-scale prospective cohort studies.
Balance Measures Over 12 Months in Individuals With Chronic Obstructive Pulmonary Disease
Authors: Harrison Samantha Louise , Araujo Tamara , Goldstein Roger , Brooks Dina
Published: April 2019

Purpose:

To describe balance for 12 mo in people with chronic obstructive pulmonary disease (COPD).

Methods:

Individuals with COPD completed the Berg Balance Scale (BBS), the Balance Evaluation Systems Test (BEST), and the Activities-Specific Balance Confidence (ABC) scale before pulmonary rehabilitation (PR), post-PR and at 3, 6, and 12 mo. If an acute exacerbation of COPD (AECOPD) occurred, balance measures were repeated after 7 d and 1 mo. Descriptive data are displayed for balance measures at 5 time-points (pre-PR, post-PR, 3 mo, 6 mo, and 12 mo) in those without exacerbations. The outcome score at 7 d and 1 mo post-AECOPD was compared with the assessment closest to the AECOPD.

Results:

A total of 42 patients were recruited and 32 patients (17 male; mean age ± standard deviation = 68.5 ± 9.9 yr; FEV1 % predicted =38 ± 15%) completed balance measures post-PR. Seventeen, 11, and 6 patients, who did not exacerbate, completed balance measures at 3, 6, and 12 mo, respectively, with no overall change in balance measures over time. Of 32 patients, 15 experienced an AECOPD and of these, 8 and 11 completed measures at 7 d and 1 mo, respectively. Balance declined from baseline to 7 d (BBS, P = .010; BEST, P = .002) and to 1 mo post-AECOPD (BBS, P = .035). Balance recovered from 7 d to 1 mo post-AECOPD but did not return to baseline levels (BBS, P = .045; BEST, P = .006). There were no changes in balance confidence post-AECOPD.

Conclusions:

Balance remained stable over 12 mo after completion of PR in those who remained exacerbation-free. The impact of an AECOPD on measures of balance persisted after 1 mo.
Association of epidermal growth factor receptor (EGFR) gene polymorphisms with endometriosis
Authors: Wang Yu-Mei , Wu Meng-Jun , Lin Yong-Hong , Chen Jie
Published: April 2019

Aims:

To investigate the association between polymorphism in the gene encoding the epidermal growth factor receptor (EGFR) and susceptibility to endometriosis among women in southwest China.

Methods:

A case-control study involving 201 endometriosis patients and 237 control women without endometriosis was carried out at West China Second Hospital of Sichuan University from June 2016 to December 2017. Two tag single-nucleotide polymorphisms (SNPs) of EGFR gene, rs11977660 and rs2072454 were selected, and the distribution of genotypes and alleles was compared between the 2 groups using the chi-squared test with 2-sided contingency tables.

Results:

Genotype at rs11977660 was significantly associated with endometriosis (P < .05 for genotype and allele). T/T+C/T genotypes were associated with significantly higher risk of developing endometriosis than the C/C genotype (OR 2.129, 95%CI 1.411–3.212). No significant association was found between genotype at rs2072454 and endometriosis.

Conclusion:

Genotypes with a T nucleotide at rs11977660 may significantly increase risk of endometriosis in Chinese.
Comparison of high risk factors (hot food, hot beverage, alcohol, tobacco, and diet) of esophageal cancer
Authors: Chai Tianci , Shen Zhimin , Zhang Peipei , Lin Yuhan , Chen Sui , Zhang Zhenyang , Lin Wenwei , Kang Mingqiang , Lin Jiangbo
Published: April 2019

Background:

Esophageal cancer (EC) is one of the most common malignant tumors with a poor prognosis and identified as one of the leading causes of cancer death in the world. Many studies have reported that the incidence of EC is closely related to the intake of alcohol, hot food, and hot beverages, as well as smoking and diet. However, there is a lack of studies on the quantitative analysis of these risk factors for EC. If the solid quantitative evidence of these risk factors is provided for the prevention of EC, the prevalence of EC can be effectively reduced. We will conduct a systematic review and meta-analysis of high risk factors for EC in order to provide reliable evidence for the prevention of EC.

Methods and analysis:

We will search PubMed (Medline), the Cochrane Central Register of Controlled Trials, Embase, and Google Scholar for related studies published without language restrictions before December 1, 2019. Two review authors will search and assess relevant studies independently. Trials used a case-control, cross-sectional, cohort studies, randomized controlled trials (RCTs), and quasi-RCTs will be included. We will perform subgroup analysis in sex, age, ethnicity, and region.

Results:

The results of this study will be published in a peer-reviewed journal.

Conclusion:

We will perform a systematic review and meta-analysis of high risk factors for EC in order to provide reliable evidence for the prevention of EC. However, because of the characteristics of disease and intervention, large-sample trials that meet the inclusion criteria of this study may be insufficient. We will consider including some high-quality small-sample related trials, which may lead to high heterogeneity and affect the reliability of the results.
Proximal humeral internal locking plate combined with a custom neutral-position shoulder and elbow sling for proximal humerus fractures
Authors: Chen Xiong , Yu Zheng-Xi , Wang Huai-Yun , Shen Feng , Lin Guo-Bing , Wang Sheng , Yin Zong-Sheng
Published: April 2019

Objectives:

The aim of this study was to investigate the effectiveness of the proximal humeral internal locking system (PHILOS) plate combined with a custom neutral-position shoulder and elbow sling for proximal humerus fractures.

Methods:

A total of 112 patients with proximal humerus fractures were assigned randomly into 2 groups. Group A (n = 56) was treated by open reduction and internal fixation (ORIF) with a PHILOS plate; group B (n = 56) was treated by ORIF with a PHILOS plate in combination with the use of a custom neutral-position shoulder and elbow sling for 30 days after surgery. The incidence of internal fixation failure, the Constant–Murley shoulder assessment, and Visual Analogue Scale (VAS) score were recorded and analyzed.

Results:

Patients included were followed up for an average of 15 months (range, 6–24 months). No significant differences were observed in mean VAS scores and mean Constant–Murley shoulder assessment scores at 1-day preoperative and postoperative day 3 between groups A and B. However, mean VAS scores and mean Constant–Murley shoulder assessment in group B were significantly improved when compared with group A at postoperative day 30 and the final follow-up. No cases of postoperative infection, loss of reduction, PHILOS break, or vascular nerve injury occurred in either group.

Conclusions:

Proximal humerus fractures treated with the combination of the PHILOS and custom neutral-position shoulder and elbow sling for 30 days after operation was associated with a lower incidence of internal fixation failure. There was no increase in adverse events compared with open reduction and internal fixation with a PHILOS plate alone.
The clinical and pathological features of toxic encephalopathy caused by occupational 1,2-dichloroethane exposure
Authors: Dang Jing , Chen Jihua , Bi Fangfang , Tian Fafa
Published: April 2019

To understand the clinical and pathological features of 1,2-dichloroethane (DCE) toxic encephalopathy.

The cases of 4 patients who were admitted to Xiangya hospital between January 8, 2008 and November 8, 2012 with diagnoses of DCE toxic encephalopathy were examined. We recorded data on gender, age of onset, exposure time to DCE, symptom onset to admission interval, symptom onset to worst symptom experience interval, and clinical manifestations, as well as cranial magnetic resonance imaging (MRI) and brain biopsy pathology results.

All 4 patients had a history of DCE exposure and presented with symptoms of intracranial hypertension. Cranial MRI revealed extensive brain edema throughout the subcortical white matter, the bilateral globus pallidus, and the cerebellar dentate nuclei. The brain biopsy confirmed severe cerebral edema, including peripherovascular edema, with swelling of various cell types, with extensive glial cell necrosis. After treatment with steroids and mannitol (3–10 weeks), all 4 patients recovered, partially or completely.

Severe brain edema and extensive glial cell necrosis were the main pathological features observed in the present cases, with a likely etiology of DCE toxicity. Early, prompt, and long-term treatment with dehydrating agents and glucocorticoids was an effective treatment for this condition.