bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyphema in Open-Globe Versus Closed-Globe Injuries in Operation Iraqi Freedom and Enduring Freedom: 2001–2011
Authors: Miller Natalie R , Justin Grant A , Kim Won I , Brooks Daniel I , Ryan Denise S , Weichel Eric D , Colyer Marcus H
Published: December 2019

Introduction

The goal of this study is to update the incidence of hyphema in Operation Iraqi (OIF) and Enduring Freedom (OEF). We wanted to assess associated ocular injuries and final visual acuity (VA) in open-globe versus closed-globe injuries with a hyphema.

Materials and Methods

We performed a retrospective review of the Walter Reed Ocular Trauma Database (WRTOD) to identify U.S. Service members and DoD civilians with hyphema who were evacuated to Walter Reed Army Medical Center between 2001 and 2011. Primary outcome measures were the final VA and differences in concomitant ocular injuries in open-globe hyphema and closed-globe hyphema.

Results

168 of 890 eyes (18.9%) in the WROTD had a hyphema. Closed-globe injuries were noted in 64 (38.1%) eyes and open-globe injuries in 104 (61.9%) eyes. A final VA of less than 20/200 was noted in 88 eyes (51.8%). Eyes with hyphema were more likely to have traumatic cataract formation (odds ratio (OR) 6.2, 95% confidence interval (CI) 4.2–9.2, P < 0.001), retinal detachment (OR 4.2, CI 2.8–6.4, P < 0.001), angle recession (OR 8.1, CI 2.9–24.3, P < 0.001), and final VA of less than 20/200 (OR 3.7, CI 2.6–5.4, P < 0.001). Traumatic cataract formation (OR 7.4, CI 2.9–18.7, P < 0.001), retinal detachment (OR 6.1, CI 2.1–17.5, P < 0.001), and a final VA less than 20/200 (OR 6.1, CI 2.4–15.4 P < 0.001) were statistically more likely to occur with an open-globe hyphema than with a closed-globe hyphema.

Conclusions

Close follow-up in patients with hyphema is important due to the associated development of traumatic cataract and retinal detachment and poor final visual outcome.
Double dark matter vision: twice the number of compact-source lenses with narrow-line lensing and the WFC3 grism
Authors: Nierenberg A M , Gilman D , Treu T , Brammer G , Birrer S , Moustakas L , Agnello A , Anguita T , Fassnacht C D , Motta V , Peter A H G , Sluse D
Published: December 2019

The magnifications of compact-source lenses are extremely sensitive to the presence of low-mass dark matter haloes along the entire sightline from the source to the observer. Traditionally, the study of dark matter structure in compact-source strong gravitational lenses has been limited to radio-loud systems, as the radio emission is extended and thus unaffected by microlensing which can mimic the signal of dark matter structure. An alternate approach is to measure quasar nuclear-narrow-line emission, which is free from microlensing and present in virtually all quasar lenses. In this paper, we double the number of systems which can be used for gravitational lensing analyses by presenting measurements of narrow-line emission from a sample of eight quadruply imaged quasar lens systems, WGD J0405−3308, HS 0810+2554, RX J0911+0551, SDSS J1330+1810, PS J1606−2333, WFI 2026−4536, WFI 2033−4723, and WGD J2038−4008. We describe our updated grism spectral modelling pipeline, which we use to measure narrow-line fluxes with uncertainties of 2–10 per cent, presented here. We fit the lensed image positions with smooth mass models and demonstrate that these models fail to produce the observed distribution of image fluxes over the entire sample of lenses. Furthermore, typical deviations are larger than those expected from macromodel uncertainties. This discrepancy indicates the presence of perturbations caused by small-scale dark matter structure. The interpretation of this result in terms of dark matter models is presented in a companion paper.
MUSE-ALMA haloes V: physical properties and environment of z ≤ 1.4 H i quasar absorbers
Authors: Hamanowicz Aleksandra , Péroux Céline , Zwaan Martin A , Rahmani Hadi , Pettini Max , York Donald G , Klitsch Anne , Augustin Ramona , Krogager Jens-Kristian , Kulkarni Varsha , Fresco Alejandra , Biggs Andrew D , Milliard Bruno , Vernet Joël D R
Published: December 2019

We present results of the MUSE-ALMA haloes, an ongoing study of the circumgalactic medium (CGM) of low-redshift galaxies (z ≤ 1.4), currently comprising 14 strong H i absorbers in 5 quasar fields. We detect 43 galaxies associated with absorbers down to star formation rate (SFR) limits of 0.01–0.1 M⊙ yr−1, found within impact parameters (b) of 250 kpc from the quasar sightline. Excluding the targeted absorbers, we report a high detection rate of 89 per cent and find that most absorption systems are associated with pairs or groups of galaxies (3–11 members). We note that galaxies with the smallest impact parameters are not necessarily the closest to the absorbing gas in velocity space. Using a multiwavelength data set (UVES/HIRES, HST, MUSE), we combine metal and H i column densities, allowing for derivation of the lower limits of neutral gas metallicity as well as emission-line diagnostics (SFR, metallicities) of the ionized gas in the galaxies. We find that groups of associated galaxies follow the canonical relations of N(H i)–b and Wr(2796)–b, defining a region in parameter space below which no absorbers are detected. The metallicity of the ISM of associated galaxies, when measured, is higher than the metallicity limits of the absorber. In summary, our findings suggest that the physical properties of the CGM of complex group environments would benefit from associating the kinematics of individual absorbing components with each galaxy member.
ACTR-25. RETHINKING THE DOGMA: HOW IMPORTANT IS TREATMENT OF THE CSF IN PATIENTS WITH PRIMARY CNS LYMPHOMA (PCNSL)?
Authors: Aregawi Dawit , Korfel Agnieszka , Schlegel Uwe , Glantz Michael
Published: December 2019

INTRODUCTION

PCNSL constitutes a small but important fraction of adult malignant primary brain tumors. These tumors frequently and often dramatically respond to high-dose methotrexate-containing regimens, but almost inevitably recur. Following initial treatment and at the time of recurrence, no widely accepted treatment paradigm exists. In particular, no consensus exists regarding the need to treat the CSF at the time of PCNSL diagnosis.

METHODS

We identified three independent cohorts of adults with PCNSL in which some patients received intra-CSF chemotherapy as part of their initial therapy, and others did not. All patients were comparable with respect to demographic and disease characteristics (study-level data). Data on CSF involvement, response, relapse, and survival were extracted and summary statistics were calculated from these three studies using the inverse variance method and random effects model.

RESULTS

The three cohorts were treated with: HD MTX/rituximab/ifosfamide followed by either HD MTX/cytarabine/ifosfamide (group Ia), or cytarabine/thiotepa and autologous stem cell transplant (group Ib) (n=80); HDMTX/rituximab/vinca alkaloids/ifosfamide/cytarabine (group II) (n=48); or HD MTX/rituximab (group III). Intra-CSF chemotherapy consisted of MTX/cytarabine/prednisolone (group Ia only, n=43); MTX/cytarabine/prednisolone (group II, n=30); or liposomal cytarabine (group III, n=21). One- and two-year survivals were greater in the IT chemotherapy compared to the no-IT chemotherapy groups (RR 1.25 [1.16–1.34] and 1.20 [1.14–1.26] respectively, p< 0.001 for both). Relapse involving the CSF was greater in the non-IT chemotherapy group (RR 2.31 [2.03–2.62], p< 0.001). In one cohort, comparison of pre-treatment CSF cytology from ventricular vs lumbar sites was possible. CSF cytology was positive in 81% of ventricular specimens vs 14.3% of lumbar specimens (p< 0.0001).

CONCLUSIONS

CSF involvement by tumor occurs in most patients with PCNSL. Including intra-CSF chemotherapy in the initial treatment regimen of these patients may improve overall survival and reduce the frequency of relapses involving the CSF. Well-designed prospective trials are warranted.
GENE-02. ESTABLISHING PERSONALIZED TREATMENT OPTIONS FOR RECURRENT HIGH-GRADE GLIOMAS
Authors: Hau Ann-Christin , Houben Linsey , Klein Eliane , Oudin Anais , Stieber Daniel , Flies Ben , Kaoma Tony , Azuaje Fransisco , Fritah Sabrina , Bjerkvig Rolf , Mittelbronn Michel , Hertel Frank , Golebiewska Anna , Niclou Simone
Published: December 2019

BACKGROUND

High grade glioma (HGG) patients develop resistance to standard treatment leading to disease progression and limited life expectancy. Recent advances in the molecular characterisation of treatment-naïve HGGs based on next generation sequencing and DNA methylation analyses have led to a better delineation of HGG-subtypes and identification of distinct genomic abnormalities opening opportunities for personalized treatment strategies.

METHODS

We collected 300 fresh glioma specimen with approximately 100 longitudinal samples of initial and recurrent tumors from 43 matched patients. We succeeded in generating a live-biobank of HGG patient-derived orthotopic xenografts (PDOX) and 3D tumor organoids that neatly recapitulates the mutational spectrum including structural DNA variations and methylation-based subtypes of gliomas. A highlight is the generation of 19 PDOXs of paired initial and relapse HGGs from 9 glioma patients, enabling high-throughput drug screens. We performed comprehensive molecular profiling using arrayCGH, DNA-methylation and targeted DNA sequencing on patient specimen and their derivatives, 3D tumor organoids and PDOXs.

RESULTS

Detailed analysis of the paired longitudinal samples indicated that PDOXs closely recapitulate the evolutionary trajectory of the parental tumors. Furthermore, targeted genomic sequencing of paired HGGs suggests that relapse tumors also accumulate somatic mutations in epigenetic effectors. Based on patient-derived material we carried out drug response screening on 3D tumor organoids using a compound library matching the majority of genes that were assessed with targeted sequencing. Differential drug responses between initial and recurrent tumors were observed and the prevailing primary drug response profiles were essentially recapitulad in the relapse setting.

CONCLUSIONS

Response assessment of treatment-naïve gliomas and their recurrences provides crucial information on the differential sensitivity between initial and relapsed HGGs and offers novel personalized therapeutic options for the relapse setting. Furthermore, in depth correlation of the profiled somatic molecular landscape with drug response will enable pharmacogenomic predictions of potential inhibitors in the clinical setting.
HOUT-17. UTILITIES OF RARE CANCERS LIKE MALIGNANT PLEURAL MESOTHELIOMA AND GLIOBLASTOMA MULTIFORME - DO THEY COMPARE?
Authors: Proescholdt Christina , Kelly Justin
Published: December 2019

BACKGROUND

Glioblastoma (GBM) is the most aggressive primary brain cancer in adults. Malignant pleural mesothelioma (MPM) is an invasive and generally fatal malignancy of the pleura mainly caused by exposure to asbestos fibers. TTFields treatment has been shown effective in both MPM and GBM with a comparable increase in median overall survival (OS). Differences in utility values however, could significantly influence assessment of cost-effectiveness for MPM and GBM, despite similar clinical efficacy.

METHODS

We reviewed the published literature adressing health state preference values or health utilities in both indications using a boolean search of the PubMed database. The results were compiled separately for both diseases and then compared to each other.

RESULTS

Estimates of health states preference values or utilities in GBM all refer to one single publication by the UK NICE. Healthy members of the NHS Value of Health Panel (VoHP) rated a total of nine descriptive health state scenarios using the standard gamble method for preference elicitation. Utilities for MPM were derived at individual patient level from the EQ-5 questionnaire collected during one trial. Other publications do not use specific mesothelioma heath state preference velues but assume applicability of utilities derived from a non small cell lung cancer (NSCLC) population.

CONCLUSIONS

GBM utilites use different health states for elicitation, while utilities used in MPM were elicited at patient level. GBM utilities can be used in a health state disease model but there are no similar published values for MPM. MPM utilities using the EQ-5 questionnaire however better describe individual utilities and their change during the course of disease. Despite similar costs and clinical efficacy of TTFields treatment for GBM and MPM, the difference in elicitation methods and sources of utilites may lead to significant disparities in cost effectiveness assessment and subsequent adoption of TTFields treatment in different indications.
PATH-13. SEX-LINKED TUMORAL MGMT STATUS AND OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Barnett Addison , Saeed Bamashmos Anas , Ali Assad , Li Hong , Bosler David , Lathia Justin , Yeaney Gabrielle , Sagar Soumya , Yu Jennifer , Murphy Erin , Chao Samuel , Suh John , Mohammadi Alireza , Stevens Glen , Angelov Lilyana , Peereboom David , Barnett Gene , Ahluwalia Manmeet
Published: December 2019

INTRO/OBJECTIVE

Glioblastoma (GBM) and MGMT have been reported to have sexual dimorphism. The primary objective of this study was to analyze the impact and association between sex and MGMT status on progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed GBM.

METHODS

582 patients with newly diagnosed GBM who underwent first surgical intervention at a single tertiary care institution between 2012 and 2018 were reviewed. Adults with documented methylated (≥ 12) and un-methylated (≤ 7) MGMT status were included. A Kaplan-Meier and Cox proportional hazard models were used to analyze the association between sex and MGMT status on PFS and OS.

RESULTS

464 adult patients (median age 63.4, 36.6% female) had documented MGMT status. Overall rate of MGMT methylated patients was 42.5%, while females were more often methylated than males (52.1% vs 37.4%, p=0.004). MGMT methylated compared to un-methylated females (median: 12.8 vs 7.4 months; 1-yr: 53% vs 27%) had a greater PFS benefit than males (median: 9.6 vs 6.8 months; 1-yr: 44% vs 23%). OS was significantly improved in MGMT methylated compared to un-methylated patients among females (p=0.001) but not among males (p=0.22). Among MGMT methylated patients, females had significantly better OS compared to males (median: 18.7 vs 12.4 months; 2-yr OS: 36.8% vs 24.3%, p=0.03). Although statistically not significant, a similar pattern was observed on PFS (median: 12.8 vs 9.6 months; 1-yr PFS: 52.6% vs 44.4%). Compared to MGMT methylated females, MGMT methylated males had a PFS HR=1.22 (95% CI=0.80 – 1.85, p=0.36), and an OS HR=1.45 (95% CI=1.03 – 2.04, p=0.032).

CONCLUSION

MGMT methylation is more common in females and methylation had a larger impact on both PFS and OS in females compared to males. These analyses highlight the need to further investigate sex differences that can inform clinical management of GBM.
NIMG-21. FROM BEYOND THE MARGIN: HIGH ANGULAR RESOLUTION Q-SPACE MRI MAY DETECT GLIOBLASTOMA TUMOR CELL INVASION INTO BRAIN PARENCHYMA
Authors: Leary Owen , Toms Steven , Zepecki John , Merck Derek , Tapinos Nikos , Gilbert Richard
Published: December 2019

BACKGROUND

Invasion of glioblastoma tumor cells beyond the visible margins is hypothesized to mediate tumor spread and recurrence, and thereby affect poor survival. Radiomic biomarkers associated with the extent of tumor infiltration are virtually non-existent.

METHODS

Seven subjects diagnosed with glioblastoma underwent high resolution “Q-Space” diffusion-weighted MRI sequences (Siemens 3T scanner, 64 gradient directions, b-value=1000s/mm2) during pre-operative MRI workup. For each subject, the largest tumor was manually segmented, and patterns of probabilistic inter-voxel coherence intersecting each segmentation generated as tractograms using DSI Studio (length=0–200mm, AT=30º). Separately, immunodeficient (Nu/J) mice were injected sub-hippocampally with patient-derived glioma stem cells (GSCs) using stereotactic guidance. Two months after injection, mice were sacrificed, resected brains were scanned on a Bruker 7T MRI using cryoprobe with T2-weighted and diffusion-weighted sequences (512 directions), and tumor-intersecting tractography displayed. 3D whole-brain reconstruction of the same xenograft model, stained with anti-human mitochondrial antibody, was performed for comparison. In one patient undergoing resection of fronto-temporal glioblastoma, BrainLab intraoperative navigation was used for stereotactic biopsy of extra-tumor parenchymal samples localized according to proximity to tumor-intersecting tractography. RNA-seq was performed on all samples using Illumina HiSeq2500 by a blinded analyst.

RESULTS

All human tumors (n=7) displayed region-specific long projecting tracts extending into brain parenchyma (Mean=23.2mm, SD=3.1mm). Maximum tract length varied from 80–130mm (Mean=102mm, SD=20.4mm). Xenograft models displayed similar tumor-intersecting tractography (n=3), with 3D reconstruction of stained GSCs replicating that pattern. RNAseq data revealed significant overrepresentation (≥2-fold) of 528 transcripts in projecting tumor tract-associated samples compared to samples obtained from the tumor mass itself and brain parenchyma unassociated with projecting tumor tracts. Functional classification revealed that 62% of these transcripts regulate cell motility as part of inter-related networks.

CONCLUSION

These imaging data, backed by region-specific transcriptomic evidence, suggest that Q-Space MRI may discriminate localizable patterns of inter-voxel coherence representing tumor-associated infiltration pathways in glioblastoma.
NCMP-16. IMMUNO-ONCOTHERAPY (IO) PROVOKED ENCEPHALITIS AND METASTATIC MIMICRY: PATIENT WITH HISTORY OF RENAL CELL CARCINOMA ON IO PRESENTS WITH SEIZURE, FIELD CUT, AND BRAIN MASS
Authors: Tosha Gatson Na , Patel Mayur , Grant Michelle , Woods Julie , Mongelluzzo Gino , Conger Andrew
Published: December 2019

With the success of immuno-oncotherapy (IO) to treat systemic cancers came the risk for multi-organ autoimmune inflammation (esophagitis, colitis, hypophysitis, pneumonitis, etc.). Immune-mediated encephalitis, however, has been only rarely described in patients treated on IO. Here we present the first case of a 70-year-old male with history of clear cell renal cell carcinoma (CCRCC, Fuhrman grade 4, April 2017) post-nephrectomy with early progressive pulmonary metastases treated with pazopanib before switching to single-agent nivolumab (February 2018) with demonstrated early response. Further progression (March 2019) added body irradiation and continued systemic nivolumab with questionable medication-induced dermatitis. Patient presented to ED in May 2019 with new-onset generalized tonic-clonic seizure, left visual field cut, and 4.6cm heterogeneous enhancing right occipital mass with vasogenic edema on brain MRI, presumed metastasis. However, unknown to the patient was a remote area of right occipital encephalomalacia (found on skull-based portion of staging PET, July 2018) presumed silent stroke or TBI endorsed 20-years-ago. Patient started anti-epileptic therapy and underwent negative CSF evaluation before neurosurgical resection. Tissue pathology concerning for lymphoproliferative malignancy versus reactive lymphocytic infiltrate with perivascular distribution of monomorphic CD4+ T-cell predominance (97%) and positive T-cell receptor (gamma, beta) gene rearrangement. While clonal T-cell populations are highly suggestive of T-cell malignancies, reactive conditions can also rarely show clonal T-cell populations. Patient underwent a negative systemic staging for lymphoma and IO was discontinued without immediate initiation of steroids. Follow up clinical evaluation reveal patient improved off IO therapy. Patient was determined to have reactive immune-mediated encephalitis secondary to IO therapy causing seizure mimicking brain metastasis of primary CCRCC. Interestingly, the prior area of encephalomalacia allowed for a cellular bed to collect, resembling brain mass. Upfront staging brain MRI prior to starting IO might have revealed susceptible area and could be considered in these patients
Trust-Based Theories of Promising
Authors: Bruno Daniele
Published: December 2019

This paper discusses the prospects of a comprehensive philosophical account of promising that relies centrally on the notion of trust. I lay out the core idea behind the Trust View, showing how it convincingly explains the normative contours and the unique value of our promissory practice. I then sketch three distinct options of how the Trust View can explain the normativity of promises. First, an effect based-view, second, a view drawing on a wider norm demanding respect to those whom one has invited to something, and finally, as a new suggestion, a Normative Interest View. This view holds that promising is a normative power that serves our interest in facilitating or enabling the relationship of trust between promisor and promisee. I argue that only those embracing the third view can fully account for the distinctive obligation that results from the giving of a valid promise in all cases.
Evidence for weak-coupling holography from the gauge/gravity correspondence for Dp-branes
Authors: Sekino Yasuhiro
Published: December 2019

Gauge/gravity correspondence is regarded as a powerful tool for the study of strongly coupled quantum systems, but its proof is not available. An unresolved issue that should be closely related to the proof is what kind of correspondence exists, if any, when gauge theory is weakly coupled. We report progress about this limit for the case associated with D$p$-branes ($0\le p\le 4$), namely, the duality between the $(p+1)$D maximally supersymmetric Yang–Mills theory and superstring theory on the near-horizon limit of the D$p$-brane solution. It has been suggested by supergravity analysis that the two-point functions of certain operators in gauge theory obey a power law with the power different from the free-field value for $p\neq 3$. In this work, we show for the first time that the free-field result can be reproduced by superstring theory on the strongly curved background. The operator that we consider is of the form ${\rm Tr}(Z^J)$, where $Z$ is a complex combination of two scalar fields. We assume that the corresponding string has the worldsheet spatial direction discretized into $J$ bits, and use the fact that these bits become non-interacting when ’t Hooft coupling is zero.
LOGARITHMIC INTERPOLATION METHODS AND MEASURE OF NON-COMPACTNESS
Authors: Besoy Blanca F , Cobos Fernando
Published: December 2019

We derive interpolation formulae for the measure of non-compactness of operators interpolated by logarithmic methods with $\theta = 0,1$ between quasi-Banach spaces. Applications are given to operators between Lorentz–Zygmund spaces.
Obesity and other medical comorbidities among NT1 patients after the Norwegian H1N1 influenza epidemic and vaccination campaign
Authors: Nordstrand Sebjørg E H , Juvodden Hilde T , Viste Rannveig , Rootwelt Terje , Karlsen Tor-Ivar , Thorsby Per M , Swanson David , Nilsen Kristian Bernhard , Hansen Berit H , Knudsen-Heier Stine
Published: December 2019

Study Objectives

Narcolepsy type 1 (NT1) may be complicated by comorbidities. We aimed to study the extent of obesity and other medical comorbidities in a Norwegian population of NT1 patients with debut of symptoms after the 2009 H1N1 influenza epidemic and vaccination campaign. We also aimed to explore factors associated with obesity.

Methods

Ninety-one patients (48 children and 43 adults) were included in this cross-sectional study, 80 of whom were H1N1-vaccinated. All participants were hospitalized and underwent sleep investigation and physical examination, and completed a semi-structured clinical interview.

Results

In children, 16 females (70%) and 10 males (40%) were classified as overweight or obese. Twenty children (42%) had a co-existing medical disorder. Medical comorbidity was significantly positively associated with BMI in children (p = .032). In adults, 19 females (58%) and 7 males (70%) were classified as overweight or obese. Twenty-six adults (61%) had a co-existing medical disorder. We found no factors significantly associated with BMI in adults. On a fatigue scale from 0 to 100, lower scores indicating more fatigue, we found a mean (SD) total fatigue score of 50 (17) in children and 39 (16) in adults.

Conclusion

In a cohort of predominantly H1N1-vaccinated NT1 patients, we found a high prevalence of overweight or obesity. Half of the cohort presented with one or more additional medical comorbidities, and patients reported a clinically relevant degree of fatigue. Our findings highlight the importance of carefully monitoring patients with NT1 with regard to the development of obesity, which is a significant risk factor for cardiovascular disorders.
Transcription Activator-Like Effectors Diversity in Iranian Strains of Xanthomonas translucens
Authors: Khojasteh Moein , Shah Syed Mashab Ali , Haq Fazal , Xu Xiameng , Taghavi S. Mohsen , Osdaghi Ebrahim , Chen Gongyou
Published: December 2019

Bacterial leaf streak caused by different pathovars of Xanthomonas translucens is the most important seedborne bacterial disease of small grain cereals. However, variations in the virulence-associated genomic areas of the pathogen remain uninvestigated. In this study, the diversity of transcription activator-like effectors (TALE) was investigated using the Southern blotting of BamHI-digested genomic DNAs in the Iranian strains of X. translucens. All 65 X. translucens strains were assigned into 13 genotypes, where 57 X. translucens pv. undulosa strains were placed in genotypes 1 to 8, and seven X. translucens pv. translucens strains were placed in genotypes 9 to 12. Interestingly, we did not find any TALE genes in the strain XtKm7 (genotype 13), which showed to be pathogenic only on barley. Virulence and aggressiveness of these strains in greenhouse conditions were in agreement with the TALE-based clustering of the strains in the pathovar level, though variations were observed in the aggressiveness of X. translucens pv. undulosa strains. In general, strains containing higher numbers of putative TALE genes were more virulent on wheat and barley than strains containing fewer. This is the first TALE-based genetic diversity analysis on X. translucens strains and provides novel insights into the virulence repertories and genomic characteristics of the pathogen. Further investigations using TALE mutagenesis and complementation analysis are warranted to precisely elucidate the role of each detected X. translucens TALE in bacterial virulence and aggressiveness either on wheat or barley.
Casein kinase 2 interacting protein 1 positively regulates caudal-related homeobox 1 in intestinal-type gastric cancer
Authors: Ma Liang , Cao Ying , Hu Jian-Jun , Chu Ming-Liang
Published: December 2019

Background

Gastric cancer (GC) is one of the most common malignancies, and intestinal-type GC is the main histopathologic type of GC in China. We previously reported that casein kinase 2 interacting protein 1 (CKIP-1) acts as a candidate tumor suppressor in intestinal-type GC. CKIP-1 participates in the regulation of multiple signaling pathways, including the Wnt/β-catenin pathway, of which caudal-related homeobox 1 (CDX1) may be a downstream target gene. The purpose of this study was to investigate the relationship between CKIP-1 and CDX1 in intestinal-type GC.

Methods

Sixty-seven gastroscopy biopsy specimens and surgically resected gastric specimens were divided into four groups: gastric mucosa group, intestinal metaplasia (IM) group, dysplasia group, and intestinal-type GC group. The expression levels of CKIP-1 and CDX1 were detected in these groups and GC cell lines, and the correlations between these expression levels were analyzed. SGC7901 and BGC823 cells were divided into CKIP-1 shRNA groups and CKIP-1 over-expression groups, and CDX1 expression was detected. β-Catenin expression was detected in intestinal-type GC tissue samples and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 cells, and its correlation with CKIP-1 expression in intestinal-type GC tissue was analyzed. The Wnt/β-catenin pathway inhibitor DKK-1 and activator LiCl were incubated with SGC7901 cells, BGC823 cells, and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 and BGC823 cells, following which CDX1 and Ki-67 expression were detected.

Results

The expression levels of CKIP-1 and CDX1 were lower in patients with intestinal-type GC than in patients with IM and dysplasia (both P < 0.05). CKIP-1 and CDX1 expression levels were positively correlated in IM, dysplasia, and intestinal-type GC tissue and cell lines (r = 0.771, P < 0.01; r = 0.597, P < 0.01; r = 0.654, P < 0.01; r = 0.811, P < 0.01, respectively). CDX1 expression was decreased in the CKIP-1 shRNA groups and increased in the CKIP-1 over-expression groups of SGC7901 and BGC823 cells compared to that in the corresponding control groups (both P < 0.05). CKIP-1 expression was negatively correlated with β-catenin expression in intestinal-type GC patients (r = −0.458, P < 0.01). Compared to the control group, β-catenin expression was increased in the CKIP-1 shRNA SGC7901 cell group and decreased in the CKIP-1 over-expression SGC7901 cell group (P 
< 0.05). CDX1 expression was increased in SGC7901 and BGC823 cells treated with DKK-1, DKK-1 increased CDX1 expression and decreased Ki-67 expression in the CKIP-1 shRNA group; the opposite result was observed in SGC7901 and BGC823 cells treated with LiCl, and LiCl decreased CDX1 expression and increased Ki-67 expression in the CKIP-1 over-expression group (both P < 0.05).

Conclusions

Through the Wnt/β-catenin signaling pathway, CKIP-1 may positively regulate CDX1 in intestinal-type GC.
Cardiovascular Outcomes With the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes and Chronic Kidney Disease
Authors: Malik Aaqib H. , Yandrapalli Srikanth , Goldberg Michael , Jain Diwakar , Frishman William H. , Aronow Wilbert S.
Published: December 2019

Diabetes mellitus (DM) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a new class of hypoglycemic agents that have shown significant promise in the reduction of cardiovascular events. Current guideline recommendations do not support the use of these agents in patients with CKD stage 3 or higher. We performed a comprehensive meta-analysis to evaluate their cardiovascular effects in patients with type 2 DM and CKD stage 3 or higher. A comprehensive search was performed in PubMed, Cochrane central, and Embase. Software R was utilized to perform a meta-analysis via the generic inverse variance method. Additionally, we conducted a network meta-analysis to compare the relative efficacy and safety of each agent. Data from 7 randomized controlled trials and 6527 participants were available. In patients with type 2 DM and CKD, SGLT-2 inhibitor use resulted in a significant relative risk reduction of myocardial infarction (22%), heart failure hospitalization (39%), and major adverse cardiac events (20%) (all P-value < 0.05). There was also a trend towards a reduction in stroke and cardiovascular mortality. In a network meta-analysis, canagliflozin was the most effective in reducing myocardial infarction, stroke, and heart failure hospitalization. Empagliflozin performed better for the outcome of cardiovascular mortality, but the results failed to reach significance. In conclusion, SGLT-2 inhibitors significantly improve cardiovascular outcomes in patients with type 2 DM and CKD stage 3 or higher, providing a compelling reason for their use in this population subgroup.
Sarcopenia and Cardiac Dysfunction
Authors: Wong Alexandra , Frishman William
Published: December 2019

Although muscle loss is part of the natural course of human aging, sarcopenia has been associated with an increased risk of physical disability and mortality in older patients. Many heart failure patients concomitantly develop deficits in muscle mass and strength, resulting in decreased quality of life and exercise capacity. An underlying state of inflammation is central to the development of sarcopenia and muscle wasting in heart failure; however, additional research in human models is needed to further delineate the pathophysiology of muscle wasting in these patients. Previous studies have shed light on many of the potential targets for therapeutic intervention of sarcopenia in heart failure; however, physical exercise remains the prominent beneficial intervention. Future research must explore other therapeutic interventions in randomized, double-blind clinical trials, which may help to supplement exercise regimens. Sarcopenia shows promise as an easily measured predictor of outcomes after transcatheter aortic valve replacement.
Controlling Parenting Behaviors in Parents of Children Born Preterm: A Meta-Analysis
Authors: Toscano Carolina , Soares Isabel , Mesman Judi
Published: December 2019

Objective:

This meta-analysis tested whether parents of preterm-born children differ from parents of full-term-born children regarding controlling parenting.

Methods:

Databases of PubMed, Scopus, Web of Science, Open Access Theses and Dissertations, and Elton B. Stephens Company were searched for cross-sectional and prospective longitudinal studies examining controlling parenting in preterm-born children.

Results:

The meta-analysis included 27 independent data sets, derived from 34 studies, with a total of 8053 participants—3265 preterm and 4788 full-term children. Parents of children born preterm were more controlling than parents of children born full-term (Hedges' g = 0.29; 95% confidence interval: 0.19–0.39; z = 5.48; p < 0.001). Heterogeneity analysis indicated significant variation in effects between studies (Q = 148.46, p < 0.001), but the effects were not moderated by gestational age, birth weight, child age, child gender, parental education, type of parenting assessment method (observational vs parental self-report), parenting dimension measured (behaviors vs attitudes), type of controlling parenting (intrusiveness vs others), study design (cross-sectional vs longitudinal), year of publication, or geographical setting of the studies (America vs Europe).

Conclusion:

Findings suggest that parents of children born preterm are at higher risk for engaging in controlling parenting strategies, stressing the importance of psychosocial follow-up support for these parents.
Application of Corneal Optical Coherence Tomography Angiography for Assessment of Vessel Depth in Corneal Neovascularization
Authors: Nanji Afshan , Redd Travis , Chamberlain Winston , Schallhorn Julie M. , Chen Siyu , Ploner Stefan , Maier Andreas , Fujimoto James G. , Jia Yali , Huang David , Li Yan
Published: December 2019

Purpose:

To map and measure the depths of corneal neovascularization (NV) using 3-dimensional optical coherence tomography angiography (OCTA) at 2 different wavelengths.

Methods:

Corneal NV of varying severity, distribution, and underlying etiology was examined. Average NV depth and vessel density were measured using 840-nm spectral-domain OCTA and 1050-nm swept-source OCTA. The OCTA results were compared with clinical slit-lamp estimation of NV depth.

Results:

Twelve eyes with corneal NV from 12 patients were imaged with OCTA. Clinically “superficial,” “midstromal,” and “deep” cases had an average vessel depth of 23%, 39%, and 66% on 1050-nm OCTA, respectively. Average vessel depth on OCTA followed a statistically significant ordinal trend according to the clinical classification of vessel depth (Jonckheere–Terpstra test, P < 0.001). In 8 cases where both 840-nm OCTA and 1050-nm OCTA were acquired, there was excellent agreement in the mean vessel depth between the 2 systems (concordance correlation coefficient = 0.94, P < 0.001). The average vessel density measured by 840-nm OCTA was higher (average 1.6-fold) than that measured by 1050-nm OCTA.

Conclusions:

Corneal OCTA was able to map corneal NV in 3 dimensions and measure vessel depth and density. The depth of corneal NV varied between different pathologies in a manner consistent with previous pathologic studies. The measured vessel density appeared to be affected by the interscan time, which affects blood flow velocity sensitivity, and the wavelength, which affects the ability to penetrate through opacity. These findings suggest possible clinical applications of OCTA for the diagnosis of corneal pathology and quantitative monitoring of therapeutic response in patients with corneal NV.
The Association of Serum Vitamin D Level With the Severity of Dry Eye Parameters in Primary Sjögren Syndrome
Authors: Lee Jee Hye , Kim Sun Joo , Byun Yong-Soo , Lee Jennifer , Park Sung-Hwan , Chung So-Hyang
Published: December 2019

Purpose:

To analyze the relationship between serum 25(OH)D3 level and dry eye parameters in primary Sjögren syndrome (SS).

Methods:

This study included 74 eyes of 74 patients diagnosed with primary SS. Dry eye parameters included tear breakup time, Schirmer I value, corneal staining score, conjunctival staining score, and Ocular Surface Disease Index. The serum concentration of 25(OH)D3 was evaluated.

Results:

The mean serum 25(OH)D3 level was 20.4 ± 8.0 ng/mL. There were strong negative correlations between serum 25(OH)D3 level and corneal staining score (P < 0.001, r = −0.446) and conjunctival staining score (P < 0.001, r = −0.455). The Schirmer I value and tear breakup time showed significant positive correlations with serum 25(OH)D3 level (P = 0.038, r = 0.261 and P = 0.003, r = 0.352, respectively). The Ocular Surface Disease Index did not show any significant correlation with serum 25(OH)D3 level.

Conclusions:

This study demonstrates that serum 25(OH)D3 level might be associated with dry eye severity in primary SS.
Conjunctival Pediatric-Type Follicular Lymphoma
Authors: Okudolo Joseph O. , Bagg Adam , Meghpara Beeran B. , Sieber Melissa R. , Eagle Ralph C. , Milman Tatyana
Published: December 2019

Pediatric-type follicular lymphoma is an uncommon B-cell lymphoma that primarily involves the lymph nodes of the head and neck of children and young adults. Ocular involvement is rare, with only 5 well-documented cases in the literature, all occurring in the conjunctiva. The authors describe a 20-year-old African American man with enlarging bilateral medial conjunctival nodules. Excisional biopsy of the larger left conjunctival lesion, clinically presumed to be pyogenic granuloma, revealed pediatric-type follicular lymphoma composed of expansile follicles with germinal centers containing mitotically active blastoid cells, which coexpressed CD20, CD10, and BCL6 and lacked expression of BCL2. Polymerase chain reaction for immunoglobulin heavy chain rearrangement identified a monoclonal B-cell population. Fluorescence in situ hybridization studies failed to demonstrate BCL2, BCL6, and MALT1 gene rearrangements. Next-generation sequencing revealed a pathogenic MAP2K1 mutation, known to be enriched in pediatric-type follicular lymphoma. This report summarizes the clinical and pathologic diagnostic findings, biologic behavior, and management of conjunctival pediatric-type follicular lymphoma.
Focal Eosinophilic Myositis Affecting the Orbicularis Muscle: Clinical and Image Aspects
Authors: Galindo-Ferreiro Alicia , Torres Nieto Maria Angeles , Barbado Ajo Julia , Schellini Silvana
Published: December 2019

Focal eosinophilic myositis (FEM) is a rare disease that is even more uncommon in affecting the periocular area. The authors are reporting the first case of FEM occurring in the lower eyelid of a 45-year-old Caucasian female who presented with localized painful area of glossy induration and peau d’orange skin lesion. Magnetic resonance image shows significant hyperintense thickening of the pre-septal orbicularis muscle region on T2-weighted images. Incisional biopsy of the induration revealed marked fibrinoid degeneration of the orbicularis muscle and adjacent fascia, mixed cellular infiltration of lymphocytes and eosinophils and a predominant CD8+ lymphocytic infiltrates in the immunohistochemical study. The final diagnosis was FEM. Oral prednisolone improved symptoms and the lesions disappeared, with no recrudescence in a one year follow-up.
An investigation of the effect of patient-controlled analgesia on long-term quality of life after major surgery: A prospective cohort study
Authors: Tai Ying-Hsuan , Wu Hsiang-Ling , Lin Shih-Pin , Tsou Mei-Yung , Chang Kuang-Yi
Published: December 2019

Background:

Chronic pain is a common postoperative complication in patients undergoing major surgery and may significantly affect their quality of life (QOL). Whether patient-controlled analgesia (PCA) can reduce the risk of chronic postsurgical pain and promote long-term QOL is still unclear.

Methods:

In this prospective cohort study, we followed up patients undergoing major surgery, recorded changes in their postoperative QOL over time using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire and chronic pain events, evaluated the long-term effects of distinct PCA techniques (intravenous, epidural, or none) on their QOL and risk of chronic pain, and explored relevant predictors. The patients’ QOL and chronic pain events were collected preoperatively, 3, 6, and 12 months after surgery. Generalized linear mixed models were used to control for individual heterogeneity and adjust for potential confounding factors.

Results:

We included 328 patients undergoing major surgery from September 22, 2015, to December 31, 2016, in this study. Multivariate regression models showed that patients using intravenous PCA had a better QOL in physical health (adjusted coefficient 3.7, 95% CI, 0.5–8.0) compared with those receiving non-PCA treatments. Distinct PCA techniques did not significantly affect QOL in psychological, social relationship, or environmental domains of the WHOQOL-BREF scale or the risk of chronic postsurgical pain.

Conclusion:

Patients using intravenous PCA had a better QOL in physical health over time after major surgery, which may have been due to factors other than pain-relieving effects.
Risk factors associated with preterm labor, with special emphasis on preterm premature rupture of membranes and severe preterm labor
Authors: Hosny Alaa El-Dien M.S. , Fakhry Mohsen N. , El-khayat Waleed , Kashef Mona T.
Published: December 2019

Background:

Preterm labor (PTL) can lead to preterm birth, which can cause neonatal mortality and morbidity. Preterm premature rupture of membranes (PPROM) and severe PTL (SPTL) are serious PTL subtypes. Hereby, we aimed to investigate risk factors associated with PPROM and SPTL, among Egyptian women.

Methods:

In this case-control study, 117 women were enrolled without any known medical risk for PTL. The control group (n = 45) had term labor (≥37 gestational weeks), while the case group (n = 72) had PTL (<37 gestational weeks). The PTL group was subdivided into those with PPROM (n = 18) and those with intact membranes (n = 54). Fifty-two PTL women, with accurate gestational age, were subdivided into SPTL (n = 31, ≤34 gestational weeks) and mild preterm labor (MPTL; n = 21, 35-36 gestational weeks). All groups were examined for different demographic characteristics, obstetrical history, clinical signs, and vaginal and urinary tract infections. Nominal logistic regression was applied to investigate significant variables associated with PPROM and intact membranes PTL, while ordinal logistic regression was used to estimate significant variables associated with SPTL and MPTL.

Results:

The final multivariate nominal model identified abortion history, heavy vaginal bleeding history, and elevated vaginal pH as significant predictors of PPROM. The same model identified age <20 years old, abortion history, heavy growth of vaginal organisms, and any growth of Gram-negative bacilli as the significant predictors of intact membranes PTL. The final multivariate ordinal model identified age <20 years old, abortion history, vaginal pH, and heavy growth of vaginal organisms as the significant predictors of SPTL and MPTL.

Conclusion:

Age <20 years old, abortion history, heavy vaginal bleeding, vaginal pH, and heavy growth of vaginal organisms were reported as risk factors for PPROM and SPTL. Most of these factors are related to infection; therefore, proper infection control is recommended during prenatal and antenatal care.
Antibiotic use in patients with acute cholecystitis after percutaneous cholecystostomy
Authors: Wu Pei-Shan , Chou Chung-Kai , Hsieh Yun-Chen , Chen Chun-Ku , Lin Yi-Tsung , Huang Yi-Hsiang , Hou Ming-Chih , Lin Han-Chieh , Lee Kuei-Chuan
Published: December 2019

Background:

Currently, evidence regarding the strategies of antibiotic use in patients with acute cholecystitis after receiving percutaneous cholecystostomy is limited. Hence, we aimed to investigate the outcomes in patients with inoperable acute cholecystitis receiving narrow or broad-spectrum antibiotics after percutaneous cholecystostomy.

Methods:

A total of 117 patients receiving percutaneous cholecystostomy were categorized into moderate and severe acute cholecystitis defined by the Tokyo guideline and then divided into group A (narrow-spectrum antibiotic use) and group B (broad-spectrum antibiotic use). The clinical outcomes and complications were analyzed.

Results:

In moderate acute cholecystitis (n = 80), group A patients (n = 62) had similar early recurrent rate (11.3% vs 16.7%; p = 0.544) and a shorter length of hospital stay (13.4 ± 8.6 vs 18.6 ± 9.4 days; p = 0.009) as compared with group B patients (n = 18). No in-hospital mortality occurred in moderate acute cholecystitis. In severe acute cholecystitis (n = 37), both groups had similar length of hospital stay (16.3 ± 12.2 vs 20.9 ± 9.5 days; p = 0.051), early recurrent rate (0% vs 16.7%; p = 0.105), and in-hospital mortality rate (5.3% vs 16.7%; p = 0.340). Although group B patients with severe cholecystitis had higher serum levels of alkaline phosphatase (Alk-P) and higher proportion of underlying malignancy, American Society of Anesthesiologists (ASA) class IV and septic shock, the clinical outcomes were not inferior to patients in group A.

Conclusion:

In moderate acute cholecystitis after percutaneous cholecystostomy, patients receiving narrow-spectrum antibiotics have comparable clinical outcomes as those treated with broad-spectrum antibiotics. However, in severe acute cholecystitis, broad-spectrum antibiotics might still be necessary to rescue these patients.