bluuebunny/crossref_metadata_2025 huggingface dataset:
Human EWS-FLI protein recapitulates in Drosophila the neomorphic functions that induce Ewing sarcoma tumorigenesis
Authors: Molnar Cristina , Reina Jose , Herrero Anastasia , Heinen Jan Peter , Méndiz Victoria , Bonnal Sophie , Irimia Manuel , Sánchez-Jiménez María , Sánchez-Molina Sara , Mora Jaume , Gonzalez Cayetano
Published: October 2022

Ewing sarcoma (EwS) is a human malignant tumor typically driven by the Ewing sarcoma-Friend leukemia integration (EWS-FLI) fusion protein. A paucity of genetically modified animal models, partially owed to the high toxicity of EWS-FLI, hinders research on EwS. Here, we report a spontaneous mutant variant, EWS-FLI1FS, that circumvents the toxicity issue in Drosophila. Through proteomic and genomic analyses, we show that human EWS-FLI1FS interacts with the Drosophila homologues of EWS-FLI human protein partners, including core subunits of chromatin remodeling complexes, the transcription machinery, and the spliceosome; brings about a massive dysregulation of transcription that affects a significant fraction of known targets of EWS-FLI in human cells; and modulates splicing. We also show that EWS-FLI1FS performs in Drosophila the two major neomorphic activities that it is known to have in human cells: activation of transcription from GGAA microsatellites and out competition of ETS transcription factors. We conclude that EWS-FLI1FS reproduces in Drosophila the known oncogenic activities of EWS-FLI that drive EwS tumorigenesis in humans. These results open up an unprecedented opportunity to investigate EWS-FLI’s oncogenic pathways in vivo in a genetically tractable organism.
Thinking about the Future: The Psychology of the Mind and Soul in Judgement Day I
Authors: Brooks Deanna
Published: October 2022

The Exeter Book poem Judgement Day I has long been considered by scholars to be an inferior Old English poem, failing to reach the literary heights or vivid drama of Judgement Day II or Christ III. However, this comparison is caused largely by the presuppositions that the modern title imposes, rather than matters of content. This paper argues that Judgement Day I is not meant to warn about the Final Judgement but instead is concerned with the present time of the reader as a way to encourage contemplation of their present actions in order to safeguard their soul’s future. To accomplish this, the poem draws on a psychological model of mind-body-soul primarily identified by Malcolm Godden, Soon-Ai Low, and Leslie Lockett. The presence of this psychological model has been previously noted by scholars in other Exeter Book poems such as The Wanderer, The Seafarer, and Soul and Body II. This study draws Judgement Day I into conversation with some of these poems and argues that its focus on safeguarding the soul for its final journey, or siðfæt, is a motif with which many of the Exeter poems engage. Judgement Day I can thus be read as a poem that engages with the themes of many other Exeter Book texts and participates actively in a larger poetic sequence throughout the manuscript.
Asset Prices and Portfolios with Externalities
Authors: D. Baker Steven , Hollifield Burton , Osambela Emilio
Published: October 2022

Elementary portfolio theory implies that environmentalists optimally hold more shares of polluting firms than non-environmentalists, and that polluting firms attract more investment capital than otherwise identical non-polluting firms through a hedging channel. Pigouvian taxation can reverse the aggregate investment results, but environmentalists still overweight polluters. We introduce countervailing motives for environmentalists to underweight polluters, comparing the implications when environmentalists coordinate to internalize pollution, or have nonpecuniary disutility from holding polluter stock. With nonpecuniary disutility, introducing a green derivative may dramatically alter who invests most in polluters, but has no impact on aggregate pollution.
Cerebellar Functional Dysconnectivity in Drug-Naïve Patients With First-Episode Schizophrenia
Authors: Cao Hengyi , Wei Xia , Zhang Wenjing , Xiao Yuan , Zeng Jiaxin , Sweeney John A , Gong Qiyong , Lui Su
Published: October 2022

Background

Cerebellar functional dysconnectivity has long been implicated in schizophrenia. However, the detailed dysconnectivity pattern and its underlying biological mechanisms have not been well-charted. This study aimed to conduct an in-depth characterization of cerebellar dysconnectivity maps in early schizophrenia.

Study design

Resting-state fMRI data were processed from 196 drug-naïve patients with first-episode schizophrenia and 167 demographically matched healthy controls. The cerebellum was parcellated into nine functional systems based on a state-of-the-art atlas, and seed-based connectivity for each cerebellar system was examined. The observed connectivity alterations were further associated with schizophrenia risk gene expressions using data from the Allen Human Brain Atlas.

Study results

Overall, we observed significantly increased cerebellar connectivity with the sensorimotor cortex, default-mode regions, ventral part of visual cortex, insula, and striatum. In contrast, decreased connectivity was shown chiefly within the cerebellum, and between the cerebellum and the lateral prefrontal cortex, temporal lobe, and dorsal visual areas. Such dysconnectivity pattern was statistically similar across seeds, with no significant group by seed interactions identified. Moreover, connectivity strengths of hypoconnected but not hyperconnected regions were significantly correlated with schizophrenia risk gene expressions, suggesting potential genetic underpinnings for the observed hypoconnectivity.

Conclusions

These findings suggest a common bidirectional dysconnectivity pattern across different cerebellar subsystems, and imply that such bidirectional alterations may relate to different biological mechanisms.
Neurodegeneration Markers in the Cerebrospinal Fluid of 100 Patients with Schizophrenia Spectrum Disorder
Authors: Runge Kimon , Balla Agnes , Fiebich Bernd L , Maier Simon J , von Zedtwitz Katharina , Nickel Kathrin , Dersch Rick , Domschke Katharina , Tebartz van Elst Ludger , Endres Dominique
Published: October 2022

Background

Schizophrenia spectrum disorders (SSD) can be associated with neurodegenerative processes causing disruption of neuronal, synaptic, or axonal integrity. Some previous studies have reported alterations of neurodegenerative markers (such as amyloid beta [Aβ], tau, or neurofilaments) in patients with SSD. However, the current state of research remains inconclusive. Therefore, the rationale of this study was to investigate established neurodegenerative markers in the cerebrospinal fluid (CSF) of a large group of patients with SSD.

Study Design

Measurements of Aβ1–40, Aß1–42, phospho- and total-tau in addition to neurofilament light (NFL), medium (NFM), and heavy (NFH) chains were performed in the CSF of 100 patients with SSD (60 F, 40 M; age 33.7 ± 12.0) and 39 controls with idiopathic intracranial hypertension (33 F, 6 M; age 34.6 ± 12.0) using enzyme-linked immunoassays.

Study Results

The NFM levels were significantly increased in SSD patients (P = .009), whereas phospho-tau levels were lower in comparison to the control group (P = .018). No other significant differences in total-tau, beta-amyloid-quotient (Aβ1–42/Aβ1–40), NFL, and NFH were identified.

Conclusions

The findings argue against a general tauopathy or amyloid pathology in patients with SSD. However, high levels of NFM, which has been linked to regulatory functions in dopaminergic neurotransmission, were associated with SSD. Therefore, NFM could be a promising candidate for further research on SSD.
Risk Factors for Psychotic Relapse After Dose Reduction or Discontinuation of Antipsychotics in Patients With Chronic Schizophrenia. A Meta-Analysis of Randomized Controlled Trials
Authors: Bogers Jan P A M , Hambarian George , Walburgh Schmidt Niels , Vermeulen Jentien M , de Haan Lieuwe
Published: October 2022

Background and hypothesis

Although maintenance treatment with antipsychotics protects against psychotic relapse, high doses may hamper recovery. Therefore, dose reduction or discontinuation may be considered in patients with chronic schizophrenia. Here, we identified risk factors for psychotic relapse when doses are reduced.

Study Design

We systematically searched MEDLINE, EMBASE, and PsycINFO from January 1950 through January 2021 and reviewed randomized controlled trials (RCTs) that reported relapse rates after antipsychotic dose reduction or discontinuation in patients with chronic schizophrenia. We calculated relative risks (RRs) with 95% confidence intervals (CIs) per person-year and sought to identify potential risk factors for relapse. The study is registered with PROSPERO (CRD42017058296).

Study Results

Forty-seven RCTs (54 patient cohorts, 1746 person-years) were included. The RR for psychotic relapse with dose reduction/discontinuation versus maintenance treatment was 2.3 per person-year (95% CI: 1.9 to 2.8). The RR was higher with antipsychotic discontinuation, dose reduction to less than 3–5 mg haloperidol equivalent (HE), or relatively rapid dose reduction (<10 weeks). The RR was lower with long-acting injectable agents versus oral antipsychotic dose reduction. Other factors that increased the risk of psychotic relapse were younger age and short follow-up time.

Conclusions

Clinicians should take several risk factors for psychotic relapse into account when considering dose reduction in patients with chronic schizophrenia. Studies of a relatively fast reduction in antipsychotic dose support a minimum dose of 3–5 mg HE. However, if the dose is tapered more gradually, relapses related to medication withdrawal might be avoided, possibly enabling lower-end doses to be achieved.
PFOA-Induced Ovotoxicity Differs Between Lean and Obese Mice With Impacts on Ovarian Reproductive and DNA Damage Sensing and Repair Proteins
Authors: Estefanía González-Alvarez Maria , Severin Andrew , Sayadi Maryam , Keating Aileen F
Published: October 2022

Perfluorooctanoic acid (PFOA) is an environmentally persistent perfluoroalkyl substance that is widely used in consumer products. Exposure to PFOA is associated with reproductive and developmental effects including endocrine disruption, delayed puberty in girls, and decreased fetal growth. In the United States, obesity affects 40% of women and 20% of girls, with higher rates in minority females. Obesity causes infertility, poor oocyte quality, miscarriage, and offspring defects. This study proposed that PFOA exposure would impact estrous cyclicity, ovarian steroid hormones, and the ovarian proteome and further hypothesized that obesity would impact PFOA-induced ovotoxicity. Female wild type (KK.Cg-a/a; lean) or KK.Cg-Ay/J mice (obese) received saline (CT) or PFOA (2.5 mg/kg) per os for 15 days beginning at 7 weeks of age. There were no effects on food intake, body weight, estrous cyclicity, serum progesterone, and heart, spleen, kidney, or uterus weight (p > .05). Ovary weight was decreased (p < .05) by PFOA exposure relative to vehicle control-treated mice in lean but not obese mice. Liquid chromatography-tandem mass spectrometry was performed on isolated ovarian protein and PFOA exposure altered the ovarian abundance of proteins involved in DNA damage sensing and repair pathways and reproduction pathways (p < .05) differentially in lean and obese mice. The data suggest that PFOA exposure alters ovary weight and differentially targets ovarian proteins in lean and obese females in ways that might reduce female fecundity.
A novel scoring system (YASHMA) predicting brain injury in asphyxiated newborns
Authors: Elbayiyev Sarkhan , Çevirici Tevfik , Güngör Ahmet Alptuğ , Kadıoğlu Şimşek Gülsüm , Kanmaz Kutman Hayriye Gözde , Canpolat Fuat Emre
Published: October 2022

Background

Hypoxic-ischemic encephalopathy is a complication of adverse intrapartum events and birth asphyxia resulting in brain injury and mortality in late preterm and term newborns.

Objectives

In this study, we aimed to predict brain damage on magnetic resonance imaging (MRI) with a new scoring system.

Methods

Yieldly And Scorable Holistic Measuring of Asphyxia (YASHMA) is generated for detection of brain injury in asphyxiated newborns. Total scores were calculated according to scores of birth weight, gestation weeks, APGAR scores at first and fifth minutes, aEEG patterns and epileptic status of patients. The major outcome of the scoring system was to determine correlation between poor scores and neonatal brain injury detected on MRI.

Results

In hypothermia group with brain injury, low gestational weeks and lowest APGAR scores, abnormal aEEG findings were statistically different from others. YASHMA scores were statistically significant with high sensitivity, specificity, AUC and 95% confidence interval values.

Conclusions

YASHMA scoring system is feasible and can be suggestive for detecting brain injury in low-income countries.
Identification of a novel polyomavirus from a marsupial host
Authors: Dunowska Magdalena , Perrott Matthew , Biggs Patrick
Published: October 2022

We report the identification and analysis of a full sequence of a novel polyomavirus from a brushtail possum (Trichosurus vulpecula) termed possum polyomavirus (PPyV). The sequence was obtained from the next-generation sequencing assembly during an investigation into the aetiological agent for a neurological disease of possums termed wobbly possum disease (WPD), but the virus was not aetiologically involved in WPD. The PPyV genome was 5,224 nt long with the organisation typical for polyomaviruses, including early (large and small T antigens) and late (Viral Protein 1 (VP1), VP2, and VP3) coding regions separated by the non-coding control region of 465 nt. PPyV clustered with betapolyomaviruses in the WUKI clade but showed less than 60 per cent identity to any of the members of this clade. We propose that PPyV is classified within a new species in the genus Betapolyomavirus. These data add to our limited knowledge of marsupial viruses and their evolution.
Nowcasting Global Poverty
Authors: Mahler Daniel Gerszon , Castañeda Aguilar R Andrés , Newhouse David
Published: October 2022

This paper evaluates different methods for nowcasting country-level poverty rates, including methods that apply statistical learning to large-scale country-level data obtained from the World Development Indicators and Google Earth Engine. The methods are evaluated by withholding measured poverty rates and determining how accurately the methods predict the held-out data. A simple approach that scales the last observed welfare distribution by a fraction of real GDP per capita growth performs nearly as well as models using statistical learning on 1,000+ variables. This GDP-based approach outperforms all models that predict poverty rates directly, even when the last survey is up to five years old. The results indicate that in this context, the additional complexity introduced by applying statistical learning techniques to a large set of variables yields only marginal improvements in accuracy.
Predictive Models for Estimating the Probability of Successful Vaginal Birth After Cesarean Delivery
Authors: Black Naomi , Henderson Ian , Al Wattar Bassel H. , Quenby Siobhan
Published: October 2022

OBJECTIVE:

To systematically review all studies that developed or validated a vaginal birth after cesarean (VBAC) prediction model.

DATA SOURCES:

MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov were searched from inception until February 2022.

METHODS OF STUDY SELECTION:

We included observational studies that developed or validated a multivariable VBAC prediction model in women with a singleton pregnancy and one previous lower segment cesarean delivery. A total of 3,758 articles were identified and screened.

TABULATION, INTEGRATION, AND RESULTS:

For 57 included studies, data were extracted in duplicate using a CHARMS (Critical Appraisal and Data Extraction for Systematic Review of Prediction Modelling Studies) checklist-based tool and included participants’ characteristics, sample size, predictors, timing of application, and performance. PROBAST (Prediction model Risk of Bias Assessment Tool) and TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis) were used to assess risk of bias and transparency of reporting. Several studies developed or validated more than one model. There were 38 unique prediction models, 42 external validations of 10 existing prediction models, and six modifications of existing models. Of the 38 unique models, only 19 (19/38, 50%) were internally validated in the initial study. No studies externally validated their model in the initial study. Age, previous vaginal birth, and previous cesarean delivery for labor dystocia were the commonest predictors. The area under the curve in included studies ranged from 0.61 to 0.95. Models used close to delivery generally outperformed those used earlier in pregnancy. Most studies demonstrated a high risk of bias (45/57, 79%), the remainder were unclear (7/57, 12%) and low (5/57, 9%). Median TRIPOD checklist adherence was 70% (range 32–93%).

CONCLUSION:

Several prediction models for VBAC success exist, but many lack external validation and are at high risk of bias. Models used close to delivery outperformed those used earlier in pregnancy; however, their generalizability and applicability remain unclear. High-quality external validation and effect studies are required to guide clinical use.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42020190930.
One-Step Compared With Two-Step Gestational Diabetes Screening and Pregnancy Outcomes
Authors: Brady Matthew , Hensel Drew M. , Paul Rachel , Doering Michelle M. , Kelly Jeannie C. , Frolova Antonina I. , Odibo Anthony O. , Barry Valene Garr , Powe Camille E. , Raghuraman Nandini , Tuuli Methodius G. , Carter Ebony B.
Published: October 2022

OBJECTIVE:

To estimate short-term maternal and neonatal outcomes with one-compared with two-step testing for gestational diabetes mellitus (GDM).

DATA SOURCES:

A systematic review of randomized controlled trials (RCTs) and observational studies comparing one-step and two-step GDM testing strategies before September 2021 was conducted. We searched Ovid Medline (1946–), EMBASE (1947–), Scopus (1960–), Cochrane Central, and ClinicalTrials.gov. The primary outcome was rate of large-for-gestational age (LGA) neonates. Secondary outcomes were clinically relevant outcomes for GDM that were selected a priori.

METHODS OF STUDY SELECTION:

Titles, abstracts, and manuscripts were screened, selected, and reviewed by the first two authors. Four RCTs (24,966 patients) and 13 observational studies (710,677 patients) were analyzed.

TABULATION, INTEGRATION, AND RESULTS:

Pooled relative risks (RRs) were calculated with 95% CIs using random-effects models and were plotted graphically with forest plots. Study heterogeneity was evaluated using Cochran Q and Higgins I2 tests. The quality of studies that met the inclusion criteria was evaluated with the Downs and Black checklist. Publication bias was assessed by using asymmetry of funnel plots and Harbord's test. There was no difference in the rate of LGA neonates (pooled RR 0.95; 95% CI 0.88–1.04) by testing strategy among RCTs, but patients who underwent one-step testing were more likely to be diagnosed with GDM (pooled RR 2.13; 95% CI 1.61–2.82) and treated with diabetes medications (pooled RR 2.24; 95% CI 1.21–4.15). One-step testing was associated with higher rates of neonatal intensive care unit (NICU) admission (pooled RR 1.12; 95% CI 1.00–1.26) and neonatal hypoglycemia (pooled RR 1.23; 95% CI 1.13–1.34). In analysis of high-quality RCTs and observational studies, one-step testing was associated with a lower rate of LGA neonates (pooled RR 0.97; 95% CI 0.95–0.98), but higher rates of GDM diagnosis, treatment, NICU admission, and neonatal hypoglycemia.

CONCLUSION:

Despite a significant increase in GDM diagnosis and treatment with one-step testing, there is no difference in rate of LGA neonates compared with two-step testing among RCTs.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42021252703.
Disability and Interpersonal Violence in the Perinatal Period
Authors: Brown Hilary K. , Saunders Natasha , Chen Simon , Leslie Kelly , Vigod Simone N. , Fung Kinwah , Guttmann Astrid , Havercamp Susan M. , Parish Susan L. , Ray Joel G. , Lunsky Yona
Published: October 2022

OBJECTIVE:

To compare the risk of interpersonal violence experienced by pregnant and postpartum individuals with physical disabilities, sensory disabilities, or intellectual or developmental disabilities with those without disabilities, and to examine whether a prepregnancy history of interpersonal violence puts individuals with disabilities, at excess risk of interpersonal violence in the perinatal period.

METHOD:

This population-based study included all individuals aged 15–49 years with births in Ontario, Canada, from 2004 to 2019. Individuals with physical (n=147,414), sensory (n=47,459), intellectual or developmental (n=2,557), or multiple disabilities (n=9,598) were compared with 1,594,441 individuals without disabilities. The outcome was any emergency department visit, hospital admission, or death related to physical, sexual, or psychological violence between fertilization and 365 days postpartum. Relative risks (RRs) were adjusted for baseline social and health characteristics. Relative excess risk due to interaction (RERI) was estimated from the joint effects of disability and prepregnancy violence history; RERI>0 indicated positive interaction.

RESULTS:

Individuals with physical (0.8%), sensory (0.7%), intellectual or developmental (5.3%), or multiple disabilities (1.8%) were more likely than those without disabilities (0.5%) to experience perinatal interpersonal violence. The adjusted RR was 1.40 (95% CI 1.31–1.50) in those with physical disabilities, 2.39 (95% CI 1.98–2.88) in those with intellectual or developmental disabilities, and 1.96 (95% CI 1.66–2.30) in those with multiple disabilities. Having both a disability and any violence history produced a positive interaction for perinatal interpersonal violence (adjusted RERI 0.87; 95% CI 0.47–1.29).

CONCLUSION:

The perinatal period is a time of relative high risk for interpersonal violence among individuals with pre-existing disabilities, especially those with a history of interpersonal violence.
Prophylactic Ureteral Stent Placement and Urinary Injury During Hysterectomy for Placenta Accreta Spectrum
Authors: Scaglione Morgan A. , Allshouse Amanda A. , Canfield Dana R. , Mclaughlin Hannah D. , Bruno Ann M. , Hammad Ibrahim A. , Branch D. Ware , Maurer Kathryn A. , Dood Robert L. , Debbink Michelle P. , Silver Robert M. , Einerson Brett D.
Published: October 2022

OBJECTIVE:

To evaluate the association between prophylactic ureteral stent placement at the time of hysterectomy for placenta accreta spectrum and genitourinary injury.

METHODS:

We conducted a retrospective cohort study of patients with placenta accreta spectrum who underwent hysterectomy at two referral centers from 2001 to 2021. The exposure was prophylactic ureteral stent placement. The primary outcome, genitourinary injury, was a composite of bladder injury, ureteral injury, or vesicovaginal fistula. Secondary outcomes included components of the primary outcome. We evaluated differences between groups using χ2 and t test. To evaluate differences in the primary outcome, we reported odds ratios (ORs) and adjusted odds ratios (aORs) using multivariable logistic regression analyses to control for potential confounding variables. We used a Cochran-Armitage χ2 trend test to evaluate difference in stent use and injury over time.

RESULTS:

In total, 236 patients were included. Prophylactic ureteral stents were used in 156 surgeries (66%). Overall, genitourinary injury occurred less frequently in the stent group compared with the no stent group (28% vs 51%, OR 0.37, 95% CI 0.21–0.65). This association persisted after controlling for urgency of delivery, three or more prior cesarean deliveries, and whether a gynecologic oncologist was present (aOR 0.27, 95% CI 0.14–0.52). Unintentional bladder injury occurred less frequently in the stent group compared with the no stent group (13% vs 25%, P=.018), as did ureteral injury (2% vs 9%, P=.019).

CONCLUSION:

Prophylactic ureteral stent placement was associated with a decreased risk of genitourinary injury during hysterectomy for placenta accreta spectrum.
Breast-Conserving Surgery or Mastectomy?
Authors: Christiansen Peer , Mele Marco , Bodilsen Anne , Rocco Nicola , Zachariae Robert
Published: October 2022

Introduction:

The early randomized controlled trials revealed no differences in survival between breast-conserving surgery (BCS) and mastectomy. However, breast cancer treatment has undergone changes, and the results of recent population-based registry studies suggest superior long-term survival after BCS. To explore the current evidence, a systematic review and meta-ana lysis of population-based observational studies from 2010 and onward was conducted.

Methods:

A literature search was conducted in the PubMed, Embase, and Cochrane databases to identify relevant literature. Keywords included “mastectomy,” “breast conserving surgery,” and “survival.” The identified studies were narratively reviewed and effect sizes (hazard ratios [HRs]) for overall (OS) and breast cancer-specific survival (BCSS) were combined with random-effects models.

Results:

A total of 30 reports were included in the review, and results from 25 studies were included in the meta-analyses. Compared with mastectomy, BCS was associated with better OS (HR = 1.34 [1.20–1.51]; N = 1,311,600) and BCSS (HR = 1.38 [1.29–1.47]; N = 494,267). Selected subgroups of patients, based on lymph node status, age (<50 years/≥50 years), and radiation therapy after mastectomy (±), all showed better overall survival after BCS. The number (range 4–12) and type of prognostic variables adjusted for in the survival analyses of the studies did not statistically significantly moderate the differences in survival between BCS and mastectomy.

Conclusions:

The combined findings from large population-based studies indicate that BCS is associated with survival benefit compared with mastectomy, suggesting that BCS be the recommended treatment of early breast cancer (T1-2N0-1M0) if a radical lumpectomy can be performed.
CHOROIDAL VASCULARITY INDEX IN HYDROXYCHLOROQUINE TOXIC RETINOPATHY
Authors: Halouani Safa , Le Hoang Mai , Querques Giuseppe , Borrelli Enrico , Sacconi Riccardo , Battista Marco , Jung Camille , Souied Eric H. , Miere Alexandra
Published: October 2022

Purpose:

To investigate choroidal involvement in eyes of patients treated with hydroxychloroquine (HCQ), by quantifying the choroidal vascularity index (CVI) and other choroidal biomarkers.

Methods:

Vertical enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) scans were performed in eyes with either advanced-stage or mild HCQ toxic retinopathy, as well as in healthy age-matched and sex-matched controls. Based on SD-OCT scans, the subfoveal and mean choroidal thickness (ChT) was measured. The CVI, total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were calculated based on a binarization image process. These variables were computed and compared between the three groups (i.e., advanced stage, mild toxicity, and healthy controls).

Results:

Forty-eight eyes of 47 patients under HCQ (26 eyes presented with advanced stage HCQ toxicity and 22 eyes with mild toxicity) and 34 eyes of 31 healthy controls were included. Both CVI and ChT were significantly different between the three groups (P < 0.001, P < 0.001). When comparing the advanced stage toxicity group to healthy controls, both the subfoveal and the mean ChT were diminished (P < 0.001). The CVI, TCA, LCA, and SCA were significantly lower in the advanced stage of toxicity group when compared with controls (P < 0.001, <0.00001, <0.0001, and P = 0.0094, respectively).

Conclusion:

Our study suggests that eyes with HCQ toxic retinopathy, especially at advanced stages, present with choroidal impairment, giving further pathophysiological insights into the unfolding of this retinal toxicity.
OPTICAL COHERENCE TOMOGRAPHY AND OCT ANGIOGRAPHY CHARACTERISTICS OF INDOCYANINE GREEN ANGIOGRAPHIC PLAQUES IN NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION
Authors: Stattin Martin , Ahmed Daniel , Haas Anna-Maria , Graf Alexandra , Zehetner Claus , Mihalics Stefan , Krepler Katharina , Ansari-Shahrezaei Siamak
Published: October 2022

Purpose:

To describe characteristics of indocyanine green (ICG) angiographic plaques in the nonexudative fellow eye of White patients with unilateral treatment-naïve exudative neovascular age-related macular degeneration through optical coherence tomography (OCT) and OCT angiography (OCTA).

Methods:

In this retrospective cross-sectional study, nonexudative eyes with ICG angiographic plaques were analyzed by OCT B-scans for the sensitivity of a double-layer sign, a pigment epithelium detachment, outer retinal atrophy, hyperreflective dots, and subretinal hyperreflective material (SRHM). The ICG angiographic plaque was matched with a macular neovascularization in OCTA en face scans and color-coded B scans.

Results:

In total, 35 ICG angiographic plaques in 33 of 291 (11%) nonexudative eyes were diagnosed. OCT revealed 27 double-layer sign (78%), eight pigment epithelium detachment (23%), 8 outer retinal atrophy (23%), eight hyperreflective dots (23%), and one subretinal hyperreflective material (3%). OCTA confirmed a macular neovascularization in 28 plaques (80%): 7 (20%) in en face scans, 3 (9%) in color-coded B scans, and 18 (51%) in both. The area size in OCTA was significantly smaller than that of ICG angiography (P = 0.002).

Conclusion:

The diagnosis of an ICG angiographic plaque in nonexudative fellow eyes of Whites with unilateral treatment-naïve exudative neovascular age-related macular degeneration was highly suggestive of a typical macular neovascularization type 1 as characterized by OCT and OCTA.
Effects of Systemic Diseases on Graft Preparation in Descemet Membrane Endothelial Keratoplasty
Authors: Özkan Burak , Koçluk Yusuf , Kasım Burcu
Published: October 2022

Objectives:

To evaluate the effects of the systemic diseases and drugs of the donor on Descemet membrane (DM) graft preparation.

Methods:

Seventy-eight corneas of 58 donors, of whom the DM grafts were used in Descemet membrane endothelial keratoplasty (DMEK) surgery, between January 2018 and January 2020, were enrolled in this retrospective study. The hospital records of the donors were analyzed. Age, sex, blood type, systemic diseases, and drugs; complete blood count; biochemistry panel for liver and kidney functions in the past 48 hours; and the drugs used in the hospital, if any, in the past 24 hours were recorded. The grafts with tears that occurred while preparation were included in group 1, and the successful grafts with no tears were included in group 2.

Results:

There were no statistically significant differences in the characteristics of the donors between groups. However, breast cancer and the use of sevelamer were found to be significantly higher in group 1 (P=0.010, P=0.033, respectively). No statistically significant difference in the use of other drugs was found between groups.

Conclusion:

Although diabetic donors have been reported to be inappropriate candidates for the preparation of DM grafts for DMEK, most of the donors with several systemic diseases including diabetes can be used in DMEK surgery, with the right technique in DM graft preparation.
Social Media Evaluation of Seasonal and Geographic Trends of Corneal Ulcers in the United States
Authors: Choi Jamie H. , Ong Erin S. , Munir Wuqaas M.
Published: October 2022

Objectives:

The purpose of this study is to evaluate if social media and Google search data can identify seasonal and geographic trends in the incidence of corneal ulcers in the United States.

Methods:

This is a case series of all corneal ulcer-related data collected from two major social media platforms and Google trends from US users between 2017 and 2021. Instagram and Twitter were searched for posts and hashtags related to “corneal ulcer.” Web and image search volume of “corneal ulcer” were collected from Google trends (https://trends.google.com). Data were compared between seasons, defined by 3-month intervals, and chi-square tests were used to determine the statistical significance.

Results:

One hundred and sixty-five individuals (79% female) and 164 individuals (79% female) posted personal new corneal ulcer diagnoses on Twitter and Instagram, respectively. Summer resulted in the highest number of both Twitter (34%, P=0.07) and Instagram (33%, P=0.68) posts. Summer was also the most popular season for Google web and image searches of “corneal ulcer” (search volume average of 58.4 and 41.2, P=0.74 and P=0.01, respectively, with 100 being peak popularity). Across all platforms, the South was the most represented (32% Twitter, 38% Instagram, 32% Google Web, and 33% Google Images).

Conclusions:

Our results indicate that social media and Google trends may reflect seasonal and geographic patterns of corneal ulcer incidence in the United States. However, further study with increased power is needed.
Masking the Red Reflex of Flash Photography With Prosthetic Lenses
Authors: Balakrishnan Akshaya C. , Badrinarayanan Aparna , Iqbal Asif
Published: October 2022

The purpose of this case report was to represent the clinical expertise in managing with a patient with visible red fundal reflex on flash photography and its management with a soft prosthetic contact lens (PCL). This unique case report discussed a 31-year-old man complaining of visible red reflex in right eye while taking photographs with flashlight. Ocular history revealed that he is status post intraocular lens implantation and strabismus surgery followed by a nonpenetrating injury with a stick in the right eye 20 years back. The middilated, slow, tonic pupil was making the fundal glow more prominent in bright flashlight. Because cosmesis was the main concern, various types of PCL trials were used. Finally, the red reflex was concealed with a type-D, gray, transparent, iris tinted PCL. Thus, PCL enhanced the aesthetic appearance and created a positive impact on the patient's quality of life and should be considered and prescribed in similar patients.
Severe Acute Respiratory Syndrome Coronavirus 2–Associated Blepharoconjunctivitis and Erythema Multiforme-Like Rash in a Young Man
Authors: Fernandez Karen B. , Sioufi Kareem , Aker Jon E. , Mercer Ryan N.
Published: October 2022

Purpose:

The aim of this study was to describe the diagnosis and management of bilateral blepharoconjunctivitis and erythema multiforme (EM)-like illness in an otherwise healthy young man who tested positive for severe acute respiratory syndrome coronavirus (SARS-CoV)-2.

Methods:

This is a case report of a 27 year-old man with a positive result for SARS-CoV-2 testing who presented with fever, eye redness, oral ulcerations, cough, sore throat, and progressive rash suspicious for EM-like illness.

Results:

A SARS-CoV-2–positive patient presented to the emergency room with a progressing skin rash, bilateral conjunctivitis, and oropharyngeal mucosal ulcers. On initial ophthalmic examination, visual acuity was 20/25 both eyes (OU), and slit lamp examination demonstrated erythema and ulceration of the eyelid margins with fluorescein uptake at the mucocutaneous junction OU. The patient was admitted for observation and supportive treatment. During and after his hospital stay, he was treated with systemic and topical steroids, topical cyclosporine ophthalmic drops, erythromycin ophthalmic ointment, and artificial tears. At his 1-week follow-up visit after hospital discharge, the patient had complete resolution of his skin findings and improvement of his ocular and oral mucosal findings. Laboratory workup and imaging studies searching for other potential autoimmune and infectious etiologies showed negative results.

Conclusions:

Topical antiinflammatory drops, artificial tears, erythromycin ointment, and systemic steroids were an effective treatment for this bilateral blepharoconjunctivitis and EM-like presentation of SARS-CoV-2.
Exposure-response Relationships of Metronidazole in Infants: Integration of Electronic Health Record Data With Population Pharmacokinetic Modeling-derived Exposure Simulation
Authors: Commander Sarah Jane , Benjamin Daniel K. , Wu Huali , Thompson Elizabeth J. , Lane Morgan , Clark Reese H. , Greenberg Rachel G. , Hornik Christoph P.
Published: October 2022

Background:

Infants frequently receive metronidazole at variable doses and duration for surgical site infection prophylaxis and treatment of intra-abdominal infections. Seizures are a rare (but potentially devastating) side effect of metronidazole, yet the prevalence of seizures in infants, as well as the relationship with metronidazole dose and exposure, are unknown.

Methods:

We examined the Pediatrix Clinical Data Warehouse for infants in neonatal intensive care units from 1997 to 2018 who received at least 1 dose of metronidazole during their first 120 days of life. We used an existing population pharmacokinetic model to simulate exposure parameters, estimating multivariable associations between metronidazole dosing and exposure parameters, and the occurrence of seizure.

Results:

There were 19,367 intravenous doses of metronidazole given to 1546 infants, and 31 experienced a seizure. Infants with a seizure had a longer median (interquartile values) duration of metronidazole exposure than those without (11 days [6, 15] vs. 7 [4, 11], P = 0.01). Each added day of metronidazole (OR = 1.06, 95% CI: 1.02–1.10), and each standard deviation increase in cumulative area under the plasma concentration−time curve (OR = 1.27, 95% CI: 1.11–1.45) were associated with increased odds of seizure. Higher simulated maximum plasma concentration was associated with lower odds of seizure (OR = 0.88, 95% CI: 0.81–0.96).

Conclusions:

Longer metronidazole exposure and higher cumulative exposure could be associated with increased odds of infant seizures. Using a large observational dataset allowed us to identify a rare adverse event, but prospective studies are needed to validate this finding and further characterize metronidazole dose- and exposure-safety relationships.
Measurement Invariance and Latent Mean Differences in the Nurses' Emotional Labour Scale
Authors: KIM Sun-Hee , LEE Eunkyung , PARK Jin-Hwa
Published: October 2022

Background

The measurement invariance and latent mean differences in emotional labor across different hospital and monthly salary levels among registered nurses have never been confirmed for the Emotional Labour Scale. These issues may influence the application and efficacy of this scale in practice.

Purpose

This study was developed to evaluate the factor structure of the nurses' Emotional Labour Scale and to examine the measurement invariance and latent mean differences for this scale across different hospital and monthly salary levels.

Methods

Data were collected from 461 registered nurses working in four general hospitals and 12 long-term care hospitals. Confirmatory factor analysis and a multigroup confirmatory factor analysis were performed to determine the internal structure and measurement invariance of the Emotional Labour Scale.

Results

The results of the confirmatory factor analysis indicate that the factor structure model proposed by the original scale fits well with our data as well as configural invariance, factor loading invariance, intercept invariance, and uniqueness invariance. Moreover, factor variance/covariance invariance across two hospital levels as well as configural invariance, factor loading invariance, and intercept invariance across two monthly salary levels were supported. The mean score for emotional control effort in the profession of general hospital nurses was lower than that for long-term care hospital nurses. No statistically significant latent mean differences were found across monthly salary levels.

Conclusions/Implications for Practice

The findings show the Emotional Labour Scale to be a valid and reliable tool for assessing registered nurses and also comparing the mean score for emotional labor across hospital and monthly salary levels to be feasible. The scale may contribute to the development of human resource strategies.
Clinical Update on Uses for Mifepristone in Obstetrics and Gynecology
Authors: Hagey Jill M. , Givens Matthew , Bryant Amy G.
Published: October 2022

Importance

Mifepristone (RU-486) is a selective progesterone receptor modulator that has antagonist properties on the uterus and cervix. Mifepristone is an effective abortifacient, prompting limitations on its use in many countries. Mifepristone has many uses outside of induced abortion, but these are less well known and underutilized by clinicians because of challenges in accessing and prescribing this medication.

Objective

To provide clinicians with a history of the development of mifepristone and mechanism of action and safety profile, as well as detail current research on uses of mifepristone in both obstetrics and gynecology.

Evidence Acquisition

A PubMed search of mifepristone and gynecologic and obstetric conditions was conducted between January 2018 and December 2021. Other resources were also searched, including guidelines from the American College of Obstetricians and Gynecologists and the Society of Family Planning.

Results

Mifepristone is approved by the Food and Drug Administration for first-trimester medication abortion but has other off-label uses in both obstetrics and gynecology. Obstetric uses that have been investigated include management of early pregnancy loss, intrauterine fetal demise, treatment of ectopic pregnancy, and labor induction. Gynecologic uses that have been investigated include contraception, treatment of abnormal uterine bleeding, and as an adjunct in treatment of gynecologic cancers.

Conclusions and Relevance

Mifepristone is a safe and effective medication both for its approved use in first-trimester medication abortion and other off-label uses. Because of its primary use as an abortifacient, mifepristone is underutilized by clinicians. Providers should consider mifepristone for other indications as clinically appropriate.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe the history of the development of mifepristone, including its mechanism of action and safety profile; and explain the uses for mifepristone in both obstetrics and gynecology.
Effect of Intrapartum Maternal Hemoglobin on Mode of Delivery and Short-Term Neonatal Outcome: A Systematic Review
Authors: Smith Julia Sandra , Bullens Lauren Maria , van der Hout-van der Jagt Marieke Beatrijs , van Runnard Heimel Pieter Jurjen , Oei Swan Gied
Published: October 2022

Importance

Maternal anemia in pregnancy is a common condition worldwide and is considered a risk factor for adverse neonatal and maternal outcome. Also high hemoglobin (Hb) levels are associated with adverse pregnancy outcomes. However, studies regarding the influence of intrapartum maternal Hb on mode of delivery and short-term neonatal outcome are limited and contradicting.

Objective

The aim of this study was to provide an overview of current evidence regarding associations between intrapartum maternal Hb levels and mode of delivery and short-term neonatal outcome. In addition, we propose directions for future research.

Evidence Acquisition

We systematically searched the electronic PubMed, EMBASE, and Cochrane databases for studies on maternal Hb levels and mode of delivery maternal and short-term neonatal outcome until January 2021. Eligible articles and their references were independently reviewed by 2 authors. Assessment was based on methodological quality and study results.

Results

We included 14 studies that evaluated the level of maternal pH in relation to clinical outcome, 6 studies on mode of delivery, 10 studies on Apgar score, 1 study on fetal distress, 2 studies on neonatal intensive care unit admission, 1 study on umbilical cord pH, and 5 studies on perinatal mortality.

Conclusions and Relevance

We found a trend toward an increased risk of cesarean delivery in anemic woman. Concerning the short-term neonatal outcomes, the evidence is conflicting, and included studies are too heterogenic to compare. Furthermore, various studies indicated a relation between high Hb levels and increased perinatal mortality. Therefore, we especially recommend attention to elevated Hb levels.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe how Hb levels affect mode of delivery and short-term neonatal outcome, and identify abnormal Hb levels and propose appropriate treatment and monitoring recommendations.
The Utility of Physical Examination in Ovarian Cancer Recurrence Detection: A Retrospective Analysis Informing Virtual Surveillance Care
Authors: Janke Monica J. , Santiago Sarah , Straubhar Alli M. , Uppal Shitanshu
Published: October 2022

(Abstracted from Int J Gynecol Cancer 2022;32:913–917)

Disease recurrence is commonly seen in ovarian cancer despite optimal treatment, with approximately 80% of those with advanced-stage disease experiencing recurrence. Because of this concerning recurrence rate, surveillance, including screening for symptoms, physical examination, serum CA-125 level, and imaging are commonly used by gynecologic oncologists.
Effect of a Novel Mindfulness Curriculum on Burnout During Pediatric Internship: A Cluster Randomized Clinical Trial
Authors: Fraiman Yarden S. , Cheston Christine C. , Cabral Howard J. , Allen Celeste , Asnes Andrea G. , Barrett Jefferson T. , Batra Maneesh , Bernstein William , Bleeker Tammy , Dietz Pam M. , Lewis Joanna , Li Su-Ting T. , Ma T. Marsha , Mahan John D. , Michelson Catherine D. , Poynter Sue E. , Vining Mark A. , Watson Katherine , Sox Colin M.
Published: October 2022

(Abstracted from JAMA Pediatr 2022;176:365–372)

Burnout, or the combination of emotional exhaustion (EE), depersonalization, and feelings of helplessness, has an adverse impact on providers and patients across the health system. It has been reported that burnout affects between 39% and 75% of pediatric interns.