bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Vulvar Squamous Intraepithelial Lesions and Psychiatric Illness
Authors: Bell Sarah G. , Kobernik Emily K. , Haefner Hope K. , Welch Kathryn C. 
Published: November 2020

Objectives
The aims of the study were to describe and to compare demographics and the prevalence of psychiatric disorders among patients with low- and high-grade vulvar squamous intraepithelial lesions.

Methods
A retrospective chart review was performed for patients presenting to a vulvar diseases clinic between 1996 and 2019 (N = 2,462). Intake questionnaire data were entered into a deidentified database. Results were compared between 80 patients with biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) and 48 patients with biopsy-confirmed low-grade squamous intraepithelial lesions (LSILs). Bivariate analysis was performed to compare demographics and psychiatric treatment and outcomes across HSIL and LSIL groups.

Results
Among 128 patients with vulvar disease, 80 (62.5%) had HSILs and 48 (37.5%) had LSILs. Patients with HSILs were significantly older (HSIL median [interquartile range] = 49.0 (39.0–61.0) vs LSIL = 36.0 [29.0–53.0], p = .006). There were no significant differences between groups across race/ethnicity, education, marital status, or self-reported household income categories. Forty percent of HSIL patients reported depression compared with 20.8% of LSIL patients (p = .03), whereas 31.3% of HSIL patients and 8.3% of LSIL patients reported anxiety (p = .002). Bipolar disorder was reported in 3.8% of HSIL patients and no LSIL patients (p = .29). There were no differences in the proportion of patients receiving psychiatric counseling, medications, or hospitalizations between groups.

Conclusions
Squamous intraepithelial lesions of the vulva are associated with psychiatric disorders above age-matched national averages; these disorders are more prominent in the HSIL group. Combining mental health services with ongoing disease treatment seem to be part of a comprehensive approach to caring for this patient population.
Autoimmune Liver Disease in Patients With Sickle Cell Disease
Authors: Waisbourd-Zinman Orith , Frenklak Rachel , Hakakian Odelia , Hilmara Didja , Lin Henry 
Published: November 2020

Objective:
Hepatic and biliary tract diseases are common in sickle cell disease (SCD) patients, likely due to sickling, hemosiderosis, viral hepatitis, or cholelithiasis. Literature is lacking on associations between SCD, autoimmune hepatitis (AIH), and/or sclerosing cholangitis (SC)-together, autoimmune liver disease (AILD). We aimed to better understand the relationship of these diseases in pediatric patients.

Materials and Methods:
A retrospective analysis of patients with SCD and AILD at the Children’s Hospital of Philadelphia (January 2008 to August 2015).

Results:
Seven patients, ages 8 to 23 years (3 males), were identified. Three had AIH, 2 SC, and 2 AIH/SC overlap, known as autoimmune SC. All patients with AIH treated with azathioprine significantly improved their liver enzymes. One patient with SC and inflammatory bowel disease underwent successful bone marrow transplant. Two SC patients died from SCD complications.

Conclusions:
In this cohort, there seems to be an association between SCD and AILD; SC in this population was severe. Physicians should be aware of this and evaluate patients with SCD and elevated liver enzymes for AILD.
Incorporating a Trauma-Informed Care Protocol Into Pediatric Trauma Evaluation
Authors: Beaulieu-Jones Brendin R. , Bingham Sarah , Rhynhart Kurt K. , Croitoru Daniel P. , Singleton Marcy N. , Rutman Maia S. , Baertschiger Reto M. 
Published: November 2020

Objectives
Trauma evaluation in the emergency department (ED) can be a stressful event for children. With the goal of minimizing pain, anxiety, and unneeded interventions in stable patients, we implemented the Pediatric PAUSE at our level 1 adult/level 2 pediatric trauma center. The Pediatric PAUSE is a brief protocol performed after the primary survey, which addresses Pain/Privacy, Anxiety/IV Access, Urinary Catheter/Rectal exam/Genital exam, Support from family or staff, and Explain to patient/Engage with PICU team. The aim was to assess whether performing the PAUSE interfered with timeliness of emergent imaging in pediatric patients and their disposition.

Methods
We identified all patients aged 0 to 18 years evaluated as trauma activations at our institution after the Pediatric PAUSE was implemented (October 1, 2016–March 31, 2017) as well as 2 analogous 6-month pre-PAUSE periods. Patient demographics, time to imaging studies, and time to ED disposition were analyzed.

Results
One hundred seventy-two patients met the study criteria, with a mean age of 10.9 years and mean injury severity score of 10.6. One hundred fifteen participants (68.5%) were transferred from other hospitals, and 101 (87.8%) had ≥1 imaging study performed before arrival. The Pediatric PAUSE was performed for 41 (25%) of 163 study participants. There was no difference in time to first imaging study in participants for whom the PAUSE was performed (18.4 vs 15.0 minutes, P = 0.09).

Conclusions
The PAUSE is a practice intervention designed to address the psychosocial needs of pediatric trauma patients and their families to help prevent posttraumatic stress symptoms. Implementation did not interfere with the timeliness of first imaging in pediatric trauma patients.
Recognition and Outcomes of Pneumococcal Meningitis in 2 Tertiary Pediatric Hospitals Since the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine
Authors: Stevens James Patrick , Lively Austin , Jerris Robert , Yildirim Inci , Lantis Patricia 
Published: November 2020

Objectives
The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality.

Methods
This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018.

Results
We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053).

Conclusions
Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes.
FDG-Avid Lung Nodule Formation by the Use of Hemostatic Powder
Authors: Oksuzoglu Kevser , Ones Tunc , Bozkurtlar Emine , Bostanci Korkut , Tureli Derya 
Published: November 2020

Abstract
FDG PET/CT is used in the diagnosis and follow-up of various malignant tumors and changes patient management in routine clinical practice. However, inflammatory, infectious, physiological, and technical causes and benign pathological conditions may lead to false-positive FDG uptake. We report a case of a 59-year-old man who was considered having a false-positive FDG-PET pulmonary nodular lesion in favor of metastasis, which was formed by the use of hemostatic powder.
Detection of Dural Metastases Before the Onset of Clinical Symptoms by 16α-[18F]Fluoro-17β-Estradiol PET in a Patient With Estrogen Receptor–Positive Breast Cancer
Authors: Boers Jorianne , Schröder Carolina P. , Hospers Geke A. P. , de Vries Erik F. J. , Glaudemans Andor W. J. M. 
Published: November 2020

Abstract
We offer an illustrative case about estrogen receptor (ER) imaging (also known as 16α-[18F]fluoro-17β-estradiol ([18F]-FES) PET) and the detection of metastatic lesions in the dural region. We present a case of a woman with ER-positive metastatic breast cancer and high [18F]-FES uptake in the dural region on PET imaging, without associated clinical symptoms. These lesions were missed on [18F]-FDG PET because of physiological [18F]-FDG uptake in the brain. This case highlighted some difficulties in the interpretation of imaging of brain metastases and demonstrated the added value of [18F]-FES PET imaging. [18F]-FES PET could be used to prove the presence of ER-positive metastases in the brain.
18F-FDG PET/CT in a Rare Case of Poland Syndrome and Gastric Cancer
Authors: Loharkar Sarvesh , Malhotra Gaurav , Asopa Ramesh V. 
Published: November 2020

Abstract
Poland syndrome is a rare congenital anomaly characterized by unilateral aplasia of the sternoclavicular head of pectoralis major muscle with varying degree of same side upper limb anomalies. A 44-year-old man, with a case of adenocarcinoma of stomach, whose CECT chest revealed complete absence of pectoralis major and minor muscles on the left side, was diagnosed with Poland syndrome without presence of typical ipsilateral limb anomalies. Follow-up PET/CT revealed metabolically active recurrent disease with typical findings of Poland syndrome. It is important to be aware of oncologic association in a patient of Poland syndrome as highlighted in the present case.
Evoked Potentials in Patients With Wilson Disease
Authors: Mihaylova Violeta M. , Kosseva Olga R. , Kotzev Iskren A. , Georgiev Georgi , Kremensky Ivo M. , Todorov Teodor N. , Tournev Ivaylo L. 
Published: November 2020

Introduction:
Wilson disease (WD) is an inherited disorder of copper metabolism presenting with a variety of symptoms but commonly as a liver or neuropsychiatric disease. Abnormal evoked responses are constantly found among patients with neurologic manifestations and sometimes in patients with hepatic presentation or in presymptomatic siblings. The aim of our study was to assess visual and brainstem auditory evoked potentials (BAEP) in patients with various presentation of WD.

Methods:
Visual evoked potentials (VEP) were performed in 36 WD patients and BAEP were done in 37 WD patients.

Results:
Brainstem auditory evoked potentials were normal in patients with isolated hepatic presentation, whereas they were abnormal in 93.5% of patients with neurologic symptoms. There was significant prolongation of the latencies of the III and V waves and of the interpeak III–V and I–V latencies in comparison with the healthy controls (T-test P = 0). Abnormal VEP were observed in 81% of the patients including six of seven neurologically asymptomatic patients. The values of N75, P100, and N145 latencies were significantly longer in all patients than in healthy controls (T-test).

Conclusions:
The data showed that VEP and BAEP are more frequently abnormal in WD than previously reported. The abnormal VEP and BAEP even without clinical signs and brain MRI abnormalities point to subclinical involvement of visual and auditory pathways caused by copper toxicity. Because VEP and BAEP are noninvasive and widely available, they should be performed in all patents with WD.
Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu
Authors: Goods Brittany A. , Askenase Michael H. , Markarian Erica , Beatty Hannah E. , Drake Riley , Fleming Ira , DeLong Jonathan H. , Philip Naomi H. , Matouk Charles C. , Awad Issam A. , Zuccarello Mario , Hanley Daniel F. , Love J. Christopher , Shalek Alex K. , Sansing Lauren H. 
Published: November 2020

ABSTRACTIntracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury, particularly over time, in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Haemorrhage Evacuation (MISTIEIII) trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-sequencing, we characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution for the first time. Our analysis revealed rapid shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic re-bleed (second local exposure to blood) that our transcriptional data indicated occurred more than 30 hours prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods like scRNA-seq can inform our understanding of complex intracerebral events.
The effects of GC-biased gene conversion on patterns of genetic diversity among and across butterfly genomes
Authors: Boman Jesper , Mugal Carina F. , Backström Niclas 
Published: November 2020

AbstractRecombination reshuffles the alleles of a population through crossover and gene conversion. These mechanisms have considerable consequences on the evolution and maintenance of genetic diversity. Crossover, for example, can increase genetic diversity by breaking the linkage between selected and nearby neutral variants. Bias in favor of G or C alleles during gene conversion may instead promote the fixation of one allele over the other, thus decreasing diversity. Mutation bias from G or C to A and T opposes GC-biased gene conversion (gBGC). Less recognized is that these two processes may –when balanced– promote genetic diversity. Here we investigate how gBGC and mutation bias shape genetic diversity patterns in wood white butterflies (Leptideasp.). This constitutes the first in-depth investigation of gBGC in butterflies. Using 60 re-sequenced genomes from six populations of three species, we find substantial variation in the strength of gBGC across lineages. When modeling the balance of gBGC and mutation bias and comparing analytical results with empirical data, we reject gBGC as the main determinant of genetic diversity in these butterfly species. As alternatives, we consider linked selection and GC content. We find evidence that high values of both reduce diversity. We also show that the joint effects of gBGC and mutation bias can give rise to a diversity pattern which resembles the signature of linked selection. Consequently, gBGC should be considered when interpreting the effects of linked selection on levels of genetic diversity.
Combinations of maternal-specific repressive epigenetic marks in the endosperm control seed dormancy
Authors: Sato Hikaru , Santos-González Juan , Köhler Claudia 
Published: November 2020

AbstractPolycomb Repressive Complex 2 (PRC2)-mediated trimethylation of histone H3 on lysine 27 (H3K27me3) and methylation of histone 3 on lysine 9 (H3K9me) are two repressive epigenetic modifications that are typically localized in distinct regions of the genome. For reasons unknown, however, they co-occur in some organisms and special tissue types. In this study, we show that maternal alleles marked by H3K27me3 in the Arabidopsis endosperm were targeted by the H3K27me3 demethylase REF6 and became activated during germination. In contrast, maternal alleles marked by H3K27me3, H3K9me2, and CHGm were protected from REF6 targeting and remained silenced. Our study unveils that combinations of different repressive epigenetic modifications time a key adaptive trait by modulating access of REF6.
A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA
Authors: Nelson Charles , Ambros Victor 
Published: November 2020

ABSTRACTlet-7 is a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using C. sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 orthologs -- also known as the let-7-family of microRNAs -- that have apparently assumed the role of targeting the lin-41 mRNA.Summary StatementWe have identified a group of Caenorhabditis species that lack let-7a, an otherwise highly conserved and nearly ubiquitous microRNA that was previously thought to be critical to bilaterian animal development.
Sustained ErbB activation causes demyelination and hypomyelination by driving necroptosis of mature oligodendrocytes and apoptosis of oligodendrocyte precursor cells
Authors: Hu Xu , Xiao Guanxiu , He Li , Niu Xiaojie , Li Huashun , Lou Tianjie , Hu Qianqian , Yang Youguang , Xu Qi , Wei Zhengdong , Qiu Mengsheng , Tanaka Kenji F. , Shen Ying , Tao Yanmei 
Published: November 2020

AbstractOligodendrocytes are vulnerable to genetic and environmental insults and its injury leads to demyelinating diseases. The roles of ErbB receptors in maintaining the CNS myelin integrity are largely unknown. Here we overactivate ErbB receptors that mediate signaling of either neuregulin or EGF family growth factors and found their synergistic activation caused deleterious outcomes in white matter. Sustained ErbB activation induced by the tetracycline-dependent mouse toolPlp-tTA resulted in demyelination, axonal degeneration, oligodendrocyte precursor cell (OPC) proliferation, astrogliosis, and microgliosis in white matter. Moreover, there was hypermyelination prior to these inflammatory pathological events. In contrast, sustained ErbB activation induced by another tetracycline-dependent mouse toolSox10+/rtTAcaused hypomyelination in the corpus callosum and optic nerve, which appeared to be a developmental deficit and did not associate with OPC regeneration, astrogliosis, or microgliosis. By tracing the differentiation states of cells expressing tTA/rtTA-dependent transgene or pulse-labeled reporter proteinsin vitroandin vivo, we found thatPlp-tTA targeted mainly mature oligodendrocytes (MOs), whereasSox10+/rtTAtargeted OPCs and newly-formed oligodendrocytes. The distinct phenotypes of mice with ErbB overactivation induced byPlp-tTA andSox10+/rtTAconsolidated their non-overlapping targeting preferences in the oligodendrocyte lineage, and enabled us to demonstrate that ErbB overactivation in MOs induced necroptosis that caused inflammatory demyelination, whereas in OPCs induced apoptosis that caused non-inflammatory hypomyelination. Early interference with aberrant ErbB activation ceased oligodendrocyte deaths and restored myelin development in both mice. This study suggests that aberrant ErbB activation is an upstream pathogenetic mechanism of demyelinating diseases, providing a potential therapeutic target.Significance statementPrimary oligodendropathy is one of the etiological mechanisms for multiple sclerosis, and oligodendrocyte necroptosis is a pathological hallmark in the disease. Moreover, the demyelinating disease is now a broad concept that embraces schizophrenia, in which white matter lesions are an emerging feature. ErbB overactivation has been implicated in schizophrenia by genetic analysis and postmortem studies. This study suggests the etiological implications of ErbB overactivation in myelin pathogenesis and elucidates the pathogenetic mechanisms.
Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2
Authors: Vo Thao , Paudel Kshitiz , Choudhary Ishita , Patial Sonika , Saini Yogesh 
Published: November 2020

AbstractBackgroundSARS-CoV-2, a novel coronavirus, and the etiologic agent for the current global health emergency, causes acute infection of the respiratory tract leading to severe disease and significant mortality. Ever since the start of SARS-CoV-2, also known as COVID-19 pandemic, countless uncertainties have been revolving around the pathogenesis and epidemiology of the SARS-CoV-2 infection. While air pollution has been shown to be strongly correlated to increased SARS-CoV-2 morbidity and mortality, whether environmental pollutants such as ground level ozone affects the susceptibility of individuals to SARS-CoV-2 is not yet established.ObjectiveTo investigate the impact of ozone inhalation on the expression levels of signatures associated with host susceptibility to SARS-CoV-2.MethodsWe analyzed lung tissues collected from mice that were sub-chronically exposed to air or 0.8ppm ozone for three weeks (4h/night, 5 nights/week), and analyzed the expression of signatures associated with host susceptibility to SARS-CoV-2.ResultsSARS-CoV-2 entry into the host cells requires proteolytic priming by the host-derived protease, transmembrane protease serine 2 (TMPRSS2). The TMPRSS2 protein andTmprss2transcripts were significantly elevated in the extrapulmonary airways, parenchyma, and alveolar macrophages from ozone-exposed mice. A significant proportion of additional known SARS-CoV-2 host susceptibility genes were upregulated in alveolar macrophages and parenchyma from ozone-exposed mice.ConclusionsOur data indicate that the unhealthy levels of ozone in the environment may predispose individuals to severe SARS-CoV-2 infection. Given the severity of this pandemic, and the challenges associated with direct testing of host-environment interactions in clinical settings, we believe that this mice-ozone-exposure based study informs the scientific community of the potentially detrimental effects of the ambient ozone levels determining the host susceptibility to SARS-CoV-2.