bluuebunny/crossref_metadata_2025 huggingface dataset:
DAS with telecommunication fibre-optic cable in urban areas can record storm-induced seismic noise
Authors: Shen Junzhu , Zhu Tieyuan
Published: September 2023

Extreme weather events threaten life and property in populated areas. Timely and precise weather event monitoring and risk assessment are critical, but can be hampered by limited meteorological stations in cities. Recent studies have shown that seismic stations are sensitive to storm-induced noise. This study aims to investigate the sensitivity of distributed acoustic sensing (DAS), a technology capable of turning existing optical fibres into dense seismic sensors, for recording storm-induced seismic noise. We analyse 4-month continuous DAS recordings (June–September 2021) from a 4.2-km-long underground fibre-optic array in State College, PA. We calibrate the DAS data by comparing it to various meteorological data (rainfall and wind speed) from nearby weather stations. We first show DAS-recorded low-frequency wind-induced noise (0.5–8 Hz) probably caused by light poles swaying in the wind, as observed resonant frequencies agree with theoretical natural frequencies of nearby light poles. We find a strong linear correlation between DAS energy and wind speed. We further characterize rain-induced noise. Detailed observations from two rain events: a moderate rain and a heavy rain from Hurricane Ida, suggest that rain-induced noise is not generated by direct raindrops hitting the ground. Instead, the low-frequency noise (2–8 Hz) is attributed to the acoustic noise generated by water flow in stormwater drainage systems. Strong high-frequency noise up to 125 Hz is likely related to the rapid rainwater filling from the surface to the drainage system during heavy rain. We show linear relations between rain-induced DAS energy and rainfall rate, where the slopes of relations are related to the volume of rainwater, suggesting the influence of surface water and rainwater flow in the drainage system on DAS signals. Our results show the possibility of using DAS-equipped pre-existing telecom fibre-optic cables for sensing windstorms and rainstorms in urban areas and their interactions with urban infrastructures.
MeCP2 ubiquitination and sumoylation, in search of a function
Authors: Kalani Ladan , Kim Bo-Hyun , Vincent John B , Ausió Juan
Published: September 2023

MeCP2 (Methyl CpG binding protein 2) is an intrinsically disordered protein that binds to methylated genome regions. The protein is a critical transcriptional regulator of the brain, and its mutations account for 95% of Rett syndrome (RTT) cases. Early studies of this neurodevelopmental disorder revealed a close connection with dysregulations of the ubiquitin system (UbS), notably as related to UBE3A, a ubiquitin ligase involved in the proteasome-mediated degradation of proteins. MeCP2 undergoes numerous post-translational modifications (PTMs), including ubiquitination and sumoylation, which, in addition to the potential functional outcomes of their monomeric forms in gene regulation and synaptic plasticity, in their polymeric organization, these modifications play a critical role in proteasomal degradation. UbS-mediated proteasomal degradation is crucial in maintaining MeCP2 homeostasis for proper function and is involved in decreasing MeCP2 in some RTT-causing mutations. However, regardless of all these connections to UbS, the molecular details involved in the signaling of MeCP2 for its targeting by the ubiquitin-proteasome system (UPS) and the functional roles of monomeric MeCP2 ubiquitination and sumoylation remain largely unexplored and are the focus of this review.
Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort
Authors: White Alexandra J , Fisher Jared A , Sweeney Marina R , Freedman Neal D , Kaufman Joel D , Silverman Debra T , Jones Rena R
Published: September 2023

Background

Fine particulate matter (PM2.5) has been inconsistently associated with breast cancer incidence, however, few studies have considered historic exposure when levels were higher.

Methods

Outdoor residential PM2.5 concentrations were estimated using a nationwide spatiotemporal model for women in the National Institutes of Health–AARP Diet and Health Study, a prospective cohort located in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, GA, and Detroit, MI) and enrolled in 1995-1996 (n = 196 905). Annual average PM2.5 concentrations were estimated for a 5-year historical period 10 years prior to enrollment (1980-1984). We used Cox regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between a 10 µg/m3 increase in PM2.5 and breast cancer incidence overall and by estrogen receptor status and catchment area.

Results

With follow-up of participants through 2017, a total of 15 870 breast cancer cases were identified. A 10 ug/m3 increase in PM2.5 was statistically significantly associated with overall breast cancer incidence (HR = 1.08, 95% CI = 1.02 to 1.13). The association was evident for estrogen receptor–positive (HR = 1.10, 95% CI = 1.04 to 1.17) but not estrogen receptor–negative tumors (HR = 0.97, 95% CI = 0.84 to 1.13; Pheterogeneity = .3). Overall breast cancer hazard ratios were more than 1 across the catchment areas, ranging from a hazard ratio of 1.26 (95% CI = 0.96 to 1.64) for North Carolina to a hazard ratio of 1.04 (95% CI = 0.68 to 1.57) for Louisiana (Pheterogeneity = .9).

Conclusions

In this large US cohort with historical air pollutant exposure estimates, PM2.5 was associated with risk of estrogen receptor–positive breast cancer. State-specific estimates were imprecise but suggest that future work should consider region-specific associations and the potential contribution of PM2.5 chemical constituency in modifying the observed association.
Utility of a microRNA panel in diagnosis and prognosis of hepatitis C–associated hepatocellular carcinoma
Authors: ALrefai Abeer Ahmed , Rizk Sara Kamal , Khamis Ahmed Kamal , Kasemy Zeinab A , Habieb Mona Salah Eldin
Published: September 2023

Background

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the leading cause of cancer mortality. Various studies have linked dysregulated microRNA expression to liver cancers, but those related to viral hepatitis–related HCC are limited.

Methods

We investigated the diagnostic and prognostic roles of circulating miR-331-3p, miR-23b-3p, and miR-3194-5p in EDTA-treated blood samples of 50 hepatitis C virus (HCV) HCC patients, 50 HCV cirrhotic patients, and 50 healthy controls using quantitative real-time polymerase chain reaction.

Results

We found that miR-23b-3p and miR-3194-5p were significantly downregulated, whereas miR-331-3p was upregulated in HCC patients compared with controls. Also, these miRNAs were significantly dysregulated in HCC compared with cirrhotic patients. For the diagnosis of HCC, miR-331-3p and the combined miRNAs panel had the highest area under the curve (AUC), followed by miR-3194-5p. The highest AUC for differentiating metastatic from nonmetastatic patients was shown by miR-331-3p and the combined miRNAs panel, followed by miR-23b-3p. Dysregulation of miRNAs was associated with poor clinicopathological manifestations. Finally, miR-331-3P was found to be an independent risk factor for metastatic lesions in HCC.

Conclusion

Overall, the assessed miR-331-3p, miR-23b-3p, and miR-3194-5p were significantly associated with poor clinicopathological features of HCC and could be used to discriminate HCV-related HCC patients from cirrhosis and differentiating metastatic from nonmetastatic patients, primarily miR-331-3p along with combined miRNAs. Moreover, miR-331-3p was found to be an independent factor for metastatic lesions.
Detection of optical emission from the supernova remnant G7.7–3.7
Authors: Domček V , Hernández Santisteban J V , Chiotellis A , Boumis P , Vink J , Akras S , Souropanis D , Zhou P , de Burgos A
Published: September 2023

We present the first optical study of the supernova remnant (SNR) G7.7–3.7, with the aim of determining its evolutionary phase since it has been suggested to be the remnant of SN 386 AD. We obtained narrow-band images in the filters H α + [N ii], H β, [O iii], [S ii] that revealed faint optical emission in the southern region of the SNR consisting of two filaments elongated in the east–west direction aligned with the X-ray emitting region of the remnant. The filaments were seen in H α + [N ii], [O iii] images and marginally in the [S ii] images, with a non-detection in H β. Long-slit spectroscopy of the three regions along one filament revealed large ratios of [S ii]/H α = (1.6–2.5), consistent with that expected for a shock-heated SNR. The [S ii] doublet ratio observed in two of the regions implies an upper limit for the electron density of the gas, with estimates falling below 400 cm−3 and 600 cm−3 in the respective areas. We discuss potential physical mechanisms that formed the observed optical filaments and we suggest that most likely they resulted by a collision of the SNR with a dense circumstellar shell lying at the southern region of the remnant.
Detecting low-mass perturbers in cluster lenses using curved arc bases
Authors: Şengül Atınç Çağan , Birrer Simon , Natarajan Priyamvada , Dvorkin Cora
Published: September 2023

Strong gravitationally lensed arcs produced by galaxy clusters have been observationally detected for several decades now. These strong lensing constraints provided high-fidelity mass models for cluster lenses that include substructure down to $10^{9{-}10}\, \mathrm{M}_\odot$. Optimizing lens models, where the cluster mass distribution is modelled by a smooth component and subhaloes associated with the locations of individual cluster galaxies, has enabled deriving the subhalo mass function, providing important constraints on the nature and granularity of dark matter. In this work, we explore and present a novel method to detect and measure individual perturbers (subhaloes, line-of-sight haloes, and wandering supermassive black holes) by exploiting their proximity to highly distorted lensed arcs in galaxy clusters, and by modelling the local lensing distortions with curved arc bases. This method offers the possibility of detecting individual low-mass perturber subhaloes in clusters and haloes along the line of sight down to a mass resolution of $10^8\, \mathrm{M}_\odot$. We quantify our sensitivity to low-mass perturbers ($M\sim 10^{7{-}9}\, \mathrm{M}_\odot$) in clusters (M ∼ 1014–15 M⊙), by creating realistic mock data. Using three lensed images of a background galaxy in the cluster SMACS J0723, taken by JWST, we study the retrieval of the properties of potential perturbers with masses $M=10^{7{-}9}\, \mathrm{M}_\odot$. From the derived posterior probability distributions for the perturber, we constrain its concentration, redshift, and ellipticity. By allowing us to probe lower mass substructures, the use of curved arc bases can lead to powerful constraints on the nature of dark matter as discrimination between dark matter models appears on smaller scales.
New evidence about HW Vir’s circumbinary planets from Hipparcos-Gaia astrometry and a reanalysis of the eclipse timing variations using nested sampling
Authors: Baycroft Thomas A , Triaud Amaury H M J , Kervella Pierre
Published: September 2023

The post common-envelope eclipsing binary HW Virginis (HW Vir) has had many circumbinary companions proposed based on eclipse timing variations. Each proposed solution has lacked in predictability and orbital stability, leaving the origin of the eclipse timing variations an active area of research. Leveraging the catalogue of Hipparcos and Gaia proper motion anomalies, we show there is slight evidence for a circumbinary companion orbiting HW Vir. We place an upper limit in mass for such a companion which excludes some previously claimed companions. We also apply this method to V471 Tauri and confirm the non-detection of a previously claimed brown dwarf. We adapt the kima nested sampling code to analyse eclipse timing variations and re-analyse archival data on HW Vir, varying the order of the ephemeris that we fit for and the amount of the data that we use. Although signals are clearly present, we find two signals around 2500 and 4000-d periods that are not coherent between different chunks of the data, so are likely to not be of planetary origin. We analyse the whole data set and find the best solution to contain four signals. Of these four we argue the outermost is the most compatible with astrometry and thus the most likely to be of planetary nature. We posit the other three pseudo-periodic signals are caused by physical processes on the white dwarf. The eventual release of the full Gaia epoch astrometry is a promising way to confirm whether circumbinary planets exist around HW Vir (and other similar systems), and explore white dwarf physics.
Evaluating the Accuracy of Methods for Detecting Correlated Rates of Molecular and Morphological Evolution
Authors: Asar Yasmin , Sauquet Hervé , Ho Simon Y W
Published: September 2023

Determining the link between genomic and phenotypic change is a fundamental goal in evolutionary biology. Insights into this link can be gained by using a phylogenetic approach to test for correlations between rates of molecular and morphological evolution. However, there has been persistent uncertainty about the relationship between these rates, partly because conflicting results have been obtained using various methods that have not been examined in detail. We carried out a simulation study to evaluate the performance of 5 statistical methods for detecting correlated rates of evolution. Our simulations explored the evolution of molecular sequences and morphological characters under a range of conditions. Of the methods tested, Bayesian relaxed-clock estimation of branch rates was able to detect correlated rates of evolution correctly in the largest number of cases. This was followed by correlations of root-to-tip distances, Bayesian model selection, independent sister-pairs contrasts, and likelihood-based model selection. As expected, the power to detect correlated rates increased with the amount of data, both in terms of tree size and number of morphological characters. Likewise, greater among-lineage rate variation in the data led to improved performance of all 5 methods, particularly for Bayesian relaxed-clock analysis when the rate model was mismatched. We then applied these methods to a data set from flowering plants and did not find evidence of a correlation in evolutionary rates between genomic data and morphological characters. The results of our study have practical implications for phylogenetic analyses of combined molecular and morphological data sets, and highlight the conditions under which the links between genomic and phenotypic rates of evolution can be evaluated quantitatively.
Two Notorious Nodes: A Critical Examination of Relaxed Molecular Clock Age Estimates of the Bilaterian Animals and Placental Mammals
Authors: Budd Graham E , Mann Richard P
Published: September 2023

The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here, we critically examine two such clades: the animals (with a focus on the bilaterians) and the mammals (with a focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what is suggested by the fossil record. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances, the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray, and we have every reason to think these problems are general. [Cambrian explosion; mammalian evolution; molecular clocks.]
Cophylogeny Reconstruction Allowing for Multiple Associations Through Approximate Bayesian Computation
Authors: Sinaimeri Blerina , Urbini Laura , Sagot Marie-France , Matias Catherine
Published: September 2023

Phylogenetic tree reconciliation is extensively employed for the examination of coevolution between host and symbiont species. An important concern is the requirement for dependable cost values when selecting event-based parsimonious reconciliation. Although certain approaches deduce event probabilities unique to each pair of host and symbiont trees, which can subsequently be converted into cost values, a significant limitation lies in their inability to model the invasion of diverse host species by the same symbiont species (termed as a spread event), which is believed to occur in symbiotic relationships. Invasions lead to the observation of multiple associations between symbionts and their hosts (indicating that a symbiont is no longer exclusive to a single host), which are incompatible with the existing methods of coevolution. Here, we present a method called AmoCoala (an enhanced version of the tool Coala) that provides a more realistic estimation of cophylogeny event probabilities for a given pair of host and symbiont trees, even in the presence of spread events. We expand the classical 4-event coevolutionary model to include 2 additional outcomes, vertical and horizontal spreads, that lead to multiple associations. In the initial step, we estimate the probabilities of spread events using heuristic frequencies. Subsequently, in the second step, we employ an approximate Bayesian computation approach to infer the probabilities of the remaining 4 classical events (cospeciation, duplication, host switch, and loss) based on these values. By incorporating spread events, our reconciliation model enables a more accurate consideration of multiple associations. This improvement enhances the precision of estimated cost sets, paving the way to a more reliable reconciliation of host and symbiont trees. To validate our method, we conducted experiments on synthetic datasets and demonstrated its efficacy using real-world examples. Our results showcase that AmoCoala produces biologically plausible reconciliation scenarios, further emphasizing its effectiveness.
Assessing the potential molecular mechanism of arsenite-induced skin cell senescence
Authors: Du Sufei , Yang Fan , Wu Liping , Hu Dexiu , Zhang Yuhong , Gong Maoyuan , Yang Yang , Yang Xingcan , Zeng Qibing
Published: September 2023

Arsenic exposure is a public health concern worldwide. Skin damage, as a typical lesion of arsenic exposure, the mechanism is still unknown. Studies have found that cellular senescence plays a key role in arsenic-induced skin damage, and the previous research found that the ERK/CEBPB signaling pathway may be an important molecular event of arsenic-induced skin cell senescence, but its specific mechanism is unknown. In this study, genetic engineering technology was used to construct stable HaCaT cell lines, and the role and mechanism of ERK/CEBPB signaling pathway in arsenic-induced HaCaT cell senescence were verified by knockdown and overexpression of ERK and CEBPB in both forward and backward. It was found that knockdown of CEBPB or ERK can downregulate the ERK/CEBPB signaling pathway and reduce arsenic-induced skin cell senescence. In contrast to knockdown, overexpression of CEBPB or ERK can upregulate the ERK/CEBPB signaling pathway and aggravate the senescence of skin cells caused by arsenic. These findings suggest that sodium arsenite can further promote SASP secretion and the expression of p53, p21 and p16 INK4a by activating the ERK/CEBPB signaling pathway, induce cell cycle arrest and trigger cellular senescence.
Gestational ozone inhalation elicits maternal cardiac dysfunction and transcriptional changes to placental pericytes and endothelial cells
Authors: Hunter Russell , Baird Brenna , Garcia Marcus , Begay Jessica , Goitom Siem , Lucas Selita , Herbert Guy , Scieszka David , Padilla Jamie , Brayer Kathryn , Ottens Andrew K , Suter Melissa A , Barrozo Enrico R , Hines Curt , Bleske Barry , Campen Matthew J
Published: September 2023

Ozone (O3) is a criteria air pollutant with the most frequent incidence of exceeding air quality standards. Inhalation of O3 is known to cause lung inflammation and consequent systemic health effects, including endothelial dysfunction. Epidemiologic data have shown that gestational exposure to air pollutants correlates with complications of pregnancy, including low birth weight, intrauterine growth deficiency, preeclampsia, and premature birth. Mechanisms underlying how air pollution may facilitate or exacerbate gestational complications remain poorly defined. The current study sought to uncover how gestational O3 exposure impacted maternal cardiovascular function, as well as the development of the placenta. Pregnant mice were exposed to 1PPM O3 or a sham filtered air (FA) exposure for 4 h on gestational day (GD) 10.5, and evaluated for cardiac function via echocardiography on GD18.5. Echocardiography revealed a significant reduction in maternal stroke volume and ejection fraction in maternally exposed dams. To examine the impact of maternal O3 exposure on the maternal-fetal interface, placentae were analyzed by single-cell RNA sequencing analysis. Mid-gestational O3 exposure led to significant differential expression of 4021 transcripts compared with controls, and pericytes displayed the greatest transcriptional modulation. Pathway analysis identified extracellular matrix organization to be significantly altered after the exposure, with the greatest modifications in trophoblasts, pericytes, and endothelial cells. This study provides insights into potential molecular processes during pregnancy that may be altered due to the inhalation of environmental toxicants.
Postoperative Discharge to Acute Rehabilitation or Skilled Nursing Facility Compared With Home Does Not Reduce Hospital Readmissions, Return to Surgery, or Improve Outcomes Following Adult Spine Deformity Surgery
Authors: Bess Shay , Line Breton G. , Nunley Pierce , Ames Christopher , Burton Douglas , Mundis Gregory , Eastlack Robert , Hart Robert , Gupta Munish , Klineberg Eric , Kim Han Jo , Kelly Michael , Hostin Richard , Kebaish Khaled , Lafage Virgine , Lafage Renaud , Schwab Frank , Shaffrey Christopher , Smith Justin S. ,   International Spine Study Group
Published: September 2023

Study Design.

Retrospective review of a prospective multicenter adult spinal deformity (ASD) study.

Objective.

The aim of this study was to evaluate 30-day readmissions, 90-day return to surgery, postoperative complications, and patient-reported outcomes (PROs) for matched ASD patients receiving nonhome discharge (NON), including acute rehabilitation (REHAB), and skilled nursing facility (SNF), or home (HOME) discharge following ASD surgery.

Summary of Background Data.

Postoperative disposition following ASD surgery frequently involves nonhome discharge. Little data exists for longer term outcomes for ASD patients receiving nonhome discharge versus patients discharged to home.

Materials and Methods.

Surgically treated ASD patients prospectively enrolled into a multicenter study were assessed for NON or HOME disposition following hospital discharge. NON was further divided into REHAB or SNF. Propensity score matching was used to match for patient age, frailty, spine deformity, levels fused, and osteotomies performed at surgery. Thirty-day hospital readmissions, 90-day return to surgery, postoperative complications, and 1-year and minimum 2-year postoperative PROs were evaluated.

Results.

A total of 241 of 374 patients were eligible for the study. NON patients were identified and matched to HOME patients. Following matching, 158 patients remained for evaluation; NON and HOME had similar preoperative age, frailty, spine deformity magnitude, surgery performed, and duration of hospital stay (P>0.05). Thirty-day readmissions, 90-day return to surgery, and postoperative complications were similar for NON versus HOME and similar for REHAB (N=64) versus SNF (N=42) versus HOME (P>0.05). At 1-year and minimum 2-year follow-up, HOME demonstrated similar to better PRO scores including Oswestry Disability Index, Short-Form 36v2 questionnaire Mental Component Score and Physical Component Score, and Scoliosis Research Society scores versus NON, REHAB, and SNF (P<0.05).

Conclusions.

Acute needs must be considered following ASD surgery, however, matched analysis comparing 30-day hospital readmissions, 90-day return to surgery, postoperative complications, and PROs demonstrated minimal benefit for NON, REHAB, or SNF versus HOME at 1- and 2-year follow-up, questioning the risk and cost/benefits of routine use of nonhome discharge.

Level of Evidence.

Level III—prognostic.
Cognition, Academic Achievement, Adaptive Behavior, and Quality of Life in Child and Adolescent Boys with Klinefelter Syndrome
Authors: Jordan Tracy L. , Foland-Ross Lara C. , Wun Vanessa L. , Ross Judith L. , Reiss Allan L.
Published: September 2023

Objective:

Klinefelter syndrome (KS; 47, XXY), the most common sex chromosome aneuploidy in males, is characterized by testicular failure and testosterone deficiency as well as a variety of cognitive, social, and emotional challenges. In the current study, we aimed to clarify the cognitive-behavioral profile of peripubertal boys with KS using measures of cognition, academic achievement, adaptive behavior, and quality of life.

Method:

We compared 47 boys with KS (7–16 years of age) with 55 performance IQ-matched boys without KS on measures of cognition (WISC-V), executive function (BRIEF-2), academic achievement (KTEA-3), adaptive behavior (Vineland-3), and quality of life (PROMIS). In exploratory analyses, we examined associations among these measures and potential associations with pubertal metrics.

Results:

Boys with KS demonstrated a significantly different profile of cognition, behavioral ratings of executive function, academic achievement, adaptive behavior, and quality of life compared with their typically developing peers, with, on average, lower functioning. The groups showed significantly different correlations between cognition and aspects of quality of life. No associations were observed between behavior and pubertal development.

Conclusion:

Taken together, these findings indicated that boys with KS are at increased risk for cognitive difficulties, which may affect academic achievement, adaptive behavior, and quality of life. Although initial exploratory analyses indicated that the magnitude of these alterations was not correlated with severity of testicular failure, longitudinal analyses currently being conducted by our group may help clarify the trajectory of these difficulties through the pubertal transition and testosterone replacement.
Complex Attention-Deficit/Hyperactivity Disorder in a Bilingual Child with Down Syndrome and Intellectual Disability
Authors: Moore Trevena , Soccorso Cara , Fogler Jason , Carroll Gretchen , Froehlich Tanya , Nyp Sarah S.
Published: September 2023

CASE:

Maria is an 8-year-old girl with Down syndrome, described by her mother as an affectionate and social child, who was referred to developmental-behavioral pediatrics by her pediatrician because of increasing aggressive behaviors and inattention.

Maria was 5 pounds at birth, delivered full-term by cesarean section, and hospitalized for 1 month after delivery because of feeding issues that required a nasogastric (NG) tube. Maternal age was 24 years, pregnancy was uncomplicated, and there were no reported prenatal exposures to substances. Additional medical history includes corrective cardiac surgery at age 11 months, mild-to-moderate hearing loss in 1 ear, and myopia.

At the time of Maria's presentation to developmental-behavioral pediatrics, she was in third grade and had an IEP with placement in a substantially separate multigrade classroom and inclusion for special classes such as music and art. She had multiple academic goals and accommodations for behaviors such as eloping from class, shoving, and growling at adults; communication Picture Exchange Communication System (PECS); and extended time to complete assignments. Previously, she had attended an inclusion setting with a 1:1 aide. Maria is followed annually at a specialty clinic that focuses on the health needs of children with Down syndrome. At home, Maria's parents speak primarily Spanish, while her 2 older brothers speak primarily English. Maria has been using 3-word phrases since she was 6 years old and understands some American Sign Language. She also uses a PECS book for communication.

During the visit, Maria was notably fidgety, frequently interrupted the parent interview despite having toys to play with, and became aggressive—hitting, kicking, pushing, and shoving—when she did not want to comply with directives. She used mostly single words and a variety of gestures to communicate. Both the parent-completed and teacher-completed Conners-3 (Long Version) produced elevated T-scores (>70) in the domains of inattention, hyperactivity/impulsivity, defiance/aggression, peer relations, Global Index scale, DSM-5 Hyperactive/Impulsive symptom scale, and DSM-5 Conduct Disorder symptom scale. The teacher endorsed full criteria for attention-deficit/hyperactivity disorder, consistent with combined presentation, and the parent endorsed symptoms in a similar pattern. Methylphenidate (2.5 mg) was trialed but tolerated poorly when it was titrated to 5 mg. Maria's mother reported that Maria's focus was somewhat better, but she was easily brought to tears and “not herself.”

What would be the next steps in Maria's evaluation/treatment? Could there be reasons for her worsening behavior other than a primary attention disorder?
Cultivating an Active Living Plan Through a Social-Ecological Evaluation
Authors: Prochnow Tyler , Patterson Megan S. , Amo Christina , Curran Laurel , Francis Allison N. , Green Emily
Published: September 2023

Physical activity (PA) social-ecological model (SEM) posits the importance of several levels of influence critical for PA promotion within communities. The purpose of this study was to examine an SEM evaluation informing a county-wide active living plan in McLennan County, Texas in the United States. Mixed-methods evaluation occurred in 4 stages: (1) county policies (n = 15) were evaluated for PA promoting strategies; (2) PA resource assessments (PARAs) were conducted via Google Maps (n = 171); (3) surveys (n = 244) included the International Physical Activity Questionnaire and interpersonal and intrapersonal factors related to PA; and (4) focus groups (n = 5) were conducted with residents (n = 30), discussing barriers and facilitators to being active. Logistic regression determined significant associations between SEM factors and meeting PA recommendations. Policy scans and PARAs identified strengths and areas of improvement (eg, equitable project selection and disparities in resource quality). Residents reporting fewer barriers (OR = 0.89, P =.01), more perceived behavioral control (odds ratio [OR] = 1.38, P = .01), more social co-participation in PA (OR = 1.20, P = .03), and living in zip codes with higher mean PARA score (OR = 1.22, P = .04) were significantly more likely to meet PA recommendations (Nagelkerke R
2 = 0.32). Focus groups also discussed safety and disparities in access and quality. This study suggests the utility of the SEM when evaluating and promoting community PA.
Systems-Level Evaluation of Safe Routes to School Policies in El Paso, Texas
Authors: Garney Whitney , Panjwani Sonya , Curran Laurel , Enderle Joan , King Laura , O'Neil Dara , Li Yan
Published: September 2023

Safe Routes to School (SRTS) policies are linked to physical health benefits for school-age children; however, few studies have assessed long-term impacts on cardiovascular disease (CVD). This study used systems science methods to predict long-term health and economic impact of SRTS among school-age children in El Paso County, Texas. We developed an agent-based model containing 2 modules: the pedestrian injury module and the CVD module. We simulated 10 000 school-age children under 2 scenarios—SRTS policies implemented and no SRTS policies implemented—and then calculated pedestrian injuries, pedestrian injury–related deaths, coronary heart disease (CHD) and stroke events, and health care costs. When SRTS policies were implemented, the model estimated 157 fewer CHD cases and 217 fewer stroke cases per 10 000 people and reduced CVD-related health care costs ($13 788 per person). The model also predicted 129 fewer pedestrian injuries and 1.3 injury-related deaths per 10 000 people and $2417 savings in injury-related health care costs. SRTS could save an estimated $16 205 per person in health care costs. This simulation shows SRTS in El Paso County could prevent pedestrian injuries among school-age children and protect cardiovascular health in the long term. Our findings provide evidence for practitioners and policy makers to advocate for SRTS policies at the local level.
Hepatic farnesoid X receptor is necessary to facilitate ductular reaction and expression of heme biosynthetic genes
Authors: Dean Angela E. , Jungwirth Emilian , Panzitt Katrin , Wagner Martin , Anakk Sayeepriyadarshini
Published: September 2023

Background:

Bile, which contains bile acids, the natural ligands for farnesoid x receptor (FXR), moves from the liver to the intestine through bile ducts. Ductular reaction often occurs during biliary obstruction. A subset of patients with erythropoietic protoporphyria, an inherited genetic mutation in heme biosynthetic enzyme ferrochelatase, accumulate porphyrin-containing bile plugs, leading to cholestasis. Here, we examined the link between FXR, bile plug formation, and how heme biosynthesis relates to this connection.

Methods:

We treated female and male wild-type and global and tissue-specific Fxr knockout mice with a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine, an inhibitor of ferrochelatase, and examined the expression of heme biosynthetic genes. We mined FXR mouse ChIP-Seq data, performed biochemical and histological analysis, and tested HepG2 and primary human hepatocytes after treatment with obeticholic acid, an FXR agonist.

Results:

We observed that hepatic but not intestinal Fxr loss resulted in reduced bile plugs and ductular reaction in the liver. Then, we examined if FXR plays a regulatory role in heme biosynthesis and found significantly lower porphyrin accumulation in 3,5-diethoxycarbonyl-1, 4-dihydrocollidine–fed Fxr knockout mice. Gene expression and FXR mouse ChIP-Seq atlas analysis revealed that FXR orchestrates the expression of multiple heme biosynthetic enzymes. Finally, human HepG2 cells and primary human hepatocytes treated with obeticholic acid, showed increased expression of several heme biosynthetic genes.

Conclusions:

Overall, our data show that hepatic Fxr is necessary to maintain ductular reaction and accumulation of bile plugs. FXR can direct the expression of multiple heme biosynthetic genes. Thus, modulating FXR activity in EPP patients may help alleviate its associated liver disease.
CD4+ T-cell subsets in autoimmune hepatitis: A review
Authors: Chen Haoran , Han Zhongyu , Fan Yiyue , Chen Liuyan , Peng Fang , Cheng Xuhua , Wang Yi , Su Junyan , Li Dongxuan
Published: September 2023

Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that can lead to hepatocyte destruction, inflammation, liver fibrosis, cirrhosis, and liver failure. The diagnosis of AIH requires the identification of lymphoblast cell interface hepatitis and serum biochemical abnormalities, as well as the exclusion of related diseases. According to different specific autoantibodies, AIH can be divided into AIH-1 and AIH-2. The first-line treatment for AIH is a corticosteroid and azathioprine regimen, and patients with liver failure require liver transplantation. However, the long-term use of corticosteroids has obvious side effects, and patients are prone to relapse after drug withdrawal. Autoimmune diseases are characterized by an imbalance in immune tolerance of self-antigens, activation of autoreactive T cells, overactivity of B cells, and increased production of autoantibodies. CD4+ T cells are key players in adaptive immunity and can secrete cytokines, activate B cells to produce antibodies, and influence the cytotoxicity of CD8+ T cells. According to their characteristics, CD4+ T cells can be divided into different subsets. In this review, we discuss the changes in T helper (Th)1, Th2, Th17, Th9, Th22, regulatory T cell, T follicular helper, and T peripheral helper cells and their related factors in AIH and discuss the therapeutic potential of targeting CD4+ T-cell subsets in AIH.
Single-cell immune profiling of mouse liver aging reveals Cxcl2 + macrophages recruit neutrophils to aggravate liver injury
Authors: Liu Yasong , Xiao Jiaqi , Cai Jianye , Li Rong , Sui Xin , Zhang Jiebin , Lu Tongyu , Chen Haitian , Chen Guihua , Li Haibo , Jiang Chenhao , Zhao Xuegang , Xiao Cuicui , Lei Yunguo , Yao Jia , Lv Guo , Liang Jinliang , Zhang Yingcai , Yang Jian-Rong , Zheng Jun , Yang Yang
Published: September 2023

Background and Aims:

Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging.

Approach and Results:

We carried out single-cell RNA sequencing on mouse liver tissues at 4 different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2
+ macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2
+ macrophages presented a senescence-associated secretory phenotype and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1β and TNF-α, Cxcl2
+ macrophages stimulated neutrophil extracellular traps formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2
+ macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples.

Conclusions:

This in-depth study illustrates that the mechanism of Cxcl2
+ macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis and provides a potential therapeutic strategy for age-related liver injury.
Retinal Tectonics after Macular Pucker Surgery: Thickness Changes and En-Face Displacement Recovery
Authors: Scarinci Fabio , Querzoli Giorgio , Cosimi Pamela , Ripandelli Guido , Romano Mario R. , Cacciamani Andrea , Munk Marion R. , Rossi Tommaso
Published: September 2023

Purpose:

To study visual function, retinal layer thickness changes and tangential displacement after Pars Plana Vitrectomy (PPV) for EpiRetinal Membrane (ERM).

Methods:

Retrospective series of patients undergoing PPV for ERM, with 6-month follow-up including best-corrected visual acuity (BCVA), Optical Coherence Tomography (OCT), M-charts, ERM grading, and InfraRed fundus photo at time 0 (T0, pre-op) at month 1 (T1), 3 (T3), 6 (T6) post-op (±1 week). Retinal layer thickness and tangential (en-face) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En-face displacement was calculated as optical flow of consecutive images.

Results:

Average BCVA improved from 0.28±0.08 logMAR at T0 to 0.16±0.25 at T6 (p=0.05), BCVA improvement correlated with BVCA at T0 (p<0.001). Vertical metamorphopsia decreased from 1.33°±0.70° at T0 to 0.82°±0.69° at T6 (p<0.05). Foveal thickness reduced from 453±53µm at T0 to 359±31µm at T6 (p<0.05) and reduction correlated with BCVA improvement (p<0.05). Foveal layers decreased (p<0.05) in all cases. Mean en-face deformation was 155.82±50.17µm and mostly occurred in the first month: T0-T1 displacement was 83.59±30.28µm, T1-T3 was 36.28±14.45µm, while T3-T6 was 39.11±22.79µm (p<0.001) on average. Peri-foveal and parafoveal deformation correlated with OCT foveal thickness reduction at all time intervals (1, 3, 6 months: p<0.01).

Conclusion:

ERM peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en-face and in-depth changes correlate with visual function.
Orbital Liposarcoma: A Surveillance, Epidemiology and End Results Database Study
Authors: Chen Teresa , Roelofs Kelsey A. , Baugh Samuel , Esfandiari Mahtash , Rootman Daniel B.
Published: September 2023

Purpose:

Orbital liposarcoma is a challenging tumor to treat due to its rarity and high rate of local recurrence, and the role of radiotherapy and chemotherapy remain unclear. Analysis of big data may improve our overall understanding of orbital disease and role of adjuvant therapies.

Methods:

Data were extracted from the Surveillance, Epidemiology and End Results (SEER) Research Plus database from 1975 to 2017. All patients with a diagnosis of liposarcoma (ICD-O3 codes 8850-8858, 8869-8862, 8870, 8880, 8881) were included. Cases were divided into 4 groups by primary site: orbit, retroperitoneum, soft tissue, and other.

Results:

A total of 16,958 patients were included. Patients with orbital involvement were younger and more likely to be female (p < 0.05). Among orbital lesions, myxoid liposarcoma was the most common histologic subtype (6/19; 31.6%) followed by well differentiated (5/19; 26.3%). This differed from the distribution of histologic subtypes encountered elsewhere, for which well-differentiated liposarcoma was the most common (retroperitoneum 979/3,136; 31%, soft tissue 3,493/11,671; 30%, and other sites 497/2,132; 23%, p < 0.05). Dedifferentiated histologic subtype was the second most common subtype found in the retroperitoneum (946/3,136; 30%), whereas it was less common in the orbit (2/19; 11%) and soft tissue (1,396/11,671; 12%) (p < 0.001). Patients with orbital liposarcoma had similar disease-specific mortality compared with soft-tissue location (p = 0.825) and lower disease-specific mortality compared with retroperitoneal location (p < 0.001). When all locations were combined, patients with well-differentiated liposarcoma had the lowest disease-specific mortality.

Conclusions:

Patients with orbital liposarcoma tend to be younger, female, and have a better prognosis than those with retroperitoneal disease, likely due to the lower incidence of dedifferentiated histologic subtype.
Neutrophil-to-Lymphocyte Ratios Distinguish Idiopathic Orbital Inflammation From Orbital Infectious Disease
Authors: Wladis Edward J. , Bohnak Carisa E. , Law James J. , Adam Alejandro P. , Rothschild Michael I. , Pauze Denis R.
Published: September 2023

Purpose:

The neutrophil-to-lymphocyte ratio (NLR) is a relatively novel biomarker to distinguish between acute stresses. This study was performed to determine whether the NLR may discern infectious orbital maladies from idiopathic orbital inflammation (IOI).

Methods:

The NLR was calculated by a review of the initial blood draws of adult patients who presented to the emergency department at a single academic medical center. Statistical comparisons were performed to identify the significance of these results.

Results:

Ten patients with IOI, 12 patients with necrotizing fasciitis (NF), and 12 patients with orbital cellulitis (OC) presented to the emergency department. The groups were not statistically significantly different in terms of age or gender. The mean NLRs were 3.48 (standard deviation = 1.80), 13.5 (standard deviation = 14.5), and 8.15 (standard deviation = 6.56) for IOI, NF, and OC, respectively. Patients with IOI had statistically significantly lower NLRs than patients with NF (p = 0.037) and OC (p = 0.034). However, the NLRs of patients with OC were not statistically significantly different from those of patients with NF (p = 0.27).

Conclusions:

The NLR appears to distinguish IOI from infectious etiologies, but does not discern between variants of infection. These results should be juxtaposed against appropriate imaging and clinical evaluations, but elevated NLR values may heighten clinicians’ concerns for an infectious process and encourage them to initiate appropriate management steps.
A Quality Improvement Project
Authors: Joy Julija A. , Gunn Jennie , Mulekar Madhuri S.
Published: September 2023

Purpose

This quality improvement project was introduced at an addiction treatment center to implement the Centers for Disease Control and Prevention's (CDC's) hepatitis C virus (HCV) treatment guidelines and offer anticraving medications to patients to improve standards of care of patients with substance use disorders.

Literature Review

Patients with opioid use disorders are at the highest risk of contracting HCV. More than 80% of people in the United States with opioid use disorders who use intravenous drugs have contracted HCV. Despite the high prevalence of HCV, patients at treatment centers are being screened only for HCV antibodies (HCV-AB) and are not receiving the CDC's HCV treatment guidelines. The CDC has treatment recommendations of hepatitis panels, full STD testing, and early follow-up care.

Method

This quality improvement project utilized the Plan-Do-Study-Act tool. With the application of Plan-Do-Study-Act, for patients identified with HCV-AB, the established CDC HCV treatment guidelines were followed, and the clinical progress of the implementation of the guidelines was monitored. Chart reviews comparing compliance of guidelines before and after the study were implemented.

Participants

A convenience sample of 125 patients were collected, and of these, 32 patients were found to be HCV-AB+.

Findings

The findings revealed that 18.75% of patients followed the CDC's HCV recommendations after the quality improvement project compared with 6.25% of patients before the intervention. The number of HIV testing offered increased by 40.00% as a result of the implementation of the project.