bluuebunny/crossref_metadata_2025 huggingface dataset:
Manifestations of the structural origin of supercooled water’s anomalies in the heterogeneous relaxation on the potential energy landscape
Authors: Mondal Arijit , Ramesh Gadha , Singh Rakesh S.
Published: November 2022

Liquid water is well-known for its intriguing thermodynamic anomalies in the supercooled state. The phenomenological two-state models—based on the assumption of the existence of two types of competing local states (or, structures) in liquid water—have been extremely successful in describing water’s thermodynamic anomalies. However, the precise structural features of these competing local states in liquid water still remain elusive. Here, we have employed a predefined structural order parameter-free approach to unambiguously identify two types of competing local states—entropically and energetically favored—with significantly different structural and energetic features in the TIP4P/2005 liquid water. This identification is based on the heterogeneous structural relaxation of the system in the potential energy landscape (PEL) during the steepest-descent energy minimization. This heterogeneous relaxation is characterized using order parameters inspired by the spin-glass transition in frustrated magnetic systems. We have further established a direct relationship between the population fluctuation of the two states and the anomalous behavior of the heat capacity in supercooled water. The composition-dependent spatial distribution of the entropically favored local states shows an interesting crossover from a spanning network-like single cluster to the spatially delocalized clusters in the close vicinity of the Widom line. Additionally, this study establishes a direct relationship between the topographic features of the PEL and the water’s thermodynamic anomalies in the supercooled state and provides alternate markers (in addition to the locus of maxima of thermodynamic response functions) for the Widom line in the phase plane.
Coexistence of photonic and phononic corner states in a second-order topological phoxonic crystal
Authors: Lei Lin-Lin , He Ling-Juan , Liu Wen-Xing , Liao Qing-Hua , Yu Tian-Bao
Published: November 2022

Recently, higher-order topological insulators (HOTIs) have been extended from the electronic system to classical wave systems. Beyond the conventional bulk-boundary correspondence, HOTIs can host zero-dimensional topologically protected corner states, which show the strong field localization and robustness against fabrication flaws. Here, we propose a second-order topological phoxonic crystal (PXC) based on a two-dimensional (2D) square lattice, of which different unit cell choices can show either a topologically trivial or non-trivial band structure characterized by the 2D Zak phase. The proposed PXC supports the coexistence of photonic and phononic topological corner states, and their robustness to disorders and defects is numerically demonstrated. Our work opens a venue for achieving simultaneous confinement of photons and phonons, which is potentially useful for exploring the interaction of photonic and phononic second-order topological states and for designing novel topological optomechanical devices.
Integrin β1 regulates marginal zone B cell differentiation and PI3K signaling
Authors: Andreani Virginia , Ramamoorthy Senthilkumar , Fässler Reinhard , Grosschedl Rudolf
Published: November 2022

Marginal zone (MZ) B cells represent innate-like B cells that mediate a fast immune response. The adhesion of MZ B cells to the marginal sinus of the spleen is governed by integrins. Here, we address the question of whether β1-integrin has additional functions by analyzing Itgb1fl/flCD21Cre mice in which the β1-integrin gene is deleted in mature B cells. We find that integrin β1–deficient mice have a defect in the differentiation of MZ B cells and plasma cells. We show that integrin β1–deficient transitional B cells, representing the precursors of MZ B cells, have enhanced B cell receptor (BCR) signaling, altered PI3K and Ras/ERK pathways, and an enhanced interaction of integrin-linked kinase (ILK) with the adaptor protein Grb2. Moreover, the MZ B cell defect of integrin β1–deficient mice could, at least in part, be restored by a pharmacological inhibition of the PI3K pathway. Thus, β1-integrin has an unexpected function in the differentiation and function of MZ B cells.
X-Ray and Ultraviolet Flares on AT Microscopii Observed by AstroSat
Authors: Kuznetsov A. A. , Karakotov R. R. , Chandrashekhar K. , Banerjee D.
Published: November 2022

We present observations of the active M-dwarf binary AT Mic (dM4.5e+dM4.5e) obtained with the orbital observatory AstroSat. During 20 ks of observations, in the far-ultraviolet (130–180 nm) and soft X-ray (0.3–7 keV) spectral ranges, we detected both quiescent emission and at least five flares on different components of the binary. The X-ray flares were typically longer than and delayed (by 5–6 minutes) with respect to their ultraviolet counterparts, in agreement with the Neupert effect. Using X-ray spectral fits, we estimated the parameters of the emitting plasma. The results indicate the presence of a hot multi-thermal corona with average temperatures in the range of ∼7–15 MK and emission measure of ∼(2.9–4.5) × 1052 cm−3; both the temperature and the emission measure increased during the flares. The estimated abundance of heavy elements in the corona of AT Mic is considerably lower than at the Sun (∼0.18–0.34 of the solar photospheric value); the coronal abundance increased during the flares due to chromospheric evaporation. The detected flares had the energies of ∼1031–1032 erg; the energy-duration relations indicate the presence of magnetic fields stronger than in typical solar flares.
Suppression of chromosome instability by targeting a DNA helicase in budding yeast
Authors: Gordon Molly R. , Zhu Jin , Sun Gordon , Li Rong
Published: November 2022

Cancers are characterized by chromosome instability (CIN), which drives tumor formation, evolution, and drug resistance. In this study, we investigated an intriguing observation that deletion of the evolutionarily conserved helicase Rrm3 leads to a wide range of chromosome instability suppression in budding yeast. CIN suppression appears to occur through increased potential for kinetochore–micro­tubule error correction. These results provide a novel link between the Rrm3 helicase localization of error-correcting enzymes and implicate the homologous human helicase, Pif1, as a potential therapeutic target for CIN suppression.
Interference on the Abbott i-STAT creatinine assay caused by hydroxyurea
Authors: Paz Matt Andrew , Seegmiller Jesse
Published: November 2022

Serum creatinine is an important biomarker used for estimating glomerular filtration rate (eGFR). The present study was designed after a patient at our institution had a significantly elevated creatinine result taken from an i-STAT point of care test that utilizes electrochemical detection. The patient’s creatinine from the i-STAT was 3.8 mg/dL and was not consistent with their clinical history. The patient’s previous creatinine taken 2 days prior was 1.39 mg/dL and 1.27 mg/dL seven days prior. Both previous readings were measured with the Siemens Dimension Vista 1500 using a colorimetric enzymatic creatinine method. A subsequent creatinine measured on the Siemens Dimension Vista 1500 was 1.30 mg/dL. Upon chart review, the clinical team noted that the patient is taking 500 mg of hydroxyurea daily for treatment of a myeloproliferative disorder. Review of the i-STAT package insert revealed hydroxyurea as a known interfering substance and states for every 100 µmol/L hydroxyurea in the specimen, creatinine will be increased by approximately 1.85 mg/dL. Review of literature described the positive interference caused by hydroxyurea for the i-STAT creatinine and glucose assays but did not explain the mechanism of this positive interference. In order to characterize the mechanism of hydroxyurea interference, we investigated the situation further. A pool of plasma was spiked with hydroxyurea. The spiked pool was serial diluted (x2, x4, x8, x16, x32, x64, x128) to observe the creatinine results in the presence of and absence of hydroxyurea. The dilution series was analyzed using the Vista enzymatic creatinine and the Abbott i-STAT enzymatic creatinine methods. The i-STAT creatinine results show increasing creatinine concentration from interference as the concentration of hydroxyurea increased. The dilution series suggests increasing positive interference with hydroxyurea. Positive creatinine interference with hydroxyurea was not observed when analyzed on the Vista platform. Hydroxyurea is a widely used treatment for myeloproliferative disorders and also for managing sickle cell disease. Hydroxyurea is known to cause positive interference in the i-STAT enzymatic creatine method that uses electrochemical detection, with the degree of interference correlating with the concentration of hydroxyurea. The Vista colorimetric enzymatic creatinine method was not observed to have hydroxyurea interference. While both methods employ enzymatic reagent systems the final detection approach is important. Patients undergoing hydroxyurea treatment should avoid i-STAT measurement systems for creatinine.
Pulmonary Tumor Thrombotic Microangiopathy (PTTM) Caused by Metastatic Ovarian High-Grade Serous Carcinoma: A Rare Case Report and Literature Review
Authors: Fujita J , Hummel K , Xu Y
Published: November 2022

Introduction/Objective

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare entity, and often diagnosed in postmortem. PTTM is usually presented as unexplained dyspnea in a patient with known or unknown history of cancer. Tumor microemboli mainly affect the pulmonary microvasculature. PTTM is resulting from coagulation cascade activation secondary to tumor microemboli induced fibrin clot formation and fibrocellular intimal proliferation.

Methods/Case Report

The patient is a 65-year-old female with past medical history of ovarian high-grade serous carcinoma, and presented to the hospital with chest pain and shortness of breath. Coronary angiography showed no new obstructive disease. Echocardiogram revealed markedly elevated right ventricular systolic pressure (65-70 mmHg), indicated pulmonary hypertension. Computed tomography of the chest revealed diffuse bilateral ground glass and solid centrilobular nodules, with no pulmonary emboli identified. She developed worsening hypoxia and expired. A lung-restricted autopsy was performed. Literature review was conducted. The important gross findings included multiple firm and red-brown nodules (approximately 0.1 cm) in bilateral lungs. Microscopic examination revealed the lung parenchyma demonstrated numerous tumor microemboli in the pulmonary arterioles and occasionally in the small arteries. The tumor microemboli consist of tumor cells with various degree of fibrin deposition and fibrocellular intimal proliferation. The tumor cells were epithelioid with moderate to marked nuclear pleomorphism, occasional cytoplasmic vacuoles, frequent apoptosis and necrosis. Immunohistochemical stains for PAX-8 and WT1 highlight the tumor microemboli. These findings are consistent with PTTM secondary to metastatic ovarian high-grade serous carcinoma. Rare cases of PTTM associated with ovarian cancer were found in PubMed.

Results (if a Case Study enter NA)

NA.

Conclusion

PTTM has poor prognosis. There are no sensitive diagnostic modalities, and majority of them are diagnosed at autopsy. We have found four reported PTTM cases caused by metastatic ovarian cancer in PubMed, including one case of clear cell carcinoma and three cases of low-grade serous carcinoma. Our current report of PTTM is associated with high-grade serous carcinoma, which is not seen in the literature. The awareness of PTTM is necessary for patients with ovarian cancer.
Intracranial Extramedullary Hematopoiesis: a Rare Entity
Authors: Morrar D , Sham S , Al-Refai R , Harshan M
Published: November 2022

Introduction/Objective

Extramedullary hematopoiesis (EMH) is characterized by ectopic proliferation and differentiation of hematopoietic precursor cells outside the bone marrow. In postnatal life, EMH occurs due to hematopoietic disorders, infection or advanced tumors and is usually seen in the spleen, liver, and lymph nodes. Intracranial EMH is an extremely rare entity that has been reported to be associated with hematological disorders, meningioma, subdural hematoma and pilocytic astrocytoma.

Methods/Case Report

To highlight the significance of identifying EMH as one of the differential diagnoses of brain lesions, we present a 67-year-old female with a history of headaches and generalized malaise. Her past medical history was significant for hypertension and mild anemia. As part of the headache workup, magnetic resonance imaging (MRI) of the brain showed a 3.7cm cystic mass in the right inferomedial parietal lobe with medial mural enhancement, associated with edema and mass effect. A similar 3mm left parietal lobe enhancing focus was also noted. These findings were suggestive of a hemangioblastoma. Resection of the larger mass showed a benign vascular lesion with endothelial hyperplasia without the appearance of cavernous hemangioma or vascular malformation. Foci of erythroid and myeloid precursors, and megakaryocytes were seen. Immunohistochemical stains were negative for GFAP, CK AE1/AE3 and inhibin ruling out glial neoplasms, metastatic carcinoma and hemangioblastoma. Hematopoietic cells were positive for CD45, while immature red cells were positive for E-cadherin and endothelial cells were positive for CD31, consistent with EMH. Further workup was negative for any underlying hematological disorders, resulting in the diagnosis of idiopathic intracranial EMH. The patient received intensity- modulated radiation therapy (IMRT) for her remaining left parietal lesion. After 3 months of regular follow-up, her headache and malaise significantly improved.

Results (if a Case Study enter NA)

NA.

Conclusion

To our knowledge, this is the first reported case of idiopathic intracranial EMH.
A Rare Case of Therapy Related Monoblastic Leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP Fusion and Hemophagocytosis
Authors: Perveze I , Hammer R
Published: November 2022

Introduction/Objective

Therapy related leukemias are often myeloid and occur as a late complication of cytotoxic therapy or radiotherapy. Most common etiologies are alkylating agents and topoisomerase II inhibitors leading to inaccurate base pairing and chromosomal breakages resulting in complex karyotypes. We describe an extremely rare case of therapy related monobalstic leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP Fusion and hemophagocytosis.

Methods/Case Report

An 81-year-old female with history of mixed cellularity Hodgkin’s lymphoma status post chemotherapy with AVD (Adriamycin, Vinblastine and Dacarbazine) and in remission presented with a complaint of newly developed skin rash on her chest. Punch biopsy showed a diffuse infiltrate of blastoid mononuclear cells with a component of monocytic differentiation present throughout the dermis. Complete blood count revealed bicytopenia (Hemoglobin 8.4 g/dl, platelets 32 x 109 per liter) and peripheral blood smear examination showed 54% blasts. Bone marrow biopsy was remarkable for infiltration by 79.2% blasts with monocytic differentiation and prominent hemophagocytosis. Immunophenotypic analysis was notable for weak positivity for p53 and a Ki67 proliferation index of 20%. These results led to the diagnosis of monobasic leukemia with hemophagocytosis. Cytogenetic analysis was abnormal with 19 out of 20 metaphases showing t(8;16)(p11.2;p13.3). Interestingly, FISH revealed the rare KAT6A- CREBBP fusion gene. The patient was hospitalized for induction chemotherapy and started on Decitabine. Her hospital course was complicated with acute kidney injury and pulmonary edema with rapid deterioration along with persistent elevation of blasts in the blood. The patient opted for hospice due to lack of improvement and died thereafter.

Results (if a Case Study enter NA)

NA.

Conclusion

AML with t(8,16) is an extremely rare entity accounting for 0.2 to 0.4% of AML cases. AML with t(8,16)/KAT6-CREBBP is frequently associated with monocytic or myelomonocytic differentiation, leukemia cutis and hemophagocytosis. While spontaneous remission can occur in a subset of neonatal t(8;16)(p11.2;p13.3), the majority of cases are therapy-related and carry a poor prognosis as seen in our patient.
Low availability of functional seed trait data from the tropics could negatively affect global macroecological studies, predictive models and plant conservation
Authors: Visscher Anne M , Vandelook Filip , Fernández-Pascual Eduardo , Pérez-Martínez Laura Victoria , Ulian Tiziana , Diazgranados Mauricio , Mattana Efisio
Published: November 2022

Background

Plant seeds have many traits that influence ecological functions, ex situ conservation, restoration success and their sustainable use. Several seed traits are known to vary significantly between tropical and temperate regions. Here we present three additional traits for which existing data indicate differences between geographical zones. We discuss evidence for geographical bias in availability of data for these traits, as well as the negative consequences of this bias.

Scope

We reviewed the literature on seed desiccation sensitivity studies that compare predictive models to experimental data and show how a lack of data on populations and species from tropical regions could reduce the predictive power of global models. In addition, we compiled existing data on relative embryo size and post-dispersal embryo growth and found that relative embryo size was significantly larger, and embryo growth limited, in tropical species. The available data showed strong biases towards non-tropical species and certain families, indicating that these biases need to be corrected to perform truly global analyses. Furthermore, we argue that the low number of seed germination studies on tropical high-mountain species makes it difficult to compare across geographical regions and predict the effects of climate change in these highly specialized tropical ecosystems. In particular, we show that seed traits of geographically restricted páramo species have been studied less than those of more widely distributed species, with most publications unavailable in English or in the peer-reviewed literature.

Conclusions

The low availability of functional seed trait data from populations and species in the tropics can have negative consequences for macroecological studies, predictive models and their application to plant conservation. We propose that global analyses of seed traits with evidence for geographical variation prioritize generation of new data from tropical regions as well as multi-lingual searches of both the grey- and peer-reviewed literature in order to fill geographical and taxonomic gaps.
Multicenter Pivotal Study Demonstrates Safety and Efficacy of a New Cellulite Procedure: Final Results at 12 Months
Authors: Stevens W Grant , Green Jeremy B , Layt Craig , Kaminer Michael S , Harrington Jennifer , Fan Larry , Wall Holly Casey , Fabi Sabrina , Magnusson Mark R
Published: November 2022

Background

Safety and efficacy endpoints for the single-arm, multicenter, open-label pivotal study, CONtrolled Focal Fibrous Band Release Method (CONFFIRM) [NCT04743635] assessing targeted verifiable subcision (TVS) for the treatment of cellulite were met at 3 months postprocedure and have been published. Final, 12-month data describing durability of treatment effect and safety are presented here for the first time.

Objectives

The authors sought to evaluate safety and efficacy out to 12 months of initial treatment for a single TVS procedure performed employing the Avéli device (Revelle Aesthetics, Inc.; Mountain View, CA) to treat cellulite on the buttock and thigh areas of adult females.

Methods

Effectiveness was determined by 3 independent physicians employing the Cellulite Severity Scale and Global Aesthetic Improvement Scale to assess improvement of baseline photographs when compared with 3-, 6- and 12-month posttreatment photographs. Blinded participant-reported outcomes and safety evaluations were also performed at all postprocedure time points.

Results

Clinically significant improvement in primary endpoint Cellulite Severity Scale scores were sustained out to 1 year, improving by 1.50 (P < .0001) at 3 months, 1.54 points at 6 months, and 1.48 points at 12 months. Adverse events were mild and mostly resolved by the 12-month visit.

Conclusions

A single TVS treatment has durable efficacy and safety in reducing cellulite on the buttocks and thighs of women with moderate to severe cellulite out to 12 months posttreatment.

Level of Evidence: 2
Risk of incident mental disorders in hypertrophic cardiomyopathy: a nationwide propensity-matched study
Authors: Park Jun-Bean , Yun Je-Yeon , Kim Bongsung , Rhee Tae-Min , Lee Hyun-Jung , Lee Heesun , Hwang In-Chang , Yoon Yeonyee E , Park Hyo Eun , Lee Seung-Pyo , Choi Su-Yeon , Kim Yong-Jin , Cho Goo-Yeong , Han Kyungdo , Kim Hyung-Kwan
Published: November 2022

Aims

We sought to determine the risk of mental disorders in patients with hypertrophic cardiomyopathy (HCM) compared with those without HCM.

Methods and results

This is a retrospective propensity score-matched cohort study using nationwide population-based data from the Korean National Health Insurance Service. Overall, 4046 patients with HCM and 12138 matched individuals were followed up until the first diagnosis of mental disorders or the end of the follow up. The primary outcome was a composite of incident mood, anxiety, stress-related, or somatoform disorders. Secondary outcomes included two components of the primary outcome (i.e. mood disorders and anxiety/stress-related/somatoform disorders). During a median follow-up period of 4.1 years, the incidence rate of the primary outcome was 54.4 and 31.5/1000 person-years among the HCM and control groups, respectively, resulting in a hazard ratio (HR) of 1.719 (95% confidence interval: 1.589–1.860). Within the first month after HCM diagnosis, the HR for the primary outcome was 3.074 (2.096–4.508). Beyond 1 month, the HRs decreased, ranging from 2.281 (1.952–2.665) during 1–12 months, to 2.087 (1.831–2.380) during 12–36 months and 1.258 (1.090–1.452) after 36 months of follow up. Similar results were observed for the secondary outcomes. In sensitivity analysis, the risk of the specific categories of mental disorders, including single or recurrent depressive episodes and anxiety disorders, was also higher in patients with HCM than matched controls.

Conclusion

HCM was significantly associated with the risk of incident mental disorders, particularly within 1 year after HCM diagnosis, underscoring the importance of screening mental health problems, including mood and anxiety disorders, in patients with HCM.
P-, SV- and SH-wave eikonal approximations for HTI media based on perturbation theory
Authors: Li Mengqi , Stovas Alexey , Lu Jun
Published: November 2022

The eikonal equation for transversely isotropic media is a complex quartic partial differential equation that causes instability in traveltime inversion. The phenomenon of shear wave splitting in a transversely isotropic model with a horizontal symmetry axis (HTI) provides information for inversion. However, the involvement of shear waves makes the computation of forward modelling and inversion more time-consuming than when only using Pwaves. Most studies of traveltime approximation based on the eikonal equation are based on an acoustic assumption, which does not work for shear waves. Therefore, based on perturbation theory, we derive approximate solutions of the eikonal equation in a heterogeneous elastic HTI model for P, SV and SH waves to improve the traveltime computation efficiency. The approximate solutions of linear, quadratic and Shanks forms are based on the linearization of the traveltime function in terms of fracture weaknesses in an isotropic background, which are suitable for joint P-, SV- and SH-wave traveltime inversion and tomography for fracture parameters. When applied for a homogenous model, the proposed formulation results in a simple and accurate traveltime approximation. The first- and second-order perturbation coefficients are used to analyse the sensitivity of the traveltime to fracture weakness. To improve the accuracy of our approximation, we also expand the approximation of the P-wave traveltime with respect to the anellipticity parameter η in an elliptic background, which is evaluated by performing an error test. Based on the accuracy and stability of the perturbation, we select a set of linear equations with respect to the fracture weaknesses and a set of more accurate nonlinear equations to serve different needs.
Identifying causal serum protein–cardiometabolic trait relationships using whole genome sequencing
Authors: Png Grace , Gerlini Raffaele , Hatzikotoulas Konstantinos , Barysenka Andrei , Rayner N William , Klarić Lucija , Rathkolb Birgit , Aguilar-Pimentel Juan A , Rozman Jan , Fuchs Helmut , Gailus-Durner Valerie , Tsafantakis Emmanouil , Karaleftheri Maria , Dedoussis George , Pietrzik Claus , Wilson James F , de Angelis Martin Hrabe , Becker-Pauly Christoph , Gilly Arthur , Zeggini Eleftheria
Published: November 2022

Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356; 22.5× WGS) and Pomak (n = 1537; 18.4× WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency < 1%). We additionally find 15 pQTL variants that are rare in non-Finnish European populations but have drifted up in the frequency in the discovery cohorts here. We identify proteins causally associated with cardiometabolic traits, including Mep1b for high-density lipoprotein (HDL) levels, and describe a knock-out (KO) Mep1b mouse model. Our findings furnish insights into the genetic architecture of the serum proteome, identify new protein–disease relationships and demonstrate the importance of isolated populations in pQTL analysis.
A randomized controlled trial of generic and localized MedlinePlus-based information resources for hard-to-reach urban Hispanic community
Authors: Zhang Tianmai M , Millery Mari , Aguirre Alejandra N , Kukafka Rita
Published: November 2022

Objective

To determine if the Conexion digital localized health information resource about diabetes and depression could increase patient activation among Hispanic low-income adults.

Materials and Methods

A nonblinded randomized controlled trial was conducted (NCT03984929). Participants at least 18 years old living in Washington Heights/Inwood, New York, were recruited from the community between July 2019 and August 2020 and randomized 1:1 to either the intervention group (localization of MedlinePlus resources customized with community components) or the control group (no localized community components). The primary outcome, patient activation, and secondary outcomes, knowledge, self-efficacy, and behavior change, were collected through surveys at 1-month follow-up.

Results

Of the 134 participants recruited, 50.7% (n = 68) completed the 1-month follow-up. We found no statistically significant differences in the sociodemographic and baseline characteristics between those who missed the 1-month survey and those who completed it. No significant differences were observed in patient activation at 1-month. However, patient activation among all participants (n = 68) significantly increased (P = .048). Statistically significant improvements were also found in self-efficacy (P < .03). In multivariate analysis, birth country outside the United States and higher self-rated attachment to the community emerged as significant predictors of higher patient activation scores.

Discussion

While the trial did not detect significant differences between groups, all participants demonstrated increased patient activation scores and improved secondary outcomes. While other factors may have contributed to this increase, our study suggests that access to carefully selected high-quality health information materials delivered digitally in the context of a community may result in improvements comparable to localized content in a hard-to-reach urban Hispanic population.

Conclusions

Our study highlights the potential of making carefully selected digital information accessible to hard-to-reach communities.
Temperature Derangement on Admission is Associated With Mortality in Burn Patients—A Nationwide Analysis and Opportunity for Improvement
Authors: Stanton Eloise , Gillenwater Justin , Pham Tam N , Sheckter Clifford C
Published: November 2022

Although single-institution studies have described the relationship between hypothermia, burn severity, and complications, there are no national estimates on how temperature on admission impacts hospital mortality. This study aims to evaluate the relationship between admission temperature and complications on a national scale to expose opportunities for improved outcomes. The US National Trauma Data Bank (NTDB) was analyzed between 2007 and 2018. Mortality was modeled using multivariable logistic regression including burn severity variables (% total burn surface area (TBSA), inhalation injury, emergency department (ED) temperature), demographics, and facility variables. Temperature was parsed into three categories: hypothermia (<36.0°C), euthermia (36.0–37.9°C), and hyperthermia (≥38.0°C). A total of 116,796 burn encounters were included of which 77.9% were euthermic, 20.6% were hypothermic and 1.45% were hyperthermic on admission. For every 1.0C drop in body temperature from 36.0°C, mortality increased by 5%. Both hypothermia and hyperthermia were independently associated with increased odds of mortality when controlling for age, gender, inhalation injury, number of comorbidities, and %TBSA burned (p < .001). All temperatures below 36.0°C were significantly associated with increased odds of mortality. Patients with ED temperatures between 32.5 and 33.5°C had the highest odds of mortality (22.0, 95% CI 15.6–31.0, p < .001). ED hypothermia and hyperthermia are independently associated with mortality even when controlling for known covariates associated with inpatient death. These findings underscore the importance of early warming interventions both at the prehospital stage and upon ED arrival. ED temperature could become a quality metric in benchmarking burn centers to improve mortality.
Leveraging the Clinical Timepoints in Lung Cancer Screening to Engage Individuals in Tobacco Treatment
Authors: Park Elyse R , Neil Jordan M , Noonan Elise , Howard Sydney E , Gonzalez Irina , Marotta Caylin , Wint Amy J , Levy Douglas E , Chang Yuchiao , Rigotti Nancy A , Haas Jennifer S
Published: November 2022

The US Preventive Services Task Force recommends lung cancer screening (LCS) to promote early lung cancer detection, and tobacco cessation services are strongly recommended in adjunct. Screen ASSIST (NCT03611881) is a randomized factorial trial to ascertain the best tobacco treatment intervention for smokers undergoing LCS; trial outreach is conducted during 3 recruitment points (RPs): when LCS is ordered (RP1), at screening (RP2), and following results (RP3). Among 177 enrollees enrolled from April 2019 to March 2020, 31.6% enrolled at RP1, 13.0% at RP2, and 55.4% at RP3. The average number of enrollees (per 1000 recruitment days) was 2.26 in RP1, 3.37 in RP2, and 1.04 in RP3. LCS provides an opportunity to offer tobacco treatment at multiple clinical timepoints. Repeated and proactive outreach throughout the LCS experience was beneficial to enrolling patients in tobacco cessation services.
tatDB: a database of Ago1-mediated targets of transfer RNA fragments
Authors: Guan Lingyu , Grigoriev Andrey
Published: November 2022

tRNA-derived fragments (tRFs) are a class of emerging post-transcriptional regulators of gene expression likely binding to the transcripts of target genes. However, only a few tRFs targets have been experimentally validated, making it hard to extrapolate the functions or binding mechanisms of tRFs. The paucity of resources supporting the identification of the targets of tRFs creates a bottleneck in the fast-developing field. We have previously analyzed chimeric reads in crosslinked Argonaute1-RNA complexes to help infer the guide-target pairs and binding mechanisms of multiple tRFs based on experimental data in human HEK293 cells. To efficiently disseminate these results to the research community, we designed a web-based database tatDB (targets of tRFs DataBase) populated with close to 250 000 experimentally determined guide-target pairs with ∼23 000 tRF isoforms. tatDB has a user-friendly interface with flexible query options/filters allowing one to obtain comprehensive information on given tRFs (or targets). Modes of interactions are supported by secondary structures of potential guide-target hybrids and binding motifs, essential for understanding the targeting mechanisms of tRFs. Further, we illustrate the value of the database on an example of hypothesis-building for a tRFs potentially involved in the lifecycle of the SARS-CoV-2 virus. tatDB is freely accessible at https://grigoriev-lab.camden.rutgers.edu/tatdb.
Deep learning-assisted genome-wide characterization of massively parallel reporter assays
Authors: Lu Fred , Sossin Aaron , Abell Nathan , Montgomery Stephen B , He Zihuai
Published: November 2022

Massively parallel reporter assay (MPRA) is a high-throughput method that enables the study of the regulatory activities of tens of thousands of DNA oligonucleotides in a single experiment. While MPRA experiments have grown in popularity, their small sample sizes compared to the scale of the human genome limits our understanding of the regulatory effects they detect. To address this, we develop a deep learning model, MpraNet, to distinguish potential MPRA targets from the background genome. This model achieves high discriminative performance (AUROC = 0.85) at differentiating MPRA positives from a set of control variants that mimic the background genome when applied to the lymphoblastoid cell line. We observe that existing functional scores represent very distinct functional effects, and most of them fail to characterize the regulatory effect that MPRA detects. Using MpraNet, we predict potential MPRA functional variants across the genome and identify the distributions of MPRA effect relative to other characteristics of genetic variation, including allele frequency, alternative functional annotations specified by FAVOR, and phenome-wide associations. We also observed that the predicted MPRA positives are not uniformly distributed across the genome; instead, they are clumped together in active regions comprising 9.95% of the genome and inactive regions comprising 89.07% of the genome. Furthermore, we propose our model as a screen to filter MPRA experiment candidates at genome-wide scale, enabling future experiments to be more cost-efficient by increasing precision relative to that observed from previous MPRAs.
O009 Keep The Chin Up: Evidence-based standardised care pathway for infants with Pierre Robin Sequence (PRS)
Authors: Goel D , Wilson A , O'Donnell A , Rao S , Herbert H , Pachter N , Hamden B , Gillett D
Published: November 2022

Background

Management of upper airway obstruction in neonates with Pierre Robin Sequence (PRS) is challenging given difficulties in grading severity of disease, difficulties obtaining early polysomnography (PSG) and variable practices with no widely accepted standard protocol. We aimed to develop a standardised care pathway for infants with PRS.

Methods

Total 190 publications were identified of which 21 were reviewed in detail. Majority were review articles or retrospective studies. Consultation was obtained from the Complex Airway Team (multidisciplinary team of neonatologist, paediatric sleep specialist, otolaryngologist, plastic surgeon, clinical nurse specialist and speech pathologist), geneticists, audiologists, the consumer group “PRS Australia” and ANZ paediatric sleep physicians. Final recommendations were based on consensus and quality of the evidence.

Results

We developed a pathway outlining sequential interventions to manage OSA based on functional assessment by PSG (7-14 day of life) and structural assessment by flexible nasal endoscopy “FNE” (0-7 day of life). Conduct of bedside PSG in NICU instead of sleep lab enables innovative, timely, patient-centred and cost-effective service delivery. We standardised reporting of glossoptosis (Yellon classification), laryngomalacia (Olney et.al) and airway (Seattle DISE scoring) on FNE. Early multidisciplinary involvement, structured assessment of feeding, synchronous airway lesions and associated genetic syndromes is also considered. The pathway allows for standardised management and discharge planning with clearly defined multidisciplinary follow-ups.

Intended outcome/impact

This project is likely first in Australia to standardise care pathway for infants with PRS encompassing collaborative, innovative and structured care delivery principles. The project provides foundation for future clinical and research collaboration.
O011 Effect of Continuous Positive Airway Pressure on Quality of Life and Treatment Burden in Children with Obstructive Sleep Apnoea
Authors: Nisbet L , Ellis K , Mihai R , Davey M , Nixon G
Published: November 2022

Introduction

Increasing numbers of children with obstructive sleep apnoea (OSA) require treatment with continuous positive airway pressure (CPAP). We aimed to assess the impact on quality of life (QOL) and treatment burden for caregivers of children requiring CPAP.

Methods

Prospective study of children commencing outpatient CPAP in a tertiary sleep unit 2020-2022. Questionnaires regarding sleep-related symptoms (PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment), QOL (OSA-18, QI-Disability), caregiver burden (Caregiver Strain Questionnaire) and overall health impact (Glasgow Children’s Benefit Inventory) were completed by caregivers at commencement of CPAP and 6 weeks later.

Progress

Complete data available to date in 24 children (6F; median age 12.5y, range 6-18y; median OAHI 9.2/hr; median BMI 30.7). OSA-related QOL significantly improved at follow-up (OSA-18 total and domain scores all p<0.001). There were significant improvements in child general QOL (p<0.0001), sleep disturbance (p<0.01) and sleep-related impairment (p<0.001). Caregivers rated CPAP as beneficial to their child’s general condition (mean 30, where maximum harm -100, maximum benefit +100). Caregiver strain reduced at follow-up (p<0.001) and benefit outweighed inconvenience (p<0.0001). 3 caregivers scored inconvenience higher than benefit; 1 scored them equally. 1 caregiver rated CPAP harmful and 3 caregivers reported no effect on their child’s general health.

Outcome

CPAP results in significant improvements in QOL and sleep-related symptoms in children with OSA, and reductions in caregiver strain. Perceived benefits generally outweighed the burden of treatment, but not for all families. Further analysis will investigate how the balance of benefit to burden relates to adherence and the effect of co-morbidities.
O015 Sleep, Stress, and Cognitive Fatigue in Canadian Wildland Firefighters
Authors: Wallace-Webb J , Coehoorn C , Angus J , Stuart-Hill L
Published: November 2022

Background

Wildland firefighting requires continuous attention while exposed to long working hours and sub-optimal sleep. These stressors may induce a state of cognitive fatigue, which poses a risk to worker safety due to impaired judgment and reduced awareness.

Methods

The current study employs a within-subject, observational design to examine the effect of sleep and schedule characteristics on variables related to stress and cognitive function. Cognitive function is measured subjectively, via validated 7-point scales (i.e. Samn-Perelli Fatigue Scale and Stanford Sleepiness Scale), and objectively, via reaction time on the psychomotor vigilance task. Sleep is measured via sleep log and wrist-worn actigraphy. Stress via autonomic nervous system imbalance is measured by changes in heart rate variability (i.e. chest monitor). Linear regression analyses will be performed to test if sleep or schedule variables predict stress or cognitive function.

Progress to date

A pilot study (N=4) was conducted during the 2021 fire season to inform methodology. As of July 2022, a representative sample of 50 firefighters (13 F) have been recruited across all regions of British Columbia (BC), Canada. Data collection for the current study is ongoing and will continue until September 2022.

Intended outcome and impact

This investigation entails both theoretical and applied benefits. Its direct relevance to occupational health and safety could improve worker safety (1) by providing insight and recommendations towards improved fatigue management policy within the BC Wildfire Service and (2) by testing the practicality of mobile tools designed to monitor levels of sleep, stress, and cognitive function.
O031 Independent validation of a physiology-based model to predict oral appliance treatment outcomes
Authors: Dutta R , Tong B , Osman A , Eckert D
Published: November 2022

Background

Oral appliance therapy (OAT) is a well-tolerated treatment for obstructive sleep apnoea (OSA). However, efficacy varies. On average, OAT reduces OSA severity by ~50% leaving a substantial proportion of OAT patients either undertreated or untreated. Thus, a major clinical priority is to develop clinically feasible prediction tools to accurately predict which patients will respond to OAT and vice versa. Accordingly, we developed a model to estimate OSA endotypes and have adapted it to predict OAT outcomes. Here we used our recently developed physiology-based OAT prediction model to predict OAT responses in an independent validation sample.

Methods

91 people with OSA who were prescribed OAT by their treating physician had an in-laboratory diagnostic study followed by an OAT efficacy polysomnography after ≥4 weeks acclimatisation. 7 polysomnography variables from the diagnostic study plus age and body mass index were included in our machine learning based model designed to predict OAT response. Prediction performance characterises according to standard apnoea/hypopnoea index (AHI) definitions were assessed.

Results

Mean accuracy of the model to predict OAT responders vs. non-responders in this independent validation sample was high across different OSA treatment outcome definitions ranging from 70% (>50% reduction in AHI), 79% (AHI<10 events/h) to 95% (AHI<5 events/h). Corresponding specificity was also high at 87%, 97% and 99%, respectively.

Discussion

These new findings provide additional support for the use routinely collected sleep study and clinical data with machine learning based approaches underpinned by OSA endotype concepts to help predict OAT treatment outcomes for people with OSA.
O033 Butyrylcholinesterase is a potential biomarker for Sudden Infant Death Syndrome
Authors: Harrington C , Al Hafid N , Waters K
Published: November 2022

Background

Autonomic dysfunction has been implicated in the pathophysiology of Sudden Infant Death Syndrome (SIDS). Butyrylcholinesterase (BChE) is an enzyme of the cholinergic system, a major branch of the autonomic system, and may provide a measure of autonomic (dys)function. This study was undertaken to evaluate BChE in infants and young children who had died from SIDS or Sudden Unexpected Death.

Methods

We measured BChE specific activity (BChEsa) in the eluate of 5μL spots punched from the dried blood spots (DBS) taken at birth as part of the newborn screening program. Results for each of 67 SUDI deaths classified by the coroner (aged 1 week – 104 weeks) = Cases, were compared to 10 date of birth - and gender-matched surviving controls (Controls), with five cases reclassified to meet criteria for SIDS.

Findings

Conditional logistic regression showed that in groups where cases were reported as “SIDS death” there was strong evidence that lower BChEsa was associated with death (OR=0·73 per U/mg, 95% CI 0·60 – 0·89, P=0·0014), whereas in the “Non-SIDS death” group there was no evidence of a linear association between BChEsa and death (OR=1·001 per U/mg, 95% CI 0·89 – 1·13, P=0·99).

Conclusion

BChEsa, measured in DBS taken 2-3 days after birth, was lower in babies who subsequently died of SIDS compared to surviving controls and other Non-SIDS deaths. We conclude that a previously unidentified cholinergic deficit, identifiable by abnormal BChEsa, is present at birth in SIDS babies and represents a measurable, specific vulnerability prior to their death.
O044 The association of the sleep regularity index with subjective cognitive function and academic skills in adolescents
Authors: Hand A , Stone E J , Lu S , Chacos E , Carskadon A M , Lockley W S , Wiley F J , Bei B , Klerman B E , Rajaratnam M W S , Phillips J K A
Published: November 2022

High-level cognitive function is essential for academic performance in adolescents. While obtaining sufficient sleep duration has been shown to support cognitive function less is known about the role of sleep regularity in cognitive function. We investigated how sleep regularity relates to self-report cognitive function in 179 Year 7 students (M±SD=12.81±0.41 years, 56% females) in Australia. Sleep/wake timing was measured via wrist actigraphy and daily sleep diaries over two-school-weeks. Sleep regularity was measured using the Sleep Regularity Index (SRI) calculated via actigraphy measured sleep (SRI range = 58-95). Self-report cognitive function was measured using the PROMIS Paediatric Cognitive Function questionnaire, which requires participants to self-report cognitive performance over the last four-weeks. Academic skills were measured using two-subtests (reading comprehension and numerical operations) from the Weschler Individual Achievement Test – Third Edition (WIAT-III). We found that adolescents with more regular sleep self-reported better subjective cognitive function (β = .39, p = .001), even when controlling for age, sex, circadian phase assessed using DLMO, and total sleep time. In contrast, average total sleep time (range = 5.78-11.30 hours) alone was not associated with subjective cognitive function (β = .06, p = .99). Higher self-reported cognitive function was also associated with improved reading and numerical ability on the WIAT-III (β = .42, p =.04; β = .37, p =.02, respectively). The SRI did not predict performance on the WIAT (p >.05). Our findings suggest regular sleep may be important in supporting optimal cognitive functioning. These results have important implications for learning adolescence.