bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D scattering microphantom sample to assess quantitative accuracy in tomographic phase microscopy techniques
Authors: Krauze Wojciech , Kuś Arkadiusz , Ziemczonok Michał , Haimowitz Max , Chowdhury Shwetadwip , Kujawińska Małgorzata 
Published: November 2022

AbstractIn this paper we present a structurally-complex biomimetic scattering structure, fabricated with two-photon polymerization, and utilize this object in order to benchmark a computational imaging system. The phantom allows to tailor the scattering by modifying its degrees of freedom i.e. refractive index contrast and scattering layer dimensions and incorporates a 3D imaging quality test, representing a single cell within tissue. While the sample may be used with multiple 3D microscopy techniques, we demonstrate the impact of scattering on three tomographic phase microscopy (TPM) reconstruction methods. One of these methods assumes the sample to be weak-scattering, while the other two take multiple scattering into account. The study is performed at two wavelengths (visible and near-infrared), which serve as a scaling factor for the scattering phenomenon. We find that changing the wavelength from visible into near-infrared impacts the applicability of TPM reconstruction methods. As a result of reduced scattering in near-infrared region, the multiple-scattering-oriented techniques perform in fact worse than a method aimed for weak-scattering samples. This implies a necessity of selecting proper approach depending on sample’s scattering characteristics even in case of subtle changes in the object-light interaction.
Perceived urban environment attributes and obesity indices in adults: an 8-Nation study from Latin America
Authors: Ferrari Gerson , Alberico Claudia , Marques Adilson , Kovalskys Irina , Gómez Georgina , Rigotti Attilio , Cortés Lilia Yadira , García Martha Yépez , Pareja Rossina G. , Herrera-Cuenca Marianella , Drenowatz Clemens , Leme Ana Carolina B. , Cristi-Montero Carlos , da Costa Roberto Fernandes , Farías‑Valenzuela Claudio , Fisberg Mauro 
Published: November 2022

AbstractThis study examines the associations between perceived urban environment attributes and obesity indices by country using data from an eight-nation study from Latin America. The data were collected from 8185 adults. The Neighbourhood Environment Walkability-abbreviated scale was used to assess perceived urban environment attributes. Obesity indices considered were body mass index, waist circumference, neck circumference, a body shape index and waist-to-height ratio. The perception of a more and better land use mix-diversity (β − 0.44; 95% CI − 0.59, − 0.28), traffic safety (− 0.39; − 0.66, − 0.12), and safety from crime (− 0.36; − 0.57, − 0.15) was associated with lower body mass index across the entire sample. Land use mix-diversity (− 1.21; − 1.60, − 0.82), street connectivity (− 0.26; − 0.37, − 0.15), and traffic safety (− 0.79; − 1.47, − 0.12) were negatively associated with waist circumference. Land use mix-diversity (− 0.11; − 0.20, − 0.03), land use mix-access (− 0.23; − 0.34, 0.12), walking/cycling facilities (− 0.22; − 0.37, − 0.08), and safety from crime (− 0.27; − 0.42, − 0.12) were negatively associated with neck circumference. No associations between perceived urban environment attributes and a body shape index were found. Land use mix-diversity (− 0.01; − 0.02, − 0.01), aesthetics (− 0.02; − 0.03, − 0.01), and safety from crime (− 0.02; − 0.04, − 0.01) were associated with waist-to-height ratio. Environmental interventions involving urban environment attributes are associated with obesity indices and, therefore, may help decrease the prevalence of overweight and obesity.
Neuroticism and adverse life events are important determinants in functional somatic disorders: the DanFunD study
Authors: Weinreich Petersen Marie , Wisbech Carstensen Tina Birgitte , Frostholm Lisbeth , Bro Wellnitz Kaare , Ørnbøl Eva , Tandrup Lamm Thomas , Meinertz Dantoft Thomas , Falgaard Eplov Lene , Jørgensen Torben , Fink Per 
Published: November 2022

AbstractSeveral psychological factors have been proposed to be associated with functional somatic disorders (FSD). However, large population-based studies investigating the importance of both personality and adverse life events (ALE) are sparse. This study aimed to investigate the association between FSD and neuroticism and the accumulated number of ALE, respectively. This cross-sectional study included a random sample of the adult Danish population (N = 7493). FSD were established by means of self-reported questionnaires and diagnostic interviews. Neuroticism was measured with the Danish version of the short-form NEO Personality Inventory. ALE were measured with the Danish version of the Cumulative Lifetime Adversity Measure. Strong positive associations were found between neuroticism and FSD, and ALE and questionnaire-based FSD. For interview-based FSD, strong positive associations were found for FSD, multi-organ type, and for the subtype of the general symptoms. The level of self-efficacy did not modify these associations, and no moderating effect of neuroticism and ALE in combination on the probability of having FSD was found. FSD were strongly associated with both neuroticism and the accumulated number of ALE, and these associations were not modified by self-efficacy. In combination, neuroticism and ALE did not have a moderating effect on the probability of having FSD.
17β-estradiol ameliorates delirium-like phenotypes in a murine model of urinary tract infection
Authors: Guidry Gena , Sparrow Nicklaus A. , Marshall Hyyat S. , De Souza Santos Roberta , Bharath Suman P. , Gezalian Michael M. , Pisarska Margareta D. , Vit Jean-Philippe , Kelly Scott A. , Karumanchi S. Ananth , Lahiri Shouri 
Published: November 2022

AbstractUrinary tract infections (UTIs) are common and frequently precipitate delirium-like states. Advanced age coincident with the postmenopausal period is a risk factor for delirium following UTIs. We previously demonstrated a pathological role for interleukin-6 (IL-6) in mediating delirium-like phenotypes in a murine model of UTI. Estrogen has been implicated in reducing peripheral IL-6 expression, but it is unknown whether the increased susceptibility of postmenopausal females to developing delirium concomitant with UTIs reflects diminished effects of circulating estrogen. Here, we tested this hypothesis in a mouse model of UTI. Female C57BL/6J mice were oophorectomized, UTIs induced by transurethral inoculation of E. coli, and treated with 17β-estradiol. Delirium-like behaviors were evaluated prior to and following UTI and 17β-estradiol treatment. Compared to controls, mice treated with 17β-estradiol had less neuronal injury, improved delirium-like behaviors, and less plasma and frontal cortex IL-6. In vitro studies further showed that 17β-estradiol may also directly mediate neuronal protection, suggesting pleiotropic mechanisms of 17β-estradiol-mediated neuroprotection. In summary, we demonstrate a beneficial role for 17β-estradiol in ameliorating acute UTI-induced structural and functional delirium-like phenotypes. These findings provide pre-clinical justification for 17β-estradiol as a therapeutic target to ameliorate delirium following UTI.
Development and validation of deep learning ECG-based prediction of myocardial infarction in emergency department patients
Authors: Gustafsson Stefan , Gedon Daniel , Lampa Erik , Ribeiro Antônio H. , Holzmann Martin J. , Schön Thomas B. , Sundström Johan 
Published: November 2022

AbstractMyocardial infarction diagnosis is a common challenge in the emergency department. In managed settings, deep learning-based models and especially convolutional deep models have shown promise in electrocardiogram (ECG) classification, but there is a lack of high-performing models for the diagnosis of myocardial infarction in real-world scenarios. We aimed to train and validate a deep learning model using ECGs to predict myocardial infarction in real-world emergency department patients. We studied emergency department patients in the Stockholm region between 2007 and 2016 that had an ECG obtained because of their presenting complaint. We developed a deep neural network based on convolutional layers similar to a residual network. Inputs to the model were ECG tracing, age, and sex; and outputs were the probabilities of three mutually exclusive classes: non-ST-elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), and control status, as registered in the SWEDEHEART and other registries. We used an ensemble of five models. Among 492,226 ECGs in 214,250 patients, 5,416 were recorded with an NSTEMI, 1,818 a STEMI, and 485,207 without a myocardial infarction. In a random test set, our model could discriminate STEMIs/NSTEMIs from controls with a C-statistic of 0.991/0.832 and had a Brier score of 0.001/0.008. The model obtained a similar performance in a temporally separated test set of the study sample, and achieved a C-statistic of 0.985 and a Brier score of 0.002 in discriminating STEMIs from controls in an external test set. We developed and validated a deep learning model with excellent performance in discriminating between control, STEMI, and NSTEMI on the presenting ECG of a real-world sample of the important population of all-comers to the emergency department. Hence, deep learning models for ECG decision support could be valuable in the emergency department.
Alteration in tyrosine phosphorylation of cardiac proteome and EGFR pathway contribute to hypertrophic cardiomyopathy
Authors: Xu Mingguo , Bermea Kevin C. , Ayati Marzieh , Kim Han Byeol , Yang Xiaomei , Medina Andres , Fu Zongming , Heravi Amir , Zhang Xinyu , Na Chan Hyun , Everett Allen D. , Gabrielson Kathleen , Foster D. Brian , Paolocci Nazareno , Murphy Anne M. , Ramirez-Correa Genaro A. 
Published: November 2022

AbstractAlterations of serine/threonine phosphorylation of the cardiac proteome are a hallmark of heart failure. However, the contribution of tyrosine phosphorylation (pTyr) to the pathogenesis of cardiac hypertrophy remains unclear. We use global mapping to discover and quantify site-specific pTyr in two cardiac hypertrophic mouse models, i.e., cardiac overexpression of ErbB2 (TgErbB2) and α myosin heavy chain R403Q (R403Q-αMyHC Tg), compared to control hearts. From this, there are significant phosphoproteomic alterations in TgErbB2 mice in right ventricular cardiomyopathy, hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM) pathways. On the other hand, R403Q-αMyHC Tg mice indicated that the EGFR1 pathway is central for cardiac hypertrophy, along with angiopoietin, ErbB, growth hormone, and chemokine signaling pathways activation. Surprisingly, most myofilament proteins have downregulation of pTyr rather than upregulation. Kinase-substrate enrichment analysis (KSEA) shows a marked downregulation of MAPK pathway activity downstream of k-Ras in TgErbB2 mice and activation of EGFR, focal adhesion, PDGFR, and actin cytoskeleton pathways. In vivo ErbB2 inhibition by AG-825 decreases cardiomyocyte disarray. Serine/threonine and tyrosine phosphoproteome confirm the above-described pathways and the effectiveness of AG-825 Treatment. Thus, altered pTyr may play a regulatory role in cardiac hypertrophic models.
Extra-hematopoietic immunomodulatory role of the guanine-exchange factor DOCK2
Authors: Scharler Cornelia , Poupardin Rodolphe , Ebner-Peking Patricia , Wolf Martin , Schreck Christina , Brachtl Gabriele , Cronemberger Andrade Andre , Krisch Linda , Daheron Laurence , Schallmoser Katharina , Jürchott Karsten , Küchler Judit , Stachelscheid Harald , Volk Hans-Dieter , Oostendorp Robert A. J. , Strunk Dirk 
Published: November 2022

AbstractStromal cells interact with immune cells during initiation and resolution of immune responses, though the precise underlying mechanisms remain to be resolved. Lessons learned from stromal cell-based therapies indicate that environmental signals instruct their immunomodulatory action contributing to immune response control. Here, to the best of our knowledge, we show a novel function for the guanine-exchange factor DOCK2 in regulating immunosuppressive function in three human stromal cell models and by siRNA-mediated DOCK2 knockdown. To identify immune function-related stromal cell molecular signatures, we first reprogrammed mesenchymal stem/progenitor cells (MSPCs) into induced pluripotent stem cells (iPSCs) before differentiating these iPSCs in a back-loop into MSPCs. The iPSCs and immature iPS-MSPCs lacked immunosuppressive potential. Successive maturation facilitated immunomodulation, while maintaining clonogenicity, comparable to their parental MSPCs. Sequential transcriptomics and methylomics displayed time-dependent immune-related gene expression trajectories, including DOCK2, eventually resembling parental MSPCs. Severe combined immunodeficiency (SCID) patient-derived fibroblasts harboring bi-allelic DOCK2 mutations showed significantly reduced immunomodulatory capacity compared to non-mutated fibroblasts. Conditional DOCK2 siRNA knockdown in iPS-MSPCs and fibroblasts also immediately reduced immunomodulatory capacity. Conclusively, CRISPR/Cas9-mediated DOCK2 knockout in iPS-MSPCs also resulted in significantly reduced immunomodulation, reduced CDC42 Rho family GTPase activation and blunted filopodia formation. These data identify G protein signaling as key element devising stromal cell immunomodulation.
The protein conformational basis of isoflavone biosynthesis
Authors: Wang Xiaoqiang , Pan Haiyun , Sagurthi Someswar , Paris Vincent , Zhuo Chunliu , Dixon Richard A. 
Published: November 2022

AbstractIsoflavonoids play important roles in plant defense and also exhibit a range of mammalian health-promoting activities. Their biosynthesis is initiated by two enzymes with unusual catalytic activities; 2-hydroxyisoflavanone synthase (2-HIS), a membrane-bound cytochrome P450 catalyzing a coupled aryl-ring migration and hydroxylation, and 2-hydroxyisoflavanone dehydratase (2-HID), a member of a large carboxylesterase family that paradoxically catalyzes dehydration of 2-hydroxyisoflavanones to isoflavone. Here we report the crystal structures of 2-HIS from Medicago truncatula and 2-HID from Pueraria lobata. The 2-HIS structure reveals a unique cytochrome P450 conformation and heme and substrate binding mode that facilitate the coupled aryl-ring migration and hydroxylation reactions. The 2-HID structure reveals the active site architecture and putative catalytic residues for the dual dehydratase and carboxylesterase activities. Mutagenesis studies revealed key residues involved in substrate binding and specificity. Understanding the structural basis of isoflavone biosynthesis will facilitate the engineering of new bioactive isoflavonoids.
Human social conditions predict the risk of exposure to zoonotic parasites in companion animals in East and Southeast Asia
Authors: Colella Vito , Wongnak Phrutsamon , Tsai Yi-Lun , Nguyen Viet-Linh , Tan D. Y. , Tong Kenneth B. Y. , Lu Na , Fang Fang , Zhijuan Yin , Wang Jiangwei , Liu Xin , Dong Junyan , Nurcahyo Wisnu , Hadi Upik K. , Venturina Virginia , Taweethavonsawat Piyanan , Tiwananthagorn Saruda , Le Thong Q. , Bui Khanh L. , Watanabe Malaika , Rani Puteri A. M. A. , Traub Rebecca J. , Beugnet Frédéric , Chalvet-Monfray Karine , Halos Lénaïg 
Published: November 2022

Abstract
Background
A recent dramatic surge in pet ownership has been observed across metropolitan areas in Asia. To date, there is a dearth of information on the risk associated with pet ownership for the transmission of parasites on a large scale in Asia, despite this continent giving rise to the largest burden of zoonotic infections worldwide.

Methods
We explored the nature and extent of zoonotic internal (endo-) and external (ecto-) parasites and arthropod-borne pathogens in 2381 client-owned dogs and cats living in metropolitan areas of eight countries in East and Southeast Asia using reliable diagnostic tests and then undertook extensive statistical analyses to define predictors of exposure to zoonotic pathogens.

Results
The estimated ORs for overall parasite infections are 1.35 [95% CIs 1.07;1.71] in young animals and 4.10 [1.50;11.2] in the animal group older than 15 years as compared with adult animals, 0.61 [0.48;0.77] in neutered animals as compared to unneutered animals, 0.36 [0.26;0.50] in animals living in urban areas as compared with rural areas, 1.14 [1.08;1.21] for each 1 °C increase of annual mean temperature which varies from 12.0 to 28.0 °C, and 0.86 [0.78;0.95] for each year of life expectancy which varies from 70.9 to 83.3 years.

Conclusions
Here we highlight the influence of human life expectancy and the neutering status of the animals, which reflect increased living standards through access to education and human and veterinary health care, to be both strongly associated with exposure to zoonotic parasites. An integrated approach of local and international authorities to implement and manage educational programs will be crucial for the control of zoonotic infections of companion animals in Asia.
CEACAM5 inhibits the lymphatic metastasis of head and neck squamous cell carcinoma by regulating epithelial–mesenchymal transition via inhibiting MDM2
Authors: Wang Xudong , Li Yanshi , Pan Min , Lu Tao , Wang Min , Wang Zhihai , Liu Chuan , Hu Guohua 
Published: November 2022

Abstract
Lymph node (LN) metastasis affects both the management and prognosis of head and neck squamous cell carcinoma (HNSCC). Here, we explored the relationship between lymphatic metastasis and CEA family member 5 (CEACAM5), including its possible regulatory role in HNSCC. The levels of CEACAM5 in tissues from patients with HNSCC, with and without LN metastases, were assessed by transcriptome sequencing. The associations between CEACAM5 and the N stage of LN metastasis in HNSCC were predicted through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and a pan-cancer analysis of CEACAM5 expression in 33 common human tumors was conducted. CEACAM5 levels were analyzed in tumor and normal tissue specimens from HNSCC patients and the correlation between CEACAM5 levels and prognosis was evaluated. The influence of CEACAM5 on cell proliferation, invasion, migration, and apoptosis was investigated in HNSCC cell lines, as were the downstream regulatory mechanisms. A mouse model of LN metastasis was constructed. CEACAM5 levels were significantly higher in HNSCC tissue without LN metastasis than in that with LN metastasis. Similar findings were obtained for the clinical specimens. CEACAM5 levels were associated with better clinical prognosis. CEACAM5 was found to inhibit the proliferation and migration and promote the apoptosis of HNSCC cells. A mouse xenograft model showed that CEACAM5 inhibited LN metastasis. In conclusions, CEACAM5 inhibited epithelial–mesenchymal transition (EMT) in HNSCC by reducing murine double minute 2 (MDM2) expression and thereby suppressing LN metastasis. CEACAM5 has potential as both a prognostic marker and a therapeutic target in HNSCC.
Simulating an End-of-Life Care Conference Using Standardized Patients: Examining Students' Professional Communication
Authors: Stead Amanda , Vinson Monica , Michael Paul , Henry Sara , Fryer Melissa , Fitzgerald Caitlin , Dow Frankie 
Published: November 2022

Purpose:
Lack of preparation for working with patients near the end of life (EoL) can lead to poor outcomes for patients and burnout for clinicians. Additionally, graduate students must also receive preparation in professional communication skills necessary for family and interprofessional interactions. Simulation provides an opportunity to practice and demonstrate these skills in a safe environment. This study examined student performance and perceptions following a simulation of clinical communication in the context of an EoL care (EoLC) conference discussion.

Method:
By utilizing a formative simulation with standardized patients, students demonstrated skills associated with navigating an EoLC conference discussion. The supervising educators and standardized patients evaluated students on their clinical communication and debriefing skills through rubrics. Students also provided feedback on the simulation experience.

Results:
Results from this simulation indicated that most students demonstrated effective clinical communication skills. Judgments from educators and standardized patients corroborate students' skill demonstration in the areas of content delivery, delivering compassionate care, communicating evidence, representing their roles, and reflection. Students struggled more in the areas of terminology use and using summary and validation skills. Student feedback about the simulation was resoundingly positive. Students remarked how the simulation advanced their learning, helped them reflect on their clinical communication skills, and provided them with exposure to fragile medical patients.

Conclusion:
This study provides an example of a high-fidelity replicable simulation that can be implemented to measure and encourage student skill development in clinical communication and EoLC.
KOBEsim: A Bayesian observing strategy algorithm for planet detection in radial velocity blind-search surveys
Authors: Balsalobre-Ruza O. , Lillo-Box J. , Berihuete A. , Silva A. M. , Santos N. C. , Castro-González A. , Faria J. P. , Huélamo N. , Barrado D. , Demangeon O. D. S. , Marfil E. , Aceituno J. , Adibekyan V. , Azzaro M. , Barros S. C. C. , Bergond G. , Galadí-Enríquez D. , Pedraz S. , Santerne A. 
Published: November 2022

Context. Ground-based observing time is precious in the era of exoplanet follow-up and characterization, especially in high-precision radial velocity instruments. Blind-search radial velocity surveys thus require a dedicated observational strategy in order to optimize the observing time, which is particularly crucial for the detection of small rocky worlds at large orbital periods.
Aims. We developed an algorithm with the purpose of improving the efficiency of radial velocity observations in the context of exoplanet searches, and we applied it to the K-dwarfs Orbited By habitable Exoplanets experiment. Our aim is to accelerate exoplanet confirmations or, alternatively, reject false signals as early as possible in order to save telescope time and increase the efficiency of both blind-search surveys and follow-up of transiting candidates.
Methods. Once a minimum initial number of radial velocity datapoints is reached in such a way that a periodicity starts to emerge according to generalized Lomb-Scargle periodograms, that period is targeted with the proposed algorithm, named KOBEsim. The algorithm selects the next observing date that maximizes the Bayesian evidence for this periodicity in comparison with a model with no Keplerian orbits.
Results. By means of simulated data, we proved that the algorithm accelerates the exoplanet detection, needing 29-33% fewer observations and a 41–47% smaller time span of the full dataset for low-mass planets (mp < 10 M⊕) in comparison with a conventional monotonic cadence strategy. For 20 M⊕ planets we found a 16% enhancement in the number of datapoints. We also tested KOBEsim with real data for a particular KOBE target and for the confirmed planet HD 102365 b. These two tests demonstrate that the strategy is capable of speeding up the detection by up to a factor of 2 (i.e., reducing both the time span and number of observations by half).