bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo
Authors: Simon Anna , Yang Ming , Marrison Joanne L. , James Andrew D. , Hunt Mark J. , O’Toole Peter J. , Kaye Paul M. , Whittington Miles A. , Chawla Sangeeta , Brackenbury William J.
Published: March 2020

Background

An emerging problem in the treatment of breast cancer is the increasing incidence of metastases to the brain. Metastatic brain tumours are incurable and can cause epileptic seizures and cognitive impairment, so better understanding of this niche, and the cellular mechanisms, is urgently required. Microglia are the resident brain macrophage population, becoming “activated” by neuronal injury, eliciting an inflammatory response. Microglia promote proliferation, angiogenesis and invasion in brain tumours and metastases. However, the mechanisms underlying microglial involvement appear complex and better models are required to improve understanding of function.

Methods

Here, we sought to address this need by developing a model to study metastatic breast cancer cell-microglial interactions using intravital imaging combined with ex vivo electrophysiology. We implanted an optical window on the parietal bone to facilitate observation of cellular behaviour in situ in the outer cortex of heterozygous Cx3cr1GFP/+ mice.

Results

We detected GFP-expressing microglia in Cx3cr1GFP/+ mice up to 350 μm below the window without significant loss of resolution. When DsRed-expressing metastatic MDA-MB-231 breast cancer cells were implanted in Matrigel under the optical window, significant accumulation of activated microglia around invading tumour cells could be observed. This inflammatory response resulted in significant cortical disorganisation and aberrant spontaneously-occurring local field potential spike events around the metastatic site.

Conclusions

These data suggest that peritumoral microglial activation and accumulation may play a critical role in local tissue changes underpinning aberrant cortical activity, which offers a possible mechanism for the disrupted cognitive performance and seizures seen in patients with metastatic breast cancer.
Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury
Authors: Long Xiaobing , Yao Xiaolong , Jiang Qian , Yang Yiping , He Xuejun , Tian Weidong , Zhao Kai , Zhang Huaqiu
Published: March 2020

Background

The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as potent mediators involved in intercellular communication.

Methods

In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and oedema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot and electron microscopy. A mouse model of TBI and an in vitro model of LPS-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p overexpressing in TBI-induced nerve injury.

Results

We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the modified neurological severity score (mNSS) and attenuated brain injury in a strictly controlled cortical impact mouse model.

Conclusions

Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-κB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.
MiR-29c-3p, a target miRNA of LINC01296, accelerates tumor malignancy: therapeutic potential of a LINC01296/miR-29c-3p axis in ovarian cancer
Authors: Xu Hui , Mao Hong-Luan , Zhao Xin-Rui , Li Yue , Liu Pei-Shu
Published: March 2020

As one of the main gynecological cancers, ovarian cancer (OC) has an unfavourable outcomes owing to its high recurrence and metastasis rate. Our previous studies have revealed that LINC01296 functions as an oncogene in OC, but the underlying mechanism has not been explored. The aim of this paper was to further investigate that how LINC01296 plays a role in OC. Through online software prediction, miR-29c-3p has been discriminated as the target miRNA of LINC01296 for further research, and subsequent luciferase assay confirmed bioinformatics prediction. Then the data obtained from the two databases (GSE119055 and GSE83693) were analyzed by GEO2R for differential gene analysis. The results indicated that the miR-29c-3p was lowly expressed in OC tissues than that in normal ovarian tissues, and its expression in recurrent OC tissues was lower than that in primary OC tissues. Simultaneously, Kaplan-Meier survival analysis illustrated that the lower expression of miR-29c-3p was interrelated to unfavourable outcomes of OC. Further, the qRT-PCR data revealed that the miR-29c-3p expression in OC cell lines (SKOV-3 and OVCAR-3) was markedly declined than that in normal control cells (IOSE80). Subsequently, the functional experiments, such as CCK8, colony formation and Transwell assays, prompted that inhibition of miR-29c-3p can obviously increase the proliferation, invasion and migration of OVCAR3 and SKOV3 cells compared with control group, while downregulation of LINC01296 showed an opposite result. It is worth noting that downregulation of LINC01296 can reverse the effect of miR-29c-3p suppression on OC cells. Finally, we detected the changes of EMT-related proteins by western blot experiment, and reached a similar conclusion that knockdown of LINC01296 reversed the EMT caused by miR-29c-3p inhibition. In sum up, the cancer-promoting function of LINC01296 was achieved by regulating the expression of miR-29c-3p, and LINC01296/miR-29c-3p axis mediates the mechanical regulation of EMT in OC cells, hoping to provide the novel biomarkers and possibilities for OC therapy.
Risk factors for candidemia: a prospective matched case-control study
Authors:   the FUNGINOS, Poissy Julien ,   Allfun French Study Groups, Damonti Lauro , Bignon Anne , Khanna Nina , Von Kietzell Matthias , Boggian Katia , Neofytos Dionysios , Vuotto Fanny , Coiteux Valérie , Artru Florent , Zimmerli Stephan , Pagani Jean-Luc , Calandra Thierry , Sendid Boualem , Poulain Daniel , van Delden Christian , Lamoth Frédéric , Marchetti Oscar , Bochud Pierre-Yves
Published: March 2020

Background

Candidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs.

Methods

This prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia.

Results

One hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia.

Discussion

While this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU).

Conclusion

This study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients’ management strategies and fungal epidemiology.
Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase
Authors: Mengel David , Liu Wen , Glynn Robert J. , Selkoe Dennis J. , Strydom Andre , Lai Florence , Rosas H. Diana , Torres Amy , Patsiogiannis Vasiliki , Skotko Brian , Walsh Dominic M.
Published: March 2020

Background

Down syndrome (DS) is the most common genetic cause of Alzheimer’s disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS—Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years. Our primary aims were (1) to assess changes in the selected plasma biomarkers in DS across age, and (2) to compare biomarkers measured in DS plasma versus age- and sex-matched controls.

Methods

Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes (Aβ42, NfL, and tau) in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. Tau was measured using an assay (NT1) which detects forms of tau containing at least residues 6–198. The stability of the 3 analytes was established using plasma from ten healthy volunteers collected at 6 intervals over a 5-day period.

Results

High Aβ42 and NT1 tau and low NfL were observed in infants. Across all ages, Aβ42 levels were higher in DS than controls. Levels of Aβ42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents, and young adults, but thereafter increased in DS compared to controls.

Conclusions

High levels of Aβ42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas the changes seen in later life are consistent with emergence of pathological alterations. These plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e., 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with AD therapies.
Microbial community diversity of traditional dough starter (Jiaozi) from two provinces in northwest China
Authors: Liu Ting , Kang Jiamu , Liu Liu , Hu Xinzhong , Wang Xiaolong , Li Xiaoping , Ma Zhen , Ren Tian
Published: March 2020

Purpose

Microbial community composition is crucial for the flavor and quality of fermented foods. However, the microbiota of Chinese traditional dough starter (Jiaozi) from different origins has scarcely been studied. The aim of this study was to determine the composition of bacterial and fungal communities in six Jiaozi collected from two provinces in northwest China.

Methods

Our study determined the composition of bacterial and fungal communities in six Jiaozi through Illumina MiSeq sequencing of the 16S rRNA gene and the ITS regions.

Result

A total of 234 operational taxonomic units (OTUs) for bacteria and 490 OTUs for fungi were identified. Furthermore, Lactobacillus, Weissella, Acetobacter, Sphingomonas, and Serratia were identified as the predominant bacterial genera in Jiaozi samples, while Saccharomyces, Candida, Alternaria, unclassified Filobasidiales, and Mycosphaerella were the most abundant fungal genera. The results revealed that the six samples could be grouped into two groups based on their province of origin. In the results of PCA and HCA analysis, the first three principal components which were chosen could explain 99.93% and 90.99% of the total bacterial and fungal communities, respectively.

Conclusion

The results indicated high levels of bacteria and fungi in traditional Jiaozi and highlighted the possible influence of geographic areas on microbial diversity.
Facial fractures: classification and highlights for a useful report
Authors: Gómez Roselló Eva , Quiles Granado Ana M. , Artajona Garcia Miquel , Juanpere Martí Sergi , Laguillo Sala Gemma , Beltrán Mármol Briggitte , Pedraza Gutiérrez Salvador
Published: March 2020

In patients with facial trauma, multidetector computed tomography is the first-choice imaging test because it can detect and characterize even small fractures and their associated complications quickly and accurately. It has helped clinical management and surgical planning, so radiologists must communicate their findings to surgeons effectively. In Le Fort fractures, there is a breach between the pterygoid plates and the posterior maxilla. These fractures are classified in three basic patterns that can be combined and associated with various complications. Conceptualized when low-speed trauma was predominant, the Le Fort classification system has become less relevant giving more importance on maxillary occlusion-bearing segments. The classification of naso-orbito-ethmoid depends on the extent of injury to the attachment of the medial canthal tendon, with possible complications like nasofrontal duct disruption. Displaced fractures of the zygomaticomaxillary complex often widen the angle of the lateral orbital wall, resulting in increased orbital volume and sometimes in enophthalmos. Severe comminution or angulation can lead to wide surgical exposure. In orbital fractures, entrapment of the inferior rectus muscles can lead to diplopia, so it is important to assess its positioning and morphology. Orbital fractures can also result in injuries to the globe or infraorbital nerve. Frontal sinus fractures that extend through the posterior sinus wall can create a communication with the anterior cranial fossa resulting in leakage of cerebrospinal fluid, intracranial bleeding. It is essential to categorize fracture patterns and highlight features that may affect fracture management in radiology reports of facial trauma.
Attractivity for Hilfer fractional stochastic evolution equations
Authors: Yang Min , Alsaedi Ahmed , Ahmad Bashir , Zhou Yong
Published: March 2020

This article is devoted to the study of the attractivity of solutions to a class of stochastic evolution equations involving Hilfer fractional derivative. By employing the semigroup theory, fractional calculus and the fixed point technique, we establish new alternative criteria to ensure the existence of globally attractive solutions for the Cauchy problem when the associated semigroup is compact.
Stability and bifurcation in a single species logistic model with additive Allee effect and feedback control
Authors: Lv Yangyang , Chen Lijuan , Chen Fengde
Published: March 2020

In this paper, we propose a single species logistic model with feedback control and additive Allee effect in the growth of species. The basic aim of the paper is to discuss how the additive Allee effect and feedback control influence the above model’s dynamical behaviors. Firstly, the existence and stability of equilibria are discussed under three different cases, i.e., weak Allee effect, strong Allee effect, and the critical case. Secondly, we prove the occurrence of saddle-node bifurcation and transcritical bifurcation with the help of Sotomayor’s theorem. The above dynamical behaviors are richer and more complex than those in the traditional logistic model with feedback control. We find that both Allee effect and feedback control can increase the species’ extinction property. We also reveal some new bifurcation phenomena which do not exist in the single-species model with feedback control (Fan and Wang in Nonlinear Anal., Real World Appl. 11(4):2686–2697, 2010 and Lin in Adv. Differ. Equ. 2018:190, 2018).
Correction to: Phage-centric ecological interactions in aquatic ecosystems revealed through ultra-deep metagenomics
Authors: Kavagutti Vinicius S. , Andrei Adrian-Ştefan , Mehrshad Maliheh , Salcher Michaela M. , Ghai Rohit
Published: March 2020

Following publication of the original article [1], the authors reported that an affiliation of the first author was missing.
Topographic analysis of macular choriocapillaris flow deficits in diabetic retinopathy using swept–source optical coherence tomography angiography
Authors: Gendelman Isaac , Alibhai A. Yasin , Moult Eric M. , Levine Emily S. , Braun Phillip X. , Mehta Nihaal , Zhao Yi , Ishibazawa Akihiro , Sorour Osama A. , Baumal Caroline R. , Witkin Andre J. , Reichel Elias , Fujimoto James G. , Duker Jay S. , Waheed Nadia K.
Published: March 2020

Background

The purpose of this study was to investigate the association between diabetic retinopathy (DR) severity and macular choriocapillaris (CC) flow deficit percentage (FD %) in different macular regions using swept-source optical coherence tomography angiography (SS-OCTA).

Methods

Diabetic patients with SS-OCTA images were graded by severity and retrospectively assessed. CC FD % was calculated in four different regions of the OCTA image: inner, middle, outer, and full-field region. The generalized estimating equations (GEE) approach for clustered eye data was used to determine effect size and significance of age and disease severity on FD % for each region.

Results

160 eyes from 90 total diabetic patients met inclusion criteria. Out of 90 patients, 33 had no DR, 17 had mild nonproliferative DR (NPDR), 8 had moderate NPDR, 10 had severe NPDR and 22 had proliferative DR. Age and DR severity had a significant positive association with FD % for each region studied with a greater effect in the two centermost regions. The increase in flow deficit percentage per year of age by region was: inner 0.12 (p < 0.001), middle 0.09 (p < 0.001), outer 0.05 (p < 0.001, full-field 0.06 (p < 0.001). The increase in flow deficit percentage per increase in diabetic retinopathy severity stage by region was: inner 0.65 (p < 0.0087), middle 0.56 (p < 0.0012), outer 0.33 (p < 0.045), full-field 0.36 (p < 0.018).

Conclusions

Topographic analysis of the CC FD % in diabetic eyes suggests that CC flow impairment corresponds to DR severity, with all studied regions of the CC significantly affected. There was greater regional impairment due to age and disease severity in the inner and middle regions.
Preliminary study of central nervous system tumors’ prevalence and incidence in Isfahan Province Iran
Authors: Tolou-Ghamari Zahra
Published: March 2020

Background

Metastatic or primary cancers of the central nervous system are a dissimilar cluster of neoplasms with different consequences and management plans. The aim of this study was to obtain prevalence and incidence of brain and other nervous system tumors.

Results

In all, 423 females and 620 males were identified. For the total population the period prevalence (PP) was calculated as 20.9 per 100,000 persons. This value corresponded to a PP of 24.5 for males and 17.2 for females. The mean (SD, range) age of the patients was 52.0 (20.7, 1–99) years. In the 7% of the population studied, age was under 20 years old of life, and in the 71%, it occurred around the age of 20 to 70 years old. In both genders, incidence rate (IR) increased from 4.2 to 5.7 per 100,000 persons. The changes of IR in males versus females were 8.2 versus 3.0 from 2011 to 6.4 versus 5.0 to 2015 per 100,000 persons.

Conclusions

Among the total population studied, there were 586 reported deaths. The PP in the male population was 1.4-times higher than females. There was a 35.7% increase in the IR over the study period.
3D seismic data attribute-based characterization of volcanic reservoirs in the BZ34-9 Block, Bohai Bay Basin, eastern China
Authors: Zhu Hongtao , Zeng Zhiwei , Zeng Hongliu , Xu Changgui
Published: March 2020

Volcanic effusive facies (VEF) and volcanic conduit facies (VCF) are two important facies units that can be found in a volcanic reservoir or edifice. Because VEF and VCF generally exhibit opposing seismic reflection characteristics, few studies have been applied to simultaneous characterization of the two facies in seismic data. We have developed an integrated 3D seismic data attribute-based characterization technique of VEF and VCF in the BZ34-9 Block, Bohai Bay Basin, eastern China. Our method is based mainly on the 3D visualization of a thresholding display so as to separately describe the strong-amplitude reflection of the VEF with its original amplitude attribute and the weak-amplitude chaotic reflection of the VCF with its variance-cube attribute. The detailed workflow comprises four steps, including seismic facies analysis, characterization of the VEF, characterization of the VCF, and merging a display of the two volcanic-facies units. The resulting 3D image of the different volcanic facies described in the BZ34-9 Block should be able to be viewed from any perspective for a better understanding of the related genesis mechanisms of the first and second members of the Shahejie (Es12) and Dongying Formations (Ed). In total, 28 volcanic edifices have been identified on the basis of the proposed method, among which three volcanic edifices exhibited inherited eruptions, in the Es12 and the Ed. Volcanic edifices in the Es12 are distributed locally in the central part of the BZ34-9 Block, showing a central eruption style, whereas those of the Ed are characterized by a widespread distribution in the southern gentle slope of the BZ34-9 Block, revealing a composite, center-fissure eruption style. The approach should be convenient to operate and would be effective in characterizing different volcanic facies simultaneously. This application can serve as a useful reference for other basins or regions with obvious volcanic influence.
Ultrasonic characterization of anisotropic rocks: Impact of transducers’ size and geometry on data interpretation
Authors: Kovalyshen Yevhen , Sarout Joel , Dautriat Jeremie , Maney Bruce , Lebedev Maxim
Published: March 2020

Typical ultrasonic laboratory measurements of rock physical properties are conducted with ultrasonic transducers that are relatively large compared to the rock sample. We have determined the impact of the transducer size on the resulting velocity estimations. To improve data interpretation, we explore two complementary avenues: (1) explicitly account for the finite size of the transducers as part of the data interpretation/correction workflow, rather than assuming point sources, and (2) reducing the effective size of the transducers at the hardware design level. Both approaches as well as their combination have been tested successfully on multiple data sets including artificial homogeneous and isotropic samples as well as natural anisotropic rocks such as shales.
CIViCpy: A Python Software Development and Analysis Toolkit for the CIViC Knowledgebase
Authors: Wagner Alex H. , Kiwala Susanna , Coffman Adam C. , McMichael Joshua F. , Cotto Kelsy C. , Mooney Thomas B. , Barnell Erica K. , Krysiak Kilannin , Danos Arpad M. , Walker Jason , Griffith Obi L. , Griffith Malachi
Published: March 2020

PURPOSE

Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org ) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC Web application.

METHODS

To address this limitation, we developed CIViCpy ( civicpy.org ), a software development kit for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples.

RESULTS

We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of > 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors.

CONCLUSION

The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online.
Recent Advances in the Development of Biomarkers and Chemoradiotherapeutic Approaches for Nasopharyngeal Carcinoma
Authors: Ma Brigette B.Y. , Chen Yu-Pei , Hui Edwin P. , Liu Xu , Chan Allen K.C. , Chan Anthony T.C. , Ma Jun
Published: March 2020

Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) is endemic in Southern China, and the prognosis of this cancer has improved in part due to advances in radiotherapy (RT) techniques, broadened therapeutic options, and more precise prognostic stratification of patients. RT is the primary curative treatment of NPC, and the incorporation of chemotherapy (induction, concurrent, adjuvant) to RT has contributed to improved survival in patients with locoregionally advanced NPC. Concurrent chemoradiotherapy (CCRT) in combination with adjuvant or induction chemotherapy is now the standard treatment of locoregionally advanced NPC, but the ideal CCRT therapeutic strategy for NPC remains controversial. Plasma EBV DNA is the archetypal tumor-derived DNA in NPC, and three generations of studies have gradually expanded its clinical applications. Recently, the advent of whole exome/genome sequencing of NPC and the promising clinical activity of immune checkpoint inhibitors have also spurred interest in the development of newer biomarkers. This review will focus on two clinical advances in NPC research that have made substantial impact on the contemporary management of NPC: (1) The integration of plasma EBV DNA in an expanding spectrum of clinical indications, and the development of promising immune-related biomarkers; (2) the current development of CCRT with special emphasis on the use of induction and adjuvant chemotherapy, as well as the potential applications of metronomic chemotherapy and immune checkpoint inhibitors in the treatment of locoregionally advanced NPC.
Human Follicle-Stimulating Hormone ß Subunit Expression Depends on FOXL2 and SMAD4
Authors: Ongaro Luisina , Schang Gauthier , Zhou Ziyue , Kumar T Rajendra , Treier Mathias , Deng Chu-Xia , Boehm Ulrich , Bernard Daniel J
Published: March 2020

Follicle-stimulating hormone (FSH), an essential regulator of mammalian fertility, is synthesized by pituitary gonadotrope cells in response to activins. In mice, activins signal via SMAD3, SMAD4, and FOXL2 to regulate transcription of the FSHβ subunit (Fshb) gene. Gonadotrope-specific deletion of Foxl2, alone or in combination with Smad4, renders mice FSH-deficient. Whether human FSHB expression is similarly regulated is not known. Here, we used a combination of transgenic and conditional knockout mouse strains to assess the roles of activins, FOXL2, and SMAD4 in regulation of the human FSHB gene. First, we cultured pituitaries from mice harboring a human FSHB transgene (hFSHB mice) and measured both murine Fshb and human FSHB messenger ribonucleic acid (mRNA) expression in response to exogenous activins or two antagonists of endogenous activin-like signaling (follistatin-288 and SB431542). Both murine Fshb and human FSHB expression were stimulated by activins and reduced by the inhibitors. Next, we analyzed human FSHB expression in hFSHB mice carrying floxed Foxl2 and Smad4 alleles. Cre-mediated ablation of FOXL2 and SMAD4 strongly reduced basal and activin-stimulated murine Fshb and human FSHB expression in cultured pituitaries. Finally, the hFSHB transgene was previously shown to rescue FSH production and fertility in Fshb knockout mice. However, gonadotrope-specific Foxl2/Smad4 knockout females carrying the hFSHB transgene have significantly reduced murine Fshb and human FSHB pituitary mRNA levels and are hypogonadal. Collectively, these data suggest that similar to Fshb regulation in mice, FOXL2 and SMAD4 play essential roles in human FSHB expression.
Science Fiction and the Rules of Uncertainty
Authors: De Ferrari Guillermina
Published: March 2020

A frequent trope in apocalyptic literature is a war between time and knowledge. Focusing on Rita Indiana’s “cli-fi” novel La mucama de Omicunlé (Omicunlé’s Maid), this essay explores the ambiguous role that uncertainty plays in apocalyptic literature. It argues that time travel seeks to revert the result of negative actions in the past, eliminating uncertainty retrospectively. And yet moral freedom, the mark of the human, requires uncertainty to function, which thwarts time travel as a messianic genre. Yet even in failure, time travel reminds us that impending disaster is contingent on specific individual and collective action, suggesting that the future could still perhaps be otherwise.
Delineating the role of membrane blebs in a hybrid mode of cancer cell invasion in three-dimensional environments
Authors: Guzman Asja , Avard Rachel C. , Devanny Alexander J. , Kweon Oh Sang , Kaufman Laura J.
Published: March 2020

The study of cancer cell invasion in 3D environments in vitro has revealed a variety of invasive modes, including amoeboid migration, characterized by primarily round cells that invade in a protease- and adhesion-independent manner. Here, we delineate a contractility-dependent migratory mode of primarily round breast cancer cells that is associated with extensive integrin-mediated extracellular matrix (ECM) reorganization that occurs at membrane blebs, with bleb necks sites of integrin clustering and integrin-dependent ECM alignment. We show that the spatiotemporal distribution of blebs and their utilization for ECM reorganization is mediated by functional β1 integrin receptors and other components of focal adhesions. Taken together, the work presented here characterizes a migratory mode of primarily round cancer cells in complex 3D environments and reveals a fundamentally new function for membrane blebs in cancer cell invasion.
Induction of ligand promiscuity of αVβ3 integrin by mechanical force
Authors: Bachmann Michael , Schäfer Markus , Mykuliak Vasyl V. , Ripamonti Marta , Heiser Lia , Weißenbruch Kai , Krübel Sarah , Franz Clemens M. , Hytönen Vesa P. , Wehrle-Haller Bernhard , Bastmeyer Martin
Published: March 2020

αVβ3 integrin can bind to multiple extracellular matrix proteins, including vitronectin (Vn) and fibronectin (Fn), which are often presented to cells in culture as homogenous substrates. However, in tissues, cells experience highly complex and changing environments. To better understand integrin ligand selection in such complex environments, we employed binary-choice substrates of Fn and Vn to dissect αVβ3 integrin-mediated binding to different ligands on the subcellular scale. Super-resolution imaging revealed that αVβ3 integrin preferred binding to Vn under various conditions. In contrast, binding to Fn required higher mechanical load on αVβ3 integrin. Integrin mutations, structural analysis and chemical inhibition experiments indicated that the degree of hybrid domain swing-out is relevant for the selection between Fn and Vn; only a force-mediated, full hybrid domain swing-out facilitated αVβ3-Fn binding. Thus, force-dependent conformational changes in αVβ3 integrin increased the diversity of available ligands for binding and therefore enhanced the ligand promiscuity of this integrin.

This article has an associated First Person interview with the first author of the paper.
Interactive Clustered Heat Map Builder: An easy web-based tool for creating sophisticated clustered heat maps
Authors: Ryan Michael C. , Stucky Mark , Wakefield Chris , Melott James M. , Akbani Rehan , Weinstein John N. , Broom Bradley M.
Published: March 2020

Clustered heat maps are the most frequently used graphics for visualization and interpretation of genome-scale molecular profiling data in biology.  Construction of a heat map generally requires the assistance of a biostatistician or bioinformatics analyst capable of working in R or a similar programming language to transform the study data, perform hierarchical clustering, and generate the heat map.  Our web-based Interactive Heat Map Builder can be used by investigators with no bioinformatics experience to generate high-caliber, publication quality maps.  Preparation of the data and construction of a heat map is rarely a simple linear process.  Our tool allows a user to move back and forth iteratively through the various stages of map generation to try different options and approaches.  Finally, the heat map the builder creates is available in several forms, including an interactive Next-Generation Clustered Heat Map that can be explored dynamically to investigate the results more fully.
An Application based Efficient Thread Level Parallelism Scheme on Heterogeneous Multicore Embedded System for Real Time Image Processing.
Authors: Indragandhi K , P K Jawahar
Published: March 2020

The recent advent of the embedded devices is equipped with multicore processor as it significantly improves the system performance. In order to utilize all the core in multicore processor in an efficient manner, application programs need to be parallelized. An efficient thread level parallelism (ETLP) scheme is proposed in this paper and uses computationally intensive edge detection algorithm for evaluation. Edge detection is the important process in various real time applications namely vehicle detection in traffic control, medical image processing etc. The main objective of ETLP scheme is to reduce the execution time and increase the CPU core utilization. The performance of ETLP scheme is evaluated with basic edge detection scheme (BEDS) for different image size. The experimental results reveal that the proposed ETLP scheme achieves efficiency of 49% and 72% for the image size 300 x 256 and 1024 x 1024 respectively. Furthermore an ETLP scheme reducing 66% execution time for image size 1024 x 1024 when compared with BEDS.
Long and Strong Security using Reputation and ECC for Cloud Assisted Wireless Sensor Networks
Authors: Rajan D Antony Joseph , Naganathan E R
Published: March 2020

Wireless sensor network plays a significant role in the construction of smart cities, and the social network includes the Internet of Things, etc. In general, networks are most vulnerable of all the wireless devices due to the massive damage caused by disrupting these networks. Hence the nodes present in the network should get validated for its reputation. Therefore a Long and Strong Security mechanism with two-level checks is proposed here. Level 1 check includes verifying node reputation value and level 2 check includes Elliptical curve cryptography (ECC). Each sensor node sends the public master key to the cloud and secretly stored in the sensor node. Before data transmission, every node checks the master key, and if the master key is a match, then it transmits the data to the next hop. This process is continued until the source reaches the destination in the network.
Logistics Optimization in Supply Chain Management using Clustering Algorithms
Authors: Mahesh Prabhu R , Hema G , Chepure Srilatha , Guptha M. Nageswara
Published: March 2020

Today’s business environment, survival and making profit in market are the prime requirement for any enterprise due to competitive environment. Innovation and staying updated are commonly identified two key parameters for achieving success and profit in business. Considerably supply chain management is also accountable for profit. As a measure to maximize the profit, supply chain process is to be streamlined and optimized. Appropriate grouping of various suppliers for the benefit of shipment cost reduction is proposed. Data relating to appropriate attributes of supplier logistics are collected. A methodology is proposed to optimize the supplier logistics using clustering algorithm. In the proposed methodology data preprocessing, clustering and validation process have been carried out. The Z-score normalization is used to normalize the data, which converts the data to uniform scales for improving the clustering performance. By employing Hierarchical and K-means clustering algorithms the supplier logistics are grouped and performance of each method is evaluated and presented. The supplier logistics data from different country is experimented. Outcome of this work can help the buyers to select the cost effective supplier for their business requirements.
Portable Ultrasound Device Usage and Learning Outcomes Among Internal Medicine Trainees: A Parallel-Group Randomized Trial
Authors: Kumar Andre , Wang Yingjie , Bentley Jason , Wang Libo , Bentley Jason , Almli Marta , Horn Jason , Witteles Ronald , Ahuja Neera , Kugler John
Published: March 2020

BACKGROUND: Little is known about how to effectively train residents with point-of-care ultrasonography (POCUS) despite increasing usage.
OBJECTIVE: This study aimed to assess whether handheld ultrasound devices (HUDs), alongside a year-long lecture series, improved trainee image interpretation skills with POCUS.
METHODS: Internal medicine intern physicians (N = 149) at a single academic institution from 2016 to 2018 participated in the study. The 2017 interns (n = 47) were randomized 1:1 to receive personal HUDs (n = 24) for patient care vs no-HUDs (n = 23). All 2017 interns received a repeated lecture series regarding cardiac, thoracic, and abdominal POCUS. Interns were assessed on their ability to interpret POCUS images of normal/abnormal findings. The primary outcome was the difference in end-of-the-year assessment scores between interns randomized to receive HUDs vs not. Secondary outcomes included trainee scores after repeating lectures and confidence with POCUS. Intern scores were also compared with historical (2016, N = 50) and contemporaneous (2018, N = 52) controls who received no lectures.
RESULTS: Interns randomized to HUDs did not have significantly higher image interpretation scores (median HUD score: 0.84 vs no-HUD score: 0.84; P = .86). However, HUD interns felt more confident in their abilities. The 2017 cohort had higher scores (median 0.84), compared with the 2016 historical control (median 0.71; P = .001) and 2018 contemporaneous control (median 0.48; P < .001). Assessment scores improved after first-time exposure to the lecture series, while repeated lectures did not improve scores.
CONCLUSIONS: Despite feeling more confident, personalized HUDs did not improve interns’ POCUS-related knowledge or interpretive ability. Repeated lecture exposure without further opportunities for deliberate practice may not be beneficial for mastering POCUS.
Patient Preferences for Physician Attire: A Multicenter Study in Japan
Authors: Kamata Kazuhiro , Kuriyama Akira , Chopra Vineet , Saint Sanjay , Houchens Nathan , Petrilli Christopher M , Kuhn Latoya , Snyder Ashley , Ishimaru Naoto , Takahashi Hiromizu , Tokuda Yasuharu
Published: March 2020

BACKGROUND

Previous studies have shown that patients have specific expectations regarding physician dress. Japan has a cultural background that is in many ways distinct from western countries. Thus, physician attire may have a different impact in Japan.

METHODS

We conducted a multicenter, cross‐sectional study to examine patients' preferences for and perceptions of physician attire in Japan. The questionnaire was developed using photographs of either a male or female physician dressed in seven different forms of attire, and it was randomly distributed to inpatients and outpatients. Respondents were asked to rate the provider pictured; they were also asked to provide preferences for different forms of attire in varied clinical settings. Preference was evaluated for five domains (knowledgeable, trustworthy, caring, approachable, and comfortable). We also assessed variation in preferences for attire by respondent characteristics.

RESULTS

A total of 1,233 (61%) patients indicated that physician dress was important, and 950 (47%) patients agreed that it influenced their satisfaction with care. Compared with all forms, casual attire with a white coat was the most preferred dress. Older patients more often preferred formal attire with a white coat in primary care and hospital settings. In addition, physician attire had a greater impact on older respondents' satisfaction and experience.

CONCLUSION

The majority of Japanese patients indicated that physician attire is important and influenced their satisfaction with care. Geography, settings of care, and patient age appear to play a role in patient preferences.
Social Disadvantage, Access to Care, and Disparities in Physical Functioning Among Children Hospitalized with Respiratory Illness
Authors: Desai Arti D , Zhou Chuan , Haaland Wren , Johnson Jakobi , Lion K Casey , Lopez Michelle A , MD Derek J Williams , Kenyon Chén C , Mangione‐Smith Rita , Johnson David P
Published: March 2020

BACKGROUND AND OBJECTIVES

Understanding disparities in child health‐related quality of life (HRQoL) may reveal opportunities for targeted improvement. This study examined associations between social disadvantage, access to care, and child physical functioning before and after hospitalization for acute respiratory illness.

METHODS

From July 1, 2014, to June 30, 2016, children ages 8‐16 years and/or caregivers of children 2 weeks to 16 years admitted to five tertiary care children's hospitals for three common respiratory illnesses completed a survey on admission and within 2 to 8 weeks after discharge. Survey items assessed social disadvantage (minority race/ethnicity, limited English proficiency, low education, and low income), difficulty/delays accessing care, and baseline and follow‐up HRQoL physical functioning using the Pediatric Quality of Life Inventory (PedsQL, range 0‐100). We examined associations between these three variables at baseline and follow‐up using multivariable, mixed‐effects linear regression models with multiple imputation sensitivity analyses for missing data.

RESULTS

A total of 1,325 patients and/or their caregivers completed both PedsQL assessments. Adjusted mean baseline PedsQL scores were significantly lower for patients with social disadvantage markers, compared with those of patients with none (78.7 for >3 markers versus 85.5 for no markers, difference ‐6.1 points (95% CI: ‐8.7, ‐3.5). The number of social disadvantage markers was not associated with mean follow‐up PedsQL scores. Difficulty/delays accessing care were associated with lower PedsQL scores at both time points, but it was not a significant effect modifier between social disadvantage and PedsQL scores.

CONCLUSIONS

Having social disadvantage markers or difficulty/delays accessing care was associated with lower baseline physical functioning; however, differences were reduced after hospital discharge.
Factors Associated with Differential Readmission Diagnoses Following Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Buhr Russell G , Jackson Nicholas J , Dubinett Steven M , Kominski Gerald F , Mangione Carol M , Ong Michael K
Published: March 2020

BACKGROUND

Readmissions after exacerbations of chronic obstructive pulmonary disease (COPD) are penalized under the Hospital Readmissions Reduction Program (HRRP). Understanding attributable diagnoses at readmission would improve readmission reduction strategies.

OBJECTIVES

Determine factors that portend 30‐day readmissions attributable to COPD versus non‐COPD diagnoses among patients discharged following COPD exacerbations.

DESIGN, SETTING, AND PARTICIPANTS

We analyzed COPD discharges in the Nationwide Readmissions Database from 2010 to 2016 using inclusion and readmission definitions in HRRP.

MAIN OUTCOMES AND MEASURES

We evaluated readmission odds for COPD versus non‐COPD returns using a multilevel, multinomial logistic regression model. Patient‐level covariates included age, sex, community characteristics, payer, discharge disposition, and Elixhauser Comorbidity Index. Hospital‐level covariates included hospital ownership, teaching status, volume of annual discharges, and proportion of Medicaid patients.

RESULTS

Of 1,622,983 (a weighted effective sample of 3,743,164) eligible COPD hospitalizations, 17.25% were readmitted within 30 days (7.69% for COPD and 9.56% for other diagnoses). Sepsis, heart failure, and respiratory infections were the most common non‐COPD return diagnoses. Patients readmitted for COPD were younger with fewer comorbidities than patients readmitted for non‐COPD. COPD returns were more prevalent the first two days after discharge than non‐COPD returns. Comorbidity was a stronger driver for non‐COPD (odds ratio [OR] 1.19) than COPD (OR 1.04) readmissions.

CONCLUSION

Thirty‐day readmissions following COPD exacerbations are common, and 55% of them are attributable to non‐COPD diagnoses at the time of return. Higher burden of comorbidity is observed among non‐COPD than COPD rehospitalizations. Readmission reduction efforts should focus intensively on factors beyond COPD disease management to reduce readmissions considerably by aggressively attempting to mitigate comorbid conditions.
Hospital Care of Opioid‐Exposed Newborns: Clinical and Psychosocial Challenges
Authors: Goyal Neera K , McAllister Jennifer
Published: March 2020

In the past two decades, the incidence of neonatal abstinence syndrome (NAS) has risen fivefold, mirroring the rise of opioid use disorder (OUD) among pregnant women. The resulting increases in length of stay and neonatal intensive care utilization are associated with higher hospital costs, particularly among Medicaid‐financed deliveries. Pregnant women with OUD require comprehensive medical and psychosocial evaluation and management; this combined with medication‐assisted treatment is critical to optimize maternal and newborn outcomes. Multidisciplinary collaboration and standardized approaches to screening for intrauterine opioid exposure, evaluation and treatment of NAS, and discharge planning are important for clinical outcomes and may improve maternal experience of care.