bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cultural Sociology of Social Media: Social Drama, Cultural Affordances and Blogging in the Wake of Hurricane Katrina
Authors: Ostertag Stephen F.
Published: August 2020

Research on social media, networks and collective action currently lacks a strong cultural component, often focusing on network formation and characteristics from afar. At the same time, research in cultural sociology often takes social media for granted, removed from analytical or theoretical attention. We know little about the perspectives of users or the shared meanings, emotions, and codes that inform social media practices and discourses. Addressing this gap requires examining how users imagine, understand and use social media in ways that foment culturally-meaningful social networks and it would “thickly describe” the discourse that they create and share across these networks. This article uses social drama theory to understand the creation of community and collective action among a group of citizen bloggers in post-Hurricane Katrina New Orleans. Informed by their shared grievances and motives, users created a collective social drama across their blogs. This social drama was an important resource with which users developed trusting social ties, voluntary relationships, a sense of community and offline collective actions. These developments were realized in part due to the cultural affordances of the blog platform, the ability to easily, efficiently and effectively communicate and consume richly meaningful and emotive texts unhindered by data limits or media modalities. The cultural affordances of blogs were such that people were able to communicate their shared grievances in the form of social drama, over an extended period of time, and develop meaningful, emotive connections with each other through social media.
Bone density and its relation to the development of acromial stress fracture following reverse total shoulder arthroplasty
Authors: Yeazell Shawn T , Inacio Jordan , Malige Ajith , Dailey Hannah , Carolan Gregory F
Published: August 2020

Background

Postoperative acromial stress fracture is a troublesome postoperative complication after reverse shoulder arthroplasty. Our study aims to utilize routinely performed preoperative computed tomography scans to identify differences in the material properties of the acromion in patients who did and did not develop a postoperative acromial stress fracture.

Methods

Treatment records and computed tomography scans for 99 reverse shoulder arthroplasties were collected. Scans were calibrated using a phantom and transferred for post-processing where the acromion, full scapula, and humeral head were isolated. The final segmented model was used to assess acromial volume and volumetric bone mineral density for each region of interest.

Results

There was no association between age and volumetric bone mineral density in any region of interest (all R2 ≤ 0.048, all p > 0.082). Patients who developed an acromial stress fracture were not significantly different from those who did not in terms of age, acromial volume, or acromial volumetric bone mineral density (all p > 0.559). Patients with known osteoporosis or osteopenia had slightly lower volumetric bone mineral density, but the differences were not significant (all p ≥ 0.072).

Conclusion

Postoperative acromial fractures following reverse shoulder arthroplasty cannot be predicted by computed tomography-derived volumetric bone mineral density or volume. These mechanical characteristics also do not predictably decrease with age or osteoporosis diagnosis.
Willardian Spiritual Formation, Novel Spiritual Disciplines, and Basketball: A Case Study
Authors: Roberts Matthew
Published: August 2020

Athletic participation provides a unique forum for the practice of spiritual disciplines. Central to Dallas Willard’s robust theory of spiritual formation is the critical role the body plays in effectively engaging in spiritual disciplines and thereby cultivating Christlikeness. I outline the central themes of Willard’s theology and philosophy of spiritual disciplines, with particular attention to how they bear on athletic participation. I distinguish between classical and novel spiritual disciplines and show how the latter are usefully appropriated towards the ordinary activities of daily life, and particularly towards the arena of athletics. Using basketball as a case study, I show in detail how this activity can be fruitfully reappropriated as a set of novel spiritual disciplines.
Blood Eosinophilic and Basophilic Trends in Recurring and Non-Recurring Eosinophilic Rhinosinusitis With Nasal Polyps
Authors: Brescia Giuseppe , Contro Giacomo , Giacomelli Luciano , Barion Umberto , Frigo Anna Chiara , Marioni Gino
Published: August 2020

Background

Very few studies have compared blood eosinophil and basophil levels before and after surgery in patients with eosinophilic CRSwNP (eCRSwNP). No investigations seem to have repeatedly measured them pre- and postoperatively in eCRSwNP patients with recurring versus non-recurring disease to examine how their levels evolved.

Objective

Hence this study to analyze blood eosinophil and basophil levels in patients with eCRSwNP immediately before surgery and afterwards, at 4 months, 1 year, and then yearly up to 5 years.

Methods

Fifty-one eCRSwNP patients were enrolled, who all had preoperative laboratory data and the results of at least 4 of the 6 scheduled postoperative follow-up tests.

Results

Seventeen patients had recurrent disease. Blood eosinophil counts (p = 0.005) and percentages (p = 0.002) were both higher in these patients than in those whose eCRSwNPs did not recur after surgery. Blood basophil counts (p = 0.04) and percentages (p < 0.05) were also significantly higher in patients whose eCRSwNPs relapsed. The time by relapse interaction was not significant for either counts or percentages, though an effect of time was detected for basophil counts (p = 0.01).

Conclusions

In eCRSwNP, the statistical analysis of repeated quantitative laboratory data can shed light on the evolution of a patient’s systemic inflammatory picture in response to previous treatments, and above all to long-term therapies. Long-term monitoring of blood eosinophil and basophil levels could be of significant value when monoclonal antibodies that inhibit IL signaling will widely enter in clinical practice for eCRSwNP treatment to follow the effectiveness of therapy over time.
Laboratory practice in the face of Covid-19
Authors: Lau Chin Shern , Kamaludin Noor Ashraf , Aw Tar Choon
Published: August 2020

In December 2019, the COVID-19 outbreak began in Wuhan and quickly spread over the world. Hospitals have had to make drastic changes to normal workflows and practices to handle the current pandemic. Laboratories face unique challenges in the management of the investigation of COVID-19. Not only must we consider the safe collection and delivery of samples, but we must also observe the latest guidelines in testing for the virus. We have introduced several new measures in our laboratory to accommodate the collection and testing of samples for COVID-19 from both within the hospital and external screening sites. These changes encompass the pre-analytical (sample collection, packaging, and delivery), analytical (evaluation, handling and preparation of samples) and post-analytical (result reporting within the hospital and to external bodies) aspects of both routine (biochemistry, haematology, transfusion and urine, stool and body fluid testing) and COVID-19 testing, to ensure the safe and efficient testing of any patient samples. In addition, more practical matters, such as laboratory staffing and continuing staff education, have also been changed to ensure the safety and well-being of laboratory staff. With the implementation of new rules and regulations, we seek to safeguard the health of all healthcare workers while streamlining the workflow for the large amount of testing required during this period. As the pandemic continues, new tests (e.g. COVID-19 serology and IL6 testing for prognosis or monitoring) are being requested, requiring even more changes and assay evaluation before implementation. All laboratories must be ready to adapt to these new challenges during the COVID-19 pandemic.
The therapeutic potential of microdosing psychedelics in depression
Authors: Kuypers Kim P.C.
Published: August 2020

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10–20 mcg) and psilocybin (<1–3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.
Coordination of a remote mHealth infrastructure for atrial fibrillation management during COVID-19 and beyond: TeleCheck-AF
Authors: van der Velden Rachel MJ , Hermans Astrid NL , Pluymaekers Nikki AHA , Gawalko Monica , Vorstermans Bianca , Martens Herm , Buskes Saskia , Crijns Harry JGM , Linz Dominik , Hendriks Jeroen M
Published: August 2020

During the coronavirus 2019 (COVID-19) pandemic, outpatient visits for patients with atrial fibrillation (AF), were converted into teleconsultations. As a response to this, a novel mobile health (mHealth) intervention was developed to support these teleconsultations with AF patients: TeleCheck-AF. This approach incorporates three fundamental components: 1) “Tele”: A structured teleconsultation. 2) “Check”: An app-based on-demand heart rate and rhythm monitoring infrastructure. 3) “AF”: comprehensive AF management.

This report highlights the significant importance of coordination of the TeleCheck-AF approach at multiple levels and underlines the importance of streamlining care processes provided by a multidisciplinary team, using an mHealth intervention, during the COVID-19 pandemic. Moreover, this report reflects on how the TeleCheck-AF approach has contributed to strengthening the health system in maintaining management of this prevalent sustained cardiac arrhythmia, whilst keeping patients out of hospital, during the pandemic and beyond.
Global sagittal spinal alignment at cervical flexion in patients with dropped head syndrome
Authors: Konishi Takamitsu , Endo Kenji , Aihara Takato , Suzuki Hidekazu , Matsuoka Yuji , Nishimura Hirosuke , Takamatsu Taichiro , Murata Kazuma , Kusakabe Takuya , Maekawa Asato , Sawaji Yasunobu , Yamamoto Kengo
Published: August 2020

Purpose:

Dropped head syndrome (DHS) is characterized by the passively correctable chin-on-chest deformity. The characteristic feature is emphasized in the cervical flexion position. The purpose of this study was to analyze the influence of cervical flexion on sagittal spinal alignment in patients with DHS.

Methods:

The study included 15 DHS subjects and 55 cervical spondylosis (CS) subjects as the control group. The following parameters were analyzed: cervical sagittal vertical axis (C-SVA), occipitoaxial angle (O–C2A), C2 slope (C2S), C2–C7 angle (C2–C7A), T1 slope (T1S), sagittal vertical axis, T1–T4 angle (T1–T4A), T5–T8 angle (T5–T8A), T9–T12 angle, lumbar lordosis, sacral slope, and pelvic tilt, in cervical flexion and neutral positions.

Results:

The values of C-SVA, O–C2A, C2S, and T1S were significantly different between CS and DHS at cervical neutral and flexion positions. C2–C7A showed significant difference in cervical neutral position, but the difference disappeared in flexion position. T1–T4A did not present a significant difference, but T5–T8A showed a difference in neutral and flexion positions.

Conclusions:

Malalignment of DHS extended not only to cervical spine but also to cranio-cervical junction and thoracic spine, except T1–T4. It is known that global sagittal spinal alignment is correlated with adjacent parameters, although in DHS the reciprocal change was lost from cranio-cervical junction to the middle part of thoracic spine at cervical flexion.
Cyclops Lesions of the Knee: A Narrative Review of the Literature
Authors: Kambhampati Srinivas B.S. , Gollamudi Srikanth , Shanmugasundaram Saseendar , Josyula Vidyasagar V.S.
Published: August 2020

Cyclops lesion is a known complication of anterior cruciate ligament reconstruction (ACLR). Although the incidence of cyclops lesion appears to be decreasing, it remains an important cause of restriction of extension after ACLR. We reviewed the available literature regarding the cyclops lesion and syndrome and cyclops-like lesions to analyze available evidence on cyclops lesions and variants of cyclops lesions. A keyword search in PubMed, Scopus, Web of Science, and EMBASE, Ovid Medline, and Ovid journals provided 47 relevant articles in the English literature, which were used to create this review. We classified cyclops lesions based on clinical presentation, pathology, and location. Risk factors, management options, tips to reduce the condition, and controversies related to the condition have been discussed. Female sex, greater graft volume, bony avulsion injuries, excessively anterior tibial tunnel, double-bundle ACLR, and bicruciate-retaining arthroplasty appear to predispose patients to cyclops lesions. Cyclops syndrome is a cyclops lesion that causes a loss of terminal extension. Arthroscopic debridement is an effective treatment for cyclops syndrome, whereas cyclops lesions are usually managed conservatively. It is important to distinguish between cyclops lesion and cyclops syndrome, as management differs based on symptoms. Cyclops lesion is diagnosed using magnetic resonance imaging. The management of choice for symptomatic lesions is surgical excision. Outcomes after excision are very good, and recurrence is rare.
“You’re a Different Kind of Black—Where You From?”: The Qualifying Role of Place in the Construction of Black Racial and Ethnic Identities among Louisiana Creole Migrants
Authors: DuCros Faustina M.
Published: August 2020

Much of the contemporary scholarship on Black identities focuses on how multiraciality, immigrant status, class, and neighborhood characteristics shape how social actors negotiate identities. In contrast, little analysis exists of how internal migration and regional origin or ancestry shape such negotiations. The study addresses this gap using interview data to examine how U.S.-born Black Louisianans with Creole heritage, who moved to Los Angeles along with their children during the Great Migration, actively negotiate racial/ethnic identities. The results show that participants negotiate identities situationally, especially when ambiguous appearances or surnames trigger interactional encounters in which they are mis-placed as “foreign” to the United States. Specifically, as migrants from one internal U.S. region to another, they use geographical references to situate Black racial and Creole ethnic identities (e.g., they refer to Louisiana or New Orleans) when interacting with non-Creole African Americans and non-Black people in Los Angeles. The study extends prior research on heterogeneous Black identities by demonstrating how internal migration, mixed racial/ethnic ancestry, and region of origin influence native-born Black American identities.
The crystal structure of arsenopalladinite, Pd8As2.5Sb0.5, and its relation to mertieite-II, Pd8Sb2.5As0.5
Authors: Karimova Oxana V. , Zolotarev Andrey A. , Johanson Bo S. , Evstigneeva Tatiyana L.
Published: August 2020

The crystal structure of arsenopalladinite, Pd8As2.5Sb0.5, from the Kaarreoja River, Inari commune, Finnish Lapland, Finland, was solved to R1 = 0.0451 on the basis of single-crystal X-ray diffraction data. The mineral is triclinic, space group P$\bar{1}$. The unit-cell parameters are: a = 7.3344(7), b = 7.3870(8), c = 7.5255(7) Å, α = 98.869(8), β = 102.566(8), γ = 119.096(11)°, V = 331.19(7) Å3 and Z = 2. The crystal structure of arsenopalladinite consists of an alternation of layers made by pnictogen (As, Sb) and layers made by palladium atoms stacked along the c axis. Arsenic and (As, Sb) nets exhibit a triangular topology (A and D nets), whereas palladium layers show triangular or pentagon–triangular nets (B and C nets). The unit-cell contains 6 layers, with the ABCDCBA stacking sequence. Although arsenopalladinite shows characteristics very similar (nets of the same topology) to the closely-related mineral mertieite-II, Pd8Sb2.5As0.5, it has a different stacking sequence.
Temperature Field Simulation and Experimental Study of Anti-backlash Single-Roller Enveloping Hourglass Worm Gear
Authors: Wang Shisong , Wang Shike , Wang Jie , Deng Xingqiao
Published: August 2020

In gear transmission, temperature rise has a non-negligible impact on the accuracy, noise and transmission efficiency. However, there is no relevant research on the temperature rise of the anti-backlash single-roller enveloping hourglass worm (ASEHW) gear. To solve this problem, based on tribology principle and Hertz contact theory, the thermal power calculation method of the ASEHW gear was proposed for the first time and thermal analysis was carried out by Ansys software. The bulk temperature of the ASEHW gear under four different rotating speed (300 r/min, 600 r/min, 900 r/min, 1200 r/min) is calculated. The main factors causing temperature rise of the ASEHW gear are analyzed theoretically. Meanwhile, an experimental study is performed to verify the simulation results and validate the theory methods. The theory presented in this paper provides a solution for the thermal power calculation of ASEHW gear. This research provides a theoretical basis for further optimization of ASEHW gear.
ACEP: improving antimicrobial peptides recognition through automatic feature fusion and amino acid embedding
Authors: Fu Haoyi , Cao Zicheng , Li Mingyuan , Wang Shunfang
Published: August 2020

Background

Antimicrobial resistance is one of our most serious health threats. Antimicrobial peptides (AMPs), effecter molecules of innate immune system, can defend host organisms against microbes and most have shown a lowered likelihood for bacteria to form resistance compared to many conventional drugs. Thus, AMPs are gaining popularity as better substitute to antibiotics. To aid researchers in novel AMPs discovery, we design computational approaches to screen promising candidates.

Results

In this work, we design a deep learning model that can learn amino acid embedding patterns, automatically extract sequence features, and fuse heterogeneous information. Results show that the proposed model outperforms state-of-the-art methods on recognition of AMPs. By visualizing data in some layers of the model, we overcome the black-box nature of deep learning, explain the working mechanism of the model, and find some import motifs in sequences.

Conclusions

ACEP model can capture similarity between amino acids, calculate attention scores for different parts of a peptide sequence in order to spot important parts that significantly contribute to final predictions, and automatically fuse a variety of heterogeneous information or features. For high-throughput AMPs recognition, open source software and datasets are made freely available at https://github.com/Fuhaoyi/ACEP.
Correction to: Epidemiology of patients presenting to a pediatric emergency department in Karachi, Pakistan
Authors: Ijaz Nadir , Strehlow Matthew , Wang N. Ewen , Pirrotta Elizabeth , Tariq Areeba , Mahmood Naseeruddin , Mahadevan Swaminatha
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Coronary spastic angina after the administration of intravenous immunoglobulin in myasthenia gravis: a case report
Authors: Yanagihashi Masaru , Okamoto Ryuichi , Morioka Harumi , Sawada Masahiro , Matsumoto Shingo , Ikeda Takanori , Kano Osamu
Published: August 2020

Background

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies that block or destroy nicotinic acetylcholine receptors at the neuromuscular junction. Most of MG patients need immunosuppression agents in addition to treatments that alleviate the symptoms. Intravenous immunoglobulin (IVIg) and plasma exchange are specific treatments given to patients with severe MG and myasthenia gravis crisis. IVIg therapy can cause an increase in serum viscosity; therefore, the risk for thromboembolic events, such as stroke, myocardial infarction, and pulmonary embolism, are reported after IVIg therapy.

Case presentation

An MG patient was treated with pyridostigmine bromide and prednisolone. The patient’s symptoms worsened 26 days after the commencement of treatment and was presented with head drop and dyspnea. The patient was diagnosed with MG crisis and IVIg was initiated. However, the patient reported chest pain and dyspnea 3 days after IVIg had started. An electrocardiogram (ECG) revealed ST elevations in leads II, III, and aVF. A cardiac catheterization was performed and stenosis, obstruction, and sclerosis were ruled out. Glyceryl trinitrate relieved the patient’s symptoms, suggesting coronary spastic angina (CSA).

Conclusions

We report the first case of CSA after IVIg. Practitioners should be aware of the potential risks of CSA when administering IVIg for MG patients, in particular in old patients with vascular risk factors.
Genetic profile of African swine fever virus responsible for the 2019 outbreak in northern Malawi
Authors: Hakizimana J. N. , Kamwendo G. , Chulu J. L. C. , Kamana O. , Nauwynck H. J. , Misinzo G.
Published: August 2020

Background

African swine fever (ASF) is an infectious transboundary animal disease which causes high mortality, approaching 100% in domestic pigs and it is currently considered as the most serious constraint to domestic pig industry and food security globally. Despite regular ASF outbreaks within Malawi, few studies have genetically characterized the causative ASF virus (ASFV). This study aimed at genetic characterization of ASFV responsible for the 2019 outbreak in northern Malawi. The disease confirmation was done by polymerase chain reaction (PCR) followed by molecular characterization of the causative ASFV by partial genome sequencing and phylogenetic reconstruction of the B646L (p72) gene, nucleotide alignment of the intergenic region (IGR) between I73R and I329L genes and translation of the central variable region (CVR) coded by B602L gene.

Results

All thirteen samples collected during this study in Karonga district in September 2019 were ASFV-positive and after partial genome sequencing and phylogenetic reconstruction of the B646L (p72) gene, the viruses clustered into ASFV p72 genotype II. The viruses characterized in this study lacked a GAATATATAG fragment between the I173R and the I329L genes and were classified as IGR I variants. Furthermore, the tetrameric amino acid repeats within the CVR of the B602L gene of the 2019 Malawian ASFV reported in this study had the signature BNDBNDBNAA, 100% similar to ASFV responsible for the 2013 and 2017 ASF outbreaks in Zambia and Tanzania, respectively.

Conclusions

The results of this study confirm an ASF outbreak in Karonga district in northern Malawi in September 2019. The virus was closely related to other p72 genotype II ASFV that caused outbreaks in neighboring eastern and southern African countries, emphasizing the possible regional transboundary transmission of this ASFV genotype. These findings call for a concerted regional and international effort to control the spread of ASF in order to improve nutritional and food security.
Coxiella burnetii is widespread in ticks (Ixodidae) in the Xinjiang areas of China
Authors: Ni Jun , Lin Hanliang , Xu Xiaofeng , Ren Qiaoyun , Aizezi Malike , Luo Jin , Luo Yi , Ma Zhan , Chen Ze , Tan Yangchun , Guo Junhui , Liu Wenge , Qu Zhiqiang , Wu Zegong , Wang Jinming , Li Youquan , Guan Guiquan , Luo Jianxun , Yin Hong , Liu Guangyuan
Published: August 2020

Background

The gram-negative Coxiella burnetii bacterium is the pathogen that causes Q fever. The bacterium is transmitted to animals via ticks, and manure, air, dead infected animals, etc. and can cause infection in domestic animals, wild animals, and humans. Xinjiang, the provincial-level administrative region with the largest land area in China, has many endemic tick species. The infection rate of C. burnetii in ticks in Xinjiang border areas has not been studied in detail.

Results

For the current study, 1507 ticks were collected from livestock at 22 sampling sites in ten border regions of the Xinjiang Uygur Autonomous region from 2018 to 2019. C. burnetii was detected in 205/348 (58.91%) Dermacentor nuttalli; in 110/146 (75.34%) D. pavlovskyi; in 66/80 (82.50%) D. silvarum; in 15/32 (46.90%) D. niveus; in 28/132 (21.21%) Hyalomma rufipes; in 24/25 (96.00%) H. anatolicum; in 219/312 (70.19%) H. asiaticum; in 252/338 (74.56%) Rhipicephalus sanguineus; and in 54/92 (58.70%) Haemaphysalis punctata. Among these samples, C. burnetii was detected in D. pavlovskyi for the first time. The infection rate of Rhipicephalus was 74.56% (252/338), which was the highest among the four tick genera sampled, whereas the infection rate of H. anatolicum was 96% (24/25), which was the highest among the nine tick species sampled. A sequence analysis indicated that 63 16S rRNA sequences could be found in four newly established genotypes: MT498683.1 (n = 18), MT498684.1 (n = 33), MT498685.1 (n = 6), and MT498686.1 (n = 6).

Conclusions

This study indicates that MT498684.1 might represent the main C. burnetii genotype in the ticks in Xinjiang because it was detected in eight of the tick species studied. The high infection rate of C. burnetii detected in the ticks found in domestic animals may indicate a high likelihood of Q fever infection in both domestic animals and humans.
Development of syngeneic murine cell lines for use in immunocompetent orthotopic lung cancer models
Authors: Nolan Kyle , Verzosa Gregory , Cleaver Tim , Tippimanchai Darinee , DePledge Lisa N. , Wang Xiao-Jing , Young Christian , Le Anh , Doebele Robert , Li Howard , Malkoski Stephen P.
Published: August 2020

Background

Immunocompetent animal models are required to study tumor-host interactions, immunotherapy, and immunotherapeutic combinations, however the currently available immunocompetent lung cancer models have substantial limitations. While orthotopic models potentially help fill this gap, the utility of these models has been limited by the very small number of murine lung cancer cell lines capable of forming orthotopic tumors in immunocompetent C57BL/6 hosts.

Methods

Primary lung tumors with specific genetic alterations were created in C57BL/6 background mice. These tumors were then passaged through other animals to increase tumorigenicity and select for the ability to grow in a non-self animal. Once tumors demonstrated growth in a non-self host, cell lines were established. Successful cell lines were evaluated for the ability to produce orthotopic lung tumors in immunocompetent hosts.

Results

We produced six murine lung cancer lines capable of orthotopic lung tumor formation in immunocompetent C57BL/6 animals. These lines demonstrate the expected genetic alterations based on their primary tumor genetics.

Conclusions

These novel cell lines will be useful for evaluating tumor-host interactions, the impact of specific oncogenic alterations on the tumor microenvironment, and immunotherapeutic approaches. This method of generating murine lines capable of orthotopic growth can likely be applied to other tumors and will broaden the applicability of pre-clinical testing of immunotherapeutic treatment regimens.
Calcineurin
Authors: Creamer Trevor P.
Published: August 2020

The serine/threonine phosphatase calcineurin acts as a crucial connection between calcium signaling the phosphorylation states of numerous important substrates. These substrates include, but are not limited to, transcription factors, receptors and channels, proteins associated with mitochondria, and proteins associated with microtubules. Calcineurin is activated by increases in intracellular calcium concentrations, a process that requires the calcium sensing protein calmodulin binding to an intrinsically disordered regulatory domain in the phosphatase. Despite having been studied for around four decades, the activation of calcineurin is not fully understood. This review largely focuses on what is known about the activation process and highlights aspects that are currently not understood.
Social ecological factors associated with physical activity and screen time amongst mothers from disadvantaged neighbourhoods over three years
Authors: Morris Kylie A. , Arundell Lauren , Cleland Verity , Teychenne Megan
Published: August 2020

Background

Mothers from socioeconomically disadvantaged neighbourhoods are at elevated risk of physical inactivity and high levels of screen time. Yet, little is known regarding the social ecological factors that are longitudinally associated with physical activity and screen time in this target group, and whether the age of their children impacts these relationships. This study aimed to longitudinally examine the social ecological factors associated with physical activity and screen time amongst mothers living in socioeconomically disadvantaged neighbourhoods, and whether these differed according to their child’s age.

Methods

Data were from 895 mothers living in socioeconomically disadvantaged neighbourhoods (mean age 36.7 years) at baseline and three-year follow-up. Mothers self-reported weekly discretionary physical activity (leisure-time, LTPA; transport-related, TRPA) and screen time durations. Linear regression models assessed associations between five intrapersonal, three social and five physical environmental factors and LTPA, TRPA and screen time, adjusting for confounding factors, clustering by neighbourhood and baseline variables. Interaction analysis was conducted for age of children (younger and older children (n = 442) and mothers with older children (aged 5–12 years) only (n = 453).

Results

In adjusted models, all intrapersonal factors (self-efficacy, enjoyment, outcome expectations, behavioural intentions and behavioural skill), social support from friends, neighbourhood cohesion and number of televisions were longitudinally associated with LTPA amongst all mothers. Interaction models showed that findings were generally consistent across groups (i.e., those with both younger and older children compared to those with older children only), with three exceptions. Physical activity enjoyment and social support from family were associated with LTPA only among mothers with older children. Neighbourhood cohesion was associated with screen time only amongst mothers with both younger and older children. No associations were detected for TRPA.

Conclusion

Intrapersonal, social and physical environmental factors were longitudinally associated with mother’s LTPA, whilst neighbourhood cohesion was longitudinally associated with screen time behaviours amongst mothers. Interventions aimed at increasing LTPA amongst mothers (particularly those from socioeconomically disadvantaged neighbourhoods) may need to target all domains of the social ecological model and may require some tailoring according to the age of children. Further work is needed to identify longitudinal associations with screen time and TRPA in this population group.
Analyzing and validating the prognostic value and mechanism of colon cancer immune microenvironment
Authors: Wang Xinyi , Duanmu Jinzhong , Fu Xiaorui , Li Taiyuan , Jiang Qunguang
Published: August 2020

Background

Colon cancer is a disease with high malignancy and incidence in the world. Tumor immune microenvironment (TIM) and tumor mutational burden (TMB) have been proved to play crucial roles in predicting clinical outcomes and therapeutic efficacy, but the correlation between them and the underlying mechanism were not completely understood in colon cancer.

Methods

In this study, we used Single-Sample Gene Set Enrichment Analysis (ssGSEA) and unsupervised consensus clustering analysis to divide patients from the TCGA cohort into three immune subgroups. Then we validated their differences in immune cell infiltration, overall survival outcomes, clinical phenotypes and expression levels of HLA and checkpoint genes by Mann–Whitney tests. We performed weighted correlation network analysis (WGCNA) to obtain immunity-related module and hub genes. Then we explored the underlying mechanism of hub genes by gene set enrichment analysis (GSEA) and gene set evaluation analysis (GSVA). Finally, we gave an overall view of gene variants and verified the correlation between TIM and TMB by comparing microsatellite instability (MSI) and gene mutations among three immune subgroups.

Results

The colon cancer patients were clustered into low immunity, median immunity and high immunity groups. The median immunity group had a favorable survival probability compared with that of the low and high immunity groups. Three groups had significant differences in immune cell infiltration, tumor stage, living state and T classification. We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration. With higher immunity, the TMB was higher. The most frequent mutations in low and median immunity groups were APC, TP53 and KRAS, while TTN and MUC16 showed higher mutational frequency in high immunity group.

Conclusions

We performed a comprehensive evaluation of the immune microenvironment landscape of colon cancer and demonstrated the positive correlation between immunity and TMB. The hub genes and frequently mutated genes were strongly related to immunity and may give suggestion for immunotherapy in the future.
Identification of MiR-211-5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma
Authors: Qin Xia , Zhang Jian , Lin Yu , Sun Xue-ming , Zhang Jia-ning , Cheng Zhi-qiang
Published: August 2020

Background

Liver cancer is among the most common malignancy worldwide. Hepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality. The high rates of recurrence and metastasis contribute to the poor prognosis of HCC patients. In recent years, increasing evidence has shown that microRNAs (miRNAs) are involved in the tumorigenesis, progression, and prognosis of HCC.

Methods

To screen for key candidate miRNAs in HCC, three microarray datasets were downloaded from Gene Expression Omnibus (GEO). The sole common differentially expressed miRNA (DEmiR) observed in the above three datasets using a Venn diagram was microRNA-211-5p (miR-211-5p). The expression of miR-211-5p from HCC tissues was measured in several HCC cell lines. Additionally, using Kaplan–Meier plots, the potential prognostic value of miR-211-5p in HCC was analyzed. Cell counting kit-8 (CCK-8) and transwell assays examined the ability of miR-211-5p to induce cell proliferation, migration, and invasion in HCC cultures. The interaction of miR-211-5p and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) was assessed both theoretically and using a luciferase reporter assay. Finally, the ability of miR-211-5p to modulate tumorigenesis in HCC in vivo was assessed after establishing a xenograft model.

Results

qRT-PCR demonstrated that the relative expression of miR-211-5p was considerably down-regulated in HCC tissues and cell lines compared with normal tissue. Kaplan–Meier plots indicated that HCC patients with decreased expression of miR-211-5p had poor overall survival. Upregulation of miR-211-5p in vitro consistently suppressed cell proliferation, migration, and invasion. In contrast, enhanced expression of ACSL4 promoted a malignant phenotype in HCC cells. Importantly, we discovered that ACSL4 was a direct downstream target of miR-211-5p in HCC, and that miR-211-5p suppressed the malignant phenotype by inhibition of ACSL4 expression. Furthermore, miR-211-5p overexpression impaired tumorigenesis and growth of HCC in vivo.

Conclusions

Targeting miR-211-5p and the downstream gene ACSL4 will possibly provide novel insight and represents a promising approach to future therapy of HCC patients.
Rh-relaxin-2 attenuates degranulation of mast cells by inhibiting NF-κB through PI3K-AKT/TNFAIP3 pathway in an experimental germinal matrix hemorrhage rat model
Authors: Li Peng , Zhao Gang , Chen Fanfan , Ding Yan , Wang Tianyi , Liu Shengpeng , Lu Weitian , Xu Weilin , Flores Jerry , Ocak Umut , Zhang Tongyu , Zhang John H. , Tang Jiping
Published: August 2020

Background

Mast cells play an important role in early immune reactions in the brain by degranulation and the consequent inflammatory response. Our aim of the study is to investigate the effects of rh-relaxin-2 on mast cells and the underlying mechanisms in a germinal matrix hemorrhage (GMH) rat model.

Methods

One hundred seventy-three P7 rat pups were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Clodronate liposome was administered through intracerebroventricular (i.c.v.) injections 24 h prior to GMH to inhibit microglia. Rh-relaxin-2 was administered intraperitoneally at 1 h and 13 h after GMH. Small interfering RNA of RXFP1 and PI3K inhibitor LY294002 were given by i.c.v. injection. Post-GMH evaluation included neurobehavioral function, Western blot analysis, immunofluorescence, Nissl staining, and toluidine blue staining.

Results

Our results demonstrated that endogenous relaxin-2 was downregulated and that RXFP1 level peaked on the first day after GMH. Administration of rh-relaxin-2 improved neurological functions, attenuated degranulation of mast cells and neuroinflammation, and ameliorated post-hemorrhagic hydrocephalus (PHH) after GMH. These effects were associated with RXFP1 activation, increased expression of PI3K, phosphorylated AKT and TNFAIP3, and decreased levels of phosphorylated NF-κB, tryptase, chymase, IL-6, and TNF-α. However, knockdown of RXFP1 and PI3K inhibition abolished the protective effects of rh-relaxin-2.

Conclusions

Our findings showed that rh-relaxin-2 attenuated degranulation of mast cells and neuroinflammation, improved neurological outcomes, and ameliorated hydrocephalus after GMH through RXFP1/PI3K-AKT/TNFAIP3/NF-κB signaling pathway.
Transgenic inhibition of astroglial NF-κB restrains the neuroinflammatory and neurodegenerative outcomes of experimental mouse glaucoma
Authors: Yang Xiangjun , Zeng Qun , Barış Mine , Tezel Gülgün
Published: August 2020

Background

Glia-driven neuroinflammation promotes neuron injury in glaucoma that is a chronic neurodegenerative disease of the optic nerve and a leading cause of irreversible blindness. Although therapeutic modulation of neuroinflammation is increasingly viewed as a logical strategy to avoid inflammatory neurotoxicity in glaucoma, current understanding of the molecular regulation of neuroinflammation is incomplete, and the molecular targets for immunomodulation remains unknown. Growing datasets pointed to nuclear factor-kappaB (NF-κB), a key transcriptional activator of inflammation, which was identified to be most affected in glaucomatous astroglia. Using a cell type-specific experimental approach, this study aimed to determine the value of astroglial NF-κB as a potential treatment target for immunomodulation in experimental mouse glaucoma.

Methods

Neuroinflammatory and neurodegenerative outcomes of experimental glaucoma were comparatively analyzed in mice with or without cre/lox-based conditional deletion of astroglialIκKβ, which is the main activating kinase involved in IκB degradation through the canonical pathway of NF-κB activation. Glial responses and the inflammatory status of the retina and optic nerve were analyzed by cell morphology and cytokine profiling, and neuron structure and function were analyzed by counting retinal ganglion cell (RGC) axons and somas and recording pattern electroretinography (PERG) responses.

Results

Analysis of glial inflammatory responses showed immunomodulatory outcomes of the conditional transgenic deletion ofIκKβin astroglia. Various pro-inflammatory cytokines known to be transcriptional targets for NF-κB exhibited decreased production inIκKβ-deleted astroglia, which included TNF-α that can induce RGC apoptosis and axon degeneration during glaucomatous neurodegeneration. Indeed, transgenic modulation of inflammatory responses by astroglialIκKβdeletion reduced neurodegeneration at different neuronal compartments, including both RGC axons and somas, and protected PERG responses.

Conclusions

The findings of this study support a key role for astroglial NF-κB in neuroinflammatory and neurodegenerative outcomes of experimental glaucoma and the potential of this transcriptional regulator pathway as a glial treatment target to provide neuroprotection through immunomodulation. By pointing to a potential treatment strategy targeting the astroglia, these experimental findings are promising for future clinical translation through transgenic applications to improve the treatment of this blinding disease.
Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury
Authors: Jiao Mengya , Li Xiangyong , Chen Liying , Wang Xiaodi , Yuan Baohong , Liu Tao , Dong Qun , Mei Hanfang , Yin Hui
Published: August 2020

Background

Interleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action.

Methods

The brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia and treated with IL-33 at a dose of 0.2 μg/day i.p. for 3 days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells and cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes.

Results

The expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 days after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation.

Conclusions

The activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner.
Interferon regulatory factor 4 as a therapeutic target in adult T-cell leukemia lymphoma
Authors: Rauch Daniel A. , Olson Sydney L. , Harding John C. , Sundaramoorthi Hemalatha , Kim Youngsoo , Zhou Tianyuan , MacLeod A. Robert , Challen Grant , Ratner Lee
Published: August 2020

Background

Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in host genes have exposed the T-cell receptor pathway through nuclear factor κB to interferon regulatory factor 4 (IRF4) as an essential driver for this malignancy. We sought to determine if IRF4 represents a therapeutic target for ATLL and to identify downstream effectors and biomarkers of IRF4 signaling in vivo.

Results

ATLL cell lines, particularly Tax viral oncoprotein-negative cell lines, that most closely resemble ATLL in humans, were sensitive to dose- and time-dependent inhibition by a next-generation class of IRF4 antisense oligonucleotides (ASOs) that employ constrained ethyl residues that mediate RNase H-dependent RNA degradation. ATLL cell lines were also sensitive to lenalidomide, which repressed IRF4 expression. Both ASOs and lenalidomide inhibited ATLL proliferation in vitro and in vivo. To identify biomarkers of IRF4-mediated CD4 + T-cell expansion in vivo, transcriptomic analysis identified several genes that encode key regulators of ATLL, including interleukin 2 receptor subunits α and β, KIT ligand, cytotoxic T-lymphocyte-associated protein 4, and thymocyte selection-associated high mobility group protein TOX 2.

Conclusions

These data support the pursuit of IRF4 as a therapeutic target in ATLL with the use of either ASOs or lenalidomide.