bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Influence of Touch Points on Tourist Experiences at Crisis Impacted Destinations
Authors: Krey Nina , tom Dieck M. Claudia , Wu Shuang , Fountoulaki Paraskevi
Published: October 2021

Customer journeys in tourism are becoming more complex, often including multiple touch points that can influence expectations, experiences, and travel behaviors. The management of these different interactions is further complicated if tourist destinations face natural or man-made crises (e.g., financial crises, COVID-19). The current research takes a comprehensive look at how negative word-of-mouth (WOM) shapes pre-consumption expectations that drive actual tourist experiences and subsequent satisfaction behaviors. Using partial least squares structural equation modeling (PLS-SEM), findings from 188 tourists confirm the influence of uncontrollable, negative WOM on destination image. Yet an actual, positive experience negates these negative pre-trip influences. Tourism managers are rewarded with satisfied and loyal tourists in response to creating positive experiences even at crisis impacted destinations.
Effects of dwell time of split injection on mixture formation and combustion processes of diesel spray
Authors: Chandra Ray Samir , Kim Jaeheun , Kakami Scinichi , Nishida Keiya , Ogata Youichi
Published: October 2021

The effects of dwell time on the mixture formation and combustion processes of diesel spray are investigated experimentally. A commercial multihole injector with a 0.123 mm hole diameter is used to inject the fuel. The injection procedure is either a single or split injection with different dwell times, whereas the total amount of injected fuel mass is 5.0 mg per hole. Three dwell times are selected, that is, 0.12, 0.32 and 0.54 ms, with a split ratio of 7:3 based on previous findings. The vapour phase is observed, and the mixture formation pertaining to the equivalence ratio is analysed using the tracer laser absorption scattering (LAS) technique. A high-speed video camera is used to visualise the spray combustion flame luminosity, whereas a two-colour pyrometer system is used to evaluate the soot concentrations and flame temperature. An analysis of the mixture formation based on the spray evaporating condition reveals a more concentrated area of the rich mixture within a 0.32 ms dwell time. In the shortest dwell time of 0.12 ms, the equivalence ratio distribution decreases uniformly from the rich mixture region to the lean mixture region. In the case involving a shorter dwell time, a suitable position for the second injection around the boundaries of the first injection is obtained by smoothly growing the lean mixture and avoiding the large zone of the rich mixture. Therefore, the shortest dwell time is acceptable for mixture formation, considering the overall distribution of the equivalence ratios. Spray combustion analysis results show that the soot formation rate of the single injection and 0.32 ms dwell time case is high and decreases quickly, implying a rapid reduction in the high amount of soot. Consequently, 0.12 ms can be considered the optimal dwell time due to the ignition delay and relatively low soot emission afforded.
Investigation on the method of battery self-heating using motor pulse current
Authors: Du Changhong , Peng Qianlei , Chen Fu , Deng Kejun , Chen Jian , Deng Chenghao , Hu Minghui
Published: October 2021

The charging and discharging performance of lithium-ion battery at low temperature will decline greatly, which seriously affects the adaptability of electric vehicles at low temperature. This paper proposes to use the inductance characteristic of the motor stator and the switching control characteristic of the motor controller to form pulse current in the battery, and realize the self-heating of the power battery at low temperature. Using this method the heating of the battery can be achieved without any additional hardware or cost. The experimental result shows the average temperature rise rate of the power battery reaches 2.88°C/min. And the influence of different parameters on the heating effect is analyzed through the experiments, including IGBT switching frequency, d-axis voltage, motor-rotor position, and battery internal resistance.
Histone Methyltransferase KMT2D Regulates H3K4 Methylation and is Involved in the Pathogenesis of Ovarian Cancer
Authors: Li Ming , Shi Mengdie , Xu Ying , Qiu Jianping , Lv Qing
Published: October 2021

To investigate the function of histone-lysine N-methyltransferase 2D (KMT2D) on the methylation of H3 lysine 4 (H3K4) in the progression of Ovarian cancer (OV). KMT2D, ESR1 and H3K4me expressions in surgical resected tumors and tumor adjacent tissues of OV from 198 patients were determined using immunohistochemistry (IHC). Human OV cell lines including SKOV3, HO-8910 cells and normal ovarian epithelial cell line IOSE80 were employed for in vitro experiment, and BALB/C female nude mice were used for in vivo study. qRT-PCR and Western blotting were implemented for measuring the KMT2D, ESR1, PTGS2, STAT3, VEGFR2, H3K4me and ELF3 levels. Chromatin immunoprecipitation (ChIP) analysis was used for studying the binding between ESR1 and H3K4me. Edu staining assay was executed to determine cell viability, and colony formation and cell invasion assay. The immunofluorescence method was utilized for the visualization of protein expression and distribution in cells. In this study, KMT2D, ESR1 and H3K4me were found upregulated in OV progression. Mutated H3K4me could inhibit the proliferation, colony formation and invasion ability of OV cells. Mutated H3K4me could also hinder the ESR1 in SKOV3 expressions and HO-8910 cells, which would further mediate PTGS2/STAT3/VEGF pathway. In vivo studies also demonstrated that mutated H3K4me inhibited OV progression via targeting ESR1. All the ChIP-PCR analysis indicated the moderator effect of H3K4me on ESR1. Our findings indicated that ESR1 played an important role in the OV progression. Besides, H3K4me could promote cell proliferation and inhibit apoptosis of OV cells. Meanwhile, it could also targets the ESR1 production to enhance the migration and invasion of OV cells, which was through the activation of ESR1-ELF3-PTGS2-STAT3-VEGF cascade signaling pathway.
Methodological reflections on historical case study and interpretive accounting research
Authors: Detzen Dominic , Hoffmann Sebastian
Published: October 2021

Commenting on our study “Accountability and ideology: The case of a German university under the Nazi regime", published in 2020 in Accounting History, Fülbier recently outlined a research agenda on the manifold ways in which the Nazi doctrine affected institutions of higher education, going beyond the scope of our original article. With this reply, we seek to reflect on research considerations emanating from such an agenda, relating to (i) conducting historical case-based research, (ii) questions of ontology and epistemology in interpretive accounting research, and (iii) the notion of what constitutes accounting in a specific research context. We hope that our reply, along with Fülbier’s commentary, inspires further research on accounting’s role in totalitarian regimes.
Predictors of laxative use in inpatients with schizophrenia on clozapine
Authors: Sazhin Vladimir , Pushkal Pushkal
Published: October 2021

Objectives:

Constipation, a clinical manifestation of gastrointestinal hypomotility, is a common and potentially serious complication of clozapine therapy, requiring laxatives for its prevention and treatment. We explored the predictive factors of the increased laxative use in inpatients receiving a long-term clozapine therapy.

Methods:

In the cross-sectional study of 93 patients in a psychiatric rehabilitation hospital, we examined a four-week prevalence of laxative use and a range of demographic and clinical factors associated with the number of prescribed laxatives.

Results:

Seventy-four percent of inpatients with schizophrenia were prescribed laxatives, and they were statistically significant older and taking higher daily doses of clozapine. In generalized Poisson regression analysis, the clozapine dose, age, and comorbid diabetes mellitus and hypothyroidism were independently associated with the number of concurrently used laxatives. No association was found between the laxatives and gender, duration of clozapine treatment, and the number of other medications with a potential to cause constipation.

Conclusion:

The clozapine dose, age, diabetes mellitus, and hypothyroidism were shown to be the independent predictors of the increased laxative use among inpatients on clozapine and might be associated with the increased risk of clozapine-induced constipation and gastrointestinal hypomotility.
Muller muscle conjunctival resection or external levator advancement; a quantitative comparison of symmetry in unilateral ptosis
Authors: Serefoglu Cabuk Kubra , Asik Nacaroglu Senay , Ozturk Karabulut Gamze , Fazil Korhan , Arslan Mehmet Selcuk , Guler Mehmet Guray , Taskapili Muhittin
Published: October 2021

Purpose

To compare muller muscle conjunctival resection (MMCR) and external levator advancement (ELA) in terms of objective and subjective symmetry in unilateral ptosis.

Methods

The patients who underwent unilateral MMCR (group1, n = 25) and ELA (group2, n = 25) were reviewed retrospectively. With the written algorithm, margin reflex distance-1 (MRD1), localization of the contour peak, and the percentage of overlapping curvatures (POC) of both upper eyelid curves were calculated. Semi-automated measurements were compared with the manual measurements. The correlation between objective and subjective symmetry was evaluated.

Results

Preoperative levator functions were similar in both groups (13.93 ± 3.25 mm and 13.3 ± 2.86 mm, respectively). We found strong correlations between manual and semi-automated measurements (ICC: 0.942, 95% CI = 0.924–0.956, p < 0.001). Preoperative MRD1 (2.15 ± 0.90 vs 1.51 ± 1.01, p = 0.022) and POC was lower in group 2 (66% vs 47.2%, p = 0.01). In the postoperative period, the increase in MRD1 and POC were similar in both groups ( p = 0.2 and p = 0.7 respectively), and the contour peak displaced temporally ( p < 0.01) providing a symmetric peak in both groups. Subjective symmetry increased as the difference in MRD1 between two eyes decreased ( r = −0.456, p = 0.001), and POC increased ( r = 0.396, p = 0.004).

Conclusions

Besides subjective symmetry, MMCR and ELA are equally effective in ensuring symmetry objectively, as measured with MRD1 and contour peak symmetry and POC in unilateral ptosis. POC may be used as a criterion of symmetry in the evaluation of ptosis.
Tuberculosis Knowledge and Delayed Health Care Seeking Among New Diagnosed Tuberculosis Patients in Primary Health Facilities in an Urban District, South Africa
Authors: Makgopa Sylvia , Madiba Sphiwe
Published: October 2021

Patients’ delay in seeking health care is a major problem in the control of tuberculosis (TB) and increases the risk of TB transmission. This study determined health-seeking practices and delays that occurred from the onset of TB symptoms until diagnosis and assessed the patients’ TB-related knowledge. This was a cross-sectional study involving 391 new TB patients recruited from health facilities at an urban sub-district in South Africa from December 2016 to March 2017. Descriptive statistics and logistic regression analyses were performed using Stata 14. Over half (56.3%) of the patients delayed seeking health care for more than 30 days after the onset of their symptoms, 32% sought treatment from informal providers, and 13.3% self-medicated. Lack of suspicion of a TB diagnosis, which was prevalent in 45% of respondents, was statistically associated with delay in seeking healthcare (AOR = 0.53, CI: 0.32-1.87). Overall TB knowledge was high, correct knowledge about TB transmission was 92.6%. TB knowledge was significantly associated with educational status (AOR = 3.96, CI: 1.69-9.28) and seeking treatment from informal sectors (AOR = 0.17, CI: 0.03-0.95). High overall TB knowledge was not statistically associated with seeking health care for TB diagnosis and treatment. We found a substantial delay between the onset of TB symptoms and seeking healthcare from a public health facility providing TB screening services. Promoting early screening and diagnosis through increasing awareness of TB is key in the elimination of TB in communities with a high TB burden
Predictors of In-hospital Mortality in Cardiogenic Shock Patients on Vasoactive or Inotropic Support
Authors: Nandkeolyar Shuktika , Doctorian Tanya , Fraser Gary , Ryu Rachel , Fearon Colleen , Tryon David , Kagabo Whitney , Abramov Dmitry , Hauschild Christopher , Stoletniy Liset , Hilliard Anthony , Sakr Antoine
Published: October 2021

Background:

Though controversial, the short-duration in-patient use of inotropes in cardiogenic shock (CS) remain an ACC/AHA Class IIa indication, and are frequently used in the initial treatment of CS. We evaluated in-patient mortality and effect on mortality risk of commonly used vasoactive inotropic medications for the medical management of SCAI stage B and C cardiogenic shock patients in a tertiary care cardiac care unit: dobutamine, dopamine, milrinone, and norepinephrine.

Methods:

We retrospectively evaluated 342 patients who received dobutamine, milrinone, dopamine, norepinephrine or a combination of these medications for SCAI stage B and C cardiogenic shock. Cox proportional hazards were used to form longitudinal mortality predictions.

Results:

Overall in-patient mortality was 18%. Each 1 µg/kg/minute increase in dobutamine independently corresponded to a 15% increase in risk of mortality. High dose dobutamine >3 µg/kg/minute is associated with 3-fold increased risk compared to ⩽3 µg/kg/minute ( P < .001). Use of milrinone, norepinephrine, and dopamine were not independently associated with mortality.

Conclusion:

We demonstrate that the overall in-hospital mortality of SCAI stage B and C cardiogenic shock patients medically managed on inotropes was not in excess of prior studies. Dobutamine was independently associated with mortality, while other vasoactive inotropic medications were not. Inotropes remain a feasible method of managing SCAI stage B and C cardiogenic shock.
Effect of reinforcements on graphite/titania/aluminium nanohybrid composites
Authors: Reddy Yendapalli Kishor Kumar , Hussain Shaik Althaf , Narahari Vamsee Krishna Reddy , Pramanik Sumit , Bhaumik Shubrajit
Published: October 2021

Aluminium alloys and their composites are often used in aerospace, automobile and biomedical applications. However, mechanical and surface properties of those alloys have not reached up to the expectation. This investigation focused to improve the wear resistance properties along with mechanical and surface properties of aluminium matrix composites. Here, novel aluminium matrix nanohybrid composites were developed using titanium oxide and graphite as reinforced via powder metallurgical route. The sintered samples were analysed by different tests such as, hardness, surface roughness, wear tests and other structural analyses. The obtained results showed that some new compounds formed during sintering were responsible for improved mechanical and surface properties for different applications. The wear test showed that there was rapid worn out of graphite from the composites having aluminium content more than 50 wt% due to the higher content of graphite (10 and 20 wt%, respectively). In addition, due to the increase of porosity in the different hybrid composites, there was an increase in coefficient of friction observed in some materials. The aluminium nanohybrid composite having 40 wt% titania and 10 wt% graphite showed best results compared with others. Therefore, the optimized hybrid composites with proper sintering condition would significantly help to get suitable structural, mechanical as well as tribological properties for many advanced applications.
Isolated central nervous system familial hemophagocytic lymphohistiocytosis (fHLH) presenting as a mimic of demyelination in children
Authors: Parida Amitav , Abdel-Mannan Omar , Mankad Kshitij , Foster Katharine , Ramdas Sithara , Ram Dipak , Eleftheriou Despina , Hemingway Cheryl , Hacohen Yael , Wassmer Evangeline
Published: October 2021

Isolated central nervous system (CNS) presentations of haemophagocytic lymphohistiocytosis (HLH), traditionally a systemic inflammatory condition, have been reported in adults and children. We identified nine patients with a diagnosis of isolated CNS familial hemophagocytic lymphohistiocytosis (fHLH) with symptom onset <18 years of age, and one asymptomatic sibling. Children with atypical chronic/recurrent CNS inflammation should be considered for immunological and genetic panel testing for fHLH even in the absence of any systemic inflammatory features. Despite haematopoietic stem cell transplantation (HSCT) being a mainstay of treatment, treatment failure and high morbidity and mortality post-HSCT suggest that alternative immune therapies may be worth considering.
Presentation, Diagnosis and Management of Innominate Artery Thromboembolism
Authors: Chang Heepeel , Rockman Caron B. , Narula Navneet , Sabari Joshua K. , Garg Karan
Published: October 2021

Purpose:

Acute thromboembolic disease of the innominate artery (IA) poses a unique set of therapeutic challenges, owing to its contribution to both the cerebral and upper extremity circulation, and risks of distal embolization via the carotid and subclavian arteries, respectively. Herein, we present a 74-year-old female who presents with acute IA thrombus treated successfully with right axillary and common carotid exposure and aspiration catheter-directed mechanical thrombectomy (CDT). Furthermore, an emerging use of CDT and its application in acute thromboembolism are outlined.

Case report:

A 74-year-old female with history of right lung transplant for pulmonary fibrosis with severe pulmonary hypertension, and stage IIIA left lung adenocarcinoma status post left lower lobectomy undergoing adjuvant chemotherapy presented with acute IA thrombus and right-sided stroke. She was treated successfully with right axillary and common carotid exposure and aspiration CDT. Computed tomography angiography performed 1 month postoperatively confirmed patent IA with no evidence of residual or recurrent thrombus.

Conclusion:

There are currently no standard guidelines on the management of acute IA thromboembolism, with mostly individual cases reported in the literature describing this rare entity. Nevertheless, this unique clinical entity mandates expeditious diagnostic and therapeutic approaches in order to avoid permanent neurologic deficits from distal embolization. Our case demonstrates that aspiration CDT may be an effective treatment modality for patients with acute IA thrombus.
Political and Socio-Economic Dynamics on the Access to Oral Sources at National Archives in Zimbabwe and South Africa
Authors: Bhebhe Sindiso , Ngoepe Mpho
Published: October 2021

Access is one of the fundamental purposes of archives as archives are preserved for use by the public. One can argue that archives that are not being consulted by the researchers may simply be referred to as “dead” or “irrelevant.” It is from this assumption that a comparative case study between National Archives of Zimbabwe (NAZ), National Archives and Record Services of South Africa (NARS), and provincial archives in South Africa’ oral history units was carried out. The major objectives being that of how accessible are the oral history holdings of NAZ and NARS to the public vis-à-vis the traditional archives such as manuscripts among others and the impact of coloniality to access. Data was collected through interviews and observations including also document analysis. The discussion on collected data revealed a massive underutilization of oral sources which is not in tandem with the spirited effort put by both NAZ and NARS in collecting the oral histories of the once marginalized groups of people. Some of the recommendations offered were the adoption of ICTs especially online archiving and social media in providing access to oral history holdings to the public including coming up with access policies which are in line with the International Council of Archives’ (ICA) (2012) Principles of Access.
‘Travelling landscapes’ and the potential of Artscapes
Authors: Stiassny Noga
Published: October 2021

What does it mean to represent trauma, heritage and/or terror-related landscapes in the present day? This article aims to offer a new perspective on the ability of such representations to initiate a journey by means of artistic creation; the author refers to such artworks as ‘ Artscapes’, claiming that Artscapes make feasible a seemingly contradictory act: on one hand, ‘time travel’ that assists in commemorating the past(s), and on the other, ‘space travel’ that has the ability to challenge collective memories, narratives and even myths associated with that past(s). By focusing on a growing trend towards diasporic Artscapes within Israeli art as a test case of this genre, the article explores the potential possessed by such works to negotiate ‘diasporic memories’ within Zionism’s national ethos.
PSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going?
Authors: Giraudet Anne-Laure , Kryza David , Hofman Michael , Moreau Aurélie , Fizazi Karim , Flechon Aude , Hicks Rodney J. , Tran Ben
Published: October 2021

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment.
Race and Campaign Resources: Candidate Identification Numbers in Brazil
Authors: Janusz Andrew , Sells Cameron
Published: October 2021

Party elites may hinder racial and ethnic minorities from winning public office by withholding resources. Prior studies have explored the distribution of money, media access, and party-list positions. In Brazil, party elites provide each candidate with a unique identification number. Voters must enter their preferred candidate’s identification number into an electronic voting machine to register their support. In this article, we replicate and extend Bueno and Dunning’s (2017) analysis of candidate identification numbers. They conclude that party elites do not provide white candidates with superior identification numbers than non-whites. We contend that assessing intraparty variation is theoretically and methodologically warranted. Using party fixed effects, we find that party elites provide non-white candidates with worse identification numbers than whites. We demonstrate that our findings are generalisable using data from other elections. Moreover, we show that party elites also withhold advantageous numbers from women and political novices.
Modulation of immune-inflammatory responses through surface modifications of biomaterials to promote bone healing and regeneration
Authors: Batool Fareeha , Özçelik Hayriye , Stutz Céline , Gegout Pierre-Yves , Benkirane-Jessel Nadia , Petit Catherine , Huck Olivier
Published: October 2021

Control of inflammation is indispensable for optimal oral wound healing and tissue regeneration. Several biomaterials have been used to enhance the regenerative outcomes; however, the biomaterial implantation can ensure an immune-inflammatory response. The interface between the cells and the biomaterial surface plays a critical role in determining the success of soft and hard tissue regeneration. The initial inflammatory response upon biomaterial implantation helps in tissue repair and regeneration, however, persistant inflammation impairs the wound healing response. The cells interact with the biomaterials through extracellular matrix proteins leading to protein adsorption followed by recruitment, attachment, migration, and proliferation of several immune-inflammatory cells. Physical nanotopography of biomaterials, such as surface proteins, roughness, and porosity, is crucial for driving cellular attachment and migration. Similarly, modification of scaffold surface chemistry by adapting hydrophilicity, surface charge, surface coatings, can down-regulate the initiation of pro-inflammatory cascades. Besides, functionalization of scaffold surfaces with active biological molecules can down-regulate pro-inflammatory and pro-resorptive mediators’ release as well as actively up-regulate anti-inflammatory markers. This review encompasses various strategies for the optimization of physical, chemical, and biological properties of biomaterial and the underlying mechanisms to modulate the immune-inflammatory response, thereby, promoting the tissue integration and subsequent soft and hard tissue regeneration potential of the administered biomaterial.
Assessment of OB/Gyn Residents’ Knowledge of Basic Obstetric Sonography and Psychomotor Skills Posttraining on a Computer-Based Simulator
Authors: Mohammad Sundus H. , Sommerich Carolyn M. , Butwin Angela N. , Evans Kevin D.
Published: October 2021

Objective:

This study sought to evaluate how a high-fidelity computer-based sonography simulator (FCBSS) can be used in training obstetrics and gynecology residents and evaluate efficacy of high-fidelity CBSS in enhancing resident’s sonographic knowledge, psychomotor skills, and level of confidence in performing sonographic fetal assessments.

Materials and Methods:

Eleven postgraduate year 1 residents (PGY1s) and ten PGY2s were assessed on sonographic performance by measuring psychomotor skills and evaluating the accuracy of the sonographic images. PGY2s received traditional sonography training while PGY1s received three individualized training sessions on a high-fidelity CBSS. At the conclusion, all residents received feedback and completed a survey to establish their current confidence level in performing and interpreting sonograms.

Results:

PGY2s scored a median of 33/66 points on the assessment, while PGY1s scored a median of 64/66 points. Statistical analysis performed from motion analysis metrics between cohorts revealed a statistically significant difference, with PGY1s demonstrating higher psychomotor skills. Interquartile ranges of PGY1s’ scores were smaller than PGY2s’, revealing consistency in knowledge and skills among the PGY1 cohort.

Conclusion:

Findings suggests that high-fidelity CBSS can be used effectively in training residents. It also demonstrates that implementation of formalized sonography training, using a high-fidelity CBSS, can be achieved and potentially expedite and enhance the learning of novice learners.
Choroidal involvement in non-infectious posterior scleritis
Authors: Vermeirsch Sandra , Testi Ilaria , Pavesio Carlos
Published: October 2021

Purpose

To provide a comprehensive overview of choroidal involvement in non-infectious posterior scleritis; including different imaging modalities and their clinical usefulness.

Methods

Narrative review.

Results

Posterior scleritis is an uncommon yet potentially sight-threatening inflammation of the sclera. During the disease process, inflammation can spread to the adjacent choroid, causing different manifestations of choroidal involvement: (1) increased choroidal thickness, (2) choroidal vasculitis, (3) presentation as a choroidal or subretinal mass in nodular posterior scleritis, and (4) choroidal folds, choroidal effusion and exudative retinal detachment.

Conclusions

Clinical characteristics and multimodal imaging can aid in diagnosing and monitoring disease progression and response to treatment in non-infectious posterior scleritis with choroidal involvement.
circ_0038718 promotes colon cancer cell malignant progression via the miR-195-5p/Axin2 signaling axis and also effect Wnt/β-catenin signal pathway
Authors: Gu Haitao , Xu Zhiquan , Zhang Jianbo , Wei Yanbing , Cheng Ling , Wang Jijian
Published: October 2021

Objective

Colon cancer (CC) is one of the most common cancers whose progression is regulated by a number of factors, including circular RNAs (circRNAs). Nonetheless, circ_0038718 is a novel circRNA, and its regulatory mechanism in CC remains unclear.

Methods

Real-time quantitative PCR (qRT-PCR) was performed to detect the expression of circ_0038718, miR-195-5p and Axin2. Western blot was conducted to determine the protein expression of Axin2 and the key proteins on Wnt/β-catenin signaling pathway. Oligo (dT) 18 primers and RNase R were employed to identify the circular features of circ_0038718, and the location of circ_0038718 in cells was detected via nucleocytoplasmic separation. Dual-luciferase reporter assay and RNA binding protein immunoprecipitation experiment were carried out to investigate the molecular mechanism of circ_0038718/miR-195-5p/Axin2. Additionally, MTT assay was conducted to assess cell proliferation; Transwell assay was performed to evaluate cell migration and invasion, respectively. The effect of circ_0038718 on CC tumor growth was tested through tumor formation in nude mice.

Results

circ_0038718 was highly expressed in CC and could sponge miR-195-5p in cytoplasm. Silencing circ_0038718 suppressed the proliferative, migratory and invasive abilities of CC cells, while the promoting effect of high circ_0038718 expression on CC cells was reversed upon miR-195-5p over-expression. Axin2 was a downstream target of miR-195-5p and could regulate the Wnt/β-catenin signaling pathway. Axin2 expression was modulated by circ_0038718/miR-195-5p. Knockdown of Axin2 could also attenuate the promoting effect of high circ_0038718 expression on CC cell malignant progression, thus inhibiting tumor growth.

Conclusion

circ_0038718 is able to facilitate CC cell malignant progression via the miR-195-5p/Axin2 axis, which will provide a new idea for finding a novel targeted treatment of CC.
Long sleep duration is associated with cognitive frailty among older community-dwelling adults: results from West China Health and Aging Trend study
Authors: Zhao Yunli , Lu Ying , Zhao Wanyu , Wang Yanyan , Ge Meiling , Zhou Lixing , Yue Jirong , Dong Birong , Hao Qiukui
Published: October 2021

Objective

To investigate the association between sleep duration and cognitive frailty among older adults dwelling in western China.

Methods

We used the baseline data from West China Health and Aging Trend (WCHAT) study. Sleep duration was classified as short sleep duration (< 6 h), normal sleep duration (6–8 h) and long sleep duration (≥ 9 h). Fried frailty criteria and Short Portable Mental Status Questionnaire were used to measure cognitive frailty. Multinomial logistic regression was conducted to estimate odds ratio (OR) and 95% confidence interval (CI).

Results

A total of 4093 older adults (age = 67.8 ± 5.9 years, 1708 males and 2385 females) were included in the analysis. The prevalence of cognitive frailty was 11.8% among older adults in western China. Approximately 11.9% participants had short sleep duration (< 6 h); 22.2% had a long sleep duration (≥ 9 h). After adjusting for covariates, only long sleep duration was significantly associated with high risk of cognitive frailty (OR = 2.07, 95%CI = 1.60–2.68, P <  0.001) in western China older adults compared to normal sleep duration.

Conclusions

Long sleep duration was significantly related to cognitive frailty in older adults. Intervention for long sleep duration may be helpful to prevent cognitive frailty.

Trial registration

Chinese Clinical Trial Registry: ChiCTR1800018895.
Effectiveness of oseltamivir treatment on clinical failure in hospitalized patients with lower respiratory tract infection
Authors: Wiemken Timothy L. , Furmanek Stephen P. , Carrico Ruth M. , Peyrani Paula , Hoft Daniel , Fry Alicia M. , Ramirez Julio A.
Published: October 2021

Background

Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season.

Methods

This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days.

Results

A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2–48.0%).

Conclusions

This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission.

Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715
Prevalence of and factors associated with receipt of provider recommendation for influenza vaccination and uptake of influenza vaccination during pregnancy: cross-sectional study
Authors: Brixner Alexandra , Brandstetter Susanne , Böhmer Merle M. , Seelbach-Göbel Birgit , Melter Michael , Kabesch Michael , Apfelbacher Christian ,   KUNO-Kids study group
Published: October 2021

Background

Seasonal influenza vaccination has been recommended for pregnant women in Germany since 2010. The aim of this study was to examine prevalence and determinants of receipt of provider recommendation for influenza vaccination as well as influenza vaccination uptake during pregnancy.

Methods

We analysed data from the “KUNO Kids Health Study”, a prospective birth cohort. During the study period (5th July 2015 to 27th June 2018) data were collected from participating mothers by interview and questionnaire. According to Andersen’s behavioural model of health services use potential influencing factors describing the circumstances and characteristics of the mothers and their pregnancies which are potentially affecting whether women receive a recommendation for a vaccination or whether they utilize influenza vaccination were classified into three domains: ‘predisposing characteristics’, ‘enabling resources’ and ‘need’. Using multivariable logistic regression models odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were calculated.

Results

As a combined result across three flu seasons, 368 of 1814 (20.3%) women received an influenza vaccination recommendation during pregnancy. Having had a high-risk pregnancy increased the odds of receiving a vaccination recommendation (OR = 1.3; 95% CI = 1.0–1.6; p = 0.045). In contrast, pregnancy onset in summer (OR = 0.7; 95% CI = 0.5–1.0; p = 0.027), autumn (OR = 0.4; 95% CI = 0.3–0.5; p < =0.001) or winter (OR = 0.5; 95% CI = 0.3–0.6; p < =0.001) (compared to spring) as well as mother’s birthplace outside Germany (OR = 0.6; 95% CI = 0.4–0.9; p = 0.023) reduced the chance of getting a vaccination recommendation.

Two hundred forty-two of one thousand eight hundred sixty-five (13%) women were vaccinated against influenza during pregnancy. Having received a vaccination recommendation was strongly associated with vaccination uptake (OR = 37.8; 95% CI = 25.5–55.9; p < =0.001). Higher health literacy status was also associated with a higher chance of vaccination uptake (OR = 1.7; 95% CI = 1.2–2.6; p = 0.008), whereas pregnancy onset in autumn (compared to spring) reduced the chance (OR = 0.5; 95% CI = 0.3–0.8; p = 0.008).

Conclusions

At 13% the uptake rate of influenza vaccination is low. Having received a recommendation to vaccinate was strongly associated with uptake but only one fifth of all mothers report such a recommendation. Raising awareness in physicians regarding vaccinating during pregnancy seems to be of essential importance to increase vaccine uptake and to prevent influenza-related complications in pregnant women.
Comparison of submucosal and subserosal approaches toward optimized indocyanine green tracer-guided laparoscopic lymphadenectomy for patients with gastric cancer (FUGES-019): a randomized controlled trial
Authors: Chen Qi-Yue , Zhong Qing , Li Ping , Xie Jian-Wei , Liu Zhi-Yu , Huang Xiao-Bo , Lin Guang-Tan , Wang Jia-Bin , Lin Jian-Xian , Lu Jun , Cao Long-Long , Lin Mi , Zheng Qiao-Ling , Tu Ru-Hong , Huang Ze-Ning , Zheng Chao-Hui , Huang Chang-Ming
Published: October 2021

Background

Application of indocyanine green (ICG) fluorescence imaging is effective in guiding laparoscopic radical lymphadenectomy for gastric cancer. However, the optimal approach for indocyanine green injection is controversial. Therefore, the objective of this study was aimed to compare the efficacy and ICG injection between the preoperative submucosal and intraoperative subserosal approaches for lymph node (LN) tracing during laparoscopic gastrectomy.

Method

This randomized controlled trial (ClinicalTrials.gov, NCT04219332) included 266 patients with potentially resectable gastric cancer (cT1–T4a, N0/+, M0) enrolled from a tertiary teaching center between December 2019 and October 2020. The primary endpoint was total number of retrieved LNs.

Results

In total, 259 patients (n = 130 and n = 129 in the submucosal and subserosal groups, respectively) were included in the per-protocol analysis. There are no significant differences in total number of retrieved LNs between the two groups (49.8 vs. 49.2, P = 0.713). The rate of LN noncompliance in the submucosal group was comparable to that in the subserosal group (32.3% vs. 33.3%, P = 0.860). No significant difference was found between the submucosal and subserosal groups in terms of the incidence (17.7% vs. 16.3%; P = 0.762) or severity of postoperative complications. The mean fluorescence cost in the submucosal group was higher than that in the subserosal group ($335.3 vs. $182.4; P < 0.001). The overall treatment satisfaction score was lower in the submucosal group than in the subserosal group (70.5 vs. 76.1%, P = 0.048).

Conclusion

ICG administered by subserosal injection was comparable to that administered by submucosal injection for lymph node tracing in gastric cancer. However, the former approach imposed a lower economic and mental burden on patients undergoing laparoscopic D2 lymphadenectomy.

Trial registration

ClinicalTrials.gov, NCT04219332.
Comparison of the chemical constituents and anti-Alzheimer’s disease effects of Uncaria rhynchophylla and Uncaria tomentosa
Authors: Xu Qing-Qing , Shaw Pang Chui , Hu Zhen , Yang Wen , Ip Siu-Po , Xian Yan-Fang , Lin Zhi-Xiu
Published: October 2021

Background

Uncaria tomentosa, which has similar chemical constituents with Uncaria rhynchophylla, has been reported to alleviate cognitive impairments in Alzheimer’s disease (AD) animal models. This study aimed to compare the chemical constituents and anti-AD effect of the ethanol extracts of U. tomentosa (UTE) and U. rhynchophylla (URE).

Methods

The high-performance liquid chromatography (HPLC) was used to compare the chemical constituents of UTE and URE. Streptozotocin (STZ) was intracerebroventricularly (ICV) injected into adult male Sprague–Dawley (SD) rats to establish AD model. UTE (400 mg/kg) or URE (400 mg/kg) was administrated intragastrically once daily to the rats for 6 consecutive weeks. Morris water maze (MWM) test was conducted to assess the neurological functions in the STZ-induced AD rats. The brain tissues of the rats were harvested for further biochemical assay.

Results

The MWM test results showed both UTE and URE could significantly improve the learning and memory impairments induced by STZ in rats. Both UTE and URE could significantly inhibit the hyperphosphorylation of tau protein, reduce the elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), enhance activities of antioxidant enzymes (SOD, CAT and GPx) and increase the protein expression of HO-1. In addition, UTE could decrease the malondialdehyde (MDA) level. Furthermore, both UTE and URE significantly enhanced Akt activation, down regulated the activation of glycogen synthase kinase 3β (GSK-3β), and induced the nuclear translocation of Nrf2 in the STZ-induced AD rats.

Conclusions

UTE and URE contained similar chemical constituents. We found for the first time that both of them could ameliorate cognitive deficits in the STZ-induced AD rats. The underlying molecular mechanism involve suppression of tau hyperphosphorylation, anti-oxidant and anti-neuroinflammation via modulating Akt (Ser473)/GSK3β (Ser9)-mediated Nrf2 activation. These findings amply implicate that both of UTE and URE are worthy of being developed clinically into pharmaceutical treatment for AD.
A genome variation map provides insights into the genetics of walnut adaptation and agronomic traits
Authors: Ji Feiyang , Ma Qingguo , Zhang Wenting , Liu Jie , Feng Yu , Zhao Peng , Song Xiaobo , Chen Jiaxin , Zhang Junpei , Wei Xin , Zhou Ye , Chang Yingying , Zhang Pu , Huang Xuehui , Qiu Jie , Pei Dong
Published: October 2021

Background

Common walnut (Juglans regia L.) is one of the top four most consumed nuts in the world due to its health benefits and pleasant taste. Despite its economic importance, the evolutionary history and genetic control of its adaptation and agronomic traits remain largely unexplored.

Results

We report a comprehensive walnut genomic variation map based on whole-genome resequencing of 815 walnut accessions. Evolutionary analyses suggest that Chinese J. regia diverged from J. sigillata with extensive hybridizations after the split of the two species. In contrast to annual crops, the genetic diversity and heterozygous deleterious mutations of Chinese common walnut trees have continued to increase during the improvement process. Selective sweep analyses identify 902 genes uniquely selected in the improved common walnut compared to its progenitor population. Five major-effect loci are identified to be involved in walnut adaptations to temperature, precipitation, and altitude. Genome-wide association studies reveal 27 genomic loci responsible for 18 important agronomic traits, among which JrFAD2 and JrANR are the potentially major-effect causative genes controlling linoleic acid content and color of the endopleura of the nut, respectively.

Conclusions

The largest genomic resource for walnuts to date has been generated and explored in this study, unveiling their evolutionary history and cracking the genetic code for agronomic traits and environmental adaptation of this economically crucial crop tree.
A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada
Authors: Murall Carmen Lía , Fournier Eric , Galvez Jose Hector , N’Guessan Arnaud , Reiling Sarah J. , Quirion Pierre-Olivier , Naderi Sana , Roy Anne-Marie , Chen Shu-Huang , Stretenowich Paul , Bourgey Mathieu , Bujold David , Gregoire Romain , Lepage Pierre , St-Cyr Janick , Willet Patrick , Dion Réjean , Charest Hugues , Lathrop Mark , Roger Michel , Bourque Guillaume , Ragoussis Jiannis , Shapiro B. Jesse , Moreira Sandrine
Published: October 2021

Background

Québec was the Canadian province most impacted by COVID-19, with 401,462 cases as of September 24th, 2021, and 11,347 deaths due mostly to a very severe first pandemic wave. In April 2020, we assembled the Coronavirus Sequencing in Québec (CoVSeQ) consortium to sequence SARS-CoV-2 genomes in Québec to track viral introduction events and transmission within the province.

Methods

Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec. We report 2921 high-quality SARS-CoV-2 genomes in the context of > 12,000 publicly available genomes sampled globally over the first pandemic wave (up to June 1st, 2020). By combining phylogenetic and phylodynamic analyses with epidemiological data, we quantify the number of introduction events into Québec, identify their origins, and characterize the spatiotemporal spread of the virus.

Results

Conservatively, we estimated approximately 600 independent introduction events, the majority of which happened from spring break until 2 weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (> 50 sequenced cases), likely due to mandatory quarantine measures in place at the time. Consistent with common spring break and “snowbird” destinations, most of the introductions were inferred to have originated from Europe via the Americas. Once introduced into Québec, viral lineage sizes were overdispersed, with a few lineages giving rise to most infections. Consistent with founder effects, the earliest lineages to arrive tended to spread most successfully. Fewer than 100 viral introductions arrived during spring break, of which 7–12 led to the largest transmission lineages of the first wave (accounting for 52–75% of all sequenced infections). These successful transmission lineages dispersed widely across the province. Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travellers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order.

Conclusions

Combined, our results reinforce how, in the absence of tight travel restrictions or quarantine measures, fewer than 100 viral introductions in a week can ensure the establishment of extended transmission chains.