bluuebunny/crossref_metadata_2025 huggingface dataset:
The Portrayal of Social Media Marketing in the Luxury Tourism Industry: A Review of the Literature and a Preliminary Analysis
Authors: Mohapatra Jyotisman Das , Dash Ashok Kumar
Published: December 2022

Luxurious tourist industry winds up with the thoughts of exclusivity with restricted access to a select number of socially isolated travellers. Our comprehensive literature survey focuses on understanding the approach of tourism academia in the context of luxury travel, which is constructed on the remarks from social media and the specialised areas with regards to the studies that were conducted prior to this. The ‘luxury tourism’, ‘elite travel’, ‘social media’ and ‘sustainability’ were used in different combinations to discover literature. This was done using Google Scholar, the ProQuest database, etc. The critical analysis was conducted based on the peer-reviewed publications. The following three areas were selected and reviewed: (a) social media’s importance in luxury tourism; (b) the behavioural features of luxury travellers who use various social media apps; and (c) existing literature surveys that provided the limitations of analysing data, specifically, in the context of luxury tourism. The examined papers and publications for the last 10 years, from March 2010 to March 2020, were considered to determine the themes and focus points, as well as to measure the value of social media in luxury travel. The article discusses the upcoming research issues, and the major hindrance in this is that it requires new conceptual and methodological frameworks to enhance deep understanding of the mediating effect between social media and the luxury tourist industry based on the findings of various reviews of literature.
Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival
Authors: Martinez Caridad , Aguayo-Hiraldo Paibel , Chaimowitz Natalia , Forbes Lisa , Rider Nicholas , Nicholas Sarah , Seeborg Filiz , Chinen Javier , Chinn Ivan , Davis Carla , Roseblatt Howard , Noroski Lenora , Omer Bilal , John Tami , Yassine Khaled , Naik Swati , Craddock John , Bhar Saleh , Allen Carl , Ahmed Nabil , Sasa Ghadir , Steffin David , Doherty Erin , George Anil , Salem Baheyeldin , Friend Brian , Hegde Meenakshi , Brenner Malcolm K. , Heslop Helen E. , Leen Ann , Peña Amanda , Wu Mengfen , Hanson I. Celine , Krance Robert A.
Published: December 2022

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients had persistent infections before transplant. Nineteen of them (34%) were 6/6 matched, and 36 (66%) were 5/6 human leukocyte antigen–matched. The OS at 2 years was 91% (95% cumulative incidence, 79-96), with a median follow-up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range, 5-39 days) and 37 days (range, 20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of acute GVHD grades 2-4 on day 100 was 16% (n = 9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients underwent correction of their immune or metabolic defects. We conclude that in the absence of MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with nonmalignant disorders. This trial has been registered at www.clinicaltrials.gov as NCT00950846.
Low-density lipoprotein cholesterol and risk of COPD: Copenhagen General Population Study
Authors: Freyberg Josefine , Landt Eskild M. , Afzal Shoaib , Nordestgaard Børge G. , Dahl Morten
Published: December 2022

Background

Randomised controlled trials found that low-density lipoprotein (LDL) cholesterol-lowering statins increase lung function and possibly decrease rate of exacerbations in individuals with COPD. However, it is unknown whether high levels of LDL cholesterol are associated with increased susceptibility to COPD.

Methods

We tested the hypothesis that high LDL cholesterol is associated with increased risk of COPD, severe COPD exacerbation and COPD-specific mortality. We examined 107 301 adults from the Copenhagen General Population Study. COPD outcomes were ascertained at baseline and prospectively through nationwide registries.

Results

In cross-sectional analysis, low LDL cholesterol was associated with increased risk of COPD (odds ratio for 1stversus4th quartile: 1.07 (95% CI 1.01–1.14)). Prospectively, low LDL cholesterol was associated with increased risk of COPD exacerbations with hazard ratios of 1.43 (1.21–1.70) for 1stversus4th quartile, 1.21 (1.03–1.43) for 2ndversus4th quartile, and 1.01 (0.85–1.20) for 3rdversus4th quartile of LDL cholesterol (p-value for trend=6×10−6). Finally, low LDL cholesterol was likewise associated with increased risk of COPD-specific mortality (log-rank test: p=0.0009). Sensitivity analyses with death as competing risk provided similar results.

Conclusion

Low LDL cholesterol was associated with increased risks of severe COPD exacerbation and COPD-specific mortality in the Danish general population. As this is opposite of that observed in randomised controlled trials with statins, our findings might be a result of reverse causation indicating that individuals with severe phenotypes of COPD have lower plasma levels of LDL cholesterol due to wasting.
ENTAIL: yEt aNoTher amyloid fIbrils cLassifier
Authors: Auriemma Citarella Alessia , Di Biasi Luigi , De Marco Fabiola , Tortora Genoveffa
Published: December 2022

Background

This research aims to increase our knowledge of amyloidoses. These disorders cause incorrect protein folding, affecting protein functionality (on structure). Fibrillar deposits are the basis of some wellknown diseases, such as Alzheimer, Creutzfeldt–Jakob diseases and type II diabetes. For many of these amyloid proteins, the relative precursors are known. Discovering new protein precursors involved in forming amyloid fibril deposits would improve understanding the pathological processes of amyloidoses.

Results

A new classifier, called ENTAIL, was developed using over than 4000 molecular descriptors. ENTAIL was based on the Naive Bayes Classifier with Unbounded Support and Gaussian Kernel Type, with an accuracy on the test set of 81.80%, SN of 100%, SP of 63.63% and an MCC of 0.683 on a balanced dataset.

Conclusions

The analysis carried out has demonstrated how, despite the various configurations of the tests, performances are superior in terms of performance on a balanced dataset.
Impact of different cover letter information and incentives on Veterans’ emotional responses to an unsolicited mailed survey about military traumas: a randomized, 3x2x2 factorial trial
Authors: Murdoch Maureen , Clothier Barbara A , Kehle-Forbes Shannon , Vang Derek , Noorbaloochi Siamak
Published: December 2022

Background

Altering cover letter information to reduce non-response bias in trauma research could inadvertently leave survey participants unprepared for potentially upsetting questions. In an unsolicited, mailed survey, we assessed participants’ change in affect post-survey after altering key cover letter information and promising different incentives. We tested direct and indirect effects of participants carefully reading the cover letter on changes in their affect post-survey.

Methods

In a 3X2X2 randomized, factorial trial, 480 male and 480 female, nationally representative Veterans who were applying for posttraumatic stress disorder disability benefits were randomized to receive one of 12 different cover letters. The cover letters provided general versus more explicit information about the survey’s trauma content and how their names were selected for study; we also promised different incentives for returning the survey. The main outcome was change in affect post-survey. We examined five potential moderators: combat or military sexual trauma exposure, posttraumatic stress disorder or serious mental illness diagnosis, and recency of military service. Mediators between reading the cover letter carefully and post-survey affect included how participants rated the cover letters’ information and whether they thought the cover letters prepared them for the survey’s content. A Bonferroni corrected alpha of 0.003 was the threshold for statistical significance.

Results

One hundred ninety men and 193 women reported their pre-and post-survey affect. Across all study conditions, out of 16 possible points, the net change in affect post-survey was less than a quarter-point for men and women. Mean changes in post-survey affect did not differ statistically significantly across any of the study factors (ps > 0.06); nor were there statistically significant interactions between any of the study factors and the 5 moderators after accounting for multiple comparisons (ps > 0.02). After controlling for pre-survey affect, reading the cover letter carefully had small effects on changes in post-survey affect, with larger associations seen in the women compared to men. Mediators’ effects were often in opposite directions for men and women.

Conclusion

General descriptions of a survey’s trauma content appear ethically defensible. Research on cover letters’ impacts on survey participants’ emotional reactions and how those impacts differ by gender is needed.
Efficacy of ustekinumab, vedolizumab, or a second anti-TNF agent after the failure of a first anti-TNF agent in patients with Crohn’s disease: a multicentre retrospective study
Authors: Rayer Cassandra , Nachury Maria , Bourreille Arnaud , Roblin Xavier , Peyrin-Biroulet Laurent , Viennot Stephanie , Flamant Mathurin , Laharie David , Caron Bénédicte , Dewitte Marie , Siproudhis Laurent , Fumery Mathurin , Bouguen Guillaume
Published: December 2022

Background

No study has performed a face-to-face comparison of biologics after the failure of the first anti-TNF agent in patients with Crohn’s disease (CD). The aim of the study was to compare the efficacy of biologics in this setting.

Methods

Patients with CD who were refractory to a first anti-TNF agent, and treated with ustekinumab (UST), vedolizumab (VDZ), or a second anti-TNF drug as a second-line biological agent at 10 French tertiary centres from 2013 to 2019 were retrospectively included in this study.

Results

Among the 203 patients included, 90 (44%) received UST, 42 (21%) received VDZ and 71 (35%) received a second anti-TNF agent. The first anti-TNF agent was discontinued due to a primary nonresponse in 42 (21%) patients. At weeks 14–24, the rates of steroid-free remission were similar between the UST, VDZ and second anti-TNF groups (29%, 38% and 44%, respectively,p = 0.15). With a mean follow-up of 118 weeks, drug survival was shorter for patients who received ustekinumab treatment (p = 0.001). In the case of trough level less than 5 µg/ml, patients treated with a second anti-TNF agent had a higher postinduction remission rate (p = 0.002), and drug survival (p = 0.0005). No other relevant factors were associated with treatment efficacy, including trough levels greater than 5 µg/ml.

Conclusions

VDZ, UST and a second anti-TNF agent exhibit similar efficacy in the short term, as second-biological line treatment in patients with CD who are refractory to a first anti-TNF agent, but shorter drug maintenance is observed for patients treated with UST.
Cultural adaptation and validation of the Malay Chronic Kidney Disease Self-management instrument (MCKD-SM)
Authors: Al Sawad Ayat Ali , Lim Soo Kun , Tang Li Yoong , Rashid Aneesa Abdul , Chew Boon-How
Published: December 2022

Background

There is growing evidence that self‐management behaviour can improve outcomes for patients with chronic kidney disease (CKD). However, no measures are available in Malay to effectively assess the self-management of CKD. The aim of this study was to translate, culturally adapt and validate the Malay Chronic Kidney Disease Self-Management (MCKD-SM) instrument for Malay-speaking health professionals and patients.

Methods

This study was carried out in two phases: the translation and cultural adaptation phase and the validation phase. The instrument was translated from English to Malay and then adapted and validated in a sample of 337 patients with CKD stages 3–4 attending a nephrology clinic in a tertiary hospital in Malaysia. Structural validity was evaluated by exploratory factor analysis. The instrument’s reliability was assessed by internal consistency and test–retest reliability. The correlations between the MCKD-SM and kidney disease knowledge and the MCKD-SM and self-efficacy were hypothesised a priori and investigated.

Results

The MCKD-SM instrument has 29 items grouped into three factors: ‘Understanding and Managing My CKD’, ‘Seeking Support’ and ‘Adherence to Recommended Regimen’. The three factors accounted for 56.3% of the total variance. Each factor showed acceptable internal reliability, with Cronbach’s α from 0.885 to 0.960. The two-week intra-rater test–retest reliability intraclass correlation coefficient values for all items ranged between 0.938 and 1.000. The MCKD-SM scores significantly correlated with kidney disease knowledge (r = 0.366, p < 0.01) and self-efficacy (r = 0.212, p < 0.01).

Conclusion

The MCKD-SM was found to be a valid and reliable patient‐reported outcome measure of pre-dialysis CKD self-management behaviour in the Malay-speaking population.
Primary intraventricular synovial sarcoma of the brain with recurrence - case presentation
Authors: McCool Anna , Turner Clinton , Turner Sarah , Heppner Peter , Saran Frank
Published: December 2022

Background

We report a case of recurrent primary intraventricular synovial sarcoma of the brain with no extracranial primary, initially reported as a haemangiopericytoma. We believe this is the first reported case of primary intraventricular synovial sarcoma at this site.

Case presentation

A 27-year-old male presented to hospital with a new onset of seizures. Imaging revealed a left ventricular trigone mass with surrounding oedema. He underwent a left occipito-temporal craniotomy and resection with the histology reported as haemangiopericytoma. Resection was followed by adjuvant radiation treatment. Seven years later follow-up imaging revealed a 4 mm contrast enhancing lesion in the previous surgical bed. The patient underwent resection. Histological analysis of the recurrence revealed a spindle cell tumour with a SS18 gene rearrangement consistent with synovial sarcoma. Retrospective fluorescent in-situ hybridisation analysis of original histology also revealed a SS18 gene rearrangement consistent with a diagnosis of synovial sarcoma.

Conclusion

Synovial sarcoma should be included as part of the differential diagnosis for patients presenting with intraventricular spindle cell tumours in the brain.
Risk prediction models of gestational diabetes mellitus before 16 gestational weeks
Authors: Wei Yiling , He Andong , Tang Chaoping , Liu Haixia , Li Ling , Yang Xiaofeng , Wang Xiufang , Shen Fei , Liu Jia , Li Jing , Li Ruiman
Published: December 2022

Background

Gestational diabetes mellitus (GDM) can lead to adverse maternal and fetal outcomes, and early prevention is particularly important for their health, but there is no widely accepted approach to predict it in the early pregnancy. The aim of the present study is to build and evaluate predictive models for GDM using routine indexes, including maternal clinical characteristics and laboratory biomarkers, before 16 gestational weeks.

Methods

A total of 2895 pregnant women were recruited and maternal clinical characteristics and laboratory biomarkers before 16 weeks of gestation were collected from two hospitals. All participants were randomly stratified into the training cohort and the internal validation cohort by the ratio of 7:3. Using multivariable logistic regression analysis, two nomogram models, including a basic model and an extended model, were built. The discrimination, calibration, and clinical validity were used to evaluate the models in the internal validation cohort.

Results

The area under the receiver operating characteristic curve of the basic and the extended model was 0.736 and 0.756 in the training cohort, and was 0.736 and 0.763 in the validation cohort, respectively. The calibration curve analysis showed that the predicted values of the two models were not significantly different from the actual observations (p = 0.289 and 0.636 in the training cohort, p = 0.684 and 0.635 in the internal validation cohort, respectively). The decision-curve analysis showed a good clinical application value of the models.

Conclusions

The present study built simple and effective models, indicating that routine clinical and laboratory parameters can be used to predict the risk of GDM in the early pregnancy, and providing a novel reference for studying the prediction of GDM.
Cerclage performance analysis – a biomechanical comparison of different techniques and materials
Authors: Hägerich L. M. , Dyrna F. G. E. , Katthagen J. C. , Michel P. A. , Heilmann L. F. , Frank A. , Raschke M. J. , Schliemann B. , Riesenbeck O.
Published: December 2022

Background

Wire cerclages play a fundamental role in fracture fixation. With an increasing variety of designs being commercially available the question arises which cerclage should be used.

This study investigates the biomechanical properties of metallic and non-metallic cerclages and their different application-types. Furthermore, potential influence of muscular interposition between bone and cerclage constructs was tested.

Methods

Samples of the following four different cerclage types were tested on 3D printed models of human humeri as well as on human cadaveric humeri with and without muscular interposition:

Titanium Cable Cerclage (CC), Steel Wire Cerclage (SWC), Suture Tape (ST), Suture Tape Cerclage (STC) with both single- (sSTC) and double-loop application (dSTC). A preinstalled self-locking mechanism secured by the provided tensioner in the STCs being the main difference to the STs.

Cyclic loading was performed to 1 kN and then linearly to a maximum load of 3 kN.

Statistical analysis was performed using either one-way ANOVA and post-hoc Tukey or Kruskal–Wallis and post-hoc Dunn test depending on normalization of data (p < 0.05).

Results

Whilst all cerclage options could withstand high loads during failure testing,onlywithin the CC and dSTC group, all samples reached the maximal testing load of 3000 N without any failure. The SWC reached 2977.5 ± 63.6 N, the ST 1970.8 ± 145.9 N, and the sSTC 1617.0 ± 341.6 N on average.

Neither muscular interposition nor bone quality showed to have a negative influence on the biomechanical properties of the cerclage constructs, presenting no significant differences.

Conclusion

All tested cerclage constructs produce reliable stability but differ in their resulting compression forces, in a simplified fracture model. Therefore, non-metallic cerclage alternatives can provide similar stability with less compression and stiffness to metallic cable constructs, but they may offer several advantages and could possibly provide future benefits. Especially, by offering more elasticity without losing overall stability, may offer a biologic benefit. Installing any cerclage constructs should be performed carefully, especially if poor bone quality is present, as the tightening process leads to high forces on the construct.
Management of radicular cyst associated with primary teeth using decompression: a retrospective study
Authors: Pei Jun , Zhao Shimin , Chen Hui , Wang Jun
Published: December 2022

Background

Radicular cysts arising from primary teeth are rare. Enucleation and marsupialization or decompression are treatment approach to odontogenic cysts. Decompression known to achieve good results in various cysts is widely used in clinic. This study aims to evaluate the efficiency of decompression in reducing radicular cysts associated with primary teeth in children.

Methods

Cases of radicular cysts associated with primary teeth treated by decompression were reviewed in the present study. Clinical information and radiologic data of pre and post decompression were measured and analyzed.

Results

Twenty-three patients treated for 25 cysts were included. All lesions with mean initial area 3.66 ± 2.00 cm2 were reduced after decompression time ranging 2 to 10 months. Mean rate of reduction was 0.77 ± 0.44 cm2/mo and large lesions (> 3.5 cm2) had a significantly higher reduction rate compared to smaller ones (< 3.5 cm2) (P < 0.00). All effected succedaneous teeth erupted after treatment at follow-up while 12 (46%) of them had root development problems.

Conclusions

Decompression represents superiority as an effective and less invasive treatment in radicular cysts associated with primary teeth.

Trial registration: This study was retrospectively registered in the Ethics Committee of Ninth People’s Hospital Affiliated with Shanghai JiaoTong University School of Medicine (No.SH9H-2022-T158-1).
Structured implementation of the Supportive and Palliative Care Indicators Tool in general practice – A prospective interventional study with follow-up
Authors: Afshar Kambiz , van Baal Katharina , Wiese Birgitt , Schleef Tanja , Stiel Stephanie , Müller-Mundt Gabriele , Schneider Nils
Published: December 2022

Background

General practitioners (GPs) play a key role in the provision of primary palliative care (PC). The identification of patients who might benefit from PC and the timely initiation of patient-centred PC measures at the end of life are essential, yet challenging. Although different tools exist to support these key tasks, a structured approach is often missing.

Objective

The study aimed at implementing the German version of the Supportive and Palliative Care Indicators Tool (SPICT-DE™) in general practices, following a structured and regional approach, in order to evaluate the effects of this tool on the identification of patients with potential PC needs and the initiation of patient-centred PC measures.

Methods

The intervention of this mixed-methods study comprised a standardised training of 52 GPs from 34 general practices in two counties in Lower Saxony, Germany, on the use of the SPICT-DE™. The SPICT-DE™ is a clinical tool which supports the identification of patients with potential PC needs. Subsequently, over a period of 12 months, GPs applied the SPICT-DE™ in daily practice with adult patients with chronic, progressive diseases, and completed a follow-up survey 6 months after the initial patient assessment. The outcome parameters were alterations in the patient’s clinical situation, and the type and number of initiated patient-centred PC measures during the follow-up interval. Additionally, 12 months after the standardised training, GPs provided feedback on their application of the SPICT-DE™.

Results

A total of 43 GPs (n = 15 female, median age 53 years) out of an initial sample of 52 trained GPs assessed 580 patients (n = 345 female, median age 84 years) with mainly cardiovascular (47%) and cancer (33%) diseases. Follow-up of 412 patients revealed that 231 (56%) experienced at least one critical incident in their disease progression (e.g. acute crisis), 151 (37%) had at least one hospital admission, and 141 (34%) died. A review of current treatment/medication (76%) and a clarification of treatment goals (53%) were the most frequently initiated patient-centred PC measures. The majority of GPs deemed the SPICT-DE™ practical (85%) and stated an intention to continue applying the tool in daily practice (66%).

Conclusions

The SPICT-DE™ is a practical tool that supports the identification of patients at risk of deterioration or dying and promotes the initiation of patient-centred PC measures.

Trial registration

The study was registered in the German Clinical Trials Register (N° DRKS00015108; 22/01/2019).
Integrated clinical case discussions – a fully student-organized peer-teaching program on internal medicine
Authors: Reifenrath Johannes , Seiferth Nick , Wilhelm Theresa , Holzmann-Littig Christopher , Phillip Veit , Wijnen-Meijer Marjo
Published: December 2022

Background

In response to students´ poor ratings of emergency remote lectures in internal medicine, a team of undergraduate medical students initiated a series of voluntary peer-moderated clinical case discussions. This study aims to describe the student-led effort to develop peer-moderated clinical case discussions focused on training cognitive clinical skill for first and second-year clinical students.

Methods

Following the Kern Cycle a didactic concept is conceived by matching cognitive learning theory to the competence levels of the German Medical Training Framework. A 50-item survey is developed based on previous evaluation tools and administered after each tutorial. Educational environment, cognitive congruence, and learning outcomes are assessed using pre-post-self-reports in a single-institution study.

Results

Over the course of two semesters 19 tutors conducted 48 tutorials. There were 794 attendances in total (273 in the first semester and 521 in the second). The response rate was 32%. The didactic concept proved successful in attaining all learning objectives. Students rated the educational environment, cognitive congruence, and tutorials overall as “very good” and significantly better than the corresponding lecture. Students reported a 70%-increase in positive feelings about being tutored by peers after the session.

Conclusion

Peer-assisted learning can improve students´ subjective satisfaction levels and successfully foster clinical reasoning skills. This highlights successful student contributions to the development of curricula.
Analysis of the effect of an artificial intelligence chatbot educational program on non-face-to-face classes: a quasi-experimental study
Authors: Han Jeong-Won , Park Junhee , Lee Hanna
Published: December 2022

Background

Education and training are needed for nursing students using artificial intelligence-based educational programs. However, few studies have assessed the effect of using chatbots in nursing education.

Objectives

This study aimed to develop and examine the effect of an artificial intelligence chatbot educational program for promoting nursing skills related to electronic fetal monitoring in nursing college students during non-face-to-face classes during the COVID-19 pandemic.

Design

This quasi-experimental study used a nonequivalent control group non-synchronized pretest–posttest design.

Methods

The participants were 61 junior students from a nursing college located in G province of South Korea. Data were collected between November 3 and 16, 2021, and analyzed using independent t-tests.

Results

The experimental group—in which the artificial intelligence chatbot program was applied—did not show statistically significant differences in knowledge (t = -0.58, p = .567), clinical reasoning competency (t = 0.75, p = .455), confidence (t = 1.13, p = .264), and feedback satisfaction (t = 1.72, p = .090), compared with the control group; however, its participants’ interest in education (t = 2.38, p = .020) and self-directed learning (t = 2.72, p = .006) were significantly higher than those in the control group.

Conclusion

The findings of our study highlighted the potential of artificial intelligence chatbot programs as an educational assistance tool to promote nursing college students’ interest in education and self-directed learning. Moreover, such programs can be effective in enhancing nursing students’ skills in non-face-to face-situations caused by the ongoing COVID-19 pandemic.
Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker
Authors: Winkler Tilo , Kohli Puja , Kelly Vanessa J. , Kehl Ekaterina G. , Witkin Alison S. , Rodriguez-Lopez Josanna M. , Hibbert Kathryn A. , Kone Mamary T. , Systrom David M. , Waxman Aaron B. , Venegas Jose G. , Channick Richard N. , Harris R. Scott
Published: December 2022

Background

Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient’s response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects.

Methods

We studied 5 controls and 4 subjects with PAH using HRCT and 13NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV2Qtotal) and its components in the vertical (CV2Qvgrad) and cranio-caudal (CV2Qzgrad) directions, and the residual heterogeneity (CV2Qr), were assessed at baseline and while breathing oxygen and nitric oxide (O2 + iNO). The length scale spectrum of CV2Qr was determined from 10 to 110 mm, and the response of regional perfusion to O2 + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Qvgrad) were derived from perfusion images, and ventilation-perfusion distributions from images of 13NN washout kinetics.

Results

O2 + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O2 + iNO, CV2Qvgrad was significantly higher in controls than in PAH (0.08 (0.055–0.10) vs. 6.7 × 10–3 (2 × 10–4–0.02), p < 0.001) with a considerable gap between groups. Qvgrad and CV2Qtotal showed smaller differences: − 7.3 vs. − 2.5, p = 0.002, and 0.12 vs. 0.06, p = 0.01. CV2Qvgrad had the largest effect size among the primary parameters during O2 + iNO. CV2Qr, and its length scale spectrum were similar in PAH and controls. Ventilation-perfusion distributions showed a trend towards a difference between PAH and controls at baseline, but it was not statistically significant.

Conclusions

Perfusion imaging during O2 + iNO showed a significant difference in the heterogeneity associated with the vertical gradient in perfusion, distinguishing in this small cohort study PAH subjects from controls.
Transcription factor c-Rel regulated by E5 affects the whole process after HPV16 infection through miR-133a-modulated feedback loop aim at mir-379-369 cluster
Authors: Zhou Juan , Li Yongpeng , Xu Ke , Rong Yan , Huang Siting , Wu Hailun , Yi Xianlin , Liu Chanzhen
Published: December 2022

Background

During the development of cervical cancer, HPV infection causes a series of changes in transcription factors and microRNAs. But their relationships with pathogenic processes are not clear.

Methods

Base on previous study, to analyse the relationship among HPV16 infection and the related transcription factors, related miRNAs, so as to further understand the molecular mechanism of HPV16 infection to cervical cancer, around the HPV16 related miRNAs we have reported, the methods of bioinformatics prediction, histology, cell model in vitro and molecular interaction were used for prediction and validation respectively

Results

The results showed that NF-κB family members(c-Rel, p65 and p50) were identified as main HPV16rmiR-transcription factors. They have different expressive characteristics in cervical lesions and play tumorigenesis or progression roles in different periods of HPV16 infection. c-Rel, p65 and p50 act as mediators which link the HPV16 E5 and HPV16 related miRNAs. Among them, c-Rel affects the occurrence and progression of cervical cancer during whole HPV16 infection stage through miR133a-3p–modulated mir-379-369 cluster with a positive feedback way which targeted c-Rel itself and its positive regulator AKT3.

Conclusion

So in the course of HPV16 infection, the E5, c-Rel, and miR-133a-3p form a positive feedback system which aim at mir-379-369 cluster for the whole process from HPV16 infection to cervical cancer.
5-Methoxyflavone alleviates LPS-mediated lung injury by promoting Nrf2-mediated the suppression of NOX4/TLR4 axis in bronchial epithelial cells and M1 polarization in macrophages
Authors: Liang Panqiao , Wang Linxin , Yang Sushan , Pan Xiping , Li Jiashun , Zhang Yuehan , Liang Yueyun , Li Jing , Zhou Beixian
Published: December 2022

Background

Acute lung injury (ALI) arises from sepsis or bacterial infection, which are life-threatening respiratory disorders that cause the leading cause of death worldwide. 5-Methoxyflavone, a methylated flavonoid, is gaining increased attention for its various health benefits. In the current study, we investigated the potential effects of 5-methoxyflavone against LPS-mediated ALI and elucidated the corresponding possible mechanism.

Methods

A mouse model with ALI was established by intratracheal instillation of LPS, and lung pathological changes, signaling pathway related proteins and apoptosis in lung tissues were estimated by H&E staining, immunofluorescence and TUNEL assay, respectively. Cell viability was evaluated by MTT assay; protein levels of pro-inflammatory mediators were measured by ELISA assay; levels of ROS and M1 macrophage polarization were assayed by flow cytometry; the expression of Nrf2 signaling, NOX4/TLR4 axis and P-STAT1 were detected by western blotting.

Results

Our results showed that 5-methoxyflavone treatment inhibited LPS-induced expression of NOX4 and TLR4 as well as the activation of downstream signaling (NF-κB and P38 MAPK), which was accompanied by markedly decreased ROS levels and pro-inflammatory cytokines (IL-6, TNF-α, MCP-1, and IL-8) in BEAS-2B cells. Moreover, we revealed that these effects of 5-methoxyflavone were related to its Nrf2 activating property, and blockade of Nrf2 prevented its inhibitory effects on NOX4/TLR4/NF-κB/P38 MAPK signaling, thus abrogating the anti-inflammatory effects of 5-methoxyflavone. Besides, the Nrf2 activating property of 5-methoxyflavone in RAW264.7 cells led to inhibition of LPS/IFN-γ-mediated STAT1 signaling, resulting in suppression of LPS/IFN-γ-induced M1 macrophage polarization and the repolarization of M2 macrophages to M1. In a mouse model of LPS-induced ALI, 5-methoxyflavone administration ameliorated LPS-mediated lung pathological changes, the increased lung index (lung/body weight ratio), and epithelial cell apoptosis. Meanwhile, we found 5-methoxyflavone effectively suppressed the hyperactive signaling pathways and the production of excessive pro-inflammatory mediators. Moreover, 5-methoxyflavone reduced LPS-mediated M1 macrophage polarization associated with elevated P-STAT1 activation in the lung tissues. In addition, 5-methoxyflavone improved the survival of LPS-challenged mice.

Conclusion

These results indicated that 5-methoxyflavone might be suitable for the development of a novel drug for ALI therapeutic.
Localized DNA tetrahedrons assisted catalytic hairpin assembly for the rapid and sensitive profiling of small extracellular vesicle-associated microRNAs
Authors: Zhang Ye , Li Wenbin , Ji Tingting , Luo Shihua , Qiu Jiuxiang , Situ Bo , Li Bo , Zhang Xiaohe , Zhang Tiange , Wang Wen , Xiao Yunju , Zheng Lei , Yan Xiaohui
Published: December 2022

The profiling of small extracellular vesicle-associated microRNAs (sEV-miRNAs) plays a vital role in cancer diagnosis and monitoring. However, detecting sEV-miRNAs with low expression in clinical samples remains challenging. Herein, we propose a novel electrochemical biosensor using localized DNA tetrahedron-assisted catalytic hairpin assembly (LDT-CHA) for sEV-miRNA determination. The LDT-CHA contained localized DNA tetrahedrons with CHA substrates, leveraging an efficient localized reaction to enable sensitive and rapid sEV-miRNA measurement. Based on the LDT-CHA, the proposed platform can quantitatively detect sEV-miRNA down to 25 aM in 30 min with outstanding specificity. For accurate diagnosis of gastric cancer patients, a combination of LDT-CHA and a panel of four sEV-miRNAs (sEV-miR-1246, sEV-miR-21, sEV-miR-183-5P, and sEV-miR-142-5P) was employed in a gastric cancer cohort. Compared with diagnosis with single sEV-miRNA, the proposed platform demonstrated a higher accuracy of 88.3% for early gastric tumor diagnoses with higher efficiency (AUC: 0.883) and great potential for treatment monitoring. Thus, this study provides a promising method for the bioanalysis and determination of the clinical applications of LDT-CHA.

Graphical Abstract
L-arginine-containing mesoporous silica nanoparticles embedded in dental adhesive (Arg@MSN@DAdh) for targeting cariogenic bacteria
Authors: López-Ruiz Marta , Navas Francisco , Fernández-García Paloma , Martínez-Erro Samuel , Fuentes Mª Victoria , Giráldez Isabel , Ceballos Laura , Ferrer-Luque Carmen Mª , Ruiz-Linares Matilde , Morales Victoria , Sanz Raúl , García-Muñoz Rafael A.
Published: December 2022

Dental caries is the major biofilm-mediated oral disease in the world. The main treatment to restore caries lesions consists of the use of adhesive resin composites due to their good properties. However, the progressive degradation of the adhesive in the medium term makes possible the proliferation of cariogenic bacteria allowing secondary caries to emerge. In this study, a dental adhesive incorporating a drug delivery system based on L-arginine-containing mesoporous silica nanoparticles (MSNs) was used to release this essential amino acid as a source of basicity to neutralize the harmful acidic conditions that mediate the development of dental secondary caries. The in vitro and bacterial culture experiments proved that L-arginine was released in a sustained way from MSNs and diffused out from the dental adhesive, effectively contributing to the reduction of the bacterial strains Streptococcus mutans and Lactobacillus casei. Furthermore, the mechanical and bonding properties of the dental adhesive did not change significantly after the incorporation of L-arginine-containing MSNs. These results are yielding glimmers of promise for the cost-effective prevention of secondary caries.

Graphical Abstract
Sedentary patterns and cardiometabolic risk factors in Mexican children and adolescents: analysis of longitudinal data
Authors: Aljahdali Abeer A. , Baylin Ana , Ruiz-Narvaez Edward A. , Kim Hyungjin Myra , Cantoral Alejandra , Tellez-Rojo Martha M. , Banker Margaret , Peterson Karen E.
Published: December 2022

Background

Sedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth’s highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data.

Methods

570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders.

Results

Each hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [β = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [β = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [β = − 1.35, 95% CI = − 1.91, − 0.79] and log serum triglycerides (mg/dL) [β = − 0.11, 95% CI = − 0.18, − 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (μIU/mL) [β = − 0.06, 95% CI = − 0.10, − 0.02].

Conclusions

Sedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers.
An AGS-associated mutation in ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the brain
Authors: Guo Xinfeng , Steinman Richard A. , Sheng Yi , Cao Guodong , Wiley Clayton A. , Wang Qingde
Published: December 2022

Background

Aicardi–Goutières syndrome (AGS) is a severe neurodegenerative disease with clinical features of early-onset encephalopathy and progressive loss of intellectual abilities and motor control. Gene mutations in seven protein-coding genes have been found to be associated with AGS. However, the causative role of these mutations in the early-onset neuropathogenesis has not been demonstrated in animal models, and the mechanism of neurodegeneration of AGS remains ambiguous.

Methods

Via CRISPR/Cas-9 technology, we established a mutant mouse model in which a genetic mutation found in AGS patients at the ADAR1 coding gene (Adar) loci was introduced into the mouse genome. A mouse model carrying double gene mutations encoding ADAR1 and MDA-5 was prepared using a breeding strategy. Phenotype, gene expression, RNA sequencing, innate immune pathway activation, and pathologic studies including RNA in situ hybridization (ISH) and immunohistochemistry were used for characterization of the mouse models to determine potential disease mechanisms.

Results

We established a mouse model bearing a mutation in the catalytic domain of ADAR1, the D1113H mutation found in AGS patients. With this mouse model, we demonstrated a causative role of this mutation for the early-onset brain injuries in AGS and determined the signaling pathway underlying the neuropathogenesis. First, this mutation altered the RNA editing profile in neural transcripts and led to robust IFN-stimulated gene (ISG) expression in the brain. By ISH, the brains of mutant mice showed an unusual, multifocal increased expression of ISGs that was cell-type dependent. Early-onset astrocytosis and microgliosis and later stage calcification in the deep white matter areas were observed in the mutant mice. Brain ISG activation and neuroglial reaction were completely prevented in the Adar D1113H mutant mice by blocking RNA sensing through deletion of the cytosolic RNA receptor MDA-5.

Conclusions

The Adar D1113H mutation in the ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the mouse brain.
APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice
Authors: Stephen T. L. , Breningstall B. , Suresh S. , McGill C. J. , Pike C. J.
Published: December 2022

The most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show astroglial interactions with amyloid plaques in the EFAD transgenic mouse model of AD. Using confocal microscopy, we observed significantly lower levels of astrocytic plaque coverage and plaque compaction (beneficial effects of glial barrier formation) with APOE4 genotype and female sex. Conversely, neurite damage and astrocyte activation in the plaque environment were significantly higher in APOE4 carriers and female mice. Astrocyte coverage of plaques was highest in APOE3 males and poorest in APOE4 females. Collectively, our findings provide new insights into the roles of astroglia and highlight the importance of addressing independent and interactive effects of APOE genotype and biological sex in understanding processes contributing to AD pathogenesis.
Automatic ML-based vestibular gait classification: examining the effects of IMU placement and gait task selection
Authors: Jabri Safa , Carender Wendy , Wiens Jenna , Sienko Kathleen H.
Published: December 2022

Background

Vestibular deficits can impair an individual’s ability to maintain postural and/or gaze stability. Characterizing gait abnormalities among individuals affected by vestibular deficits could help identify patients at high risk of falling and inform rehabilitation programs. Commonly used gait assessment tools rely on simple measures such as timing and visual observations of path deviations by clinicians. These simple measures may not capture subtle changes in gait kinematics. Therefore, we investigated the use of wearable inertial measurement units (IMUs) and machine learning (ML) approaches to automatically discriminate between gait patterns of individuals with vestibular deficits and age-matched controls. The goal of this study was to examine the effects of IMU placement and gait task selection on the performance of automatic vestibular gait classifiers.

Methods

Thirty study participants (15 with vestibular deficits and 15 age-matched controls) participated in a single-session gait study during which they performed seven gait tasks while donning a full-body set of IMUs. Classification performance was reported in terms of area under the receiver operating characteristic curve (AUROC) scores for Random Forest models trained on data from each IMU placement for each gait task.

Results

Several models were able to classify vestibular gait better than random (AUROC > 0.5), but their performance varied according to IMU placement and gait task selection. Results indicated that a single IMU placed on the left arm when walking with eyes closed resulted in the highest AUROC score for a single IMU (AUROC = 0.88 [0.84, 0.89]). Feature permutation results indicated that participants with vestibular deficits reduced their arm swing compared to age-matched controls while they walked with eyes closed.

Conclusions

These findings highlighted differences in upper extremity kinematics during walking with eyes closed that were characteristic of vestibular deficits and showed evidence of the discriminative ability of IMU-based automated screening for vestibular deficits. Further research should explore the mechanisms driving arm swing differences in the vestibular population.