bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambra1 modulates the tumor immune microenvironment and response to PD-1 blockade in melanoma
Authors: Frias Alex , Di Leo Luca , Antoranz Asier , Nazerai Loulieta , Carretta Marco , Bodemeyer Valérie , Pagliuca Chiara , Dahl Christina , Claps Giuseppina , Mandelli Giulio Eugenio , Andhari Madhavi Dipak , Pacheco Maria Pires , Sauter Thomas , Robert Caroline , Guldberg Per , Madsen Daniel Hargbøl , Cecconi Francesco , Bosisio Francesca Maria , De Zio Daniela
Published: March 2023

Background

Loss of Ambra1 (autophagy and beclin 1 regulator 1), a multifunctional scaffold protein, promotes the formation of nevi and contributes to several phases of melanoma development. The suppressive functions of Ambra1 in melanoma are mediated by negative regulation of cell proliferation and invasion; however, evidence suggests that loss of Ambra1 may also affect the melanoma microenvironment. Here, we investigate the possible impact of Ambra1 on antitumor immunity and response to immunotherapy.

Methods

This study was performed using an Ambra1-depletedBrafV600E/Pten−/−genetically engineered mouse (GEM) model of melanoma, as well as GEM-derived allografts ofBrafV600E/Pten−/−andBrafV600E/Pten−/−/Cdkn2a−/−tumors with Ambra1 knockdown. The effects of Ambra1 loss on the tumor immune microenvironment (TIME) were analyzed using NanoString technology, multiplex immunohistochemistry, and flow cytometry. Transcriptome and CIBERSORT digital cytometry analyses of murine melanoma samples and human melanoma patients (The Cancer Genome Atlas) were applied to determine the immune cell populations in null or low-expressing AMBRA1 melanoma. The contribution of Ambra1 on T-cell migration was evaluated using a cytokine array and flow cytometry. Tumor growth kinetics and overall survival analysis inBrafV600E/Pten−/−/Cdkn2a−/−mice with Ambra1 knockdown were evaluated prior to and after administration of a programmed cell death protein-1 (PD-1) inhibitor.

Results

Loss of Ambra1 was associated with altered expression of a wide range of cytokines and chemokines as well as decreased infiltration of tumors by regulatory T cells, a subpopulation of T cells with potent immune-suppressive properties. These changes in TIME composition were associated with the autophagic function of Ambra1. In theBrafV600E/Pten−/−/Cdkn2a−/−model inherently resistant to immune checkpoint blockade, knockdown of Ambra1 led to accelerated tumor growth and reduced overall survival, but at the same time conferred sensitivity to anti-PD-1 treatment.

Conclusions

This study shows that loss of Ambra1 affects the TIME and the antitumor immune response in melanoma, highlighting new functions of Ambra1 in the regulation of melanoma biology.
CT-guided percutaneous cyanoacrylate injection targeting the spinal cerebrospinal fluid leak: a potential therapeutic option for spontaneous intracranial hypotension
Authors: Liao Liang , Tonnelet Romain , Schmitt Emmanuelle , Planel Sophie , Zhu François , Muszynski Patricio , Harsan Oana , Anxionnat René , Bracard Serge , Braun Marc
Published: March 2023

Background

We report the first case series of spontaneous intracranial hypotension (SIH) patients who underwent CT-guided percutaneous cyanoacrylate injection targeting the cerebrospinal fluid (CSF) leak.

Methods

A retrospective analysis was performed for all consecutive cases of SIH patients with CSF leak confirmed on CT myelography, treated by CT-guided percutaneous cyanoacrylate injection at our institution from 2016 to 2022. On pretreatment brain and spine MRIs, we analyzed signs of SIH according to the Bern score, and dichotomized cases into positive/negative for spinal longitudinal extradural CSF collection (SLEC-P or SLEC-N). The leaks detected on CT myelography were classified into three types according to Schievink
et al
. We collected the Headache Impact Test 6 (HIT-6) scores throughout a 6-month follow-up, with a brain CT scan at each visit.

Results

11 patients were included (mean age 48.4 years, six men). Five SLEC-P type 1, three SLEC-P type 2, and three SLEC-N type 3 leaks were identified. All patients had significant signs of SIH on pretreatment brain MRI (mean Bern score 7.8±1.1). Six patients underwent a foraminal puncture, and five patients had a cervical epidural approach. Two patients experienced mild and transient locoregional pain after cervical epidural injection. Mean HIT-6 score at baseline was 66.8±3.2 and at the 6-month follow-up was 38±3.6 (P<0.001). All patients achieved improvement in their symptoms, with 82% of them (9/11) having complete resolution of headaches and SIH findings on CT scans at 6 months. No clinical worsening or recurrence was observed.

Conclusions

CT-guided percutaneous cyanoacrylate injection may be a potential therapeutic option for the different types of CSF leak causing SIH.
Generic and disease-adapted cardiovascular risk scores as predictors of atherosclerosis progression in SLE
Authors: Panopoulos Stylianos , Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G
Published: March 2023

Objective

Studies show that generic cardiovascular risk (CVR) prediction tools may underestimate CVR in SLE. We examined, for the first time to our knowledge, whether generic and disease-adapted CVR scores may predict subclinical atherosclerosis progression in SLE.

Methods

We included all eligible patients with SLE without a history of cardiovascular events or diabetes mellitus, who had a 3-year carotid and femoral ultrasound follow-up examination. Five generic (Systematic Coronary Risk Evaluation (SCORE), Framingham Risk Score (FRS), Pooled Cohort Risk Equation, Globorisk, Prospective Cardiovascular Münster) and three ‘SLE-adapted’ CVR scores (modified Systematic Coronary Risk Evaluation (mSCORE), modified Framingham Risk Score (mFRS), QRESEARCH Risk Estimator V.3 (QRISK3)) were calculated at baseline. The performance of CVR scores to predict atherosclerosis progression (defined as new atherosclerotic plaque development) was tested with Brier Score (BS), area under the receiver operating characteristic curve (AUROC) and Matthews correlation coefficient (MCC), while rank correlation was tested with Harrell’sc-index. Binary logistic regression was also applied to examine determinants of subclinical atherosclerosis progression.

Results

Twenty-six (21%) of 124 included patients (90% female, mean age 44.4±11.7 years) developed new atherosclerotic plaques after a mean of 39.7±3.8 months’ follow-up period. Performance analysis showed that plaque progression was better predicted by the mFRS (BS 0.14, AUROC 0.80, MCC 0.22) and QRISK3 (BS 0.16, AUROC 0.75, MCC 0.25).c-Index showed no superiority for discrimination between mFRS and QRISK3. In the multivariate analysis, QRISK3 (OR 4.24, 95% CI 1.30 to 13.78, p=0.016) among the CVR prediction scores and age (OR 1.13, 95% CI 1.06 to 1.21, p<0.001), cumulative glucocorticoid dose (OR 1.04, 95% CI 1.01 to 1.07, p=0.010) and antiphospholipid antibodies (OR 3.66, 95% CI 1.24 to 10.80, p=0.019) among disease-related CVR factors were independently associated with plaque progression.

Conclusions

Application of SLE-adapted CVR scores such as QRISK3 or mFRS, as well as monitoring for glucocorticoid exposure and the presence of antiphospholipid antibodies, can help to improve CVR assessment and management in SLE.
Diagnostic performance of a device for acoustic heart sound analysis in patients with suspected myocardial infarction
Authors: Lehmacher Jonas , Neumann Johannes T , Sörensen Nils Arne , Goßling Alina , Schmidt Samuel Emil , Zeller Tanja , Blankenberg Stefan , Westermann Dirk , Clemmensen Peter M
Published: March 2023

Background

As only a small proportion of patients with chest pain suffers from myocardial infarction (MI), safe rule-out of MI is of immense importance. Recently an ultrasensitive microphone performing diastolic heart sound analysis (CADScorSystem) for rule-out of coronary artery disease (CAD) has emerged. In this explorational study, we aimed to evaluate the feasibility of the CADScorSystem for diagnosis of MI in the setting of a large emergency department.

Methods

Patients presenting to the emergency department with suspected MI were included. Acoustic heart sound analysis was performed in all patients and automated CAD-score values were calculated via a device-embedded algorithm, which also requires inclusion of three clinical variables: age, sex and presence of hypertension. Patients additionally received serial high-sensitive troponin T measurement measurements to assess the final diagnosis according to third Universal Definition of Myocardial Infarction applying the European Society of Cardiology 0 hour/3 hours algorithm. Diagnostic parameters for MI, considering different CAD-score cut-offs, were computed.

Results

Of 167 patients, CAD-scores were available in 61.1%. A total of eight patients were diagnosed with MI. At a cut-off value of <20, CAD-score had a negative predictive value (NPV) of 90.7 (78.4–96.3). The corresponding positive predictive value (PPV) was 6.8 (2.7–16.2). For the adjusted CAD-score (age, sex, hypertension), at a cut-off value of <20, NPV was 90.0 (59.6–99.5) with a PPV of 10.8 (5.3–20.6).

Conclusion

In this explorative analysis, a transcutaneous ultrasensitive microphone for heart sound analysis resulted in a high NPV analogous to the findings in rule-out of stable CAD in elective patients yet inferior to serial high-sensitivity cardiac troponin measurements and does not seem feasible for application in an emergency setting for rule-out of MI.

Trial registration number

NCT02355457.
Harnessing digital health to optimise the delivery of guideline-based cardiac rehabilitation during COVID-19: an observational study
Authors: Gibson Irene , McCrudden Zoe , Dunne Denise , Harris Aisling , Hynes Lisa , Murphy Ella , Murphy Andrew William , Byrne Molly , McEvoy John William
Published: March 2023

Background

The COVID-19 pandemic accelerated the uptake of digital health interventions for the delivery of cardiac rehabilitation (CR). However, there is a need to evaluate these interventions.

Methods

We examined the impact of an evidence-based, digital CR programme on medical, lifestyle and psychosocial outcomes. Delivered by an interdisciplinary team of healthcare professionals, the core components of this 12-week programme included lifestyle modification, medical risk factor management, psychosocial and behavioural change support. To support self-management, patients were provided with a Fitbit, a home blood pressure (BP) monitor and an interactive workbook. Patients received access to a bespoke web-based platform and were invited to attend weekly, online group-based supervised exercise sessions and educational workshops. Outcomes were assessed at baseline, end of programme and at 6-month follow-up.

Results

Over a 3-month period, 105 patients (88% with coronary heart disease) were referred with 74% (n=77) attending initial assessment. Of these, 97% (n=75) enrolled in the programme, with 85% (n=64) completing the programme, 86% (n=55) of completers attended 6-month follow-up. Comparing baseline to end of programme, we observed significant improvements in the proportion of patients meeting guideline-recommended targets for physical activity (+68%, p<0.001), BP (+44%, p<0.001) and low-density lipoprotein cholesterol (+27%, p<0.001). There were significant reductions in mean weight (−2.6 kg, p<0.001). Adherence to the Mediterranean diet score improved from 5.2 to 7.3 (p<0.001). Anxiety and depression levels (Hospital Anxiety and Depression score) both reduced by more than 50% (p<0.001). The majority of these improvements were sustained at 6-month follow-up.

Conclusion

Outcomes from this study suggest that interdisciplinary digital CR programmes can be successfully implemented and help patients achieve guideline recommended lifestyle, medical and therapeutic targets.
Posterior spinal artery infarct
Authors: Panesar Harrypal , Conry Aoife , Finocchi Vanina , Desai Chaitya , Bracewell Robert Martyn
Published: March 2023

Posterior spinal artery syndrome has a variable presentation and often poses a clinical challenge. We describe an acute posterior spinal artery syndrome in a man in his 60s with vascular risk factors, who presented with altered sensation in the left arm and left side of his torso but with normal tone, strength and deep tendon reflexes. MR imaging showed a left paracentral T2 hyperintense area affecting the posterior spinal cord at the level of C1. Diffusion-weighted MRI (DWI) showed high signal intensity in the same location. He was medically managed as having ischaemic stroke and made a good recovery. Three-month MRI follow-up showed a persisting T2 lesion but the DWI changes had resolved, consistent with the time course for infarction. Posterior spinal artery stroke has a variable presentation and is probably under-recognised clinically, requiring careful attention to MR imaging for its diagnosis.
Caesarean section in women with axial spondyloarthritis and psoriatic arthritis: a population-based study
Authors: Götestam Skorpen Carina , Lydersen Stian , Salvesen Kjell Åsmund , Koksvik Hege Suorza Svean , Jakobsen Bente , Wallenius Marianne
Published: March 2023

Background

There is sparse documentation on pregnancy outcomes in women with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Data on disease activity are often lacking, preventing the direct investigation of the effect of inflammation on pregnancy outcomes. A caesarean section (CS) implies a higher risk for complications than vaginal delivery. It delays mobilisation after birth necessary to counteract inflammatory pain and stiffness.

Objective

To explore a possible association of inflammatory active disease and CS rates in women with axSpA and PsA.

Methods

Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a Norwegian nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with axSpA (n=312) and PsA (n=121) included in RevNatus 2010–2019 were cases. Singleton births, excluding mothers with rheumatic inflammatory diseases, registered in MBRN during the same period time (n=575 798) served as population controls.

Results

CS occurred more frequently in both axSpA (22.4%) and PsA (30.6%) groups compared with population controls (15.6%), with even higher frequencies in inflammatory active axSpA (23.7%) and PsA (33.3%) groups. Compared with population controls, women with axSpA had higher risk for elective CS (risk difference 4.4%, 95% CI 1.5% to 8.2%) but not emergency CS. Women with PsA had higher risk for emergency CS (risk difference 10.6%, 95% CI 4.4% to 18.7%) but not elective CS.

Conclusion

Women with axSpA had higher risk for elective and women with PsA for emergency CS. Active disease amplified this risk.
Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease: an extension study (RESCUE 2)
Authors: Tran Ai Phuong , Tassone D.F , Ding N S , Nossent Johannes
Published: March 2023

The persistence of immunogenicity in patients with immune-mediated inflammatory diseases (IMID) on disease-modifying antirheumatic therapy (DMARD) has been less well studied. This extension study evaluates the SARS-CoV2 antibody decay kinetics 6 months following two doses of ChAdO1nCov-19 (AZ) and BNT162b (Pfizer) and subsequent response following an mRNA booster.

Results

175 participants were included. Six months after initial AZ vaccination, 87.5%, 85.4% and 79.2% (p=0.756) in the withhold, continue and control groups remained seropositive compared with 91.4%, 100% and 100% (p=0.226), respectively, in the Pfizer group. Both vaccine groups developed robust humoral immune responses following a booster with seroconversion rates being 100% for all three intervention categories. The mean SARS-CoV-2 antibody levels were significantly lower in the targeted synthetic DMARD (tsDMARD) group that continued therapy compared with the control (2.2 vs 4.8 U/mL, p=0.010). The mean time interval until loss of protective antibodies in the IMID group was 61 days for the AZ and 137.5 days for the Pfizer vaccine. Within each DMARD class the interval until loss of protective antibody titres in the csDMARD, bDMARD and tsDMARD groups were 68.3, 71.8 and 64.0 days in the AZ group and 185.5, 137.5 and 116.0 days in the Pfizer group, respectively.

Conclusion

Antibody persistence was longer in the Pfizer group due to a higher peak antibody level following second vaccination with levels of protection in IMID on DMARD therapy similar to controls except in those on tsDMARDs where it was lower. A third mRNA vaccine booster can restore immunity in all groups.
Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases: results from an umbrella review and international Delphi study
Authors: van der Togt Céleste J T , Van den Bemt Bart , Aletaha Daniel , Alten Rieke , Chatzidionysiou Katerina , Galloway James , Isaac John , Mulleman Denis , Verschueren P , Vulto Arnold G , Welsing Paco M J , Verhoef Lise , den Broeder Alfons A
Published: March 2023

Objectives

To develop evidence-based points to consider for cost-effective use of biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the treatment of inflammatory rheumatic diseases, specifically rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis.

Methods

Following EULAR procedures, an international task force was formed, consisting of 13 experts in rheumatology, epidemiology and pharmacology from seven European countries. Twelve strategies for cost-effective use of b/tsDMARDs were identified through individual and group discussion. For each strategy, PubMed and Embase were systematically searched for relevant English-language systematic reviews and, for six strategies, additionally for randomised controlled trials (RCTs). Thirty systematic reviews and 21 RCTs were included. Based on the evidence, a set of overarching principles and points to consider was formulated by the task force using a Delphi procedure. Level of evidence (1a–5) and grade (A–D) were determined for each point to consider. Individual voting on the level of agreement (LoA; between 0 (completely disagree) and 10 (completely agree)) was performed anonymously.

Results

The task force agreed on five overarching principles. For 10 of 12 strategies, the evidence was sufficient to formulate one or more points to consider, leading to 20 in total, regarding response prediction, drug formulary use, biosimilars, loading doses, low-dose initial therapy, concomitant conventional synthetic DMARD use, route of administration, medication adherence, disease activity–guided dose optimisation and non-medical drug switching. Ten points to consider (50%) were supported by level 1 or 2 evidence. The mean LoA (SD) varied between 7.9 (1.2) and 9.8 (0.4).

Conclusion

These points to consider can be used in rheumatology practices and complement inflammatory rheumatic disease treatment guidelines to incorporate cost-effectiveness in b/tsDMARD treatment.
Dynamic assessment of the double contour sign by ultrasonography helps to distinguish between gout and calcium pyrophosphate deposition disease
Authors: Cipolletta Edoardo , Abhishek Abhishek , Di Matteo Andrea , Grassi Walter , Filippucci Emilio
Published: March 2023

Objective

To test whether the double contour (DC) sign has a different dynamic behaviour in gout and calcium pyrophosphate deposition (CPPD) and whether the dynamic assessment of the DC sign increases its accuracy in gout diagnosis.

Methods

This cross-sectional analysis included patients with gout meeting the 2015 ACR/EULAR classification criteria and patients with crystal-proven diagnosis of CPPD. Hyaline cartilages were explored by ultrasound (US) to detect the DC sign (ie, abnormal hyperechoic band over the superficial margin of hyaline cartilages) and its dynamic behaviour during joint movement was evaluated ((ie, movement of the DC sign together with subchondral bone (DC sign), or in the opposite direction (pseudo DC sign)).

Results

Eighty-one patients with gout and 84 patients with CPPD underwent US assessment. Among them, 47 patients with gout and 9 patients with CPPD had evidence of the DC sign. During dynamic assessment, in all 47/47 patients with gout there was a DC sign. Conversely, in 7/9 (77.8%) patients with CPPD, there was a pseudo DC sign (p<0.01).

The presence of DC sign during static assessment had a sensitivity, specificity and accuracy of 58.0% (95% CI 46.5% to 68.9%), 89.3% (95% CI 80.6% to 95.0%) and 73.9% (95% CI 66.5% to 80.5%) for gout, respectively. The dynamic evaluation improved the DC sign’s diagnostic performance (p=0.01) as the specificity (97.6% (95% CI 91.7% to 99.7%)) and the accuracy (78.2% (95% CI 71.1% to 84.2%)) increased without loss in sensitivity.

Conclusion

The dynamic US assessment of the DC sign may help to differentiate the DC sign due to MSU crystals from the pseudo DC sign seen in CPPD, as they move in opposite directions.
Loss of life expectancy due to stroke and its subtypes in urban and rural areas in China, 2005–2020
Authors: Wang Zixin , Liu Wei , Ren Yi , Zhang Chen , Yang Jia , Wang Lijun , Zhou Maigeng , Yin Peng , Hao Junwei , Ma Qingfeng
Published: March 2023

Stroke is characterised by high mortality and disability rate in China. This study aimed to explore the temporal trends in years of life lost (YLL) and loss of life expectancy due to stroke and its subtypes in urban and rural areas in China during 2005–2020. Data were obtained from China National Mortality Surveillance System. Abbreviated life and stroke-eliminated life tables were generated to calculate loss of life expectancy. The YLL and loss of life expectancy due to stroke in urban and rural areas at both national and provincial level during 2005–2020 were estimated. In China, the age-standardised YLL rate due to stroke and its subtypes were higher in rural areas than in urban areas. The YLL rate due to stroke showed a downward trend in both urban and rural residents from 2005 to 2020, decreased by 39.9% and 21.5%, respectively. Loss of life expectancy caused by stroke decreased from 1.75 years to 1.70 years from 2005 to 2020. During which, loss of life expectancy due to intracerebral haemorrhage (ICH) decreased from 0.94 years to 0.65 years, while that of ischaemic stroke (IS) increased from 0.62 years to 0.86 years. A slightly upward trend was observed in loss of life expectancy caused by subarachnoid haemorrhage (SAH), from 0.05 years to 0.06 years. Loss of life expectancy due to ICH and SAH was always higher in rural areas than in urban areas, whereas that of IS was higher in urban areas than in rural areas. Rural males suffered the greatest loss of life expectancy due to ICH and SAH, while the highest loss of life expectancy caused by IS was found in urban females. Furthermore, Heilongjiang (2.25 years), Tibet (2.17 years) and Jilin (2.16 years) were found to have the highest loss of life expectancy caused by stroke in 2020. Loss of life expectancy caused by ICH and SAH was higher in western China, while the disease burden of IS was heavier in northeast China. Stroke remains a major public health problem in China, although the age-standardised YLL rate and loss of life expectancy due to stroke decreased. Evidence-based strategies should be conducted to reduce the premature death burden caused by stroke and prolong life expectancy in Chinese population.
Beta blockers in traumatic brain injury: a systematic review and meta-analysis
Authors: Hart Shannon , Lannon Melissa , Chen Andrew , Martyniuk Amanda , Sharma Sunjay , Engels Paul T
Published: March 2023

Background

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Beta blockers have shown promise in improving mortality and functional outcomes after TBI. The aim of this article is to synthesize the available clinical data on the use of beta blockers in acute TBI.

Methods

A systematic search was conducted through MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for studies including one or more outcomes of interest associated with use of beta blockers in TBI. Independent reviewers evaluated the quality of the studies and extracted data on all patients receiving beta blockers during their hospital stay compared with placebo or non-intervention. Pooled estimates, CIs, and risk ratios (RRs) or ORs were calculated for all outcomes.

Results

13 244 patients from 17 studies were eligible for analysis. Pooled analysis demonstrated a significant mortality benefit of overall use of beta blocker (RR 0.8, 95% CI 0.68 to 0.94,I2=75%). Subgroup analysis of patients with no preinjury use of beta blocker compared with patients on preinjury beta blockers showed no mortality difference (RR 0.99, 95% CI 0.7 to 1.39,I2=84%). There was no difference in rate of good functional outcome at hospital discharge (OR 0.94, 95% CI 0.56 to 1.58,I2=65%); however, there was a functional benefit at longer-term follow-up (OR 1.75, 95% CI 1.09 to 2.8,I2=0%). Cardiopulmonary and infectious complications were more likely in patients who received beta blockers (RR 1.94, 95% CI 1.69 to 2.24,I2=0%; RR 2.36, 95% CI 1.42 to 3.91,I2=88%). Overall quality of the evidence was very low.

Conclusions

Use of beta blockers is associated with decreased mortality at acute care discharge as well as improved functional outcome at long-term follow-up. Lack of high-quality evidence limits definitive recommendations for use of beta blockers in TBI; therefore, high-quality randomized trials are needed to further elucidate the utility of beta blockers in TBI.

PROSPERO registration number

CRD42021279700.
The multiple exp-function method to obtain soliton solutions of the conformable Date–Jimbo–Kashiwara–Miwa equations
Authors: Eidinejad Zahra , Saadati Reza , Li Chenkuan , Inc Mustafa , Vahidi Javad
Published: March 2023

Considering the importance of using nonlinear evolution equations in the investigation of many natural phenomena, in this paper, we consider the [Formula: see text]-dimensional Date–Jimbo–Kashiwara–Miwa ([Formula: see text]-dimensional DJKM) equation, we will investigate the solutions for this equation. Using the multiple exp functions method, we obtain analytical solutions for this equation, which are one-soliton, two-soliton and three-soliton solutions and these solutions include three categories of soliton wave solutions, i.e., one-wave solutions, two-wave solutions and three wave solutions. We have performed all calculations with a computer algebra system such as Maple and have also provided a graphical representation of the obtained solutions.
CORRELATION MATRIX OF EQUI-CORRELATED NORMAL POPULATION: FLUCTUATION OF THE LARGEST EIGENVALUE, SCALING OF THE BULK EIGENVALUES, AND STOCK MARKET
Authors: AKAMA YOHJI
Published: March 2023

Given an N-dimensional sample of size [Formula: see text] form a sample correlation matrix [Formula: see text]. Suppose that N and T tend to infinity with [Formula: see text] converging to a fixed finite constant [Formula: see text]. If the population is a factor model, then the eigenvalue distribution of [Formula: see text] almost surely converges weakly to Marčenko–Pastur distribution such that the index is Q and the scale parameter is the limiting ratio of the specific variance to the ith variable [Formula: see text]. For an N-dimensional normal population with equi-correlation coefficient [Formula: see text], which is a one-factor model, for the largest eigenvalue [Formula: see text] of [Formula: see text], we prove that [Formula: see text] converges to the equi-correlation coefficient [Formula: see text] almost surely. These results suggest an important role of an equi-correlated normal population and a factor model in Laloux et al. [(2000) Random matrix theory and financial correlations, International Journal of Theoretical and Applied Finance3 (3), 391–397]: the histogram of the eigenvalue of sample correlation matrix of the returns of stock prices fits the density of Marčenko–Pastur distribution of index [Formula: see text] and scale parameter [Formula: see text]. Moreover, we provide the limiting distribution of the largest eigenvalue of a sample covariance matrix of an equi-correlated normal population. We discuss the phase transition as to the decay rate of the equi-correlation coefficient in N.
Enhanced CO2 Reduction to Ethylene with Hollow Cu2O Structure by Facet-Controlled Etching
Authors: Li Jing , Meng Chen , Wang Honglin , Lin Rui , Wang Min , Zhu Hongwei
Published: March 2023

Various catalysts have been used for achieving the CO2 reduction reaction (CO2RR), among which Cu2O has received widespread attention due to its high activity and selectivity. In this work, we focus on the morphology control of Cu2O nanoboxes (NBs) regulated by poly (vinyl pyrrolidone) and graphene oxide and report the synthesis of a hollow structure by facet-controlled etching. Cu2O NBs etched for 8 days exhibited enhanced CO2RR selectivity and activity, reaching a superior C2H4 Faraday efficiency of [Formula: see text]35.4% at −1.2 V (versus Ag/AgCl), which was much higher than that of unetched catalysts. The improved performance was attributed to the synergistic effect of various crystal facets exposed on the NB surface. The hollow NBs showed relatively high structural stability, demonstrating the potential for practical applications. This study introduces an efficient approach to boost the catalyst properties by specifically constructing the structure and controlling the morphology.
A Survey of Multi-Agent Systems on Distributed Formation Control
Authors: Liu Yefeng , Liu Jingjing , He Zengpeng , Li Zhenhong , Zhang Qichun , Ding Zhengtao
Published: March 2023

Multi-agent formation control is an important part of distributed perception and cooperation, which is convenient to complete various complex tasks and would be a key research direction in the future. This paper reviews the corresponding problems of formation control and the existing centralized and distributed formation control strategies. In particular, we discuss four types of distributed formation control methods based on position and displacement in the global coordinate system and distance and bearing in the nonglobal coordinate system, respectively. Moreover, this paper analyzes affine formation which does not require the global coordinate system. Combined with the current practical applications of multi-agent systems, the latest research for the formation control of the unmanned aerial vehicle (UAV), unmanned ground vehicle (UGV), unmanned surface vehicle (USV) and autonomous underwater vehicle (AUV) is given. Finally, the challenges and opportunities in this burgeoning field are discussed.
Network-Based Method to Investigate the Promoted Cell Apoptosis Mechanisms of Oridonin in OSCC through the RNA-Transcriptome
Authors: Wu Guohui , Guo Yusheng , Liu Yang , Cai Xiangsheng , Deng Tanggang , Pei Tianchu , Huang Long , Chen Kai , Pan Xuan
Published: March 2023

The morbidity of oral cancer is high in the world. Oridonin is a traditional Chinese medicine that can effectively inhibit oral squamous cell carcinoma (OSCC) growth, but its mechanism remains unclear. Our previous data showed that oridonin inhibited CAL-27 cell proliferation and promoted apoptosis. Herein, we explored the mechanism and target of oridonin in human OSCC through RNA sequencing and integration of multiple bioinformatics analysis strategies. Differences in gene expression can be analyzed with RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), gene set enrichment analysis (GSEA), Disease Ontology (DO), and other enrichment analyses were used to evaluate differentially expressed genes (DEGs). Protein–protein interaction (PPI) networks were built via the STRING database. It was found that tumor necrosis factor (TNF) signaling pathway, cytokine–cytokine receptor interaction, and nuclear factor-kappa B (NF-kappaB) signaling pathway were associated with the therapeutic effects of oridonin in OSCC. Three key genes (BIRC3, TNFSF10, and BCL6) were found to associate with cell apoptosis in OSCC cells treated with oridonin. Quantitative PCR assays verified the expression of apoptosis-related DEGs: TNFSF10, BIRC3, AIFM2, BCL6, BCL2L2, and Bax. Western blots were employed for verifying proteins expression associated with DEGs: cleaved caspase 3, Bax, Bcl-w, anti-cIAP2, and anti-TRAIL. In conclusion, our findings reveal the molecular pathways and targets by which oridonin can treat and induce cytotoxic effects in OSCC: by affecting the signaling including TNF, NF-κB, and cytokine-cytokine receptor interaction and by regulating the key gene BIRC3, TNFSF10, and BCL6. It should be noted that further clinical trial validation is very necessary. Combined with current research trends, our existing research may provide innovative research drugs for the treatment of OSCC.
Investigating Supercritical Bended Flow Using Physical Model and CFD
Authors: Souli Hamza , Ahattab Jihane , Agoumi Ali
Published: March 2023

The flow in the bend channel used as spillway chute is complex due to the turbulence, the presence of shock waves, and vibrations. These transverse waves can damage the hydraulic structure. Our aim in this paper is to investigate the distribution of water surface in five curved channels with five relative curvatures

ρ

, different bottom slopes (1%, 2%, 10%, and 18%) and three different cross-sections. The objective is to give a solution to reduce the height difference between the inner and the outer walls. To achieve this goal, we used physical models to investigate the flow patterns, explore critical zones, and test several solutions to have a better performance. The reliability and accuracy of the numerical results were validated using the physical modelling for each case tested. Moreover, a comparison between the measured data, theoretical calculations, and numerical outcomes was done, to find a fitting law between the maximum wave height and the bend number. Furthermore, an optimal position of the guide wall was identified in real project of a spillway. The results of the physical model and numerical simulation show a good agreement; thus, the numerical model can play a crucial role in order to study hydraulic parameters, pressure, and velocity field and find solutions for hydraulic problems that occur in these structures.
Fatigue and Its Contributing Factors in Chinese Patients with Primary Pituitary Adenomas
Authors: Zhang Xiaomei , Li Yanqing , Zhang Dandan , Zhong Yueping , Li Tian
Published: March 2023

Background. Pituitary adenomas (PAs) refers to a group of benign tumors that develop in the pituitary gland and are often characterized by fatigue. However, fatigue has not been documented in any Chinese research involving people with primary PA. The study sought to examine the prevalence, predictors, and correlation of fatigue with the quality of life (QoL) among PA patients in China. Methods. In total, 203 primary PA patients were included in this cross-sectional study. A series of questionnaires were administered, including the Multidimensional Fatigue Inventory (MFI), M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT), Short-Form 36 Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). Data analysis was accomplished by Pearson or Spearman correlations, linear regression, and simple path analysis. Results. Severe fatigue prior to the initial diagnosis and preparation for surgery affected 50% of PA patients. Depression, sleep disturbance, and MDASI-BT symptom total scores were independently able to predict patient fatigue. Sleep disturbance mediates the influence of depression on fatigue (IE sleep = 0.296, 95% CI: LB = 0.148 to UB = 0.471). Conclusions. Chinese patients with primary PA often report experiencing fatigue. Depression and poor sleep quality were shown to be significant contributors to PA patients’ fatigue. Depression affects PA patients’ fatigue directly or indirectly. Medical professionals should take a proactive approach to PA patients suffering from fatigue before initial diagnosis and preoperative preparation to determine necessary interventions early, thus reducing fatigue and ultimately enhancing their QoL.
Heartbeat-Evoked Potential in Major Depressive Disorder: A Biomarker for Differential Treatment Prediction between Venlafaxine and rTMS?
Authors: Zwienenberg Lauren , van Dijk Hanneke , Enriquez-Geppert Stefanie , van der Vinne Nikita , Gevirtz Richard , Gordon Evian , Sack Alexander T. , Arns Martijn
Published: March 2023

Introduction: Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment. Methods: Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz. Results: In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = −0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%). Conclusion: These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.
Acral Fibrochondromyxoid Tumor Presenting as Enlarging Nodule Involving the Distal Fingertip and Hyponychium: A Case Report
Authors: Miller Rhiannon C. , Magro Cynthia M. , Melnick Laura E , Lipner Shari R.
Published: March 2023

An acral fibrochondromyxoid tumor is a newly described type of benign soft tissue neoplasm that presents as a single nodular lesion on a finger or toe. There has only been one previous report on this tumor, a case series that described the initial pathologic and clinical findings; however, details on clinical history, physical examination, and outcome are unknown. In this report, we describe a case of a 39-year-old male who presented with a painful enlarging mass involving the distal right 3rd finger and hyponychium. Punch biopsy was performed and the lesion was identified as an acral fibrochondromyxoid tumor on microscopic examination. X-ray showed no bony involvement. The tumor was successfully excised with complete resolution of pain symptoms. We discuss the clinical features and immunohistochemistry findings of our case in the context of the current limited knowledge about this very rare tumor.
Outcomes of Elective Compared to Non-Elective Fetal Reduction by Radiofrequency Ablation in Monochorionic Multifetal Pregnancies
Authors: Meislin Rachel , Stone Joanne , Lookstein Robert , Stoffels Guillaume , Rebarber Andrei , Fox Nathan S. , Vieira Luciana
Published: March 2023

Introduction: Higher order fetal gestation is associated with adverse pregnancy outcomes, and monochorionic (MC) pregnancies have unique complications. Multifetal pregnancy reduction (MPR) by radiofrequency ablation (RFA) may be used to optimize the outcomes of a single fetus. The purpose of this study was to determine whether pregnancy outcomes differ for elective reduction compared to reduction for medically complicated MC multifetal pregnancies. Methods: This was a retrospective cohort of patients with MC twins and higher order multiples who underwent MPR via RFA at a single institution between 2008 and 2021. Patients undergoing elective reduction were compared to patients undergoing reduction due to a complication of MC pregnancy. Pregnancy outcomes were evaluated. Results: Forty-eight patients who underwent RFA reduction between 2008 and 2021 were included in the analysis. Sixteen patients (33.3%) underwent elective RFA for MPR, and 32 (66.7%) underwent an RFA procedure for a complicated pregnancy. All pregnancies with RFA performed for elective indication had a continuing pregnancy (live birth rate 100%). There were no reported pregnancy losses within 4 weeks of the procedure when performed for a solely elective indication (n = 0) compared to 6.3% of complicated multifetal pregnancy (n = 2; 6.3%) (p = 0.001). Conclusion: In this retrospective cohort study, elective reduction of MC twins using RFA was associated with no cases of fetal loss or PPROM within 4 weeks of the procedure and a 100% live birth rate.
Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia
Authors: Chevalier Philippe , Roy Pascal , Bessière Francis , Morel Elodie , Ankou Bénédicte , Morgan Gina , Halder Indrani , London Barry , Minobe Wayne A. , Slavov Dobromir , Delinière Antoine , Bochaton Thomas , Paganelli Franck , Lesavre Nathalie , Boiteux Clément , Mansourati Jacques , Maury Philippe , Clerici Gaël , Winum Pierre François , Huebler Sophia P. , Carroll Ian A. , Bristow Michael R.
Published: March 2023

Background

Cardiac adrenergic receptor gene polymorphisms have the potential to influence risk of developing ventricular fibrillation (VF) during ST‐segment‐elevation myocardial infarction, but no previous study has comprehensively investigated those most likely to alter norepinephrine release, signal transduction, or biased signaling.

Methods and Results

In a case–control study, we recruited 953 patients with ST‐segment‐elevation myocardial infarction without previous cardiac history, 477 with primary VF, and 476 controls without VF, and genotyped them for
ADRB1
Arg389Gly and Ser49Gly,
ADRB2
Gln27Glu and Gly16Arg, and
ADRA2C
Ins322‐325Del. Within each minor allele‐containing genotype, haplotype, or 2‐genotype combination, patients with incident VF were compared with non‐VF controls by odds ratios (OR) of variant frequencies referenced against major allele homozygotes. Of 156 investigated genetic constructs, 19 (12.2%) exhibited significantly (
P
<0.05) reduced association with incident VF, and none was associated with increased VF risk except for
ADRB1
Gly389 homozygotes in the subset of patients not receiving β‐blockers.
ADRB1
Gly49 carriers (prevalence 23.0%) had an OR (95% CI) of 0.70 (0.49–0.98), and the
ADRA2C
322–325 deletion (Del) carriers (prevalence 13.5%) had an OR of 0.61 (0.39–0.94). When present in genotype combinations (8 each), both
ADRB1
Gly49 carriers (OR, 0.67 [0.56–0.80]) and
ADRA2C
Del carriers (OR, 0.57 [0.45– 0.71]) were associated with reduced VF risk.

Conclusions

In ST‐segment‐elevation myocardial infarction, the adrenergic receptor minor alleles
ADRB1
Gly49, whose encoded receptor undergoes enhanced agonist‐mediated internalization and β‐arrestin interactions leading to cardioprotective biased signaling, and
ADRA2C
Del322‐325, whose receptor causes disinhibition of norepinephrine release, are associated with a lower incidence of VF.

Registration

URL:
https://clinicaltrials.gov
; Unique identifier: NCT00859300.
Group Hegemonic Leadership as an Analytical Framework for Understanding Regional Hegemony in Africa
Authors: Isike Christopher , Schoeman Maxi
Published: March 2023

This paper revisits the literature on regional power-hood and its application to Africa with a view to answering two key questions: one, whether we can talk of regional hegemons in the continent in real terms, and two, whether group hegemonic leadership better explains regional hegemonic behavior in Africa. It uses Sandra Destradi conceptual framework and Miriam Prys’ typology of regional power-hood to answer these questions, with South Africa and Nigeria as case studies. Using Prys’ typology which distinguishes between regional detached powers, regional hegemons and regional dominators as an analytical framework, the paper confirms what already exists in the literature, viz. that neither South Africa nor Nigeria neatly fit the conception of regional hegemons in Africa. However, it uses both countries as empirical cases to argue that they already act as hegemonic leaders and in cooperative ways that suggest group or shared leadership, using specific Common African Positions they have led in Africa. The analysis concludes by laying out the normative basis for a Group Hegemony composed of not only South Africa and Nigeria, but also other sub-regional leaders in the continent. This is based on the hard power shortfalls and internal weaknesses of both our case studies including their relative soft power resources which have utility in an increasingly intersocial international system.
Africa’s International Relations and the Legend of ‘Common Positions’
Authors: Ayodele Odilile
Published: March 2023

IR scholars and analysts often view the African Union’s apparent deference to common positions with a collectivist lens. However, in this article, I argue that the legend of common African positions (CAPs) has not yet been animated, as African leaders do not always work collectively for structural and political reasons. Two significant factors complicate analysing Africa’s IR in Africa: first, Africa is not a monolith. With fifty-five states and numerous linguistic, cultural, and historical paths, there is more that is different than is the same. Second, conventional IR theories are rooted in Global North worldviews and are, therefore, not the most appropriate tool to study African countries’ collective decision-making. I focus on the United Nations as the site where the Africa Group’s successes and failures are saliently illustrated, specifically the Ezulwini Consensus. The Africa Group’s contestation within the various UN bodies, particularly with the UN Peace and Security Council, where they have long lobbied for representation, underscores the strength and structural obstacles to Africa’s collective action. Taking an interpretative approach and analysing from an epistemological and normative level, I offer an alternative lens through which to view the CAPs. Leaning on the philosophies of Ubuntu and Ujamaa, I propose a framework to explore the African Union’s process of developing common positions.
Preliminary Results of Analysis of Osteological Material from the Polish-Ukrainian Excavations in Olbia (2016–2018)
Authors: Twardecki Alfred , Yanish Yevheniia
Published: March 2023

The authors present an analysis of the bone material obtained during the excavations of the Polish-Ukrainian archaeological mission in Olbia in 2016–2018. Particular attention is paid to the analysis of the chronologically homogeneous deposit of about 6,000 bones, which are mostly raw materials or semi-finished products and rarely the final products for a workshop producing bone tools. This analysis allows for the determination of the meat part of the diet of Olbia inhabitants at the turn of the 4th and 5th centuries, as well as assumptions related to the climate prevailing in Olbia at that time.