bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Influenza Immunization on CYP3A4 Activity In Vivo
Authors: Hayney Mary S. , Muller Daniel
Published: November 2003

Many reports of interactions between drugs metabolized by CYP3A4 and influenza vaccine have been made. The authors hypothesized that changes in CYP3A4 activity following influenza immunization would correlate with cytokine production or age. Twenty‐four subjects had an erythromycin breath test (ERMBT) and blood draw for lymphocyte culture prior to and on day 7 following influenza immunization. Cytokine production by lymphocytes cultured with influenza antigen was measured by ELISA. Eight men and sixteen women ranging in age from 20 to 66 years (mean = 38.7 years; SE = 2.9) participated in the study. Interferon γ (IFNγ) production inversely correlated with change in ERMBT (correlation coefficient = −0.614; p < 0.02), although the overall change in ERMBT was not statistically significant (mean = −4%; p = 0.28). The IFNγ production correlates with change in ERMBT. This correlation supports in vitro findings of decreased CYP3A4 expression and activity with IFNγ exposure.
Design of a sliding mode controller with a nonlinear time-varying sliding surface
Authors: Eksin Ibrahim , Tokat Sezai , Güzelkaya Müjde , Söylemez M. Turan
Published: November 2003

In this study, a new sliding surface design approach for second-order systems is proposed that varies the sliding surface in a nonlinear and time-varying fashion. The control law is reformulated by using the new surface that is defined in the new co-ordinate axis. The nonlinear surface is then moved in a proper direction by using a time-varying function. Simulations are performed on a second-order nonlinear model of a two-link planar manipulator system. The results of the new design methodology are compared with a classical sliding mode controller and a sliding mode controller possessing a discretely moving sliding surface. It has been shown that the proposed method has improved the system performance in terms of a decrease in the reaching time, robustness to disturbances and smoother phase plane trajectory. The decrease obtained in the reaching time is quite valuable, as it improves the robustness of the controlled system to external disturbances and parameter variations.
Lack of evidence of foetal microchimerism in female Spanish patients with systemic sclerosis
Authors: Selva-O’Callaghan A , Mijares-Boeckh-Behrens T , Prades E Balada , Solans-Laqué R , Simeón-Aznar C P , Fonollosa-Pla V , Vilardell-Tarrés M
Published: November 2003

Our objective was to study the presence of microchimerism in a series of 47 female Spanish patients with scleroderma (SSc) and to compare with a control group. Polymerase chain reaction was used to identify Y-chromosome sequences in DNA extracted from peripheral blood cells.Y-chromosome sequences were found in DNA from peripheral blood cells in four out of 47 (8.5%) patients with scleroderma (two limited and two diffuse) and in two out of 40 (5%) healthy women (no statistical differenceswere found). When we compared SSc patients and healthy controls who had had at least one male child, four out of 29 (13.7%) and two out of 26 (7.6%) had microchimerism respectively (no statistically significant differences were found). Patients with both scleroderma and persistent microchimerism had had a male offspring. Foetal microchimerism does not seem to play a major role in most cases of female Spanish patients with SSc.
Ménière’s disease patient information and support: which website?
Authors: Sen P. , Papesch M.
Published: November 2003

Management of Ménière’s disease remains problematic. Many different therapies are available, with variable success. Ménière’s patients frequently research the Internet for information about the disease and to make contact with other patients. Internet websites providing this information have grown in number vastly in the past few years. This paper aims to identify the best websites available for Ménière’s patients. Using Internet search engines the top 50 websites were evaluated using a Website Global Scoring and Evaluation Proforma. From the above the top ranking 15 websites were identified.
Congenital internal auditory canal stenosis
Authors: Baek Seung Kuk , Chae Sung Won , Jung Hak Hyun
Published: November 2003

Congenital internal auditory canal stenosis is a rare cause of sensorineural hearing loss in children. A retrospective analysis including clinical manifestation and radiological findings was made for seven patients who were diagnosed with congenital internal auditory canal stenosis from 1996 to 2002. Chief presenting symptoms were hearing loss, facial nerve palsy, dizziness, and tinnitus. Hearing loss including deafness was found in five cases, vestibular function loss in four cases, and profound functional loss of facial nerve in two cases. In all cases, the diameter of the internal auditory canal was less than 2 mm on high-resolution temporal bone computed tomography (CT) scan. Two cases revealed bilateral internal auditory canal stenosis, and others were unilaterally involved cases. Congenital internal auditory canal stenosis can be an important cause of sensorineural hearing loss, facial nerve palsy, and vestibular dysfunction. High resolution temporal bone CT scan and magnetic resonance (MR) imaging were important tools for diagnosis.
Role of endoscopic dacryocystorhinostomy in treating acquired lacrimal fistulae
Authors: Subbaiah Sanjay
Published: November 2003

Acquired lacrimal fistula occurs in an improperly and inadequately treated lacrimal sac abscess. This study was done to evaluate the success of endoscopic dacryocystorhinostomy (EDCR) in treating such lacrimal fistula. A retrospective analysis of nine cases of acquired lacrimal fistulae in seven patients, treated by EDCR without any external surgery was carried out. Cessation of epiphora and closure of fistula were considered, successful outcomes. All the nine fistulae closed, and all patients were relieved of their epiphora within two weeks of surgery. It can be concluded that EDCR is effective for treating an acquired lacrimal fistula.
What is the right size of the adenoid curette?
Authors: Shaalan Hisham F.
Published: November 2003

The use of an adenoid curette of appropriate size is recommended in operative textbooks for adequate adenoid removal and avoidance of potential injury to the eustachian tubes. The aim of this study is to calculate the right size of adenoid curettes to be used for children of different ages. The inter-tubal space (ITS) between the torus tubarius on both sides is the narrowest passage for adenoid curettage, and is identified in this study as the nasopharyngeal dimension to be considered in selecting the size of the adenoid curette. This prospective study is carried out on a series of 72 adenoidectomy cases aged from three to nine years at the Hearing and Speech Institute in Cairo, Egypt. The inter-tubal dimension (ITD) is measured for each child at the end of adenoidectomy and the results are recorded against the patient’s age. The ITD ranged from 17–21 mm in our series with no significant difference between males and females. There is an increase in ITD with age with a sharp increase at ages five and seven years. Accordingly, the patients are divided into three age groups and recommendations for appropriate adenoid curette sizes ranging from 18 to 21 mm are given for each group.
Celon® radiofrequency thermo-ablative palatoplasty for snoring - a pilot study
Authors: Tatla T. , Sandhu G. , Croft C. B. , Kotecha B.
Published: November 2003

A prospective non-randomized study was designed to investigate the effects of Celon® radio-frequency thermo-ablation (RFTA) of the soft palate in patients with snoring/mild obstructive sleep apnoea. Ten patients, fulfilling various inclusion/exclusion criteria, underwent single operator sub-mucosal RFTA palatoplasty as an office procedure. Two separate procedures six weeks apart involved each patient receiving six distinct sub-mucosal lesions on each visit. Questionnaires including visual analogue scales (VAS) were used to evaluate post-operative pain and subjective snoring (scored by patient/partner). Polysomnography (PSG) was performed pre-operation and three months following the second procedure. Using non-parametric statistical analysis, a significant reduction in VAS snoring was noted from initial levels to those scored at six and 16 weeks in nine of 10 patients (p = 0.013 and p = 0.007 respectively). (Five of these nine showed a greater than 50 per cent reduction in score). Objectively, six of 10 patients had a reduction in the apnoea-hypopnea Index between the two PSGs, (four of these six showed a greater than 50 per cent reduction) however, this was not statistically significant. Subjective assessment of the PSG snoring signal by the senior author showed eight of 10 patients had either a reduced or much reduced signal at four months. VAS pain confirmed both procedures are well tolerated with minimal analgesia requirements. Minor complaints of transient mild palatal swelling, dry throat, catarrh and referred otalgia were noted and one patient developed mucosal ulceration following both procedures that healed within three weeks. Swallowing and speech were unaffected. These results confirm similar findings using the Somnus® Unit, although the Celon® device provides additional advantages ncluding inherent safety in a bipolar electrode tip, auto-stop energy application and reduced procedure time.
Diphtheria: the patch remains
Authors: Nandi Raj , De Mriganka , Browning Simon , Purkayastha Prabhati , Bhattacharjee A. K.
Published: November 2003

This study analysed the number of patients admitted with diphtheria to a teaching hospital in the state of Assam in India over a period of five years and compared the disease characteristics and management with outcomes and incidences of diphtheria reported in the literature. It was a retrospective analysis of data elicited from clinical records of patients admitted to hospital.

A total of 101 admissions were recorded during a five-year period between March 1997 to March 2002, mostly with pharyngeal diphtheria (90 per cent). The majority of patients had no history of immunization (70 per cent). Significant presenting features were a tonsillar patch, sore throat, respiratory distress and fever. All patients were treated with anti-diphtheritic serum and intravenous antibiotics. Steroids were given to 81 per cent of patients and tracheostomy was carried out in 10 per cent of cases. The mortality was 16 per cent.

Diphtheria of the respiratory tract remains a potentially fatal disease commonly presenting with membranous pharyngitis. Early diagnosis and treatment with anti-diphtheritic serum and antibiotics remain the cornerstone of treatment. Inadequate immunization cover is deemed responsible for the continued menace of diphtheria.
Intermittent self-nasal packing for intractable epistaxis in a patient with Ehlers-Danlos syndrome
Authors: Goodyear P. W. A. , Strachan D. R. , Firth A. L.
Published: November 2003

Intractable epistaxis is a difficult problem to manage, particularly in a case complicated by Ehlers-Danlos syndrome. This is the first report describing intermittent self-packing of the nasal cavities at home to reduce hospital admissions and control symptoms. Some of the potential problems and complications are highlighted.
Which Ad Works, When, Where, and how Often? Modeling the Effects of Direct Television Advertising
Authors: Tellis Gerard J. , Chandy Rajesh K. , Thaivanich Pattana
Published: November 2003

The authors develop a model to decompose the effects of television advertising for a toll-free referral service, at the hourly level. The model estimates which ad works, when, in which station, and for how long. Results of the analysis show that ads do stimulate direct response, but their effects dissipate very rapidly. Effectiveness and profitability vary substantially by creative, television station, and station x time of the day. The results underscore the need for managers to undertake such analyses and for researchers to use such a disaggregate approach.
A New Dimension Reduction Approach for Data-Rich Marketing Environments: Sliced Inverse Regression
Authors: Naik Prasad A. , Hagerty Michael R. , Tsai Chih-Ling
Published: November 2003

In data-rich marketing environments (e.g., direct marketing or new product design), managers face an ever-growing need to reduce the number of variables effectively. To accomplish this goal, the authors introduce a new method called sliced inverse regression (SIR), which finds factors by taking into account the information contained in both the dependent and independent variables. Sliced inverse regression objectively identifies appropriate factors through simple statistical tests for determining the number of factors to retain and for assessing the significance of factor-loading coefficients. The authors make conceptual connections between SIR and several existing approaches, including principal components regression (PCR) and partial least squares regression (PLSR). Using Monte Carlo experiments, the authors demonstrate that SIR performs better than these approaches. Two empirical examples—designing a new executive business program and direct marketing by a catalog company—are presented to illustrate the application of SIR and to show that it outperforms both PLSR and PCR in these cases. In addition, the authors discuss how direct marketers can apply SIR to analyze large databases and to thus target customers effectively. In conclusion, SIR is a promising methodology in data-intensive marketing environments.
Cast Demographics, Unobserved Segments, and Heterogeneous Switching Costs in a Television Viewing Choice Model
Authors: Shachar Ron , Emerson John W.
Published: November 2003

An accurate television viewing choice model is an important tool for television executives and advertisers. The authors present a new viewing choice model, which differs from the traditional Rust-Alpert model in three ways: (1) It introduces a new show characteristic—the demographic characteristics of a show's cast; (2) it allows the preferences over the traditional show categories to be a function of both observable and unobservable individual characteristics; and (3) it allows the cost of switching among the viewing alternatives to vary across show types and individual characteristics. Cross-validated predictive testing shows that this model fits the data better than the Rust–Alpert model does. Furthermore, the authors demonstrate that network executives can improve ratings by using this model. The authors predict that by following their scheduling strategies (in particular, by broadcasting comedies after 10:00 P.M.), ABC, CBS, and NBC could have increased their average ratings by 12.9%, 7.5%, and 6.7%, respectively, on selected evenings.
Impact of Product-Harm Crises on Brand Equity: The Moderating Role of Consumer Expectations
Authors: Dawar Niraj , Pillutla Madan M.
Published: November 2003

Brand equity is a valuable yet fragile asset. The mounting frequency of product-harm crises and ill-prepared corporate responses to such crises can have profound consequences for brand equity. Yet there is little research on the marketing impact of crises. The authors employ the expectations–evidence framework to understand the impact of firms' responses to crises on customer-based brand equity. The results of a field survey and two laboratory experiments indicate that consumers interpret firm response on the basis of their prior expectations about the firm. The interaction of expectations and firm response is shown to affect postcrisis brand equity. The authors draw implications for the expectations–evidence framework and for the outcomes of different types of firm response (i.e., unambiguous support, ambiguous response, and unambiguous stonewalling) on brand equity.
An Experimental and Theoretical Analysis of Price-Matching Refund Policies
Authors: Jain Sanjay , Srivastava Joydeep
Published: November 2003

Price-matching refund policies, or offers by firms to match competitor's prices, are common in both consumer and industrial marketing. Much of the previous theoretical work in economics suggests that price-matching refunds are associated with higher prices. In contrast, the trade press postulates that price-matching policies are associated with lower prices. Given these inconsistent views regarding price-matching policies, the authors experimentally examine how consumers view and interpret such policies and then develop a model that incorporates these consumer interpretations as well as asymmetries across stores. In the model, the asymmetry across stores is the key to deriving the conditions under which a signaling equilibrium exists in the presence of price-matching policies. The critical point is that the competition-reducing and price discrimination effects, which seem to form the basis of most of the previous theoretical literature, can be counteracted by the presence of differentiated firms and uninformed consumers. The model suggests that under some conditions, price-matching policies can lead to more intense price competition. Furthermore, all firms will not find it profitable to offer refunds, and consistent with consumer expectations, the firms with lower prices will offer refunds.
Internet Recommendation Systems
Authors: Ansari Asim , Essegaier Skander , Kohli Rajeev
Published: November 2003

Several online firms, including Yahoo!, Amazon.com , and Movie Critic, recommend documents and products to consumers. Typically, the recommendations are based on content and/or collaborative filtering methods. The authors examine the merits of these methods, suggest that preference models used in marketing offer good alternatives, and describe a Bayesian preference model that allows statistical integration of five types of information useful for making recommendations: a person's expressed preferences, preferences of other consumers, expert evaluations, item characteristics, and individual characteristics. The proposed method accounts for not only preference heterogeneity across users but also unobserved product heterogeneity by introducing the interaction of unobserved product attributes with customer characteristics. The authors describe estimation by means of Markov chain Monte Carlo methods and use the model with a large data set to recommend movies either when collaborative filtering methods are viable alternatives or when no recommendations can be made by these methods.
Testing the Reliability of Weight Elicitation Methods: Direct Rating versus Point Allocation
Authors: Bottomley Paul A. , Doyle John R. , Green Rodney H.
Published: November 2003

Two commonly used methods of assigning numerical judgments (i.e., importance weights) to attributes in order to signify their relative importance are point allocation (PA) and direct rating (DR). These methods may seem to be minor variants of each other, yet they produce very different profiles of attribute weights when rank ordered from most to least important. The weights elicited by DR were more reliable than those elicited by PA in a test–retest situation. An important practical implication of this is for multicriteria decision making. Using people's test–retest data as attribute weights on simulated alternative values revealed that the same alternative would be chosen on 88% of occasions with DR, but only 74% of occasions with PA. Moreover, subjects reacted more favorably to DR than to PA.
Okay to Treat
Authors: Ferri Grace M.
Published: January 2024

In this narrative medicine essay, an internal medicince resident grapples with the question of “How much is enough?” when treating someone with terminal cancer.
Setup margins based on the inter‐ and intrafractional setup error of left‐sided breast cancer radiotherapy using deep inspiration breath‐hold technique (DIBH) and surface guided radiotherapy (SGRT)
Authors: Rudat Volker , Shi Yanyan , Zhao Ruping , Yu Wei
Published: January 2024

Purpose

The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left‐sided breast cancer radiotherapy using deep inspiration breath‐hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins.

Methods

The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV‐CBCT. Three hundred and three radiotherapy fractions of 23 left‐sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre‐treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula.

Results

The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter‐ and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins.

Conclusion

With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left‐sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV‐CBCTs, thereby saving treatment time and radiation exposure.
Are Outcomes From an Exercise Therapy and Patient Education Program for Osteoarthritis Associated With Hip and Knee Replacement Within Two Years? A Register‐Based Study of 9,339 Patients With Osteoarthritis
Authors: Ackerman Ilana N. , Johansson Melker S. , Grønne Dorte T. , Clausen Stine , Ernst Martin Thomsen , Overgaard Søren , Odgaard Anders , Roos Ewa M. , Skou Søren T.
Published: January 2024

Objective

The objective of this study was to determine whether short‐term outcomes from exercise therapy and patient education for osteoarthritis (OA) are associated with hip or knee replacement within two years.

Methods

Individual‐level data from the Good Life with osteoArthritis in Denmark (GLA:D) Registry were linked to the Danish National Patient Registry and other national registries. Cox proportional hazards models were used to investigate associations between program outcomes (baseline to three‐month changes) and time to primary hip or knee replacement. Patients who did not receive joint replacement were censored at two years, time of death, or emigration.

Results

A total of 2,304 and 7,035 patients with clinically diagnosed hip and knee OA, respectively, were included. Of these, 30% with hip OA and 10% with knee OA had joint replacement within two years. Postprogram improvements in hip‐related quality of life and arthritis self‐efficacy (pain subscale) were associated with a reduced hazard of hip replacement (adjusted hazard ratios [HRs] for a 10‐unit improvement: 0.74 [95% confidence interval (CI) 0.69–0.80] and 0.90 [95% CI 0.85–0.96], respectively). Improvements in knee pain, knee‐related quality of life, and arthritis self‐efficacy (pain subscale) were associated with a lower hazard of knee replacement (adjusted HRs for 10‐unit improvement: 0.81 [95% CI 0.76–0.86] to 0.90 [95% CI 0.86–0.95], 0.70 [95% CI 0.63–0.78] to 0.79 [95% CI 0.72–0.86], and 0.89 [95% CI 0.83–0.94], respectively).

Conclusion

The magnitude of improvement in key measures after exercise therapy and education was significantly associated with the likelihood of surgery. Progression to hip replacement was three times higher than progression to knee replacement. This information can guide patient–clinician conversations around anticipated program outcomes.
Photo‐induced Oriented Crystallization of Intracellular Nanocrystals Based on Phase Separation for Diagnostic Bioimaging and Analysis
Authors: Liu Hao , Liu Zhiming , Xiao Jiang , Liu Xiaohui , Jiang Hui , Wang Xuemei
Published: January 2024

Biomineral crystals form complex nonequilibrium structures based on the multistep nucleation theory, via transient amorphous precursors. However, the intricate nature of the biological system results in the inconsistent frequency of nucleation and crystallization, which making it problematic to obtain homogeneous nanocrystals, limits their application in biomedicine. Here, it is reported that homogeneous nanocrystals of photoinduced oriented crystallization with protein coronas are based on intracellular liquid–liquid phase separation for in situ analysis and mapping of surface‐enhanced Raman spectroscopy (SERS). Near‐infrared light promotes the formation of intracellular dense phases, accelerates the nucleation of gold atoms at secondary structure sites of proteins, and promotes the growth of crystals. Homogeneous gold nanocrystals with stable SERS signals can be used to analysis different cell cycles and acquire in situ molecular information of metastatic tumor cells. Of note are tag molecule is embedded in protein coronas of gold nanocrystals to enable the mapping of patient tumor tissue samples and the portable recognition of tumor cells. Thus, this study proposes a new strategy for biomineralization of intracellular homogeneous gold nanocrystals and its potential application.
Self‐Supplied Reactive Oxygen Species‐Responsive Mitoxantrone Polyprodrug for Chemosensitization‐Enhanced Chemotherapy under Moderate Hyperthermia
Authors: Zhang Hongjie , Wang Jing , Wu Ruiying , Zheng Benyan , Sang Yanxiang , Wang Bibo , Song Lei , Hu Yuan , Ma Xiaopeng
Published: January 2024

Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME‐responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self‐supply ROS‐responsive cascade polyprodrug (PMTO) is designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO is degraded by endogenous ROS of the TME, another part of the polyprodrug backbone becomes cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy is further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrates remarkable antitumor efficacy, effectively addressing the limitations associated with MTO.
Salmon trade duration: The application of firm‐level trade transaction data from the Norwegian salmon industry
Authors: Jaghdani Tinoush Jamali , Johansen Ulf , Thakur Maitri , Glauben Thomas
Published: January 2024

Seafood products are mainly provided through trade to international markets and Norway is the major international player for the export of salmon products. It is argued that fresh or chilled salmon, which are perishable products and Norway's main seafood export, need stable trade partners to safely and properly reach consumption markets. In this study, the firm‐to‐firm level trade transactional data for both exporters and importers for the 2005–2018 period was utilized for a trade duration analysis. The Kaplan–Meier survival estimators, Cox proportional hazard model, and frailty model were used to study the stability of trade relations between the partners through survival and hazard models. The study considers the heterogeneous firm trade model along with a theoretical framework. The results show that, on average, the trade duration for the salmon trade between firms is 2.39 years, which is relatively low for a perishable product such as salmon. It shows that the market entry and exit is relatively fast, and that the survival rate between the EU as a major demand market and non‐EU countries is not very different. However, core and periphery markets can be defined by considering the survival rate, as major processing hubs in the EU, such as Poland and France as core markets, have higher survival rates compared with other countries that can be considered peripheries. Both extensive and intensive margins were found to reduce the hazard ratio. Different hazard ratios were also found between different types of exporter or ones utilizing different means of transport. We conclude that the trade duration between the partners can be increased if the competition in the market increases, which is probably possible in markets like the United States where other exporters such as Chile are available.
Harmonizing florbetapir and PiB PET measurements of cortical Aβ plaque burden using multiple regions‐of‐interest and machine learning techniques: An alternative to the Centiloid approach
Authors: Chen Kewei , Ghisays Valentina , Luo Ji , Chen Yinghua , Lee Wendy , Wu Teresa , Reiman Eric M. , Su Yi
Published: January 2024

INTRODUCTION

Machine learning (ML) can optimize amyloid (Aβ) comparability among positron emission tomography (PET) radiotracers. Using multi‐regional florbetapir (FBP) measures and ML, we report better Pittsburgh compound‐B (PiB)/FBP harmonization of mean‐cortical Aβ (mcAβ) than Centiloid.

METHODS

PiB‐FBP pairs from 92 subjects in www.oasis‐brains.org and 46 in www.gaain.org/centiloid‐project were used as the training/testing sets. FreeSurfer‐extracted FBP multi‐regional Aβ and actual PiB mcAβ in the training set were used to train ML models generating synthetic PiB mcAβ. The correlation coefficient (R) between the synthetic/actual PiB mcAβ in the testing set was assessed.

RESULTS

In the testing set, the synthetic/actual PiB mcAβ correlation R = 0.985 (R2 = 0.970) using artificial neural network was significantly higher (p ≤ 6.6e‐4) than the FBP/PiB correlation R = 0.927 (R2 = 0.860), improving total variance percentage (R2) from 86% to 97%. Other ML models such as partial least square, ensemble, and relevance vector regressions also improved R (p = 9.677e−05/0.045/0.0017).

DISCUSSION

ML improved mcAβ comparability. Additional studies are needed for the generalizability to other amyloid tracers, and to tau PET.

Highlights

Centiloid is a calibration of the amyloid scale, not harmonization.

Centiloid unifies the amyloid scale without improving inter‐tracer association (R2).

Machine learning (ML) can harmonize the amyloid scale by improving R2.

ML harmonization maps multi‐regional florbetapir SUVRs to PiB mean‐cortical SUVR.

Artificial neural network ML increases Centiloid R2 from 86% to 97%.
Amino‐λ3‐iodane‐Enabled Electrophilic Amination of Arylboronic Acid Derivatives
Authors: Kiyokawa Kensuke , Kawanaka Kazuki , Minakata Satoshi
Published: January 2024

In this report, we describe the use of amino‐λ3‐iodanes in the electrophilic amination of arylboronic acids and boronates. Iodine(III) reagents with transferable amino groups, including one with an NH2 group, were synthesized and used in the amination, allowing the synthesis of a wide range of primary and secondary (hetero)arylamines. Mechanistic studies by DFT calculations indicate that the reaction proceeds through an electrophilic amination process from a tetravalent borate complex with a B−N dative bond.
Vitamin D and Marine n‐3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double‐Blind, Placebo‐Controlled Trial
Authors: Costenbader Karen H. , Cook Nancy R. , Lee I‐Min , Hahn Jill , Walter Joseph , Bubes Vadim , Kotler Gregory , Yang Nicole , Friedman Sonia , Alexander Erik K. , Manson JoAnn E.
Published: January 2024

Objective

In the 5.3‐year randomized, 2 × 2 factorial, double‐blind, placebo‐controlled Vitamin D and Omega‐3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.61–0.99). Omega‐3 (n‐3) fatty acid supplementation showed a statistically nonsignificant reduction (HR 0.85, 95% CI 0.67–1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with two years of postintervention observation.

Methods

Of the 12,786 men aged ≥50 and 13,085 women aged ≥55 initially randomized, we observed surviving and willing participants for two more years. We continued to confirm annual participant‐reported new AD by medical record review. Cox models calculated HRs for all confirmed incident AD, (and secondary endpoints, including probable cases, and individual ADs), during the observational and randomized periods.

Results

A total of 21,592 participants (83.5%) were observed for two more years; 514 participants developed incident confirmed AD (236 since prior report), of whom 255 had been randomized to vitamin D versus 259 to vitamin D placebo (HR 0.98 [95% CI 0.83–1.17] at 7 years). AD was confirmed in 234 participants initially randomized to n‐3 fatty acids versus 280 randomized to its placebo (HR 0.83 [95% CI 0.70–0.99] at 7 years). Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results as follows: HR 0.85 (95% CI 0.70–1.04) for vitamin D and HR 0.87 (95% CI 0.71–1.06) for n‐3 fatty acids.

Conclusion

Two years after trial termination, the protective effects of 2000 IU/day of vitamin D dissipated, but 1,000 mg/day of n‐3 fatty acids had a sustained effect in reducing AD incidence.
Myositis‐Associated Autoantibodies in Patients With Juvenile Myositis Are Associated With Refractory Disease and Mortality
Authors: Sherman Matthew A. , Noroozi Farhadi Payam , Pak Katherine , Trieu Edward P. , Sarkar Kakali , Targoff Ira N. , Neely Megan L. , Mammen Andrew L. , Rider Lisa G. ,   for the Childhood Myositis Heterogeneity Collaborative Study Group
Published: January 2024

Objective

Myositis‐associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile‐onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity.

Methods

Patients with juvenile myositis in cross‐sectional natural history studies who underwent testing for myositis autoantibodies were included. Demographics, myositis autoantibodies, clinical characteristics, medications received, and outcomes of those with and without MAAs were compared. Multivariable logistic regression was performed to determine whether the number of MAAs detected was associated with severe disease features.

Results

Among 551 patients, 36% had an MAA and 13% had more than one MAA. Among those who were MAA positive, there was a higher frequency of overlap myositis (18% vs 5.9%, P < 0.001). MAA positivity was associated with certain clinical features, including Raynaud phenomenon (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.41–4.28) and ILD (OR 3.43, 95% CI 1.75–6.96), as well as a chronic disease course (OR 1.72, 95% CI 1.10–2.72) and mortality (OR 3.76, 95% CI 1.72–8.43). The number of MAAs was also associated with mortality (OR 1.83, 95% CI 1.16–2.86).

Conclusion

MAAs were prevalent in a large cohort of patients with juvenile myositis. ILD, refractory disease, and mortality were associated with MAA positivity. Prospective studies are needed to determine whether early detection of MAAs may lead to improved outcomes for patients with juvenile myositis.
Flatness‐based sliding mode control for stabilizing a spherical pendulum on a quadrotor
Authors: Martinez‐Vasquez Adrian Humberto , Castro‐Linares Rafael
Published: January 2024

This paper presents the problem of transporting a suspended load by a quadrotor. A full model considering the quadrotor and the dynamics of the suspended load, in a three‐dimensional space, is proposed considering as control inputs the torques and the thrust force due to the motors. The solution proposed consists of simple control strategies based on the tangent linearization of the model, which is controllable and therefore flat. A sliding mode control technique is developed for the thrust force and torques associated with the Euler angles in order to track a desired trajectory of the vehicle in a three‐dimensional space with minimum oscillation of the suspended load. The control strategy results to be relatively simple to implement and achieves local stability of the tracking errors, as well as robustness to internal nonlinearities, which are neglected in the linearization process and other external disturbances. The attractiveness of the sliding surfaces and the stability of the tracking errors are formally studied using Lyapunov stability theory. Simulation results are given to show the performance of the proposed control strategy.
Adaptive robust control of nonaffine nonlinear systems via an improved event‐triggered mechanism
Authors: Wan Quan , Pan Yingnan , Lu Qing , Jing Yanhui
Published: January 2024

This paper aims to address the problem of event‐based adaptive robust control for a class of nonaffine nonlinear systems against actuator faults and unknown deception attacks. Firstly, different from the widely used relative threshold triggering mechanism, an improved event‐triggered mechanism with the time‐varying function threshold is devised for effectively saving more communication costs between controller and actuator. Then, based on a class of modified filter‐based coordinate transformations and the improved event‐triggered mechanism, the intermediate virtual control laws are devised to construct actual controllers, which not only guarantees robust stabilization of the system but also relaxes the universal assumptions on control coefficients and attack weights. Besides, the design challenges resulting from the presence of coupling terms in the nonaffine nonlinear system are successfully overcome by virtue of mean value theorem and the property of fuzzy basis function. Theoretical analysis proves that all signals of the closed‐loop system are semiglobally uniformly ultimately bounded (SUUB) and the Zeno behavior can be averted. Finally, the effectiveness of the proposed strategy is verified via comprehensive simulation results.
Multivariate simulation‐based forecasting for intraday power markets: Modeling cross‐product price effects
Authors: Hirsch Simon , Ziel Florian
Published: January 2024

Intraday electricity markets play an increasingly important role in balancing the intermittent generation of renewable energy resources, which creates a need for accurate probabilistic price forecasts. However, research to date has focused on univariate approaches, while in many European intraday electricity markets all delivery periods are traded in parallel. Thus, the dependency structure between different traded products and the corresponding cross‐product effects cannot be ignored. We aim to fill this gap in the literature by using copulas to model the high‐dimensional intraday price return vector. We model the marginal distribution as a zero‐inflated Johnson's distribution with location, scale, and shape parameters that depend on market and fundamental data. The dependence structure is modeled using copulas, accounting for the particular market structure of the intraday electricity market, such as overlapping but independent trading sessions for different delivery days and allowing the dependence parameter to be time‐varying. We validate our approach in a simulation study for the German intraday electricity market and find that modeling the dependence structure improves the forecasting performance. Additionally, we shed light on the impact of the single intraday coupling on the trading activity and price distribution and interpret our results in light of the market efficiency hypothesis. The approach is directly applicable to other European electricity markets.
Mapping active civic learning in primary schools across England—A call to action
Authors: Body Alison , Lau Emily , Cunliffe Jack , Cameron Lindsey
Published: January 2024

Encouraging children to become ‘good citizens’ who positively contribute towards society through charitable and philanthropic action as part of their civic participation has become a core focus of policy and practice. Yet the opportunities afforded to children for active civic learning within primary education remain under‐researched. This article presents findings from a multi‐survey study that seeks to unpick ‘what’ and ‘how’ active civic learning is happening in primary schools across England. By mapping active civic learning across the country, we find that these opportunities are unequally dispersed. Specifically, from an early age, children from more affluent backgrounds are more likely to be prepared for active civic engagement, orientated around ideas of social justice, than those from disadvantaged backgrounds. This raises significant challenges for education policy and practice and calls for greater attention to be paid to civic learning for all children in early and middle childhood.
Synthesis, thermoluminescence characterizations, and photon attenuation parameters of MgAl2O4 structure doped with different ions
Authors: Qaid Saif M. H. , Asemi Nassar N. , Ahmed Abdullah , Alkadi Muath , Alawsh Sufyan
Published: January 2024

In this work, different ion co‐doped Mg1‐xAl2O4 nanophosphors, coded as M5Cr‐5LaA, M5Cr‐5CuA, M0.07Si‐0.03CeA, and M0.05Ti‐0.05LaA, where 5Cr‐5La, 5Cr‐5Cu, 0.07Si‐0.03Ce, and 0.05Ti‐0.05La representing the added ions (mol%), were prepared using the sol–gel method. Phase structure, transmission electron microscope (TEM) images, and element feasibility were checked using X‐ray diffraction, TEM analysis, and energy dispersive X‐ray (EDX) spectroscopy. Their thermoluminescence (TL) response was checked using a 5 Gy γ‐test dose. The M0.05Ti‐0.05LaA sample was found to be best for the TL response with an ~1.1 times response compared with that of the MTS‐700 commercial detector. A wide range of dose–responses for the M0.05Ti‐0.05LaA sample was found up to a 20 Gy γ‐dose with the lowest detectable dose of ⁓23 μGy. Photon attenuation parameter results were Zeff ⁓10, which mean that the M0.05Ti‐0.05LaA sample could be considered as a near tissue equivalent material. Due to this study, the M0.05Ti‐0.05LaA sample can be considered as a promising detector for application in personal and medical dosimetric monitoring.
Caffeic acid phenethyl ester mediates apoptosis in serum‐starved HT29 colon cancer cells through modulation of heat shock proteins and MAPK pathways
Authors: Yahya Showket , Sulaiman Mahaboob Khan , Sudhandiran Ganapasam
Published: January 2024

Colorectal cancer (CRC) is among the most prevalent gastrointestinal cancers of epithelial origin worldwide, with over 2 million cases detected every year. Emerging evidence suggests a significant increase in the levels of inflammatory and stress‐related markers in patients with CRC, indicating that oxidative stress and lipid peroxidation may influence signalling cascades involved in the progression of the disease. However, the precise molecular and cellular basis underlying CRC and their modulations during bioactive compound exposure have not yet been deciphered. This study examines the effect of caffeic acid phenethyl ester (CAPE), a natural bioactive compound, in HT29 CRC cells grown under serum‐supplemented and serum‐deprived conditions. We found that CAPE inhibited cell cycle progression in the G2/M phase and induced apoptosis. Migration assay confirmed that CAPE repressed cancer invasiveness. Protein localisation by immunofluorescence microscopy and protein expression by western blot analysis reveal increased expressions of key inflammatory signalling mediators such as p38α, Jun N‐terminal kinase and extracellular signal‐regulated kinase (ERK) proteins. Molecular docking data demonstrates that CAPE shows a higher docking score of −5.35 versus −4.59 to known p38 inhibitor SB203580 as well as a docking score of −4.17 versus −3.86 to known ERK1/2 inhibitor AZD0364. Co‐immunoprecipitation data reveals that CAPE treatment effectively downregulates heat shock protein (HSP) expression in both sera‐supplemented and limited conditions through its interaction with mitogen‐activated protein kinase 14 (MAPK14). These results suggest that stress induction via serum starvation in HT29 CRC cells leads to the induction of apoptosis and co‐ordinated activation of MAPK‐HSP pathways. Molecular docking studies support that CAPE could serve as an effective inhibitor to target p38 and MAPK compared to their currently known inhibitors.
Design, Synthesis, and Evaluation of An Anti‐trypanosomal [1,2,4]Triazolo[1,5‐a]pyrimidine Probe for Photoaffinity Labeling Studies
Authors: Lucero Bobby , Francisco Karol R. , Varricchio Carmine , Liu Lawrence J. , Yao Yuemang , Brancale Andrea , Brunden Kurt R. , Caffrey Conor R. , Ballatore Carlo
Published: January 2024

Studies have shown that depending on the substitution pattern, microtubule (MT)‐targeting 1,2,4‐triazolo[1,5‐a]pyrimidines (TPDs) can produce different cellular responses in mammalian cells that may be due to these compounds interacting with distinct binding sites within the MT structure. Selected TPDs are also potently bioactive against the causative agent of human African trypanosomiasis, Trypanosoma brucei, both in vitro and in vivo. So far, however, there has been no direct evidence of tubulin engagement by these TPDs in T. brucei. Therefore, to enable further investigation of anti‐trypanosomal TPDs, a TPD derivative amenable to photoaffinity labeling (PAL) was designed, synthesized, and evaluated in PAL experiments using HEK293 cells and T. brucei. The data arising confirmed specific labeling of T. brucei tubulin. In addition, proteomic data revealed differences in the labeling profiles of tubulin between HEK293 and T. brucei, suggesting structural differences between the TPD binding site(s) in mammalian and trypanosomal tubulin.
Towards 2D Borane Chemistry in Hexagonal Cyclic Compounds
Authors: López‐Sánchez Rubén , Ferrer Maxime , Oliva‐Enrich Josep M. , Alkorta Ibon , Elguero José
Published: January 2024

A comprehensive comparison between known benzene mono‐substituted compounds R−Ph and the corresponding isoelectronic unknown R‐cyclohexaborane(12) molecules is carried out from a geometric and electronic structure point of view, with R={H, BH2, CH3, NH2, OH, F ; AlH2, SiH3, PH2, SH, Cl ; NO2, OCH3}. We suggest new chemical names for the 2D borane compounds and analyze the geometric and electronic structure carbon vs. boron comparatives by means of HOMO‐LUMO gaps, bonding schemes, electron density topological properties and predicted NMR chemical shifts. The predictions on the properties in planar hexagonal cyclic boranes may help in the design of synthesis procedures for these yet‐unkown compounds.