bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced cardiovascular risk score following bilateral cataract phacoemulsification surgery: A retrospective observational cohort study
Authors: Matias Maria João , Alves-Peixoto Pedro , Miranda Vítor , Aguiar Catarina Pestana , Ambrósio João , Rocha António , Chibante-Pedro João
Published: February 2023

Objective

To assess the cardiovascular risk (CV risk) change following bilateral phacoemulsification cataract surgery.

Methods

We performed a retrospective observation cohort study on 112 selected patients who underwent uncomplicated bilateral cataract surgery at Centro Hospitalar de Entre o Douro e Vouga (CHEDV) between 2018 and 2019. This patient cohort was further subdivided in 2 different groups: Good VA – no to mild visual impairment, ≤0.48 LogMAR; Bad VA – moderate to severe visual impairment, >0.48 LogMAR. We compared the changes in the CV risk score components in our patient cohort and between subgroups Good VA and Bad VA, before and after surgery, using paired t-test or Wilcoxon rank-sum test, and repeated measures ANOVA with Tukey post-hoc tests, respectively. Visual Acuity (VA) before and after surgery was correlated with the patients’ CV risk score. At last, linear regression models were built to explain changes in CV risk variables considering the change in VA.

Results

Cataract surgery resulted in improved VA. Notably, following surgery our patient cohort showed reduced low-density lipoprotein (LDL) levels after surgery, from 111.17±36.26 mg/dL to 104.22±37.53 mg/dL, and reduced systolic arterial pressure (SAP), from 139.1±15.0 mmHg to 133.7±12.0 mmHg. Ultimately, this translated to an improved CV risk score within 6 months of cataract surgery, from 17.39±11.44% to 16.51±11.27%. Of note, these improvements were mostly present in the Bad VA group of patients, where baseline VA and incidence of dyslipidemia were worse.

Conclusion

Our results suggest that phacoemulsification cataract surgery may be an important tool in addressing CV risk.
Evolving Therapeutic Scenario of Stage III Non-Small-Cell Lung Cancer
Authors: Baudoux Nathalie , Friedlaender Alex , Addeo Alfredo
Published: February 2023

Lung cancer remains the leading cause of cancer-related death with an incidence that continues to increase in both sexes and all ages. However, 80% to 90% of lung cancers are non-small cell lung cancer (NSCLC) and the remaining 10% to 20% are small cell lung cancer. Adenocarcinoma is the most common histologic subtype of lung cancer worldwide. More frequently, lung cancer diagnosis is made in advanced stages. Stage III NSCLC refers to locoregionally advanced disease without metastases and represents about 30% NSCLC cases. Despite the absence of metastases at diagnosis, the outcome is generally poor. Stage III comprises a heterogeneous group and optimal management requires the input of a multidisciplinary team. All modalities of oncologic treatment are involved: surgery, chemotherapy, radiotherapy, and more recently, immunotherapy and targeted therapy. We will discuss the different therapeutic options in stage III NSCLC, both in operable and inoperable scenarios, and the role of immunotherapy and targeted therapy.
Experiences and constructions of womanhood and motherhood among Spanish Roma women
Authors: Herrero-Arias Raquel , Parra-Casado Daniel La , Ferrández-Ferrer Alicia , Sanchís-Ramón María-José , Ortiz-Barreda Gaby
Published: February 2023

Roma women face multiple inequalities at the intersections of ethnicity, gender, and class. Framed by Romani feminism, studies have explored Roma women’s own perspectives and experiences, drawing attention to the diversity within this group and the specificities of their social position due to the complex forms of discrimination they face. Drawing on interviews with Spanish Roma women, this article contributes to and extends this strand of research by exploring Roma women’s experiences and constructions of womanhood and motherhood. We found the construction of womanhood to be focused on the effective management of responsibilities, particularly caring and household tasks. Moreover, Roma women defined motherhood as a valued experience for them and their communities. A homemaker position was associated with mattering, something, we argue, which needs to be understood in the context of racial hostility, exclusion, and precarity in which Roma women live.
Understanding the Impact of Insufficient Sleep in Children with Behavior Problems on Caregiver Stress: Results from a U.S. National Study
Authors: Gissandaner Tre D , Stearns Melanie A , Sarver Dustin E , Walker Benjamin , Ford Hannah
Published: February 2023

Research indicates strong connections between child ADHD, child ODD/CD, and sleep. Children experiencing these concerns also have caregivers who report feeling more stress. However, no studies have examined how child ADHD and ODD/CD interact together and with insufficient sleep to potentially exacerbate caregiver stress. Data were acquired from the 2018/2019 National Survey of Children’s Health, a nationally representative survey of parents or caregivers conducted across the United States (U.S.). The current study used data for children 6-17 years old with a final analytic sample size of 41,541, representing a total of 47,357,862 U.S. youth. Overall child ADHD and ODD/CD were each uniquely associated with increased caregiver stress, while adequate child sleep duration was related to decreased caregiver stress. However, these findings were qualified by a significant two-way interaction that revealed that caregiver stress among children with comorbid ADHD and ODD/CD was not significantly greater than that of children with ODD/CD alone. Significant interactions between sleep and ODD/CD on caregiver stress were generally not observed, except potentially in females with ADHD. Our findings underscore the importance of considering strategies to reduce both youth symptoms and caregiver stress simultaneously. Additionally, ensuring adequate sleep for all children is recommended.
Tourists of their own past: Aural palimpsests from the Mao era
Authors: Zhang Shelley
Published: February 2023

This article explores how individuals in contemporary China use songs to both express and protect their memories of the Cultural Revolution and Mao era. As individuals who experienced the Cultural Revolution find ways to voice their recollections of the past, they casually listen to and perform songs from the Mao era, pursue domestic tourism, and engage with other material culture from that time. Their actions index individuals’ complicated nostalgias and continual negotiations with their political presents. Drawing from ethnographic fieldwork in the Hunan province, this article analyzes song objects as ‘aural palimpsests’ that allow individuals to gesture towards their political presents without criticizing the government or articulating traumatic memories. Aural palimpsests are performed and heard in architectural spaces that shape how music from different eras and genres become layered atop one another to create new social meaning in a contemporary China that is still grappling with its recent history.
Children as Covert Human Intelligence Sources: Spies First, Children Second
Authors: Arthur Raymond , Kirk Tracy
Published: February 2023

The Covert Human Intelligence Sources (Criminal Conduct) Act 2021 empowers the police, and other authorities, throughout the United Kingdom to use children as Covert Human Intelligence Sources (CHIS) and to authorise these children to engage in criminality, with no criminal liability, in return for information. In this article, we analyse the risk of severe physical and emotional harm that children face when acting as a CHIS and engaging in criminal behaviour to preserve their cover. This practice of using a child as a CHIS and encouraging children to engage in criminal conduct also runs counter to the Youth Justice Board for England and Wales’ ‘Child First’ vision of a youth justice system that respects children rights and operates in children’s best interests. Throughout the article we argue that, despite the existing safeguards, the emphasis should be on helping children to escape a criminal lifestyle, rather than entrenching them further in a life of criminality by encouraging them to act as a CHIS.
White Americans’ Evaluations of the Alt-Right
Authors: Banda Kevin K. , Cluverius John
Published: February 2023

Citizens’ perceptions of the alt-right are not well explored in political science. We view the alt-right as a successor of the Tea Party movement. While the Tea Party described itself as organized around spending, the size of government, and the American Constitution, examinations of the movement found that the unifying concerns of people who identified with it or viewed it favorably were negative feelings about racial minorities and patriarchal views of gender roles. Using panel survey data, we show that whites with higher levels of hostile sexism, racial resentment, perceptions of discrimination against whites, and who were more favorable towards Donald Trump evaluated the alt-right movement more positively. We find no evidence that self-placed ideology informed these evaluations. On the whole, latent cultural conservatism appears to inform evaluations of the relatively unknown — at the time — alt-right movement.
A Systematic Review of Interventions to Promote Self-Determination for Students With Extensive Support Needs
Authors: Alsaeed Abdulaziz , Mansouri Mary Curran , Shogren Karrie A. , Raley Sheida K. , Kurth Jennifer A. , Leatherman Elizabeth M. , Lockman Turner Elissa
Published: February 2023

Intervening to enhance self-determination has been linked to enhanced in-school outcomes (e.g., academic and transition goal attainment and access to general education) and post-school outcomes (e.g., competitive employment, community participation) for students with and without disabilities in inclusive schools. However, research is needed to examine the extent to which students with extensive support needs (ESN) are included in this body of research. This systematic review aims to identify empirical research articles that examined the outcomes of interventions designed to promote abilities and skills associated with self-determination for students with ESN. Results suggest that research on self-determination for students with ESN in school contexts is limited across grade levels, particularly in inclusive settings. Consequently, there is a need for ongoing research to consider effective self-determination assessments to inform the design and implementation of interventions that promote self-determination for students with ESN in inclusive settings. Implications for research and practice are discussed.
Study on the influence of cornering characteristics of complex tread tires on rolling resistance based on finite element method
Authors: Ge Yunfei , Yan Yifei , Yan Xiangzhen , Meng Zhaohong
Published: February 2023

The existence of tire slip angle and camber angle causes that the test results of conventional rolling resistance tester are often very different from the measured results installed on the vehicle. In addition, the test cost of rolling resistance tester with sideslip and roll is high. To solve the above problems, the effects of cornering characteristics on rolling resistance of complex tread tires were analyzed by finite element method (FEM). The numerical simulation model of a tire with complex tread patterns was established, and the reliability of the established numerical simulation model was verified by the experiments. The response relationships between tire lateral force, sideslip angle, camber angle and rolling resistance under multiple pure sideslip conditions and combined conditions were compared and analyzed, as well as the contribution rate of each tire component to rolling resistance under the corresponding conditions. The obtained research results can provide support for vehicle chassis adjustment and energy saving and consumption reduction in tire structure design.
Analysis of preferred weight configuration for barebow shooting style
Authors: Pietra Francesco , Loveday Philip , Reid Robert
Published: February 2023

The barebow archery shooting style limits the stabilisation system to weights connected to the riser, which is the central part of the bow. No scientific study is available to guide the barebow archer in the choice of the best weight configuration. In the following work, a human-centred methodology was developed to address this problem from both a scientific and user-oriented perspective. The proposed methodology is based on subjective metrics (archers’ sensations using the equipment), objective metrics (measurable quantities) and precision. The study sought a correlation between the subjective and objective metrics to provide insight into the problem of configuring a bow. Eleven weight configurations were considered. The vibration was measured at five positions on the bow and the 3D dynamic motion was measured using an inertial measurement unit. Seven archers completed a questionnaire to evaluate the subjective shooting sensations. The results show that the two best weight configurations are the 250–200 g and the 350–200 g, at the central and lower attachment points, respectively. A strong correlation exists between the vibration level of the bow and the feeling archers associated with the shooting, and between the dynamic motion of the bow and the comfort of the shooting. No correlation was found between the vibration time and the physical sensations felt by the archers. Determining the influence of the weight configuration on shooting accuracy, with statistical significance, would require an impractically large number of arrows to be shot for each weight configuration. A new methodology was developed to correlate the archers’ physical sensations to measurable parameters and this was applied to understand the barebow weight selection problem. This methodology could be further developed to correlate additional subjective and objective metrics. An understanding of these correlations would allow objective metrics, which can be simulated in the design process, to be used to ensure satisfaction of subjective metrics by the final design.
Examining contract modifications in purchasing personal protective equipment: A bargaining approach
Authors: Boyer Eric J. , Faria João Ricardo
Published: February 2023

This paper presents a bargaining model of contract outcomes as a function of contract uncertainties associated with critical supply purchasing after a crisis. It examines contract modifications and termination. The model yields the following results: (1) contract modification by the government alone (unilateral modification) does not change the optimal contract; (2) contract modification by mutual agreement (bilateral modification) makes the optimal contract dependent on product price, acquisition costs, transaction costs, and uncertainty; (3) mutual contract modifications are affected negatively by government costs of contract modification and are affected positively by supplier's costs of contract modification; (4) the government may find it necessary to terminate a contract if the contract elasticity of government utility is zero, and the contractor may want to terminate the contract when its supply price equals the acquisition price.
Pancreatic colloid adenocarcinoma arising from intraductal papillary mucinous neoplasm: Radiologic-pathologic correlation with cinematic rendering
Authors: Markovitz Michael , Jiang Kun , Kim Daniel , Rose Trevor , Permuth Jennifer B , Jeong Daniel
Published: February 2023

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas have the potential for malignant progression into adenocarcinoma. Colloid or mucinous non-cystic carcinoma of the pancreas is an uncommon variant neoplasm that can arise within an intestinal type IPMN and have a relatively improved prognosis but may mimic the more lethal tubular or ductal adenocarcinoma. Colloid carcinoma is an infiltrating ductal epithelial neoplasm containing primarily extracellular stromal mucin pools and scant amount of centrally floating neoplastic cells. While several reports have evaluated the unique pathologic and immunohistochemical profile of colloid carcinomas, there has been limited radiologic–pathologic correlation in the literature. We report a case of an 83-year-old female who presented for evaluation of slowly progressive abdominal pain and was found to have colloid carcinoma arising from an IPMN. This is one of the first reports to correlate the multimodality radiology including cinematic rendering (CR) and histopathology features associated with this tumor. An enhanced understanding of the correlation between imaging appearance and specific histopathologic findings may aid in the early recognition and treatment of this rare neoplasm. Emphasis is placed on CR as this may help guide surgical management.
Subsidence Rates Associated With Porous 3D-Printed Versus Solid Titanium Cages in Transforaminal Lumbar Interbody Fusion
Authors: Toop Nathaniel , Dhaliwal Joravar , Grossbach Andrew , Gibbs David , Reddy Nihaal , Keister Alexander , Mallory Noah , Xu David , Viljoen Stephanus
Published: February 2023

Study Design

Retrospective Cohort Study.

Objective

To determine whether 3D-printed porous titanium (3DPT) interbody cages offer any clinical or radiographic advantage over standard solid titanium (ST) interbody cages in transforaminal lumbar interbody fusions (TLIF).

Methods

A consecutive series of adult patients undergoing one- or two-level TLIF with either 3DPT or ST “banana” cages were analyzed for patient reported outcome measures (PROMs), radiographic complications, and clinical complications. Exclusion criteria included clinical or radiographic follow-up less than 1 year.

Results

The final cohort included 90 ST interbody levels from 74 patients, and 73 3DPT interbody levels from 50 patients for a total of 124 patients. Baseline demographic variables and comorbidity rates were similar between groups ( P > .05). Subsidence of any grade occurred more frequently in the ST group compared with the 3DPT group (24.4% vs 5.5%, respectively, P = .001). Further, the ST group was more likely to have higher grades of subsidence than the 3DPT group ( P = .009). All PROMs improved similarly after surgery and revision rates did not differ between groups (both P > .05). On multivariate analysis, significant positive correlators with increasing subsidence grade included greater age ( P = .015), greater body mass index ( P = .043), osteoporosis/osteopenia ( P < .027), and ST cage type ( P = .019).

Conclusions

When considering interbody material for TLIF, both ST and 3DPT cages performed well; however, 3DPT cages were associated with lower rates of subsidence. The clinical relevance of these findings deserves further randomized, prospective investigation.
Perioperative COVID-19 Screening at a Tertiary Ophthalmic Institution
Authors: Gendi Steve W. , Akotoye Christian , Kalur Aneesha , Muste Justin C. , Valentim Carolina C.S. , Iyer Amogh I. , Seth Kanika , Singh Rishi P.
Published: February 2023

Purpose: To characterize the rate of COVID-19 positivity during presurgical screening and the surgical outcomes of ophthalmic patients who were positive for COVID-19 and to report the overall cost. Methods: This retrospective study included patients 18 years or older who had ophthalmic surgical procedures at a tertiary institution between May 11, 2020, and December 31, 2020. Patients without a valid presurgical COVID-19 test within 3 days before their scheduled procedure, who had incomplete or mislabeled visits, or who had incomplete or missing data in their file were excluded. COVID-19 screening was completed using a polymerase chain reaction (PCR) kit. Results: Of the 3585 patients who met the inclusion criteria, 2044 (57.02%) were women; the mean age was 68.2 years ± 12.8 (SD). Thirteen asymptomatic patients (0.36%) tested positive for COVID-19 via PCR screening. Three patients had a known positive COVID-19 infection within the 90 days before surgery; thus, 10 patients (0.28%) were found to have asymptomatic naïve COVID-19 infection via PCR testing. Testing was associated with a total charge of US $800 000. Five of the 13 patients (38.46%) who tested positive for COVID-19 experienced a delay in their surgery; the mean delay was 17.23 ± 22.97 days. Conclusions: Asymptomatic ophthalmic surgical patients had a low positivity rate with a limited impact on surgery scheduling at a significant cost. Further studies would be valuable in evaluating a targeted presurgical screening population as opposed to universal testing.
Animating Entrepreneurship: The Educational and Analytical Merits of Creating Cartoons
Authors: Campbell Betsy
Published: February 2023

Creating works of fiction is an underdeveloped approach for introductory entrepreneurship education. This article describes the rationale and flow of an award-winning undergraduate course that requires students to create short animated music videos designed to teach entrepreneurship to children. It outlines the expanded benefits that accompany this creative constructionist method for teaching entrepreneurship, especially as a gateway into the entrepreneurship curriculum for undergraduate students. The article adds to the growing body of literature on uses of fiction in entrepreneurship education.
The pandemic veneer: COVID-19 research as a mobilisation of collective intelligence by the global research community
Authors: Hook Daniel W , Wilsdon James R
Published: February 2023

The global research community responded with speed and at scale to the emergence of COVID-19, with around 4.6% of all research outputs in 2020 related to the pandemic. That share almost doubled through 2021, to reach 8.6% of research outputs. This reflects a dramatic mobilisation of global collective intelligence in the face of a crisis. It also raises fundamental questions about the funding, organisation and operation of research. In this Perspective article, we present data that suggests that COVID-19 research reflects the characteristics of the underlying networks from which it emerged, and on which it built. The infrastructures on which COVID-19 research has relied – including highly skilled, flexible research capacity and collaborative networks – predated the pandemic, and are the product of sustained, long-term investment. As such, we argue that COVID-19 research should not be viewed as a distinct field, or one-off response to a specific crisis, but as a ‘pandemic veneer’ layered on top of longstanding interdisciplinary networks, capabilities and structures. These infrastructures of collective intelligence need to be better understood, valued and sustained as crucial elements of future pandemic or crisis response.
Implementing molecular tuberculosis diagnostic methods in limited-resource and high-burden countries
Authors: Vasiliu Anca , Saktiawati Antonia Morita Iswari , Duarte Raquel , Lange Christoph , Cirillo Daniela Maria
Published: February 2023

Tuberculosis (TB) is one of the deadliest infectious diseases in the world with more than a million people dying of TB each year. Accurate and timely TB diagnosis has the potential to alleviate the global TB burden; therefore, one of the pillars of the End TB Strategy developed by the World Health Organization (WHO) is the early diagnosis of TB, including universal drug-susceptibility testing (DST). The WHO emphasises the importance of DST before treatment initiation, using molecular WHO-recommended rapid diagnostic tests (mWRDs). Currently available mWRDs are nucleic acid amplification tests, line probe assays, whole genome sequencing, and targeted next-generation sequencing. However, implementing the sequencing mWRDs in routine laboratories in low-income countries is constrained by the existing infrastructure, high cost, the specialised skills needed, data storage, and the current delay in results compared with other routine methods. These limitations are pronounced in resource-limited settings, which often have a high TB burden and need for innovative TB diagnostic technologies. In this article we propose several possible solutions, like adapting infrastructure capacity to needs, advocating for lowering costs, building bioinformatics and laboratory capacity, and increasing the use of open-access resources for software and publications.
Updated definition of exercise pulmonary hypertension
Authors: Zeder Katarina , Olschewski Horst , Kovacs Gabor
Published: February 2023

In the recently published European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of pulmonary hypertension (PH) the haemodynamic definitions of PH were updated and a new definition for exercise PH was introduced. Accordingly, exercise PH is characterised by a mean pulmonary arterial pressure/cardiac output (CO) slope >3 Wood units (WU) from rest to exercise. This threshold is supported by several studies demonstrating prognostic and diagnostic relevance of exercise haemodynamics in various patient cohorts. From a differential diagnostic point of view, an elevated pulmonary arterial wedge pressure/CO slope >2 WU may be suitable to identify post-capillary causes of exercise PH. Right heart catheterisation remains the gold standard to assess pulmonary haemodynamics both at rest and exercise. In this review, we discuss the evidence that led to the reintroduction of exercise PH in the PH definitions.
Inverted Modelling: An Effective Way to Support Motion Planning of Legged Mobile Robots
Authors: Zhao Chenyao , Guo Weizhong
Published: February 2023

This paper presents an effective way to support motion planning of legged mobile robots—Inverted Modelling, based on the equivalent metamorphic mechanism concept. The difference from the previous research is that we herein invert the equivalent parallel mechanism. Assuming the leg mechanisms are hybrid links, the body of robot being considered as fixed platform, and ground as moving platform. The motion performance is transformed and measured in the body frame. Terrain and joint limits are used as input parameters to the model, resulting in the representation which is independent of terrains and particular poses in Inverted Modelling. Hence, it can universally be applied to any kind of legged robots as global motion performance framework. Several performance measurements using Inverted Modelling are presented and used in motion performance evaluation. According to the requirements of actual work like motion continuity and stability, motion planning of legged robot can be achieved using different measurements on different terrains. Two cases studies present the simulations of quadruped and hexapod robots walking on rugged roads. The results verify the correctness and effectiveness of the proposed method.
A multimodal deep learning model to infer cell-type-specific functional gene networks
Authors: Afshar Shiva , Braun Patricia R. , Han Shizhong , Lin Ying
Published: February 2023

Background

Functional gene networks (FGNs) capture functional relationships among genes that vary across tissues and cell types. Construction of cell-type-specific FGNs enables the understanding of cell-type-specific functional gene relationships and insights into genetic mechanisms of human diseases in disease-relevant cell types. However, most existing FGNs were developed without consideration of specific cell types within tissues.

Results

In this study, we created a multimodal deep learning model (MDLCN) to predict cell-type-specific FGNs in the human brain by integrating single-nuclei gene expression data with global protein interaction networks. We systematically evaluated the prediction performance of the MDLCN and showed its superior performance compared to two baseline models (boosting tree and convolutional neural network). Based on the predicted cell-type-specific FGNs, we observed that cell-type marker genes had a higher level of hubness than non-marker genes in their corresponding cell type. Furthermore, we showed that risk genes underlying autism and Alzheimer’s disease were more strongly connected in disease-relevant cell types, supporting the cellular context of predicted cell-type-specific FGNs.

Conclusions

Our study proposes a powerful deep learning approach (MDLCN) to predict FGNs underlying a diverse set of cell types in human brain. The MDLCN model enhances prediction accuracy of cell-type-specific FGNs compared to single modality convolutional neural network (CNN) and boosting tree models, as shown by higher areas under both receiver operating characteristic (ROC) and precision-recall curves for different levels of independent test datasets. The predicted FGNs also show evidence for the cellular context and distinct topological features (i.e. higher hubness and topological score) of cell-type marker genes. Moreover, we observed stronger modularity among disease-associated risk genes in FGNs of disease-relevant cell types. For example, the strength of connectivity among autism risk genes was stronger in neurons, but risk genes underlying Alzheimer’s disease were more connected in microglia.
The effect of combining therapeutic drug monitoring of antihypertensive drugs with personalised feedback on adherence and resistant hypertension: the (RHYME-RCT) trial protocol of a multi-centre randomised controlled trial
Authors: Peeters L. E. J. , Kappers M. H. W. , Boersma E. , Massey E. K. , van Dijk L. , van Gelder T. , Koch B. C. P. , Versmissen J.
Published: February 2023

Background

Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined.

Methods

This is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling.

Discussion

This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adherence. Furthermore, if this trial shows positive outcomes for the intervention it can be directly implemented in clinical practice, which would be a great improvement in the treatment of RH.

Trial registration. RHYME-RCT is registered in the Dutch Trial Register on 27/12/2017 (NTR6914) and can be found in the International Clinical Trials Registry Platform.
The effects of high versus low frequency of combined physical and cognitive training on cognitive function in older adults with cognitive decline: a quasi-experimental study
Authors: Chuang I-Ching , Chen I-Chen , Su Ken-Hsien , Wu Yih-Ru , Wu Ching-Yi
Published: February 2023

Background

The effects of combined training can be affected by training characteristics such as frequency, session length, and duration. No empirical studies to date have directly compared how combined physical and cognitive training offered at different training frequencies affects cognitive function for older adults with cognitive decline. This study investigated the impact of training frequency on cognitive outcomes after combined physical and cognitive training for older adults with cognitive decline.

Methods

A quasi-experimental study was conducted in community facilities and day care centers. The study assigned 89 older adults with cognitive decline into high-frequency (HF) or low-frequency (LF) training groups. The participants received 90- to 105-min training sessions, one (LF) or three (HF) times a week, for 12 weeks. Outcome measures were the Montreal Cognitive Assessment, Word List subtest of the Wechsler Memory Scale, Digit Symbol Substitution Test (DSST), and Stroop Color Word Test.

Results

The HF group demonstrated greater improvement in immediate memory measured by the WL-IM (F = 8.7, P = 0.004) and in executive function measured by the SCWT (F = 5.89, P = 0.017) than the LF group. Compared with the HF group, the LF group showed a great improvement in delayed memory measured by the WL-DM (F = 9.62, P = 0.003). The HF and LF groups both increased in processing speed and global cognitive function.

Conclusions

Our study indicated that the different training frequency of combined physical and cognitive training may result in benefits on different cognitive functions in older adults with cognitive decline. These findings may assist clinical practitioners in choosing appropriate training frequencies based on various intervention purposes for the elderly with cognitive decline.

Trial registration

ClinicalTrials.gov Identifier NCT03619577 (08/08/2018).
Biomarkers of macular neovascularisation activity using optical coherence tomography angiography in treated stable neovascular age related macular degeneration
Authors: Hanumunthadu Daren , Saleh Azahir , Florea Daniela , Balaskas Konstantinos , Keane Pearse A , Aslam Tariq , Patel Praveen J.
Published: February 2023

Background

The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA).

Methods

Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval.

Results

All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm2 ± 4.6mm2 and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe.

Conclusions

MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe.
Diagnostic pathways of Chagas disease in Spain: a qualitative study
Authors: Iglesias-Rus Laura , Boquete Teresa , Romay-Barja María , Benito Agustín , Jordan Briggitte , Blasco-Hernández Teresa
Published: February 2023

Background

Due to the mobility of the population in recent years and the spread of Chagas disease (CD) to non-endemic regions, early diagnosis and treatment of CD has become increasingly relevant in non-endemic countries. In order for screening to be effective, health system accessibility must be taken into consideration. This study uses Tanahashi’s Health Service Coverage model to gain a deeper understanding of the main diagnostic pathways for Chagas disease in a non-endemic country and the barriers and bottlenecks present in each pathway.

Methods

This study used a qualitative design with a phenomenological approach. Twenty-one interviews, two focus group sessions, and two triangular group sessions were conducted between 2015 and 2018 with 37 Bolivian men and women diagnosed with CD in Madrid, Spain. A topic guide was designed to ensure that the interviewers obtained the data concerning knowledge of CD (transmission, symptoms, and treatment), attitudes towards CD, and health behaviour (practices in relation to CD). All interviews, focus groups and triangular groups were recorded and transcribed. A thematic, inductive analysis based on Grounded Theory was performed by two researchers.

Results

Three main pathways to CD diagnosis were identified: 1) pregnancy or blood/organ donation, with no bottlenecks in effective coverage; 2) an individual actively seeking CD testing, with bottlenecks relating to administrative, physical, and time-related accessibility, and effectiveness based on the healthcare professional’s knowledge of CD; 3) an individual not actively seeking CD testing, who expresses psychological discomfort or embarrassment about visiting a physician, with a low perception of risk, afraid of stigma, and testing positive, and with little confidence in physicians’ knowledge of CD.

Conclusions

Existing bottlenecks in the three main diagnostic pathways for CD are less prevalent during pregnancy and blood donation, but are more prevalent in individuals who do not voluntarily seek serological testing for CD. Future screening protocols will need to take these bottlenecks into consideration to achieve effective coverage.
De novo HNF1A mutation of young maturity-onset diabetes 3 of a young girl—Case report
Authors: Peng Haoran , Li Jianbo , Wang Zhang
Published: February 2023

Young maturity-onset diabetes of the young type3(MODY3) as a special type of diabetes, the probability of diagnosis is low. This article reports on a case and reviews the relevant knowledge of the disease. We report an 11-year-and-11-month-old girl whose grandmother died from diabetic complications while the rest of the families were non-diabetes. The proband was initially treated with insulin and metformin but the threatment proved inefficient. After an exome-targeted capture sequencing test, she was diagnosed with mature-onset diabetes of young type 3 (MODY3), and sulfonylureas make sense. The key to mody treatment is a correct and timely diagnosis, which contributes to helping patients overcome the problems of MODY3, especially for blood sugar control.
Development and psychometric evaluation of a self-management behaviours scale in rheumatoid arthritis patients (RA-SMBS)
Authors: Chen Jinglin , Song Yuqing , Ou Lihong , Wang Xia , Wang Ying , Chen Yanling , Chen Hong
Published: February 2023

Background

Self-management behaviours can be crucial to improving disease symptoms and health outcomes in rheumatoid arthritis (RA) patients. Currently, the tools available for measuring self-management behaviours in RA patients are either generalized for patients with chronic diseases, which lack specificity or have poor reliability in the only specific scale—self-care behaviours scale (SCBS). The aim of this study was to develop a self-management behaviours scale for RA patients and evaluate its psychometric properties.

Methods

The study included two steps: scale development and the psychometric evaluation. The items were developed from a literature review, in-depth individual interviews, nominal group technique, Delphi expert consultation, and a pilot test. For the psychometric evaluation, a sample of 561 patients with RA was recruited. Item analysis, content validity, exploratory and confirmatory factor analysis, convergent and discriminant validity, and internal consistency reliability were conducted to examine the psychometric properties of the RA-SMBS.

Results

The final scale consists of 23 items with 4 dimensions, including medication management, exercise and joint protection, resource utilization and emotional management, and symptom management. The content validity index was 0.78. Exploratory factor analysis explained 61.89% of the total item variance. Confirmatory factor analysis indicated that the RA-SMBS fit well. Good internal consistency reliability was demonstrated (Cronbach's alpha = 0.908), and the test–retest reliability was found to be acceptable (ICC = 0.628, r = 0.780).

Conclusions

The scale has good content validity, construct validity, and internal consistency reliability. It can be used to assess the level of self-management behaviours in RA patients.
Quantification of parasite clearance in Plasmodium knowlesi infections
Authors: T. Thurai Rathnam Jeyamalar , Grigg Matthew J. , Dini Saber , William Timothy , Sakam Sitti Saimah , Cooper Daniel J. , Rajahram Giri S. , Barber Bridget E. , Anstey Nicholas M. , Haghiri Ali , Rajasekhar Megha , Simpson Julie A.
Published: February 2023

Background

The incidence of zoonotic Plasmodium knowlesi infections in humans is rising in Southeast Asia, leading to clinical studies to monitor the efficacy of anti-malarial treatments for knowlesi malaria. One of the key outcomes of anti-malarial drug efficacy is parasite clearance. For Plasmodium falciparum, parasite clearance is typically estimated using a two-stage method, that involves estimating parasite clearance for individual patients followed by pooling of individual estimates to derive population estimates. An alternative approach is Bayesian hierarchical modelling which simultaneously analyses all parasite-time patient profiles to determine parasite clearance. This study compared these methods for estimating parasite clearance in P. knowlesi treatment efficacy studies, with typically fewer parasite measurements per patient due to high susceptibility to anti-malarials.

Methods

Using parasite clearance data from 714 patients with knowlesi malaria and enrolled in three trials, the Worldwide Antimalarial Resistance Network (WWARN) Parasite Clearance Estimator (PCE) standard two-stage approach and Bayesian hierarchical modelling were compared. Both methods estimate the parasite clearance rate from a model that incorporates a lag phase, slope, and tail phase for the parasitaemia profiles.

Results

The standard two-stage approach successfully estimated the parasite clearance rate for 678 patients, with 36 (5%) patients excluded due to an insufficient number of available parasitaemia measurements. The Bayesian hierarchical estimation method was applied to the parasitaemia data of all 714 patients. Overall, the Bayesian method estimated a faster population mean parasite clearance (0.36/h, 95% credible interval [0.18, 0.65]) compared to the standard two-stage method (0.26/h, 95% confidence interval [0.11, 0.46]), with better model fits (compared visually). Artemisinin-based combination therapy (ACT) is more effective in treating P. knowlesi than chloroquine, as confirmed by both methods, with a mean estimated parasite clearance half-life of 2.5 and 3.6 h, respectively using the standard two-stage method, and 1.8 and 2.9 h using the Bayesian method.

Conclusion

For clinical studies of P. knowlesi with frequent parasite measurements, the standard two-stage approach (WWARN’s PCE) is recommended as this method is straightforward to implement. For studies with fewer parasite measurements per patient, the Bayesian approach should be considered. Regardless of method used, ACT is more efficacious than chloroquine, confirming the findings of the original trials.
Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results
Authors: Gotkine Marc , Caraco Yoseph , Lerner Yossef , Blotnick Simcha , Wanounou Maor , Slutsky Shalom Guy , Chebath Judith , Kuperstein Graciela , Estrin Elena , Ben-Hur Tamir , Hasson Arik , Molakandov Kfir , Sonnenfeld Tehila , Stark Yafit , Revel Ariel , Revel Michel , Izrael Michal
Published: February 2023

Background

Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells. AstroRx® was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, and act as an immunomodulator. Intrathecal injection of AstroRx® to animal models of ALS slowed disease progression and extended survival. Here we report the result of a first-in-human clinical study evaluating intrathecal injection of AstroRx® in ALS patients.

Methods

We conducted a phase I/IIa, open-label, dose-escalating clinical trial to evaluate the safety, tolerability, and therapeutic effects of intrathecal injection of AstroRx® in patients with ALS. Five patients were injected intrathecally with a single dose of 100 × 106 AstroRx® cells and 5 patients with 250 × 106 cells (low and high dose, respectively). Safety and efficacy assessments were recorded for 3 months pre-treatment (run-in period) and 12 months post-treatment (follow-up period).

Results

A single administration of AstroRx® at either low or high doses was safe and well tolerated. No adverse events (AEs) related to AstroRx® itself were reported. Transient AEs related to the Intrathecal (IT) procedure were all mild to moderate. The study demonstrated a clinically meaningful effect that was maintained over the first 3 months after treatment, as measured by the pre-post slope change in ALSFRS-R. In the 100 × 106 AstroRx® arm, the ALSFRS-R rate of deterioration was attenuated from − 0.88/month pre-treatment to − 0.30/month in the first 3 months post-treatment (p = 0.039). In the 250 × 106 AstroRx® arm, the ALSFRS-R slope decreased from − 1.43/month to − 0.78/month (p = 0.0023). The effect was even more profound in a rapid progressor subgroup of 5 patients. No statistically significant change was measured in muscle strength using hand-held dynamometry and slow vital capacity continued to deteriorate during the study.

Conclusions

Overall, these findings suggest that a single IT administration of AstroRx® to ALS patients at a dose of 100 × 106 or 250 × 106 cells is safe. A signal of beneficial clinical effect was observed for the first 3 months following cell injection. These results support further investigation of repeated intrathecal administrations of AstroRx®, e.g., every 3 months.

Trial Registration: NCT03482050.