bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of remimazolam in mechanical ventilation in the ICU: a protocol for systematic evaluation and meta-analysis
Authors: Yang Xuelian , Yang Yulian , Miao Gelan , Yang Chaobing , Liu Li , Lei Xianying
Published: December 2024

Introduction

Remimazolam is a novel ultra-short-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A receptors to induce sedative effects. Remimazolam was approved by China for procedural sedation in 2020. Intensive care unit (ICU) patients frequently exhibit impaired liver and renal function as well as haemodynamic instability; thus, the pharmacokinetic properties of remimazolam may offer advantages for ICU sedation. A comprehensive evaluation of the relevant studies warrants further discussion. This systematic review aims to compare the efficacy and safety of the novel intravenous anaesthetic remimazolam with that of commonly used anaesthetics in the ICU.

Methods and analysis

The following databases will be searched: Embase, Cochrane Library, PubMed, MEDLINE, Web of Science, CNKI and WanFang to retrieve relevant randomised controlled trials (RCTs). This protocol was developed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2020. RCTs about the use of remimazolam for sedation during ICU mechanical ventilation will be included. Two investigators will independently screen articles and extract data according to predefined inclusion and exclusion criteria. Following a qualitative evaluation of each study, data analysis will be conducted using Review Manager 5.4 software. The planned start and end dates for the study were placed on 1 June 2024 and 31 October 2024, respectively.

Ethics and dissemination

This protocol for the systematic evaluation and meta-analysis does not involve individual patient data; thus, ethical approval is not required. This will be the first meta-analysis to assess the sedative efficacy and safety of remimazolam in the ICU and to provide evidence to inform clinical decision-making. The findings will be disseminated through conference presentations and publications in peer-reviewed journals relevant to the field.

PROSPERO registration number

CRD42024554425
Higher risk profile among patients with TET2-mutated giant cell arteritis: a cluster analysis
Authors: Guedon Alexis F , Ouafdi Asmaa , Belfeki Nabil , Dellal Azeddine , Ghriss Nouha , Scheen Marc , Haidar Fadi , Espitia Olivier , Scoazec Jean-Yves , Fain Olivier , Marzac Christophe , Hermine Olivier , Solary Eric , Rossignol Julien , Mekinian Arsène
Published: December 2024

Objective

We aimed to assess the prevalence of clonal haematopoiesis (CH) in patients with giant cell arteritis (GCA) compared with controls and individuals with other autoimmune diseases (AIDs) and to identify high-risk clinical/genetic profiles that could influence disease outcomes.

Methods

In a prospective observational study at three hospitals, we included 49 patients diagnosed with GCA, 48 patients with other AIDs and 27 control participants. We used next-generation sequencing to detect clonal haematopoiesis (CH) among them.

Results

CH was detected in 55.1% of patients with GCA, 59.3% of controls and 18.8% of patients with other AIDs. The most commonly mutated genes in GCA and control groups wereDNMT3AandTET2. No significant differences in CH prevalence were found between patients with GCA and controls or other AID when adjusted for age and sex. Cluster analysis revealed two distinct groups within the patients with GCA, one of which displayed a higher prevalence of TET2 and JAK2 variants, and was associated with worse prognosis.

Conclusions

CH is prevalent among patients with GCA but does not differ significantly from controls or other autoimmune conditions. However, specific genetic profiles, particularly mutations in TET2 and JAK2, are associated with a higher risk cluster within the GCA cohort. This observation highlights the interest of detecting CH in patients with GCA in both routine practice and clinical trials for better risk stratification. Further prospective studies are needed to determine if management tailored to the genetic profile would improve outcomes.
Does regulation delay mines? A timeline and economic benefit audit of British Columbia mines
Authors: Collard Rosemary , Dempsey Jessica , Al Bouchi Youssef , Bawaan Nathan
Published: December 2024

Seeking to capitalize on a surge in global demand for critical minerals, the Canadian mining sector claims that regulatory processes like Environmental Assessment (EA) impede and delay mining’s economic benefits. This paper investigates whether regulation has delayed mining projects and how much economic benefit mines have delivered in British Columbia (BC), focusing the mines’ performance post-EA. We audit the 27 mines granted an EA certificate in BC since 1995 and projected to open by 2022, comparing each mine’s forecasted and actual timelines and economic benefits (production, employment, and taxes), and identifying publicly-stated reasons for any mine delays. Seven of the 27 mines opened on time: 13 remain non-operational, and of the 14 mines that have operated, seven were delayed. Regulation was cited as a factor in only three of the 20 delayed projects; economic factors like commodity prices were the most common cause of delay. Lack of data and transparency on economic benefits significantly constrained our benefit audit, but BC mines for which data are available are underperforming across production (−77%), employment (−82%), and tax revenue (−100%). These findings suggest economic underperformance and mine delays post-EA are common, with delays typically resulting from economic factors, not government regulations.
Water Stress Corrosion in a Directly Bonded Borofloat Glass Interface
Authors: Birckigt Pascal , Rothhardt Carolin , Zeitner Uwe D. , Risse Stefan
Published: December 2024

In this article, the phenomenon of water stress corrosion (WSC) at borofloat glass interfaces joined by hydrophilic direct bonding is explored. In particular, the impact of the surface waviness and surrounding atmosphere is studied through time-resolved measurements of the bonding energy during surface separation. We present a model for sub-critical crack growth and discuss the underlying WSC reaction. Key findings are that, firstly, the presence of humid air, and secondly, mechanical stress stored at the interface due to elastic contact point deformation increase the number of water molecules with sufficient kinetic energy to participate in the WSC reaction, that is, increase the reaction rate. This study provides crucial insights into the conditions aggravating WSC and gives implications for improving the durability and performance of mechanically stressed glass interfaces in various applications, such as micro-electro-mechanical systems (MEMS) and advanced optics.
Large‐Scale Multiobject Emulation Platform for Noncooperative Target Missions in Space
Authors: Chi Hao , Wang Guolei , Chen Ken , Zhang Jiwen
Published: December 2024

On‐ground emulation is crucial to cutting‐edge space technology involving the rendezvous and maintenance of noncooperative objects. However, existing systems are restricted to two objects and have a limited range of motion, and they cannot emulate some real space missions. The introduction of mobile robots is a potential solution, but on the one hand, their relatively low precision may ruin the emulation; on the other hand, how to take full advantage of mobile robots’ larger range of motion in on‐ground emulation is still to be solved. This paper presents a novel emulation platform for noncooperative object missions in space that can complete high‐precision kinetic emulations of large‐scale and multiobject motion. We use different kinds of mobile robots in our system and overcome the poor kinetic accuracy of mobile platforms. First, the composition and kinetics of the whole system are characterized. We simplify the hyper‐redundant system and propose a trajectory mapping method based on the workspace of mobile manipulators. Then, a dynamic programming method is proposed to plan the joint trajectories of mobile manipulators. We propose a feasibility function based on manipulability and the singularity avoidance coefficient, which ensures that the mobile base moves smoothly and that high‐precision manipulators have enough space to compensate for the movement errors of mobile bases. Finally, experimental results verify the feasibility and effectiveness of the system and the planning methods.
Supplementary Data from Tumor-Associated Microglia Secrete Extracellular ATP to Support Glioblastoma Progression
Authors: Wu Caren Yu-Ju , Chen Yiyun , Lin Ya-Jui , Wei Kuo-Chen , Chang Kwang-Yu , Feng Li-Ying , Chen Ko-Ting , Li Gordon , Ren Alexander Liang , Nitta Ryan Takeo , Wu Janet Yuling , Cho Kwang Bog , Pant Ayush , Choi John , Mackall Crystal L. , Kim Lily H. , Wu An-Chih , Chuang Jian-Ying , Huang Chiung-Yin , Jackson Christopher M. , Chen Pin-Yuan , Lim Michael
Published: December 2024

Supplementary figures
Tertiary Lymphoid Structures in Pancreatic Cancer are Structurally Homologous, Share Gene Expression Patterns and B-cell Clones with Secondary Lymphoid Organs, but Show Increased T-cell Activation
Authors: Lehmann Jonas , Thelen Martin , Kreer Christoph , Schran Simon , Garcia-Marquez Maria A. , Cisic Igor , Siepmann Klara , Hagen Elena M. , Eckel Hans Nikolaus Caspar , Lohneis Philipp , Kruger Stephan , Boeck Stefan , Ormanns Steffen , Rudelius Martina , Werner Jens , Popp Felix , Klein Florian , von Bergwelt-Baildon Michael S. , Bruns Christiane J. , Quaas Alexander , Wennhold Kerstin , Schlößer Hans A.
Published: December 2024

Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance. Immunofluorescence microscopy identified structural homologies between TLSs and SLOs. In RNA expression analyses of laser-microdissected TLSs and paired SLOs, we observed largely overlapping expression patterns of immune-related gene clusters but distinct expression patterns of T-cell and complement-associated genes. Immune cells in TLS expressed essential markers of germinal center formation. Increased activation of tumor-draining lymph nodes in patients with high numbers of TLSs highlights the relevance of these tumor-related structures to systemic immune response. In line with this, we identified an overlap of expanded B-cell receptor clonotypes in TLSs and SLOs, which suggests a vivid cross-talk between the two compartments. We conclude that combined therapeutic approaches exploiting TLS-mediated antitumor immune responses may improve susceptibility of PDAC to immunotherapy.
Figure 2 from Kinetics of Nirogacestat-Mediated Increases in B-cell Maturation Antigen on Plasma Cells Inform Therapeutic Combinations in Multiple Myeloma
Authors: Shearer Todd , Comstock Melissa , Williams Rex L. , Johnson Mark C. , Cendrowicz Ewa , Leonowens Cathrine , Smith Margaret , Baughman Todd M. , Breitbach Caroline J. , Cheng Shinta , Green Damian J.
Published: December 2024

BCMA dynamics in multiple myeloma cells before and after nirogacestat exposure. mbBCMA density in six multiple myeloma cell lines was measured (A) before and (B) after 24-hour exposure to varying concentrations of nirogacestat (0.1–1,000 nmol/L). The fold increase in mbBCMA density after 24-hour nirogacestat exposure is shown in C. sBCMA concentration after 24-hour exposure to varying concentrations of nirogacestat is shown in D. Changes in (E) mbBCMA density and (F) sBCMA concentration upon exposure to 250 nmol/L nirogacestat for 3, 6, 24, and 48 hours and after washout are shown. All experiments were performed in triplicate, with sBCMA measured in duplicate. ABC, antibody-binding capacity.
ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta-Cell Function in Children and Adolescents with Type 1 Diabetes
Authors: Haller Michael J. , Bell Kirstine J. , Besser Rachel E.J. , Casteels Kristina , Couper Jenny J. , Craig Maria E. , Elding Larsson Helena , Jacobsen Laura , Lange Karin , Oron Tal , Sims Emily K. , Speake Cate , Tosur Mustafa , Ulivi Francesca , Ziegler Anette-G. , Wherrett Diane K. , Marcovecchio M. Loredana
Published: December 2024

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 T1D are included. Lastly, opportunities and challenges associated with the recent US Food and Drug Administration (FDA) approval of teplizumab as an immunotherapy to delay progression are discussed.
Action observation and imitation: Corticospinal responses and hemispheric dominance
Authors: Hashemi Niloufaralsadat , Chau Tom , Beal Deryk S.
Published: December 2024

The response of the motor neuron system to the observation of lateralized movements and expectation mismatches remains elusive. We investigated how observation of hand movement modulates corticospinal excitability as measured by motor evoked potentials to single pulse transcranial magnetic stimulation (TMS). Twenty-seven adults watched a series of egocentric video recordings of hands, with one hand either squeezing a foam ball as expected or both hands remaining stationary. Task conditions comprised observation-only and observation with synchronous imitation of the depicted motor action. Single TMS pulses were delivered to the motor cortex contralateral to the dominant hand at the video frame of maximal hand closure for squeeze videos and randomly for no-squeeze videos (in both observation-only or observation with synchronous imitation). We analyzed MEPs, from the First Dorsal Interosseous (FDI) muscle of the dominant hand. Observation alone (absence of motor intention) did not enhance corticospinal excitability; however, when paired with imitation (presence of motor intention), it tended to increase MEP amplitudes, regardless of the attended side (dominant or non-dominant) or depicted action (squeeze or not). Among conditions in which the dominant hand remained stationary, MEP amplitudes were elevated (p = 0.004) in observation with imitation of non-dominant hand squeezing, suggesting hemispheric dominance in coordinating motor actions. Additionally, MEP latencies tended to decrease during synchronous imitation of squeeze videos. Our findings support the consideration of observation with synchronous imitation as a task for brain state-dependent brain stimulation protocols for optimizing neuromotor recovery.
7. Intuition revived
Authors: Skovsmose Ole
Published: December 2024

In the preface to Mathematics as an Educational Task, Hans Freudenthal states that his educational interpretation of mathematics betrays the influence of L. E. J. Brouwer’s view on mathematics. In this chapter we explore the nature of this possible influence. According to Brouwer, intuition plays a crucial role in any form of mathematical construction, which he specifies in terms of mental acts. He finds that mathematics does not have any adequate articulation in language, and that mathematical formalisms are nothing but imprecise and mischievous depictions of genuine mathematical processes. Freudenthal characterises mathematics as a human activity, thereby subsuming the overall intuitionist outlook that Brouwer had condensed into the notion of mental activity. While Brouwer installed intuition in a central position in mathematics, Freudenthal created a vast space for intuition in all kinds of activities in mathematics education. In his writings, Freudenthal does not demonstrate any interest in socio-political issues related to mathematics. Structuralism and the Modern Mathematics Movement are manifestations of the dogma of neutrality, and so is Freudenthal’s formulation of mathematics as a human activity. However, although he does not repudiate a dogma of neutrality, he simultaneously provides ideas that help in formulating a critical mathematics education.
16. Globalisation of mathematics education and the world’s first monoculture
Authors: Wolfmeyer Mark
Published: December 2024

The global spread of mass schooling supports ideologies of human capital and consumerism that we can consider as the world’s first monoculture. Educational organisations with global reaches, such as the International Association for the Evaluation of Educational Achievement and the Organisation for Economic Co-operation and Development, spread particular mathematics education goals that present opportunities for analysis and critique by mathematics educators who seek to advance causes beyond or in opposition to the consumer industrial complex. In this chapter I utilise Joel Spring’s review of perspectives on globalisation and education to motivate extended analysis of one example of ‘assessment spread’ within mathematics education, namely the Trends in International Mathematics and Science Study. Complementary methods of analysis (historical/contextual and content-based) reveal a strong association between mathematics education assessment spread and the rise of a world culture emphasising human capital and lifelong consumerism.
18. Mathematics education as a racialized field
Authors: Jett Christopher C. , Davis Julius
Published: December 2024

Racism is endemic in society, in education, and in mathematics education. Thus, as a discipline, mathematics education functions as a racialized field. In this chapter, we explore critical race theory ( CRT) as a theoretical frame to address this problem. In so doing, we offer offshoots of CRT – BlackCrit, LatCrit, TribalCrit, AsianCrit, and critical Whiteness theory – for mathematics educators to use in their scholarship. We also issue a call to mathematics educators regarding the urgent need to advance race-related work. We conclude the chapter by posing thought-provoking questions for consideration and action.
4. Italy, NRRP, and Industrial Policy
Authors: Barbieri Giovanni , Cerniglia Floriana , Mosconi Franco
Published: December 2024

This chapter assesses the National Recovery and Resilience Plan (NRRP) as an industrial policy tool within the Next Generation EU framework, despite limited explicit reference to an industrial strategy. The NRRP emerges during a unique moment for the European Union (EU), characterized by the suspension of the Stability and Growth Pact and the relaxation of state aid restrictions, which have collectively expanded public intervention opportunities. This marks a significant shift from the post-1990s ideological emphasis on competition over state involvement, particularly in Italy, where reductions in capital expenditure since 2009 have constrained public infrastructure and private investment. This chapter delves into the current landscape highlighting the potential for a more effective approach to industrial strategy using public investment. By focusing on “Mission 1” (Competitiveness) and “Mission 4” (Education and Research), the chapter aims to elucidate the NRRP’s industrial policy direction including reinforcing the special economic zones (SEZs) established in 2017.
Impact of COVID-19 on the Livelihoods, Health, Well-being and Pay Disparity of Women Workers in Unorganised Sector in India
Authors: Gotmare Preeti R. , Mukhtar Md. Shams , Bhat Lekha D. , Sumalatha BS
Published: December 2024

The COVID-19 pandemic has significantly impacted the livelihoods, health, pay disparity and well-being of women workers in the unorganised sector, particularly in fields such as agriculture, fisheries and handloom. These women are especially vulnerable to exploitation, gender inequality and human rights violations, as they lack institutional support welfare measures and are poorly organised. The pandemic has only worsened their situation. A field survey was conducted using structured questionnaires with 769 women workers from five districts in Tamil Nadu and Kerala states of India to understand the magnitude and different dimensions of their experiences related to pay disparity and health during pandemic times. The study was conducted after both waves of COVID-19. The study focuses on their livelihoods, health, pay disparity, well-being, working conditions, household dynamics, health scenarios and authorities’ support during the pandemic. The data were supplemented with qualitative inputs with in-depth interviews with women workers across these districts. The results indicate that pay disparity and livelihoods were significant issues faced by women workers during the pandemic, along with financial difficulties, health issues and increased workloads. 84.65 per cent of women workers are aware of wage discrimination, while 48 per cent reported pay disparity at their workplace, 78 per cent were unpaid for overtime, and 88 per cent worked without training or safety measures. However, it was found that 99.7 per cent of women workers had been vaccinated. Based on the study results, there is an urgent need for national and state-level policies and support specifically aimed at women workers in the unorganised sector in India. Failure to address these issues will result in ongoing problems related to pay inequality, poverty, health risks and social marginalisation.
The Frustrations of Free Trade and the Africa–European Union Samoa Agreement
Authors: Langan Mark , Price Sophia
Published: December 2024

The Samoa Agreement between the European Union (EU) and the Organisation of African, Caribbean and Pacific States (OACPS) includes strict language on concluding controversial Economic Partnership Agreements (EPAs) between their members. Skeptical OACPS members have instead called for greater intra-African economic integration embodied in the African Continental Free Trade Area (AfCFTA). However, there are concerns that the EU aims to use the AfCFTA as a stepping-stone for a vast bicontinental free trade zone. Building upon elite interviews with African diplomatic officials, this article questions whether the pan-Africanism at the heart of the AfCFTA is compatible with the more integrative Eurafrican agenda embodied in the Samoa Agreement.
Uncovering Attitudes to Family Migration—A Conjoint Survey Experiment with a Dyadic Approach
Authors: Gschwind Lutz , Wejryd Johan , Hultin Rosenberg Jonas , Ahlén Anton , Borevi Karin
Published: December 2024

Family migration constitutes by far the largest form of entry into countries with established democracies. Yet, it remains widely neglected in the literature on public attitudes. One of the key challenges in researching this topic is its inherent complexity. Family migration involves not only the claims of outsiders seeking entry, but also those of insiders wishing to reunite with family members. To address both dimensions simultaneously, we designed a conjoint survey experiment using an innovative dyadic approach. Respondents were presented with hypothetical cases of aspiring family migrants, alongside their respective family members already residing in the destination country. Key attributes, such as financial resources and types of family relationships, were randomized for each pair. We conducted the survey with 5,000 respondents across France, Germany, Italy, Sweden, and the United Kingdom. Our results suggest that respondents pay close attention to the characteristics of the incoming family migrant, such as language skills, while also being concerned with the economic resources of the family member already residing in the destination country. These findings indicate that research on public attitudes cannot treat family reunification as just one among many immigration motives. Study designs must also systematically account for the status of the family member already living in the destination country.
Comparing Four Caring Theories for Application in Iran
Authors: Ahmadi Chenari Hadi , Forouzanfar Hasan , Barzgar Behnam , Masabi Narges Shafie , Eftekhari Asghar , Baumann Steven L.
Published: December 2024

This paper provides a comparison and critique of four nursing theories that define nursing as caring for nursing in Iran. The theory evaluation model provided by Meleis was used to organize this comparison. It consists of five phases: description, analysis, criticism, test, and support. The four theories are Jean Watson’s theory of human caring, Katie Eriksson’s theory of caritative caring, Kari Martinsen’s philosophy of caring, and Anne Boykin and Savina Schoenhofer’s theory of nursing as caring. While little has been written on the development of caring theory specific to an Iranian context, the authors in this paper seek to move forward the conversation and support the application of nursing as caring in Iran.
Collision observation of collaborative robots based on generalized momentum deviation
Authors: Zhao Pengbing , Gao Zheng , Liu Xiang , Zeng Yanbin , Zhou Yuansheng
Published: December 2024

Stable collision detection method is the guarantee of cooperative robot in the process of human-robot interaction. In this paper, a robot collision detection method without additional sensors is proposed. An external moment observer based on generalized momentum deviation is constructed to realize collision detection by the deviation of robot theoretical momentum and actual momentum. Considering the influence of the external torque generated by the robot end load at the joint on the observer, this paper eliminates the interference of the load to the observer by compensating the equal torque generated by the load at the joint. Simulations and experiments demonstrate that the proposed collision observer can effectively eliminate the interference of terminal load and realize the function of collision detection accurately and quickly.
Clinical features and two-year outcomes in systemic lupus erythematosus patients with heart failure and reduced, mid-range and preserved ejection fractions
Authors: Li Zhe , Zhu Shuhua , Tang Wenjun , Zhang Haitao , Le Weibo , Luo Song , Zhou Chen , Wang Yang , Xu Shutian , Hu Weixin , Li Shijun
Published: December 2024

Objective

We retrospectively analyzed the clinical features and prognosis of SLE patients with HF.

Methods

Patients with SLE and HF who were hospitalized in Jinling Hospital from January 2013 to May 2021 and followed up for 2 years after discharge were included. Risk factors for death and ESKD were analyzed. According to cardiac ultrasound, patients were subdivided into the HFrEF, HFmrEF and HFpEF groups, and differences in clinical features and prognosis among the three groups were analyzed.

Results

Among 376 SLE patients with HF, the distribution was 13.30% HFrEF, 14.89% HFmrEF, and 71.81% HFpEF. Median ages at SLE and HF diagnosis were 29.00 (21.25, 42.00) and 35.25 (27.29, 49.31) years, with a median SLE duration of 49 (7, 120) months. The 2-year overall and renal survival rates were 86.97% and 63.56%, respectively. Multivariate COX analysis identified age, NPSLE, blood NT-proBNP, CD20+ B cells, Alb, and UA as death risk factors, and Scr, PCT, CD20+ B cells, urine RBP, and right kidney size as ESKD risk factors. The 2-year survival rates were 70% for HFrEF, 82.14% for HFmrEF, and 91.11% for HFpEF; renal survival rates were 46%, 58.93%, and 67.78%, respectively. HFrEF had lower survival rates than HFpEF, while HFmrEF showed intermediate rates and clinical features, with some significantly different from HFpEF but not HFrEF. No significant differences in SLE remission or relapse rates were found among non-ESKD survivors.

Conclusions

SLE patients with HF tend to have an early disease onset, high SLE activity and long course, with HFpEF being the predominant phenotype. HFrEF has a poorer prognosis compared to HFpEF, while HFmrEF has an intermediate prognosis and shares more clinical similarities with HFrEF.
Multiplicative versus additive modelling of causal effects using instrumental variables for survival outcomes – a comparison
Authors: John Eleanor R , Crowther Michael J , Didelez Vanessa , Sheehan Nuala A
Published: December 2024

Instrumental variables (IVs) methods have recently gained popularity since, under certain assumptions, they may yield consistent causal effect estimators in the presence of unmeasured confounding. Existing simulation studies that evaluate the performance of IV approaches for time-to-event outcomes tend to consider either an additive or a multiplicative data-generating mechanism (DGM) and have been limited to an exponential constant baseline hazard model. In particular, the relative merits of additive versus multiplicative IV models have not been fully explored. All IV methods produce less biased estimators than naïve estimators that ignore unmeasured confounding, unless the IV is very weak and there is very little unmeasured confounding. However, the mean squared error of IV estimators may be higher than that of the naïve, biased but more stable estimators, especially when the IV is weak, the sample size is small to moderate, and the unmeasured confounding is strong. In addition, the sensitivity of IV methods to departures from their assumed DGMs differ substantially. Additive IV methods yield clearly biased effect estimators under a multiplicative DGM whereas multiplicative approaches appear less sensitive. All can be extremely variable. We would recommend that survival probabilities should always be reported alongside the relevant hazard contrasts as these can be more reliable and circumvent some of the known issues with causal interpretation of hazard contrasts. In summary, both additive IV and Cox IV methods can perform well in some circumstances but an awareness of their limitations is required in analyses of real data where the true underlying DGM is unknown.
Marginal semiparametric accelerated failure time cure model for clustered survival data
Authors: Niu Yi , Fan Duze , Ding Jie , Peng Yingwei
Published: December 2024

The semiparametric accelerated failure time mixture cure model is an appealing alternative to the proportional hazards mixture cure model in analyzing failure time data with long-term survivors. However, this model was only proposed for independent survival data and it has not been extended to clustered or correlated survival data, partly due to the complexity of the estimation method for the model. In this paper, we consider a marginal semiparametric accelerated failure time mixture cure model for clustered right-censored failure time data with a potential cure fraction. We overcome the complexity of the existing semiparametric method by proposing a generalized estimating equations approach based on the expectation–maximization algorithm to estimate the regression parameters in the model. The correlation structures within clusters are modeled by working correlation matrices in the proposed generalized estimating equations. The large sample properties of the regression estimators are established. Numerical studies demonstrate that the proposed estimation method is easy to use and robust to the misspecification of working matrices and that higher efficiency is achieved when the working correlation structure is closer to the true correlation structure. We apply the proposed model and estimation method to a contralateral breast cancer study and reveal new insights when the potential correlation between patients is taken into account.
Patient Satisfaction with the Empathic Communication Skills of Nurses at a Tertiary Care Hospital, Uttarakhand
Authors: Rawat Rashmi , Arora Smriti , Sharma Suresh K. , Godiyal Jyoti
Published: December 2024

Background and Aim

Empathic communication has a great impact on patient satisfaction and health outcomes. With the advent of technology in healthcare human touch in caring for patients is diminishing gradually. This study explores the satisfaction of the patients with the empathic communication of nurses.

Methods

A descriptive cross-sectional study design was used to conduct the study. Data were collected by a self-structured 5-point Likert scale to assess the satisfaction of patients with the empathic communication skills of nurses in the month of August 2021.

Results

The mean age of the participants was 43.36 ± 15.76. 41% of respondents have an overall moderate satisfaction with the empathic communication skills of nurses, 33.33% had low satisfaction and only 25.7% had high satisfaction with empathic communication skills of nurses. Furthermore, a significant number of patients (87.5%) reported that their opinion was recognized and respected by nurses and more than 80% reported that nurses were good in communication.

Conclusion

This study provides significant data about one of the most important factors in the improvement of patient satisfaction. Nurse’s empathic communication skills can be improved and sustained by training programmers on regular basis.
It's not just a job: Meaningful work, self-stigma, and life satisfaction in people with visual impairment
Authors: Chui Cheryl Hiu-kwan , Lai Virgo
Published: December 2024

Background

Although employment has been positively linked to quality of life, recent theorising suggests the need for a broadened conceptualisation of paid work incorporating dimensions of subjective work experience as a key social determinant of life satisfaction in people with disabilities. There is also a need for further examination on the underlying mechanism between work and wellbeing outcomes amongst people with disabilities.

Objective

In this study, we put forth the concept of meaningful work, and examined its associations with self-stigma, and life satisfaction in people with visual impairment.

Methods

A total of 302 people with visual impairment completed a survey in Hong Kong. We analysed the data using linear regression and mediation analyses.

Results

We found that meaningful work was positively associated with life satisfaction and negatively associated with self-stigma. Self-stigma was negatively associated with life satisfaction and mediated the association between meaningful work and life satisfaction.

Conclusions

The findings showed that meaningful work is a positive and important social determinant of life satisfaction among people with visual impairment, while self-stigma serves as an underlying mechanism.
The Use of Extrinsic Performance Feedback and Reward to Enhance Upper Limb Motor Behavior and Recovery Post-Stroke: A Scoping Review
Authors: Palidis Dimitrios J. , Gardiner Zoe , Stephenson Amelia , Zhang Kevin , Boruff Jill , Fellows Lesley K.
Published: December 2024

Background

During post-stroke motor rehabilitation, patients often receive feedback from therapists or via rehabilitation technologies. Research suggests that feedback may benefit motor performance, skill acquisition, and action selection. However, there is no consensus on how extrinsic feedback should be implemented during stroke rehabilitation to best leverage specific neurobehavioral mechanisms to optimize recovery.

Objective

To identify the existing evidence and research gaps regarding the effects of extrinsic feedback on upper extremity motor function in stroke survivors, and to map the evidence onto neurobehavioral concepts of motor performance, motor learning, and action selection.

Methods

The MEDLINE, PsychInfo, EMBASE, and CINHAL databases were searched for relevant articles. A sequential screening process and data extraction were performed by 2 independent reviewers, and the results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines.

Results

A total of 29 studies were identified that met the criteria for inclusion. Beneficial effects of feedback were reported for clinical outcomes of rehabilitation interventions as well as motor performance, motor learning, and action selection post-stroke. Three studies showed that the addition of rewarding elements to positive performance feedback benefited learning or recovery.

Conclusions

Extrinsic feedback has the potential to improve outcomes of stroke rehabilitation through effects on motor performance, motor learning, or action selection. To understand how these specific neurobehavioral processes contribute to recovery, clinical trials should include more granular behavioral measures. Rewarding feedback may be particularly beneficial, but more research is needed regarding the specific implementation of feedback.
Impact of Neglect on the Relationship Between Upper Limb Motor Function and Upper Limb Performance in the (Hyper)acute Poststroke Phase
Authors: Veerbeek Janne M. , Rühe Henrik , Ottiger Beatrice , Bohlhalter Stephan , Nyffeler Thomas , Cazzoli Dario
Published: December 2024

Visuospatial neglect (VSN) is a negative, strong, and independent predictor of poor outcome after stroke, and is associated with poorer upper limb (UL) motor recovery in terms of function or capacity (ie, in standardized, lab-based testing). Although the main aim of stroke rehabilitation is to re-establish optimal functioning in daily life, the impact of VSN on UL performance (ie, in unstructured, everyday environments) is largely unknown. In this proof of principle study, the impact of VSN on the strength of the association between UL motor function (Jamar Hand Dynamometer) and UL performance (Upper Limb Lucerne ICF-based Multidisciplinary Observation Scale) was investigated in 65 (hyper)acute first-ever stroke patients. In a moderator analysis, the interaction term was negative and significant, showing that VSN suppresses the use of UL motor function in daily life (ie, performance). This finding suggests that, when considering UL performance in the (hyper)acute phase after stroke, interventions aimed to reduce deficits in both UL motor function and visuospatial function should already be started in the acute stroke unit setting.
Comparison of a compression for seven days or overnight after endovenous radiofrequency ablation of superficial vein: A randomized controlled trial
Authors: Taengsakul Nawaphan , Buttakosa Mullika , Kijrattana Marisa
Published: December 2024

Objective

To compare the efficacy of compression stockings worn for 7 days or overnight after EVRFA.

Methods

A single-centre, prospective, non-inferiority randomised controlled trial. The study included patients with clinical class C2–C4 chronic venous disease who underwent endovenous radiofrequency ablation (EVRFA) at Chulabhorn Hospital between October 2021 and October 2023. Sixty patients were assigned to wear the overnight compression group ( n = 30) or for the 7-day compression group ( n = 30). The primary outcome was targeted vein obliteration at 12 weeks. The secondary outcome measures were the revised Venous Clinical Severity Score (r-VCSS), Aberdeen Varicose Veins Severity Score (AVSS), pain score, complications and patient satisfaction.

Results

At 12 weeks, both groups had a 100% target vein occlusion rate. There was no statistically significant difference in the r-VCSS, AVSS, patient satisfaction score, complications or pain score at day 1, day 14 and 12–16 weeks after the procedure. Overnight compression improved r-VCSS significantly.

Conclusion

Overnight compression was non-inferior to compression for 7 days after EVRFA.
Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in KRAS-mutated colorectal cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid , Park Yong Sung , Stephan Clifford , Kopetz E. Scott , Ellis Lee M. , Bhattacharya Rajat
Published: December 2024

Background:

KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Objective:

Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Design:

In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that enhance the efficacy of MEK inhibitors in vitro, and we validated the drugs’ efficacy in vivo.

Methods:

HTS was performed using three-dimensional CRC spheroids. Trametinib, the anchor drug, was probed with two “clinically ready” libraries of 252 drugs to identify effective drug combinations. The effects of the drug combinations on CRC cell proliferation and apoptosis were further validated using cell growth assays, flow cytometry, and biochemical assays. Proteomic and immunostaining studies were performed to determine the drugs’ effects on molecular signaling and cell division. The effects of the drug combinations were examined in vivo using CRC patient-derived xenografts.

Results:

HTS identified paclitaxel as being synergistic with trametinib. In vitro validation showed that, compared with monotherapies, this drug combination demonstrated strong inhibition of cell growth, reduced colony formation, and enhanced apoptosis in multiple KRAS-mutated CRC cell lines. Mechanistically, combining trametinib with paclitaxel led to alterations in signaling mediators that block cell-cycle progression. Trametinib also enhanced paclitaxel-mediated microtubule stability resulting in significantly higher defects in mitosis. Finally, the combination of trametinib with paclitaxel exhibited significant inhibition of tumor growth in several KRAS-mutant patient-derived xenograft mouse models.

Conclusion:

Our data provide evidence supporting clinical trials of trametinib with paclitaxel as a novel therapeutic option for patients with KRAS-mutated, metastatic CRC.
Algorithmic configurations in caring arrangements
Authors: Trifuljesko Sonja , Ruckenstein Minna
Published: December 2024

This article examines heterogeneous forms of human relationalities with algorithms envisioned in the development of a public algorithmic system and their anticipated effects. To do that, we focus on the distinct shapes given to both technologies and people by discourses and practices, together with their underlying logics and associated values. Analysing the blog posts documenting the emergence of Omaolo, a digital platform for healthcare and social welfare in Finland, we identify two algorithmic configurations: the ‘service engine’, which aligns with the public administration goals of standardising social and healthcare services in order to provide financial benefits; and the ‘treatment facilitator’, which advances the prevalent goals of social and healthcare professionals preoccupied with the fulfilment of situated care needs. We demonstrate that each of the configurations has different implications for social and healthcare organisations in which algorithmic technologies are deployed, for the professionals working there and for the people seeking public support. While the service engine might seem to undermine the collective bases of public service delivery, the treatment facilitator evidently supports them. Our findings remind us of the importance of research endeavours that acknowledge the complex and creative nature of development work, and consider the various parties and interests involved, in an attempt to attain more caring arrangements for the uses of data and algorithmic techniques in the public sector and beyond.
Southern California basin and non-basin classification algorithm for ground-motion site amplification model applications
Authors: Nweke Chukwuebuka C , Shams Rashid
Published: December 2024

In ground-motion modeling, the estimated level of ground shaking at any given location for an expected earthquake scenario depends on the contributions from the source component (type of fault mechanism and size of the fault slip), the path component (distance between the source and site of interest, and the geologic characteristics of that region), and the site component (the local geology at the site of interest). Each component captures some level of variability and uncertainty in the overall ground-motion estimate. In particular, the site component represents the potential amplification (or de-amplification) of the seismic waves that may lead to magnified and prolonged ground shaking at any given location. This feature is referred to as site effects and in current ground-motion models (GMMs) is dependent on the time-averaged shear wave velocity in the upper 30 m of the earth’s crust ( Vs30) and the depth to a particular shear wave velocity iso-surface (“basin depth,” zx). The latter is responsible for determining the contributions of basin effects, which is additional ground-motion amplification due to three-dimensional effects such as trapped seismic waves that lead to surface wave generation. However, an evaluation of the relationship between zx and basin locations reveals cases of misclassification that is a result of geologic variability (i.e. zx is not sufficient in differentiating basins from non-basins). The study performed in this article proposes a resolution in the form of a statistical classification model that determines the probability of a location residing within or outside a basin based on simple geologic features such as ground surface texture.
Synergistic enhancing of micellization and thermodynamic properties of some Gemini cationic surfactants related to benzo[d]thiazol-3-ium bromide
Authors: El-Dossoki Farid I. , Migahed Mohamed A. , Gouda Mahmoud M. , El-Maksoud Samir A. Abd
Published: December 2024

Herrin, three Gemini cationic surfactants related to benzo[d]thiazol-3-ium bromide with variable hydrocarbon chain lengths (TBC n = 6, 12, and 18) were synthesized successfully and confirmed by using IR and 1HNMR spectroscopies. Critical micelle concentration and different thermodynamic properties of all surfactants under study were measured using conductivity, density, molal volume, and refractive index techniques. The Critical micelle concentration of TBC 6, TBC 12, and TBC 18 surfactants measured from the different techniques shows an acceptable agreement. The molecular weight of the investigated surfactants was decreased with the order: TBC 18 > TBC 12 > TBC 6. An increase in the magnitudes of the association constant, Gibbs free energy of micellization, molar refraction, polarizability, and binding constant proved the effect of hydrocarbon chain length on increasing surfactant’s micellization as follows: TBC 18 < TBC 12 < TBC 6. The enhancement in surfactant properties was also indicated under the effect of different concentrations of inorganic salts (NaI, NaBr, NaCl, MnCl2, CuCl2, and CoCl2). This effect was measured using conductivity and refractive index measurements. Different salts were indicated to adsorb on head groups of micelles, leading to an increase in the degree of ionization of the surfactant solution and improved aggregation of the surfactant at lower concentrations. The increase in the negative value of Gibbs free energy of association in the presence of salts proved an increase in the stability of micelles formed in a 15% DMSO-water solvent at 298.15 K.