bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world analysis of the efficacy and safety of nusinersen in pediatric patients with spinal muscular atrophy
Authors: Li Wenjing , Zhang Qin , Miao Hongjun , Xu Jin 
Published: February 2025

Abstract

Background
Spinal muscular atrophy (SMA) is a rare neurodegenerative disease that significantly affects multiple systems in children. Nusinersen, the first approved treatment for SMA, enhances SMN protein production by targeting the RNA splicing site of the SMN2 gene, thus improving motor function. However, the high cost of nusinersen treatment raises concerns about its economic feasibility.

Methods
This study retrospectively analyzed clinical data of 42 pediatric SMA patients treated with nusinersen from January 2022 to October 2024 at our hospital. We assessed the efficacy, safety, and economic impact of nusinersen in different SMA types. Motor function was evaluated using the CHOP-INTEND, HINE-2, HFMSE, and RULM scales. Safety was assessed based on adverse reactions and events, and economic evaluation considered total treatment costs and average cost per injection.

Results
Nusinersen significantly improved motor function in SMA patients, especially in type I patients, who showed notable increases in CHOP-INTEND and HINE-2 scores. The RULM score had the highest increase among type II patients, while improvements were relatively lower in type III patients. Regarding safety, the incidence of adverse events was 40.48%, with fever being the most common adverse reaction, occurring in 36.36% of cases. Economic analysis indicated that the total treatment cost was highest for type III patients, though the cost differences among types were not statistically significant (P > 0.05).

Conclusion
Nusinersen demonstrated significant clinical efficacy and favorable safety in pediatric SMA patients, with improved economic feasibility after insurance coverage. Our findings support early SMA screening and presymptomatic nusinersen administration to maximize therapeutic benefits. Further multicenter, large-sample, long-term follow-up studies are warranted to validate and expand upon these findings.
Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2
Authors: Schmidt Henri , Zhang Minsi , Chakarov Dimitar , Bansal Vineet , Mourelatos Haralambos , Sánchez-Rivera Francisco J. , Lowe Scott W. , Ventura Andrea , Leslie Christina S. , Pritykin Yuri 
Published: February 2025

Abstract
We present GuideScan2 for memory-efficient, parallelizable construction of high-specificity CRISPR guide RNA (gRNA) databases and user-friendly design and analysis of individual gRNAs and gRNA libraries for targeting coding and non-coding regions in custom genomes. GuideScan2 analysis identifies widespread confounding effects of low-specificity gRNAs in published CRISPR screens and enables construction of a gRNA library that reduces off-target effects in a gene essentiality screen. GuideScan2 also enables the design and experimental validation of allele-specific gRNAs in a hybrid mouse genome. GuideScan2 will facilitate CRISPR experiments across a wide range of applications.
A qualitative study exploring participants’ experiences of the SCOPE2 trial: chemoradiotherapy dose escalation in oesophageal cancer
Authors: Holland-Hart Daniella , Longo Mirella , Bridges Sarah , Nixon Lisette , Hawkins Maria , Crosby Tom , Nelson Annmarie 
Published: February 2025

Abstract

Introduction
This qualitative study explored patients’ experiences and perceptions of the SCOPE2 trial. The trial studied radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemo-radiation. SCOPE2 embedded a phase II trial for patients with a poor early response using positron emission tomography (PET) scans.

Methods
This longitudinal interview study took place between 2017 and 2021. Patients eligible for chemoradiotherapy were recruited from five clinical sites in the UK. Participants were invited to participate in three semi-structured interviews across four different time points: baseline (before treatment) and at 2–3 months, 3–6 months or 6 months + after baseline. This paper focuses on recruitment to the trial, practical management, the impact of COVID-19 and reflections of being on the trial. Real-time reporting to the trial team was used to inform potential improvements to trial conduct and recruitment. The interviews were thematically analysed.

Results
Ten participants were interviewed in 16 longitudinal interviews. There were five female and five male interview participants; three participants were accompanied by companions during their interviews. Recruitment to the trial and qualitative study was challenging. Motivations for joining the trial included altruism, potentially receiving better care and monitoring and the opportunity to improve their quality of life. Participants required adequate time to consider information and regular updates regarding trial and treatment process. Participants felt that their trial experience was minimally impacted by COVID-19, although some delays to treatment were reported.

Conclusion
Increased opportunities for patients to discuss and receive appropriate and timely information from trial staff and third sector partners could enhance patients’ understanding of future trials, treatments and procedures. Slow recruitment to the trial and qualitative study was further impeded by the COVID-19 pandemic and future trials would benefit from a more fully integrated approach to qualitative recruitment.

Clinical trial registration
ClinicalTrials.gov: NCT02741856 registered on 12 April 2016; ISRCTN: 9,712,546 registered on 26 October 2016.
A proinflammatory response and polarized differentiation of stromal elements characterizes the murine myeloma bone marrow niche
Authors: Ghamlouch Hussein , Gagler Dylan C. , Blaney Patrick , Boyle Eileen M. , Wang Yubao , Avigan Jason , Choi Jinyoung , Landgren Ola , Tsirigos Aristotelis , Maura Francesco , Morgan Gareth J. , Davies Faith E. 
Published: February 2025

Abstract

Background
The bone marrow (BM) niche contains non-hematopoietic elements including mesenchymal stromal cells (MSC) and bone marrow endothelial cells (BMEC) which provide mechanical support, and control hematopoietic cell growth and differentiation. Although it is known that multiple myeloma (MM) cells interact closely with the BM microenvironment, little is known about the impact of MM on non-hematopoietic niche-forming cells.

Methods
To address the role of the niche in MM pathogenesis, we utilized the 5TGM1 murine model. During the asymptomatic precursor stage of the model, we isolated the rare non-hematopoietic cells and performed single cell RNA sequencing. Using in-silico methods we characterized the individual cellular components of the niche, their relative abundance and differentiation state before and after exposure to MM cells as well as their intercellular interactions.

Results
MM engraftment increased the abundance of MSC-lineage cells, BMECs and enhanced endothelial to mesenchymal transition. An inflammatory and oxidative stress signal was identified together with polarization of MSC differentiation away from osteocyte formation towards adipocytes which provide growth factors that are known to support MM expansion. BMEC differentiation was polarized towards sinusoidal endothelial cells with a pro-angiogenic/pro-inflammatory phenotype.

Conclusions
MM cells impact the BM niche by generating a pro-inflammatory microenvironment with MSC differentiation being changed to generate cell subsets that favor MM growth and survival. In order to induce remission and improve long-term outcome for MM patients these inflammatory and oxidative stress signals need to be reduced and normal niche differentiation trajectories restored.
Overcoming barriers to implementation of patient engagement in clinical trials: feasibility testing of an embedded study
Authors: Castonguay Geneviève , Bédard Sylvain , Dubois Anick , Lessard Émilie , Rivard Léna , Rouly Ghislaine , Boivin Antoine 
Published: February 2025

Abstract

Background
Patient engagement is attracting considerable interest as a potential strategy to improve the conduct of clinical trials, with evidence of significant improvement in research participant recruitment. However, impact on the retention and adherence of clinical trial participants requires further studies. Embedded studies are specific research designs where a secondary study is “embedded” into a larger host study. We aimed to investigate the feasibility of embedding a study of patient partnership in research, within an ongoing multi-center clinical trial on drug treatment.

Methods
We developed and embedded a patient engagement intervention (embedded study) into a phase 3 randomized clinical drug trial (host study). The patient engagement intervention consisted of discussions between host study participants and a patient partner, to improve research participants’ experience and retention in the clinical trial. We carried out individual semi-structured interviews with patient partners and other research team members involved in the development and implementation of the embedded study, as well as an analysis of project documents. Data were analyzed using qualitative thematic analysis.

Results
Factors impacting feasibility and lessons learned for future embedded studies on engagement science were identified. Barriers that curtailed the implementation of patient engagement into an ongoing clinical trial included: the late integration of the embedded study into the host clinical trial, different visions of patient partnership and its potential benefits, differences in communication style and preferences, a lack of fit between the specific needs of the host study and the proposed engagement model, and an overall sense of burden. Integrating patient partners into the host clinical trial was seen as potentially beneficial in improving the experience of participants in the host clinical trial through experience sharing, providing support for the consent process, and improving knowledge transfer.

Conclusions
This feasibility study offers insights into how contextual factors and decisions made during the design phase can impact the implementation of patient engagement studies embedded in a clinical trial. Findings suggest that knowledge of the clinical trial context (e.g., organizational, administrative, regulatory, ethics) and early collaboration among embedded study and host study teams before initiation of both studies are key conditions for success.
Detection of thrombus in a venous air trap chamber using ultrasound imaging: a case report
Authors: Ito Yoshiaki , Tanaka Toshiyuki 
Published: February 2025

Abstract

Background
During hemodialysis, the formation of thrombi inside the venous air trap chamber is associated with high venous pressure. Direct observation inside the venous air trap chamber involves invasive procedures and risks affecting the closed-circuit system. Methods for non-invasive observation inside venous air trap chambers have not yet been generalized.

Case presentation
A thrombus was identified in the filter inside a venous air trap chamber during emergency hemodialysis performed on a man in his 60s with acute renal dysfunction. During subsequent hemodialysis sessions, we regularly monitored the venous air trap chamber using ultrasound imaging and employed colour Doppler to identify the thrombus. Images were also captured that revealed signs of anomalies.

Conclusions
Ultrasound imaging allows non-invasive observation of the interior of a venous air trap chamber. Employing this non-invasive method poses less risk to patients and can potentially be applicable to continuous renal replacement therapy in circuit configurations that use chambers.
Improving power distribution networks with dwarf mongoose optimization for improved photovoltaic incorporation in rural-urban settings
Authors: Chen Guo , Honggang JIA , Jian Zeng , Zhiqi Zhang , Xingxing Zhou 
Published: February 2025

Abstract
This paper aimed to assess new connotations and characteristics of power distribution networks in new situations like integrating photovoltaic (PV) systems. Power system emission reduction is an ongoing subject of discourse, and solar energy production using PV is gaining popularity. Centralized and unidirectional systems, nevertheless, provide difficulties. An investigation is expected to comprehend the network’s design and PV integration capacity’s (PV-IC’s) responsiveness to subsequent generations.With an emphasis on low and medium-voltage networks, the paper presents a unique dwarf mongoose optimization (DMO)approachfor developing efficient network configurations. It analyzes the effect of network configuration on PV-IC.This study is experimented with MATLAB/Simulink platform based on the DMO technique. Different PV system numbers and peak powers, together with alternate providing substations, have been modeled for a certain set of load locations. The load time series computed shows rural-urban zones, and the proposed DMO is implemented on several topological generations. The computed results indicate that network topologies must be changed to accommodate raised solar energy production and PV-IC, with rural regions attaining up to 8.2 kW using TF (+). Our proposed DMO approach surpassed alternatives, with rural regions having a higher PV-based load of 190 kW compared to 120 kW in urban areas. Voltage control tactics, like RPC and Curt, benefit up to 55% of rural customers versus 15% in urban areas. Policy changes for household PV incorporation may be needed to maximize solar energy use.
Black psychiatrists’ experience of discrimination and related behaviours in the workplace: UK survey
Authors: Hombo Jade , Owusu-Mensah Lovita , Orrell Martin , Kwentoh Mona-Lisa 
Published: February 2025

Aims and method
In the UK, Black doctors experience higher levels of discrimination, bullying and harassment compared with other doctors. This study aims to explore the impact of this on perceived well-being and mental health. A UK survey of 109 Black psychiatrists asked about racism, othering, microaggressions, bullying and harassment, plus any links to career progression or mental well-being.

Results
Sixty-three survey participants (57.8%) had faced workplace microaggressions, 44 (40.4%) had experienced workplace bullying and 41 (37.6%) had faced workplace harassment. Forty-seven (43.1%) participants reported a detrimental impact on their mental health, with 35 (32.1%) considering quitting and 24 (22%) reporting a poorer work performance.

Clinical implications
These experiences are unacceptable and can be traumatic. The impact of racism and discrimination can also undermine effective service delivery. Barriers to reporting can prolong mistreatment and deter professional aspirations among Black psychiatrists. Collective action is needed to drastically improve the workplace environment, including the widespread institutional adoption of an anti-discriminatory stance.
Effects of Lorentz symmetry violation on a spin-1/2 neutral particle in a doubly anharmonic potential
Authors: Oliveira A. S. , Okada Kim , Belich Humberto 
Published: February 2025

Abstract
We investigate the quantum dynamics of a spin-1/2 neutral particle under the effects of Lorentz&#xD;symmetry violation, characterized by a fixed time-like background vector and azimuthal electric&#xD;fields added to the potential of a pure quartic oscillator. These effects, induced by the background&#xD;vector that defines a preferred spacetime direction, modify the dynamics of the spin-1/2 neutral&#xD;particle and give rise to a doubly anharmonic oscillator-like potential. The main challenge is to find&#xD;analytical solutions to the Schr¨odinger equation, considering that this nonlinear potential models&#xD;realistic quantum physics scenarios. Finally, we obtain bound-state solutions in the nonrelativistic&#xD;limit for the Schr¨odinger-Pauli equation of a spin-1/2 neutral particle. An interesting quantum&#xD;effect is observed: the constant associated with the pure quartic oscillator term is quantized,&#xD;meaning it depends on the system’s quantum numbers.
The Landmark Series: Extent of Surgery for Low-Risk Differentiated Thyroid Cancer
Authors: Ullmann Timothy M. , Sosa Julie A. 
Published: February 2025

Abstract
The management of patients with differentiated thyroid cancers (DTCs) at low risk for disease progression or relapse after treatment remains controversial. These patients have excellent disease-specific survival. Therefore, minimizing the impact of treatments on patients’ quality of life is particularly important. For these reasons, the pendulum has swung in recent years to favor less extensive surgery toward lobectomy instead of total thyroidectomy, away from prophylactic (central compartment) lymphadenectomy, and even in some cases, omitting surgery altogether. This review discusses several of the influential studies from the past two decades that have had an impact on the management for these patients, including a shift toward more personalized care.
Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence
Authors: Sghaier Asma , El Ghali Amine , Fradi Khalil , Chiba Dorra , Hamila Fehmi , Youssef Sabri 
Published: February 2025

Background: We have little knowledge about the synchronous occurrence of gastrointestinal stromal tumors (GISTs) and other types of histologic tumors. This association is very rare. Case presentation: We describe a case of synchronous stromal tumor and adenocarcinoma of the left side colonic localization. Immunohistochemistry identified c-Kit expression. The discovery of colonic adenocarcinoma was on operative specimen after histologic examination. The patient underwent left carcinologic colectomy with stoma. Follow-up at one year postoperatively did not detect tumor recurrence. Discussion: Clinical implications of the association between these two neoplasms are not clearly described. Treatment depends on the dominance of one histologic type. Knowledge of the genetic data of this association offers opportunity of treatment with the new targeted-therapy molecules. Surgical resection, may remain the curative treatment. Conclusions: Synchronous adenocarcinoma and GIST has been more commonly described in the stomach. The pathogeneses of tumorigenesis may not be the same for the two tumors. More studies seem be necessary to clarify a potential role of different genes in the development of adenocarcinomas. And therefore, above all their therapeutic implications
Buying Cheap: Brand Switching During Economic Distress and Its Disparate Impact on Consumers
Authors: Dutta Shantanu , Singhvi Divya , Singhvi Somya 
Published: February 2025

Problem definition: Improving the surplus of low-income consumers during economic distress is of primary concern for many governments. This paper uses an economic model to investigate consumers’ brand switching during economic distress and highlights its disparate impact on low-income consumers. Our modeling framework also captures how retailers and national-brand manufacturers strategically adjust the market prices in response to brand switching and shelf space constraints. To generate prescriptive insights, we also analyze the effectiveness of commonly observed government interventions that fall into two major categories: (i) consumer-focused (e.g., cash subsidy) and (ii) retailer-focused (e.g., price control). Methodology/results: Our analysis indicates that market access for low-income consumers can decline significantly because of the brand switching behavior. Furthermore, not all government interventions are equally effective in increasing the welfare of low-income consumers. In fact, retailer-focused schemes such as price control (PC) can backfire and decrease access for low-income consumers. Although cash subsidy (CS) can increase the surplus of low-income consumers, it is always at the expense of high-income consumers. Managerial implications: We study an important but understudied challenge that highlights how strategic behavior by retailers can exacerbate affordability and accessibility concerns during economic distress. Model calibration using NielsenIQ Homescan Panel data shows that our model captures the data well and generates practical insights for policymakers. These results suggest that the success of government interventions depends critically on whether they account for the strategic behavior of different stakeholders in the supply chain. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0380 .
Chromosome evolution and speciation: Revisiting Bush et al. (1977)
Authors: Moritz Craig , Potter Sally 
Published: February 2025

Whether and how chromosome change can drive speciation has long attracted the interest of evolutionary biologists. In a seminal paper, Bush et al. (1977) demonstrated wide variation in rates of macroscopic chromosome change across vertebrates and a positive correlation with rates of speciation at genus-level, and then considered possible causal processes. We revisit the key findings of this paper, highlighting how rapidly advancing knowledge of genome organisation and function shed new light on this long standing question. The central findings of Bush et al. (1977) have endured. There is now great opportunity to apply new genome technologies to understand the interaction of genome change and function in the classic systems of chromosomal speciation discovered through classical cytogenetics.
Managing heart failure at home: a remote monitoring pilot project in a community heart failure service
Authors: Hyland Rebecca , Bailey Lisa , Owen Eloise 
Published: February 2025

Background/Aims The service described in this study took part in NHS England's ‘managing heart failure @home’ initiative, with a pilot project that implemented remote monitoring for patients with heart failure. The project aimed to improve quality of life, promote self-management and facilitate recognition of deteriorating symptoms. This study described and evaluated the 6-month pilot project. Methods A total of 44 patients attending the heart failure service were recruited into the project and provided with the required technology for remote monitoring. Data were collected at baseline, 3 months and 6 months regarding patients' New York Heart Association classifications and clinic capacity. Quality of life was assessed using the EQ-5D and Kansas City Cardiomyopathy Questionnaire. Patient confidence in self-managing their condition was assessed using the Person-Centered Coordinated Care Experience Questionnaire. Data regarding the distance between local services and patients' homes and number of in-person visits avoided were used to estimate the environmental impact. Results Improvements in overall quality of life, New York Heart Association classifications and patient confidence in self-management were observed across the sample. Daily clinic capacity increased by 45% and an estimated 3808 miles of patient travel were prevented. A case study illustrated the utility of remote monitoring for patients who live far away from services. Conclusions The remote monitoring project had several benefits for patients and the service. Challenges and considerations for other trusts that may wish to implement remote monitoring for patients with heart failure are discussed.