bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling NHS England 111 demand for primary care services: a discrete event simulation
Authors: Pilbery Richard , Smith Madeleine , Green Jonathan , Chalk Daniel , O'Keeffe Colin A
Published: September 2023

Objectives

This feasibility study aimed to model in silico the current healthcare system for patients triaged to a primary care disposition following a call to National Health Service (NHS) 111 and determine the effect of reconfiguring the healthcare system to ensure a timely primary care service contact.

Design

Discrete event simulation.

Setting

Single English NHS 111 call centre in Yorkshire.

Participants

Callers registered with a Bradford general practitioner who contacted the NHS 111 service in 2021 and were triaged to a primary care disposition.

Primary and secondary outcome measures

Face validity of conceptual model. Comparison between real and simulated data for quarterly counts (and 95% CIs) for patient contact with emergency ambulance (999), 111, and primary and secondary care services. Mean difference and 95% CIs in healthcare system usage between simulations and difference in mean proportion of avoidable admissions for callers who presented to an emergency department (ED).

Results

The simulation of the current system estimated that there would be 39 283 (95% CI 39 237 to 39 328) primary care contacts, 2042 (95% CI 2032 to 2051) 999 calls and 1120 (95% CI 1114 to 1127) avoidable ED attendances. Modifying the model to ensure a timely primary care response resulted in a mean percentage increase of 196.1% (95% CI 192.2% to 199.9%) in primary care contacts, and a mean percentage decrease of 78.0% (95% CI 69.8% to 86.2%) in 999 calls and 88.1% (95% CI 81.7% to 94.5%) in ED attendances. Avoidable ED attendances reduced by a mean of −26 (95% CI −35 to −17).

Conclusion

In this simulated study, ensuring timely contact with a primary care service would lead to a significant reduction in 999 and 111 calls, and ED attendances (although not avoidable ED attendance). However, this is likely to be impractical given the need to almost double current primary care service provision. Further economic and qualitative research is needed to determine whether this intervention would be cost-effective and acceptable to both patients and primary care clinicians.
Unintended consequences of the 18-week referral to treatment standard in NHS England: a threshold analysis
Authors: Quinn Laura , Bird Paul , Remsing Sandra , Reeves Katharine , Lilford Richard
Published: September 2023

Objective

In 2012, an ‘18-week referral to treatment standard’ was introduced in England. Among people on the list of those waiting for hospital treatment at a point in time, the standard states that at least ‘92% of patients should have been waiting for less than 18 weeks’. Targets can have unintended consequences, where patients are prioritised based on the target rather than clinical need. Such an effect will be evident as a spike in the number of hospital trusts at the target threshold, referred to as a threshold effect. This study examines for threshold effects across all non-specialist acute NHS England hospital trusts by financial year.

Methods

A retrospective observational study of publicly available data examined waiting times for patients on the waiting list. We examined trust performance against the 92% target by financial year, from 2015/16 to 2021/22, using Cattaneoet al’s manipulation density test (test for discontinuity/spike in data around target threshold) for all patients and by type of treatment.

Results

The proportion of NHS hospital trusts meeting the 92% target deteriorated over time. From 2015/16 to 2019/20, there was strong evidence of a threshold effect at the 92% target (p<0.001). There was no evidence of a threshold effect in 2020/21 (p=0.063) or 2021/22 (p=0.090). Threshold effects were present across most types of treatment in 2016/17 and fewer types from 2017/18 onwards.

Conclusion

We observed striking evidence of a threshold effect suggesting that while targets change behaviour, they do so in a selective way, focusing on the threshold rather than a pervasive improvement in practice. However, at the height of the pandemic, as almost no trusts could reach the target, the threshold effect disappeared.
Associations between air pollution and the risk of first admission and multiple readmissions for cardiovascular diseases
Authors: Zhang Shiyu , Chen Lan , Qian Zhengmin (Min) , Li Dan , Cai Miao , Wang Chongjian , Zhang Zilong , Vaughn Michael G. , Keith Amy E. , Li Haitao , Lin Hualiang
Published: September 2023

Objectives

We aimed to investigate the associations between air pollutants and the risk of admission and multiple readmission events for cardiovascular disease (CVD).

Methods

A total of 285 009 participants free of CVD at baseline from the UK Biobank were included in this analysis. Four major cardiovascular admission events were identified during the follow-up: chronic ischaemic heart disease (CIHD), cerebrovascular disease, atrial fibrillation and heart failure. We used Prentice, Williams and Peterson-Total Time model to examine the association between ambient air pollution and first admission, as well as multiple readmissions for these CVDs.

Results

During a median follow-up of 12 years, 17 176 (6.03%) participants were hospitalised with CVDs, and 6203 (36.11%) patients with CVD had subsequent readmission events for CVDs. We observed significant associations between air pollution and both first admission and readmission for CVDs, with generally stronger associations on readmission for cardiovascular events. For example, the adjusted HRs for the first admission and subsequent readmission for cerebrovascular disease were 1.130 (95% CI 1.070 to 1.194) and 1.270 (95% CI 1.137 to 1.418) for each IQR increase of particulate matter with a diameter ≤2.5 µm. The corresponding HRs for CIHD were 1.060 (95% CI 1.008 to 1.114) and 1.120 (95% CI 1.070 to 1.171). Sex stratified analyses showed that the associations were generally more pronounced among females than males.

Conclusion

This study provides evidence that ambient air pollutants might play an important role in both first admission and readmission for cardiovascular events. In addition, patients with pre-existing CVDs may be more vulnerable to air pollution compared with healthy population.
Unilateral focused ultrasound subthalamotomy in early Parkinson’s disease: a pilot study
Authors: Martínez Fernández Raúl , Natera Villalba Elena , Rodriguez-Rojas Rafael , del Álamo Marta , Pineda-Pardo Jose A , Obeso Ignacio , Mata-Marín David , Guida Pasqualina , Jimenez-Castellanos Tamara , Pérez-Bueno Diana , Duque Alicia , Máñez Miró Jorge U , Gasca-Salas Carmen , Matarazzo Michele , Obeso Jose A
Published: September 2023

Background

Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson’s disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD).

Methods

Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients’ impression of change.

Results

Twelve patients with PD (median age 52.0 (IQR 49.8–55.3) years, median time from diagnosis 3.0 (2.1–3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment.

Conclusion

Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted.

Trial registration number

NCT04692116
Eosinophilic granulomatosis polyangiitis (EGPA) complicated with periaortitis, precipitating role of dupilumab? A case report a review of the literature
Authors: Kai Martine , Vion Pierre-Adrien , Boussouar Samia , Cacoub Patrice , Saadoun David , Le Joncour Alexandre
Published: September 2023

Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis that affects small size vessels. Only four cases of periaortitis associated with EGPA have been reported in the literature. We report the case of a 67-year-old woman with EGPA who developed periaortitis 11 months after the initiation of dupilumab for uncontrolled asthma with hypereosinophilia. Complete remission of the periaortitis, and of EGPA, was obtained after switching from dupilumab to mepolizumab combined with oral prednisone therapy. Dupilumab has been associated with hypereosinophilia, that is usually asymptomatic and transitory, but symptomatic cases including EGPA were exceptionally reported. Although causality has not yet been established, caution is advisable when prescribing dupilumab for uncontrolled asthma with features that might suggest EGPA.
Rituximab for the treatment of acute exacerbation of interstitial lung disease associated with connective tissue disease
Authors: León Román Francisco , Pintado-Cort Beatriz , García-Casado Diana , Muñiz-González Francisco , López García-Asenjo José Antonio , Díaz-Rodríguez Cristina , Montoro-López María Nieves , Loucel-Bellino Mauricio , Recio-Moreno Beatriz , Rebollo-Garrido Sara , Martínez-Hernández Yaiza , Cusacovich Ivan
Published: September 2023

Background

Acute exacerbation of interstitial lung disease (AE-ILD) is a severe complication with a poor prognosis. No clinical trials have supported the use of rituximab in AE-ILD associated with connective tissue disease.

Methods

We present a series of four cases in which administration of rituximab was associated with appropriate clinical, radiological and functional progress.

Results

The four patients were alive 30 days after discharge following their exacerbation.

Conclusions

Given the speed of action, safety and efficacy profile observed for rituximab, we believe that this agent should be further investigated in clinical trials so that it could be included in the daily clinical management of this severe condition.
Music therapy, quality of life and efficacy of immunotherapy for NSCLC
Authors: Duan Xu , Jia Yingxue , Chai Jiaying , Li Wen , Tang Lingxue , Li Anlong , Ge Han , Huang Runze , Cheng Huaidong
Published: September 2023

Objective

Our study examines how non-small cell lung cancer (NSCLC) survivors undergoing immunotherapy can experience reduced anxiety and psychological distress, improved quality of life (QOL) and increased immunotherapy efficacy.

Methods

133 men and 20 women with NSCLCs were enrolled. In a randomised controlled trial involving a care as usual group (CG) and a music therapy group (MTG), the researchers employed various tools such as the Self-Rating Anxiety Scale, Symptom Distress Thermometer, Functional Assessment of Cancer Therapy-General version 4 and Response Evaluation Criteria in Solid Tumours. These measures were used to evaluate anxiety, psychological distress, QOL and immunotherapy efficacy in patients undergoing immunotherapy before and after patients’ completion.

Results

After the intervention, patients in the MTG demonstrated a noteworthy reduction in anxiety (t=6.272, p≤0.001) and distress (t=10.111, p≤0.001), as well as an increase in QOL (t=−7.649, p≤0.001). Moreover, compared with patients in the CG, those in the MTG demonstrated a remarkable drop in anxiety (t=−4.72, p≤0.001) and distress (t=−7.29, p≤0.001), a significant increase in QOL (t=5.363, p≤0.001) and a significant improvement in immunotherapy efficacy (z=−2.18, p≤0.05) after the intervention.

Conclusions

The use of individual music therapy sessions appears to be effective in reducing anxiety and distress, while also increasing QOL and immunotherapy efficacy in patients with NSCLCs undergoing immunotherapy.
End-of-life care costs and place of death across health and social care sectors
Authors: Wang Jiunn , Shand Jenny , Gomes Manuel
Published: September 2023

Objectives

This study explores the relationship between end-of-life care costs and place of death across different health and social care sectors.

Methods

We used a linked local government and health data of East London residents (n=4661) aged 50 or over, deceased between 2016 and 2020. Individuals who died in hospital were matched to those who died elsewhere according to a wide range of demographic, socioeconomic and health factors. We reported mean healthcare costs and 95% CIs by care sectors over the 12-month period before death. Subgroup analyses were conducted to investigate if the role of place of death differs according to long-term conditions and age.

Results

We found that mean difference in total cost between hospital and non-hospital decedents was £4565 (95% CI £3132 to £6046). Hospital decedents were associated with higher hospital cost (£5196, £4499 to £5905), higher mental healthcare cost (£283, £78 to £892) and lower social care cost (−£838, −£1,209 to −£472), compared with individuals who died elsewhere. Subgroup analysis shows that the association between place of death and healthcare costs differs by age and long-term conditions, including cancer, mental health and cardiovascular diseases.

Conclusion

This study suggests that trajectories of end-of-life healthcare costs vary by place of death in a differential way across health and social care sectors. High hospital burden for cancer patients may be alleviated by strengthening healthcare provision in less cost-intensive settings, such as community and social care.
Comment: Surprising salmonid response to water diversion at four run-of-river hydroelectric projects in British Columbia
Authors: McCleary Richard J. , Ptolemy Ronald A.
Published: September 2023

Although the authors have completed an ambitious long-term field experiment involving the effects of water diversion on fish and invertebrates inhabiting steep mountain stream ecosystems, certain aspects of their study design and their interpretations create doubt and skepticism. Additional information is required on how the authors addressed challenging aspects of the research environment and how the sample sites were configured. A substantial decrease in water velocity during the treatment phase may have impacted capture probability. The authors downplay challenges of electrofishing in streams with extremely low conductivity. The authors do not discuss the potential effects of the dams at the boundary between the control and treatment sites, which may include entrainment and migration obstruction. The authors identify opportunities to extrapolate their findings to other systems but have not sufficiently characterized the environment and limiting factors within their study sites to facilitate extrapolation to different ecosystems. Additional work is required to explain how the alterations in this environment contributed to the increase in fish biomass that was observed.
Amenity complexity and urban locations of socio-economic mixing
Authors: Juhász Sándor , Pintér Gergő , Kovács Ádám J. , Borza Endre , Mónus Gergely , Lőrincz László , Lengyel Balázs
Published: September 2023

Cities host diverse people and their mixing is the engine of prosperity. In turn, segregation and inequalities are common features of most cities and locations that enable the meeting of people with different socio-economic status are key for urban inclusion. In this study, we adopt the concept of economic complexity to quantify the sophistication of amenity supply at urban locations. We propose that neighborhood complexity and amenity complexity are connected to the ability of locations to attract diverse visitors from various socio-economic backgrounds across the city. We construct the measures of amenity complexity based on the local portfolio of diverse and non-ubiquitous amenities in Budapest, Hungary. Socio-economic mixing at visited third places is investigated by tracing the daily mobility of individuals and by characterizing their status by the real-estate price of their home locations. Results suggest that measures of ubiquity and diversity of amenities do not, but neighborhood complexity and amenity complexity are correlated with the urban centrality of locations. Urban centrality is a strong predictor of socio-economic mixing, but both neighborhood complexity and amenity complexity add further explanatory power to our models. Our work combines urban mobility data with economic complexity thinking to show that the diversity of non-ubiquitous amenities, central locations, and the potentials for socio-economic mixing are interrelated.
Non-geometric pumping effects on the performance of interacting quantum-dot heat engines
Authors: Monsel Juliette , Schulenborg Jens , Splettstoesser Janine
Published: September 2023

Periodically driven quantum dots can act as counterparts of cyclic thermal machines at the nanoscale. In the slow-driving regime of geometric pumping, such machines have been shown to operate in analogy to a Carnot cycle. For larger driving frequencies, which are required to increase the cooling power, the efficiency of the operation decreases. Up to which frequency a close-to-optimal performance is still possible depends on the magnitude and sign of on-site electron–electron interaction. Extending our previous detailed study on cyclic quantum-dot refrigerators [Phys. Rev. B 106, 035405 (2022)], we here find that the optimal cooling power remains constant up to weak interaction strength compared to the cold-bath temperature. By contrast, the work cost depends on the interaction via the dot’s charge relaxation rate, as the latter sets the typical driving frequency for the onset of non-geometric pumping contributions.
Uncertainty Measures in Fuzzy Set-Valued Information Systems Based on Fuzzy β-Neighborhood Similarity Relations
Authors: Ren Jie , Zhu Ping
Published: September 2023

Uncertainty measures are instrumental in describing the classification abilities in information systems, and uncertain information has been measured and processed with granular computing theory. While the fuzzy set-valued information system is a generalization of fuzzy information systems, the relationship between the information granulation and the uncertainty in fuzzy set-valued information systems remains to be studied. This paper probes into uncertainty measures in fuzzy set-valued information systems based on the fuzzy [Formula: see text]-neighborhood and the idea of granulation. Specifically, the fuzzy [Formula: see text]-neighborhood similarity relation that reflects the similarity between two objects is defined in terms of the nearness degree. We propose the concepts of information granules and granular structures induced by fuzzy [Formula: see text]-neighborhood similarity relations, based on which we introduce the granularity measures and rough approximation measures of granular structures in fuzzy set-valued information systems. Given the situation of decision information systems, we propose the granularity-based rough approximation measures by combining granularity measures with rough approximation measures. Experiment results and effectiveness analysis show that the measures we proposed are reasonable and feasible.
Game-Theoretic Decision-Making and Payoff Design for UAV Collision Avoidance in a Three-Dimensional Airspace
Authors: Deniz Meryem , Zhao Lu , Wan Yan , Lewis Frank L.
Published: September 2023

Safety and efficiency are primary goals of air traffic management. With the integration of unmanned aerial vehicles (UAVs) into the airspace, UAV traffic management (UTM) has attracted significant interest in the research community to maintain the capacity of three-dimensional (3D) airspace, provide information, and avoid collisions. We propose a new decision-making architecture for UAVs to avoid collision by formulating the problem into a multi-agent game in a 3D airspace. In the proposed game-theoretic approach, the Ego UAV plays a repeated two-player normal-form game, and the payoff functions are designed to capture both the safety and efficiency of feasible actions. An optimal decision in the form of Nash equilibrium (NE) is obtained. Simulation studies are conducted to demonstrate the performance of the proposed game-theoretic collision avoidance approach in several representative multi-UAV scenarios.
UAV 3D Trajectory Planning and Optimization Using A* Algorithm Based on Free Space Method
Authors: Li Zhaoying , Fei Yuheng , Shi Ruoling
Published: September 2023

Due to the complexity of three-dimensional (3D) map modeling, the A* algorithm is inefficient in planning 3D trajectories for unmanned aerial vehicles (UAVs). This paper designs a method for planning 3D trajectories using A* algorithm based on free space method to address this issue. The method translates the 3D trajectory planning problem into a two-dimensional (2D) trajectory planning problem through flight surface extraction, thereby enhancing the efficiency of trajectory planning. In addition, a trajectory optimization method considering safety parameters and offset costs is designed for the waypoints that fail to meet UAV restrictions. The optimization method consists of longitudinal trajectory altitude adjustment and horizontal trajectory smoothing to ensure the trajectory aligns with the UAV climb rate constraint, normal overload constraint and minimum turning radius constraint. Simulation results show that the designed method delivers higher efficiency in 3D trajectory planning and optimization than the conventional method, and the optimized trajectory adheres to the above constraints.
Information Entropy-Based Cooperative Surveillance in Areas with Obstacles
Authors: Karimi Samine , Saghafi Fariborz
Published: September 2023

This paper solves the problem of searching a surveillance region and tracking possible radio emitters by multiple unmanned aerial vehicles cooperating through communication links in a decentralized manner. An innovative entropy-based approach is utilized to obtain the routes and tasks (search/track) for the vehicles. Another significant contribution of this research is the assumption of each vehicle being equipped with only one simple and cost-effective direction finding (DF) sensor. The routes and tasks are determined by minimizing a well-defined entropy-based cost function. The proposed surveillance scheme allows one to find a feasible and near-optimal solution. The algorithm’s efficiency is verified through various simulations.
A Modular Social Sensing System for Personalized Orienteering in the COVID-19 Era
Authors: Pilato Giovanni , Persia Fabio , Ge Mouzhi , Chondrogiannis Theodoros , D’Auria Daniela
Published: September 2023

Orienteering or itinerary planning algorithms in tourism are used to optimize travel routes by considering user preference and other constraints, such as time budget or traffic conditions. For these algorithms, it is essential to explore the user preference to predict potential points of interest (POIs) or tourist routes. However, nowadays, user preference has been significantly affected by COVID-19, since health concern plays a key tradeoff role. For example, people may try to avoid crowdedness, even if there is a strong desire for social interaction. Thus, the orienteering or itinerary planning algorithms should optimize routes beyond user preference. Therefore, this article proposes a social sensing system that considers the tradeoff between user preference and various factors, such as crowdedness, personality, knowledge of COVID-19, POI features, and desire for socialization. The experiments are conducted on profiling user interests with a properly trained fastText neural network and a set of specialized Naïve Bayesian Classifiers based on the “Yelp!” dataset. Also, we demonstrate how to approach and integrate COVID-related factors via conversational agents. Furthermore, the proposed system is in a modular design and evaluated in a user study; thus, it can be efficiently adapted to different algorithms for COVID-19-aware itinerary planning.
Beyond Digital Financial Services: Exploring Mobile Money Agents in Tanzania as General ICT Intermediaries
Authors: Raghunath Ananditha , Ndubuisi-Obi Innocent , Mpogole Hosea , Anderson Richard
Published: September 2023

Tanzanian mobile money and telecom agents (called wakala(s) in Swahili) have played a crucial role in expanding digital financial services (DFS) to rural areas. However, wakalas are losing their ability to financially sustain themselves providing intermediation services that their communities require. This work explores the potential for the wakala network to extend intermediation services to emerging information and communication technologies (ICTs) beyond the scope of commercial DFS by uncovering the social and institutional factors that currently shape wakala practices. First, we investigate how two different models of intermediation from information and communication technologies for development literature can inform broader strategies for intermediation through human infrastructures. We then complement this analysis with an on-the-ground quantitative survey and focus groups with community members and wakalas in Kagera, Tanzania. Our focus groups reveal that community members face challenges with new ICTs that require sustained intermediation and that wakalas encounter mounting financial instability and are thus receptive to intermediating for other ICTs. Finally, we present three factors that influence the broadening of the wakalas’ role of general ICT intermediaries: (1) aligning incentives and addressing the limits of pro bono actions, (2) providing appropriate training and a suitable support infrastructure, and (3) fostering trust-building and reciprocity.
Exploiting Flat Namespace to Improve File System Metadata Performance on Ultra-Fast, Byte-Addressable NVMs
Authors: Cai Miao , Shen Junru , Tang Bin , Huang Hao , Ye Baoliu
Published: September 2023

The conventional file system provides a hierarchical namespace by structuring it as a directory tree. Tree-based namespace structure leads to inefficient file path walk and expensive namespace tree traversal, underutilizing ultra-low access latency and superior sequential performance provided by non-volatile memories (NVMs). This article proposes FlatFS+, an NVM file system that features a flat namespace architecture while providing a compatible hierarchical namespace view. FlatFS+ incorporates three novel techniques: the direct file path walk model, range-optimized
B

r

tree, and compressed index key design with scan and write dual optimization, to fully exploit flat namespace to improve file system metadata performance on ultra-fast, byte-addressable NVMs. Evaluation results demonstrate that FlatFS+ achieves significant performance improvements for metadata-intensive benchmarks and real-world applications compared to other file systems.
Five Priorities to Help Learners in the Online Classroom
Authors: Steele John , Dyer Thomas , Mandernach Jean
Published: September 2023

To maximize online student learning, instructors should prioritize their time towards instructional strategies that students deem most impactful, such as providing individualized, one-to-one feedback; adopting a holistic feedback approach; engaging in asynchronous discussion forums; curating relevant content resources; and presenting instructional content in efficient, versatile formats. As research reveals, learners value instructor feedback and engagement in online discussions above all else, thereby guiding where educators should focus their limited instructional time.
Formation and Optical Characteristics of GaN:Eu/GaN Nanowires for Applications in Light-Emitting Diodes
Authors: Tatebayashi Jun , Otabara Takaya , Yoshimura Takuma , Hada Raiki , Yoshida Ryo , Ichikawa Shuhei , Fujiwara Yasufumi
Published: September 2023

This paper reviews our recent research about the formation and optical characteristics of GaN:Eu/GaN nanowires (NWs) by metalorganic vapor phase epitaxy for application in GaN-based red light-emitting diodes (LEDs). Two types of GaN:Eu/GaN NWs with different configurations are introduced, core–shell and axial geometries. The configuration of GaN:Eu layers on GaN core NWs can be controlled by changing the growth conditions, and affects the properties of Eu luminescence in the GaN NWs. Next, the optimization of the p-GaN growth conditions is performed to allow to form the p-GaN shell layers on the NWs with the pedestal of the NWs free from radial overgrowth, resulting in efficient electrical isolation between top and bottom part of the NWs. Then, the fabrication process of the NW LEDs towards future possible realization of flexible devices is established, including an etch-back process of the PDMS membranes to expose the top p-GaN contact layers. Finally, a proto-type of p-GaN/GaN:Eu/n-GaN NW LEDs on sapphire substrates is fabricated to characterize the device properties. Sharp red luminescence at room temperature from Eu3+ ions is observed under current injection. These results would pave the way towards the realization of flexible light-emitting devices utilizing NW structures based on compound semiconductors.
Porous Structure Induced Dielectric Loss Suppression for CB-g-PFOTES/PVDF Composites
Authors: Liu Hui , Li Cui , Ma Lili , Xin Meng , Wen Xin
Published: September 2023

Polymer-based dielectrics have long been the focus of research in the field of flexible thin-film capacitors. However, the low energy storage density of polymer-based dielectrics has been an obstacle for practical applications, since the enhancement of the dielectric constant is often accompanied by an increase in the dielectric loss. In this study, a novel core–shell structured CB-g-PFOTES nanoparticles with porous carbon black (CB) as the core and 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane (PFOTES) as the outer shell were successfully synthesized and further embedded into polyvinylidene fluoride (PVDF) matrix. As a result, the core–shell structured CB-g-PFOTES nanoparticles displayed notable improvements in the dielectric properties of composites. Typically, the CB-g-PFOTES/PVDF composites with a filler content of 2.5 wt% exhibited outstanding dielectric properties with a high dielectric constant of 33.2 and an extremely low dielectric loss of 0.0238 at 102 Hz. The significant suppression of dielectric loss was due to the fact that the porous structure of the CB effectively limits the interfacial charge transfer within the polymer matrix. This work provides a novel type of nanofiller for the fabrication of high dielectric nanocomposites, which is expected to further realize application in high energy storage density dielectric materials.
2022 Cannon lecture: an ode to signal transduction: how the growth hormone pathway revealed insight into height, malignancy, and obesity
Authors: Carter-Su Christin , Argetsinger Lawrence S. , Svezhova Nadezhda
Published: September 2023

Walter Cannon was a highly regarded American neurologist and physiologist with extremely broad interests. In the tradition of Cannon and his broad interests, we discuss our laboratory’s multifaceted work in signal transduction over the past 40+ years. We show how our questioning of how growth hormone (GH) in the blood communicates with cells throughout the body to promote body growth and regulate body metabolism led to insight into not only body height but also important regulators of malignancy and body weight. Highlights include finding that 1) A critical initiating step in GH signal transduction is GH activating the GH receptor-associated tyrosine kinase JAK2; 2) GH activation of JAK2 leads to activation of a number of signaling proteins, including STAT transcription factors; 3) JAK2 is autophosphorylated on multiple tyrosines that regulate the activity of JAK2 and recruit signaling proteins to GH/GH receptor/JAK2 complexes; 4) Constitutively activated STAT proteins are associated with cancer; 5) GH activation of JAK2 recruits the adapter protein SH2B1 to GH/GH receptor/JAK2 complexes where it facilitates GH regulation of the actin cytoskeleton and motility; and 6) SH2B1 is recruited to other receptors in the brain, where it enhances satiety, most likely in part by regulating leptin action and neuronal connections of appetite-regulating neurons. These findings have led to increased understanding of how GH functions, as well as therapeutic interventions for certain cancer and obese individuals, thereby reinforcing the great importance of supporting basic research since one never knows ahead of time what important insight it can provide.
Inhibitory tagging in the superior colliculus during visual search
Authors: Conroy Christopher , Nanjappa Rakesh , McPeek Robert M.
Published: September 2023

Searching a cluttered scene for an object of interest is a ubiquitous task in everyday life, which we often perform relatively quickly and efficiently. It has been suggested that to achieve such speed and efficiency an inhibitory-tagging mechanism inhibits saccades to objects in the scene once they have been searched and rejected. Here, we demonstrate that the superior colliculus represents this type of inhibition during search, consistent with its role in saccade target selection.
Variable task switching in the feeding network of Aplysia is a function of differential command input
Authors: Evans Colin G. , Barry Michael A. , Perkins Matthew H. , Jing Jian , Weiss Klaudiusz R. , Cropper Elizabeth C.
Published: September 2023

We study a type of motor program that can be induced either by stimulating a higher-order projection neuron that induces a persistent state, or by coactivating projection neurons that configure activity but do not produce a state change. We show that when an activity is configured without a state change, it is possible to immediately return to an intermediate state that subsequently can be converted to any type of motor program.
Parallel processing of value-related information during multi-attribute decisions
Authors: Nakahashi Ayuno , Cisek Paul
Published: September 2023

We show that during value-based decisions, humans do not always use all reward-related information to make their choice, but instead can “jump the gun” using partial information. In particular, when different sources of information were in conflict, early decisions were mostly based on fast bottom-up information, and sometimes followed by corrective changes-of-mind based on slower top-down information. This supports parallel decision processes among different information sources, as opposed to a single integrated “common currency.”
Pantoprazole‐Induced Bone Loss through Gastrin Secretion: A Stereological Study
Authors: Saki Forough , Shams Mesbah , Dastghaib Sanaz , Koohpeyma Farhad
Published: September 2023

Background. Recent researches have failed to uncover a clear explanation for proton pump inhibitors’ bone‐loss effects. In light of pantoprazole’s effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion. Methods. Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats’ femoral bones were examined stereologically at the end of the investigation. Results. The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups. Conclusion. Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.
Sorghum- and Chickpea-Based Ready-to-Eat Extrudate Flakes: Quality Attributes and In Vitro Digestibility
Authors: Kaur Jashandeep , Singh Baljit , Dhull Sanju Bala , Singh Arashdeep , Purewal Sukhvinder Singh
Published: September 2023

The study is aimed at the development of whole sorghum-based ready-to-eat extruded snacks using chickpea at different barrel temperature (BT) (130, 145, and 170°C) and feed moisture (FM) (14, 16, and 18%) conditions, and quality changes on the functionality aspects of prepared snacks were evaluated. Data revealed that with increment in barrel temperature and feed moisture, the antioxidant properties, viz., ferric reducing antioxidant potential (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition, total phenolic content (TPC), and hardness of the flakes amplified; however, elevated barrel temperature and decreased feed moisture enhanced the expansion ratio, water solubility index, and overall acceptability of lakes. The results of the (

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) color values indicated that the rates of Maillard’s reaction were higher when the BT and FM processes were intensified. Enhanced extrusion conditions (BT and FM) lead to higher levels of resistant starch and improved in vitro protein digestibility. The estimated glycemic index of the flakes ranges from 52 to 54, thus showing low estimated glycemic index (E-GI) of flakes. Slowly digestible starch and Exp-GI reveal a positive correlation among themselves. Results from the present study showed that highly acceptable flakes with commercialization properties can be successfully formulated using extrusion processing.
A Novel Adaptive Square Root UKF with Forgetting Factor for the Time-Variant Parameter Identification
Authors: Zhang Yanzhe , Ding Yong , Bu Jianqing , Guo Lina
Published: September 2023

The unscented Kalman filter (UKF) serves as an efficient estimator widely utilized for the recursive identification of parameters. However, the UKF is not well suited for tracking time-variant parameters. Moreover, the unscented transformation (UT) used in the UKF typically relies on Cholesky decomposition to perform the square root operation of the covariance matrix. This method necessitates the matrix to maintain symmetry and positive definiteness. Due to the adverse influence of rounding error and noise, it becomes challenging to guarantee the positive definiteness of the matrix in each recursive step for practical engineering. The square root UKF (SRUKF) eliminates the need for the square root operation in the UT by directly updating the square root of the covariance matrix during each recursion. However, the SRUKF still relies on the rank 1 update to the Cholesky factorization to perform the recursive process, which also necessitates the matrix to be positive definite. Furthermore, the SRUKF is ineffective in the identification of time-variant parameters. Therefore, this paper proposes a modification to the SRUKF that ensures unconditional numerical stability by utilizing QR decomposition. Subsequently, the modified square root UKF (MSRUKF) method is enhanced by incorporating an adaptive forgetting factor that can be adjusted based on the residual information from each recursive step. This adaptation leads to the development of the adaptive SRUKF with forgetting factor (ASRUKF-FF) method, which significantly improves the tracking capability for time-variant parameters. To validate the effectiveness of the proposed method, this paper demonstrates its application in identifying the time-variant stiffness and damping parameters of a three-story frame structure. In addition, the method is employed to estimate the time-variant stiffness of the bridge excited by vehicles. The simulation results show that the proposed method has the superiority of high accuracy, strong robustness, and widespread applicability, even with incomplete measurements and inappropriate parameter settings.
The Effect of Lycium ruthenicum Murry Anthocyanins on the Apoptosis and Proliferation of H9c2 Cell Induced by Hypoxia
Authors: Li Jinming , Wang Mengjie , Wu Hua , Chen Xinlei , Xing Qianwen , Shen Tong , Wang Shuo , Wu Xiaoqing
Published: September 2023

Based on the strong antioxidant activity of anthocyanins, this study was aimed to explore the potential influence of Lycium ruthenicum Murry anthocyanins (LRMA) on hypoxia-induced apoptosis and proliferation of H9c2 rat cardiomyocytes. The cell viability was first tested after exposure to normoxia, hypoxia, and hypoxia + LRMA. After being incubated for 12 h under normoxia and 24 h under hypoxia in 50 μg/mL LRMA or 100 μM Salidroside, respectively, LDH content, cell morphology, and cell cycle progression were analyzed. In addition, cellular apoptosis along with the expression of B-cell lymphoma-2 (Bcl2) and BCL2-associated X (Bax) was explored. After that, RNA-seq and bioinformatics analysis revealed the lncRNAs-miRNAs-mRNAs ceRNA network related to hypoxia adaptation of H9c2 cells modulated by LRMA. The final step was to detect the expression of cyclin T2 (CCNT2), cyclin-dependent kinase 9 (CDK9), and forkhead box P1 (FOXP1). The results revealed that LRMA significantly attenuated the reduction of viability and protected H9c2 cells under hypoxic condition. In addition, LRMA not only restored the proliferation activity of H9c2 cells but also promoted apoptosis through stimulating Bcl2 enhancement and Bax inhibition induced by hypoxic stimulation. This study also identified distinct pairs of ceRNA and the hypoxia-related differentially expressed genes regulated by LRMA, including 862 lncRNAs (694 upregulated and 168 downregulated), 7 miRNAs (1 upregulated and 6 downregulated), and 351 mRNAs (226 upregulated and 125 downregulated). The results also suggested that the hypoxia-related genes regulated by LRMA were mainly enriched in cell proliferation and division, cell energy metabolism, inflammatory response, and cell development. However, LRMA could effectively promote the proliferation of H9c2 cells through enhancing CCNT2, CDK9, and FOXP1 under hypoxic conditions. Overall, LRMA could alleviate the proliferation inhibition and apoptosis in hypoxia-induced H9c2 cells.
Supplementary material and method from S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells
Authors: Nagira Yoji , Nagira Morio , Nagai Ryohei , Nogami Wataru , Hirata Michinari , Ueyama Azumi , Yoshida Tetsuya , Yoshikawa Mai , Shinonome Satomi , Yoshida Hiroshi , Haruna Miya , Miwa Hiroto , Chatani Natsumi , Ohkura Naganari , Wada Hisashi , Tanaka Hidekazu
Published: September 2023

Supplementary Information
Figure S3 from S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells
Authors: Nagira Yoji , Nagira Morio , Nagai Ryohei , Nogami Wataru , Hirata Michinari , Ueyama Azumi , Yoshida Tetsuya , Yoshikawa Mai , Shinonome Satomi , Yoshida Hiroshi , Haruna Miya , Miwa Hiroto , Chatani Natsumi , Ohkura Naganari , Wada Hisashi , Tanaka Hidekazu
Published: September 2023

Concentration of S-531011 in serum and tumor after a single intravenous administration of S-531011 in CT26.WT tumor-bearing hCCR8 KI mice.
Figure S1 from S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells
Authors: Nagira Yoji , Nagira Morio , Nagai Ryohei , Nogami Wataru , Hirata Michinari , Ueyama Azumi , Yoshida Tetsuya , Yoshikawa Mai , Shinonome Satomi , Yoshida Hiroshi , Haruna Miya , Miwa Hiroto , Chatani Natsumi , Ohkura Naganari , Wada Hisashi , Tanaka Hidekazu
Published: September 2023

The binding activity of S-531011 against various chemokine receptors, PD-1, PD-L1, CTLA4, or mouse CCR8
Supplementary Figure 4 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

Clinical parameters comparison of AMT-562 and AMT-562-T1000 in cynomolgus monkey.
Supplementary Figure 3 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

Stability and toxicity in monkey of HER2-targeting ADCs based on T800 and T1000.
Figure S4 from T Cell–intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia
Authors: Lam Vi , Roleder Carly , Liu Tingting , Bruss Nur , Best Scott , Wang Xiaoguang , Phillips Tycel , Shouse Geoffrey , Berger Allison J. , Alinari Lapo , Wang Lili , Siddiqi Tanya , Pennock Nathan D. , Danilov Alexey V.
Published: September 2023

Figure S4 shows 1x104 A20 lymphoma cells were treated with the indicated doses of TAK-981 for 48 hours.
Supplementary Figure 14 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

AMT-562 overcome U3-1402 resistance in lung cancer models.
Figure S3 from T Cell–intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia
Authors: Lam Vi , Roleder Carly , Liu Tingting , Bruss Nur , Best Scott , Wang Xiaoguang , Phillips Tycel , Shouse Geoffrey , Berger Allison J. , Alinari Lapo , Wang Lili , Siddiqi Tanya , Pennock Nathan D. , Danilov Alexey V.
Published: September 2023

Figure S3 shows Hallmark enrichment plot of RNA collected from naïve T cells from patients with CLL treated with TAK-981
Supplementary Figure 13 from AMT-562, a Novel HER3-targeting Antibody–Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shuhui , Hu Wenhao , Meng Xun
Published: September 2023

HER3 expression in NSCLC and clinical trial status of U3-1402.
Figure S1 from T Cell–intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia
Authors: Lam Vi , Roleder Carly , Liu Tingting , Bruss Nur , Best Scott , Wang Xiaoguang , Phillips Tycel , Shouse Geoffrey , Berger Allison J. , Alinari Lapo , Wang Lili , Siddiqi Tanya , Pennock Nathan D. , Danilov Alexey V.
Published: September 2023

Figure S1 shows CD3+ T cells were pre-treated with TAK-981 at the indicated doses for 1 h, followed by TCR stimulation and quantification of western blots of figure 1