bluuebunny/crossref_metadata_2025 huggingface dataset:
Next steps for workplace‐based assessments of entrustable professional activities
Authors: Stumbar Sarah E. , Eliason Sarah , Toonkel Rebecca , Amie Katrina , Bonnin Rodolfo , Gralnik Leonard , Kantor Julie , Minor Suzanne
Published: February 2024

Background

Florida International University Herbert Wertheim College of Medicine (FIU‐HWCOM) participated in the AAMC Core Entrustable Professional Activities (EPA) implementation pilot. Entrustment decision processes based on data from workplace‐based assessments (WBAs) were piloted. Outcomes illustrated challenges including variability across EPAs with regards to learner level alignment and feasibility of data collection in the form of WBAs. In addition, students reported discomfort requesting WBA completion by preceptors and dissatisfaction with associated feedback.

Approach

To guide future directions, we conducted a survey of third‐year students to better understand their experience with and perceptions of WBAs used to evaluate EPAs at FIU‐HWCOM.

Evaluation

Survey response was 96% (n = 107/112). Most (84%) reported that WBAs were not valuable to their development and that preceptors often did not complete WBAs in a timely fashion. Many (47%) reported not receiving verbal feedback. Most students (78%) used language in written responses demonstrating confusion between the EPAs and the WBAs used to assess them.

Implications

The use of WBAs to assess EPAs did not have its intended impact at FIU‐HWCOM. For future classes, WBA forms will consist of paper cards with questions directly assessing performance of skills aligned with EPAs 1, 5 and 6 only. To continue to promote feedback, students will be required to collect WBAs on all clerkships, but the number of required WBAs will be less than prior and no entrustment decisions will be made.
Clinical outcomes of baloxavir versus oseltamivir in immunocompromised patients
Authors: Ringer Matthew , Malinis Maricar , McManus Dayna , Davis Matthew , Shah Sunish , Trubin Paul , Topal Jeffrey E. , Azar Marwan M.
Published: February 2024

Background

Neuraminidase inhibitors, including oseltamivir, are the treatment standard for influenza. Baloxavir, a novel antiviral, demonstrated comparable outcomes to oseltamivir in outpatients with influenza. Baloxavir was equally effective as oseltamivir in a retrospective study of hospitalized patients with influenza at our institution. However, the efficacy of baloxavir in immunocompromised patients is unclear.

Methods

We conducted a retrospective cohort study of immunocompromised adult patients hospitalized with influenza A who received baloxavir from January 2019 to April 2019 or oseltamivir from January 2018 to April 2018. Demographic and clinical outcomes were assessed. Primary outcomes were time from antiviral initiation to resolution of hypoxia and fever. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) care, ICU LOS, and 30‐day mortality.

Results

Of 95 total patients, 52 received baloxavir and 43 received oseltamivir. Other than younger age (57.5 vs. 65; p = .035) and longer duration between vaccination and symptom onset (114 vs. 86 days; p = .001) in the baloxavir group, baseline characteristics did not differ. H1 was the predominant subtype in the baloxavir group (65.3%) versus H3 in the oseltamivir group (85.7%). When comparing baloxavir to oseltamivir, there was no significant difference in median time from antiviral initiation to resolution of hypoxia (59.9 vs. 42.5 h) and to resolution of fever (21.6 vs. 26.6 h). There were no differences in secondary outcomes.

Conclusion

Baloxavir was not associated with longer time to resolution of hypoxia or fever in comparison to oseltamivir. Results must be taken in context of variations in seasonal influenza subtype and resistance rates.

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A carboxysome‐based CO2 concentrating mechanism for C3 crop chloroplasts: advances and the road ahead
Authors: Nguyen Nghiem D. , Pulsford Sacha B. , Förster Britta , Rottet Sarah , Rourke Loraine , Long Benedict M. , Price G. Dean
Published: February 2024

The introduction of the carboxysome‐based CO2 concentrating mechanism (CCM) into crop plants has been modelled to significantly increase crop yields. This projection serves as motivation for pursuing this strategy to contribute to global food security. The successful implementation of this engineering challenge is reliant upon the transfer of a microcompartment that encapsulates cyanobacterial Rubisco, known as the carboxysome, alongside active bicarbonate transporters. To date, significant progress has been achieved with respect to understanding various aspects of the cyanobacterial CCM, and more recently, different components of the carboxysome have been successfully introduced into plant chloroplasts. In this Perspective piece, we summarise recent findings and offer new research avenues that will accelerate research in this field to ultimately and successfully introduce the carboxysome into crop plants for increased crop yields.
Gaza: A decolonial geography
Authors: Agha Zena , Esson James , Griffiths Mark , Joronen Mikko
Published: February 2024

This commentary addresses three objectives: (1) to situate and contextualise the ongoing military assault on Gaza within longer colonial histories in Palestine; (2) to collate resources that can equip geographers—specialist and non‐specialist, academic and non‐academic—with resources to build decolonial politics on Palestine–Israel; and (3) to contribute to discussions on what we, as geographers, can do to support Palestinian calls for liberation. These objectives are informed by a strong conviction that now is not a time for equivocation or silence. Palestinians, both in Palestine and in exile, need robust support and solidarity. This commentary offers one example of the form this support and solidarity can take in the context of academia. It does so by calling forth our discipline's plural and deep commitment to justice and thoroughgoing critique of the deleterious power structures and colonial legacies that have brought us to this current moment of crisis in Palestine.
Diagnostic utility of the total nucleated cell count for differentiation of septic and sterile peritoneal effusions in dogs
Authors: DiDomenico Amy E. , Jacob Megan E. , Stowe Devorah M. , Gruber Erika J.
Published: February 2024

Background

Rapid and accurate diagnosis of septic peritonitis is critical for initiating appropriate medical and surgical management.

Objectives

The aim of this study was to determine the diagnostic utility of the total nucleated cell count (TNCC), absolute neutrophil count, neutrophil percentage, and total protein (TP) to distinguish septic versus non‐septic peritoneal effusions in dogs.

Methods

Electronic medical records were retrospectively searched for peritoneal fluid samples from 2008 to 2018 and classified as septic or non‐septic based on bacterial culture and/or cytology results. Receiver operator characteristic curves (ROCs) were used to describe the overall diagnostic utility of each test, with optimal cutpoints analyzed to dichotomize continuous variables. Positive and negative likelihood ratios were calculated at these cutpoints.

Results

A total of 166 unique samples, including 87 septic and 79 non‐septic peritoneal effusions, were included. There were no significant differences in dog sex, age, or days hospitalized between groups. Septic effusions had significantly higher TP, TNCC, absolute neutrophil count, and neutrophil percentage compared with non‐septic effusions. The area under the curve of the ROC curves was TNCC (0.80), absolute neutrophil count (0.80), neutrophil percentage (0.64), and TP (0.63). For TNCC and absolute neutrophil count, optimal cutoffs were 17.13 × 103 cells/μL and 19.88 × 103 cells/μL, resulting in positive and negative likelihood ratios of 2.39 and 0.28 and 2.85 and 0.28, respectively.

Conclusions

Total nucleated cell counts and absolute neutrophil counts aid in the differentiation of septic and non‐septic peritoneal effusions with similar diagnostic utility but are not sufficiently sensitive or specific to use without concurrent microscopic evaluation.
Algebraically generated groups and their Lie algebras
Authors: Kraft Hanspeter , Zaidenberg Mikhail
Published: February 2024

The automorphism group of an affine variety is an ind‐group. Its Lie algebra is canonically embedded into the Lie algebra of vector fields on . We study the relations between subgroups of and Lie subalgebras of . We show that a subgroup generated by a family of connected algebraic subgroups of is algebraic if and only if the Lie algebras generate a finite‐dimensional Lie subalgebra of . Extending a result by Cohen–Draisma (Transform. Groups 8 (2003), no. 1, 51–68), we prove that a locally finite Lie algebra generated by locally nilpotent vector fields is algebraic, that is, for an algebraic subgroup . Along the same lines, we prove that if a subgroup generated by finitely many connected algebraic groups is solvable, then it is an algebraic group. We also show that a unipotent algebraic subgroup has derived length . This result is based on the following triangulation theorem: Every unipotent algebraic subgroup of with a dense orbit in is conjugate to a subgroup of the de Jonquières subgroup. Furthermore, we give an example of a free subgroup generated by two algebraic elements such that the Zariski closure is a free product of two nested commutative closed unipotent ind‐subgroups. To any affine ind‐group , one can associate a canonical ideal . It is linearly generated by the tangent spaces for all algebraic subsets that are smooth in . It has the important property that for a surjective homomorphism , the induced homomorphism is surjective as well. Moreover, if is a subnormal closed ind‐subgroup of finite codimension, then has finite codimension in .
Multilinear rough singular integral operators
Authors: Grafakos Loukas , He Danqing , Honzík Petr , Park Bae Jun
Published: February 2024

We study ‐linear homogeneous rough singular integral operators associated with integrable functions on with mean value zero. We prove boundedness for from to when and in the largest possible open set of exponents when and . This set can be described by a convex polyhedron in .
Pre‐intervention myocardial stress is a good predictor of aortic valvuloplasty outcome for fetal critical aortic stenosis and evolving HLHS
Authors: Green Laura , Chan Wei Xuan , Prakash Indumita , Tulzer Andreas , Tulzer Gerald , Yap Choon Hwai
Published: February 2024

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS‐eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre‐FAV image‐based computations could robustly distinguish between CAS‐eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image‐based finite element biomechanics modelling of nine CAS‐eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS‐eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes.

image

Key points

Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions.

Computational simulations show that a biomechanics parameter, pre‐intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters.

An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested.
Building a Partnership Between a University and Local High School to Foster and Grow Interest in Biomedical Sciences and Engineering
Authors: Castile Ryan M. , Jobe Jamie , Iannucci Leanne E. , Reals Rebecca F. , Pavey Shawn N. , Fitzgerald Jon , Lake Spencer P.
Published: February 2024

To help foster interest in science, technology, engineering, and math (STEM), it is important to develop opportunities that excite and teach young minds about STEM-related fields. Over the past several years, our university-based research group has sought to help grow excitement around the biomechanics and biomedical engineering fields. The purposes of this technical brief are to (1) discuss the development of a partnership built between a St. Louis area high school and biomechanics research lab and (2) provide practical guidance for other researchers looking to implement a long-term outreach program. The partnership uses three different outreach opportunities. The first opportunity consisted of 12th-grade students visiting university research labs for an up-close perspective of ongoing biomedical research. The second opportunity was a biomedical research showcase where research-active graduate students traveled to the high school to perform demonstrations. The third opportunity consisted of a collaborative capstone project where a high school student was able to carry out research directly in a university lab. To date, we have expanded our reach from 19 students to interacting with over 100 students, which has yielded increased interest in STEM related research. Our postprogram survey showed that outreach programs such as the one described herein can increase interest in STEM within all ages of high school students. Building partnerships between high schools and university researchers increases the interest in STEM amongst high school students, and gives graduate students an outlet to present work to an eager-to-learn audience.
Rational design of ICD-inducing nanoparticles for cancer immunotherapy
Authors: Zhang Zhanzhan , Pan Zheng , Li Qiushi , Huang Qingqing , Shi Linqi , Liu Yang
Published: February 2024

Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures’ potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.
Human Bocavirus 1 NP1 acts as an ssDNA-binding protein to help AAV2 DNA replication and cooperates with RPA to regulate AAV2 capsid expression
Authors: Zhao Yanqun , Liu Wei , Li Yanjie , Ma Jing , Liu Ting , Cui Huichan , Deng Yongheng , Liao Xiaochen , Wang Zekun
Published: February 2024

Adeno-associated virus (AAV) requires co-infection with helper virus for efficient replication. We previously reported that Human Bocavirus 1 (HBoV1) genes, including
NP1
,
NS2
, and
BocaSR
, were critical for AAV2 replication. Here, we first demonstrate the essential roles of the NP1 protein in AAV2 DNA replication and protein expression. We show that NP1 binds to single-strand DNA (ssDNA) at least 30 nucleotides (nt) in length in a sequence-independent manner. Furthermore, NP1 colocalized with the BrdU-labeled AAV2 DNA replication center, and the loss of the ssDNA-binding ability of NP1 by site-directed mutation completely abolished AAV2 DNA replication. We used affinity-tagged NP1 protein to identify host cellular proteins associated with NP1 in cells cotransfected with the HBoV1 helper genes and AAV2 duplex genome. Of the identified proteins, we demonstrate that NP1 directly binds to the DBD-F domain of the RPA70 subunit with a high affinity through the residues 101–121. By reconstituting the heterotrimer protein RPA
in vitro
using gel filtration, we demonstrate that NP1 physically associates with RPA to form a heterologous complex characterized by typical fast-on/fast-off kinetics. Following a dominant-negative strategy, we found that NP1-RPA complex mainly plays a role in expressing AAV2 capsid protein by enhancing the transcriptional activity of the p40 promoter. Our study revealed a novel mechanism by which HBoV1 NP1 protein supports AAV2 DNA replication and capsid protein expression through its ssDNA-binding ability and direct interaction with RPA, respectively.

IMPORTANCE

Recombinant adeno-associated virus (rAAV) vectors have been extensively used in clinical gene therapy strategies. However, a limitation of these gene therapy strategies is the efficient production of the required vectors, as AAV alone is replication-deficient in the host cells. HBoV1 provides the simplest AAV2 helper genes consisting of
NP1
,
NS2
, and
BocaSR
. An important question regarding the helper function of HBoV1 is whether it provides any direct function that supports AAV2 DNA replication and protein expression. Also of interest is how HBoV1 interplays with potential host factors to constitute a permissive environment for AAV2 replication. Our studies revealed that the multifunctional protein NP1 plays important roles in AAV2 DNA replication via its sequence-independent ssDNA-binding ability and in regulating AAV2 capsid protein expression by physically interacting with host protein RPA. Our findings present theoretical guidance for the future application of the HBoV1 helper genes in the rAAV vector production.
Structural insights into the interaction between adenovirus C5 hexon and human lactoferrin
Authors: Dhillon Arun , Persson B. David , Volkov Alexander N. , Sülzen Hagen , Kádek Alan , Pompach Petr , Kereïche Sami , Lepšík Martin , Danskog Katarina , Uetrecht Charlotte , Arnberg Niklas , Zoll Sebastian
Published: February 2024

Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment and subsequently integrins for entry. CAR and integrins are however located deep within the tight junctions in the mucosa where they would not be easily accessible. Recently, a model for CAR-independent AdV entry was proposed. In this model, human lactoferrin (hLF), an innate immune protein, aids the viral uptake into epithelial cells by mediating interactions between the major capsid protein, hexon, and yet unknown host cellular receptor(s). However, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a new cryo-EM structure of HAdV-5C hexon at high resolution alongside a hybrid structure of HAdV-5C hexon complexed with human lactoferrin (hLF). These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily
via
its N-terminal lactoferricin (Lfcin) region, interacting with hexon’s hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts and also identify additional regions within hLF that critically contribute to hexon binding. Our study sheds more light on the intricate mechanism by which HAdV-C5 utilizes soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development.

IMPORTANCE

Our study delves into the structural aspects of adenovirus (AdV) infections, specifically HAdV-C5 in the respiratory epithelium. It uncovers the molecular details of a novel pathway where human lactoferrin (hLF) interacts with the major capsid protein, hexon, facilitating viral entry, and bypassing traditional receptors such as CAR and integrins. The study’s cryo-EM structures reveal how hLF engages hexon, primarily through its N-terminal lactoferricin (Lfcin) region and hexon’s hypervariable region 1 (HVR-1). Mutational analyses identify critical Lfcin contacts and other regions within hLF vital for hexon binding. This structural insight sheds light on HAdV-C5’s mechanism of utilizing soluble hLF/Lfcin for cellular entry, holding promise for gene therapy and vaccine development advancements in adenovirus research.
Analysis of guideline recommendations for treatment of asthma exacerbations in children: a Pediatric Emergency Research Networks (PERN) study
Authors: Craig Simon , Collings Madeline , Gray Charmaine , Benito Javier , Velasco Roberto , Lyttle Mark D , Roland Damian , Schuh Suzanne , Shihabuddin Bashar , Kwok Maria , Mahajan Prashant , Johnson Mike , Zorc Joseph , Khanna Kajal , Fernandes Ricardo , Yock-Corrales Adriana , Santhanam Indumathy , Cheema Baljit , Ong Gene Yong-Kwang , Jaiganesh Thiagarajan , Powell Colin , Nixon Gillian , Dalziel Stuart , Babl Franz E , Graudins Andis
Published: February 2024

Rationale

There is significant practice variation in acute paediatric asthma, particularly severe exacerbations. It is unknown whether this is due to differences in clinical guidelines.

Objectives

To describe and compare the content and quality of clinical guidelines for the management of acute exacerbations of asthma in children between geographic regions.

Methods

Observational study of guidelines for the management of acute paediatric asthma from institutions across a global collaboration of six regional paediatric emergency research networks.

Measurements and main results

158 guidelines were identified. Half provided recommendations for at least two age groups, and most guidelines provided treatment recommendations according to asthma severity.

There were consistent recommendations for the use of inhaled short-acting beta-agonists and systemic corticosteroids. Inhaled anticholinergic therapy was recommended in most guidelines for severe and critical asthma, but there were inconsistent recommendations for its use in mild and moderate exacerbations. Other inhaled therapies such as helium-oxygen mixture (Heliox) and nebulised magnesium were inconsistently recommended for severe and critical illness.

Parenteral bronchodilator therapy and epinephrine were mostly reserved for severe and critical asthma, with intravenous magnesium most recommended. There were regional differences in the use of other parenteral bronchodilators, particularly aminophylline.

Guideline quality assessment identified high ratings for clarity of presentation, scope and purpose, but low ratings for stakeholder involvement, rigour of development, applicability and editorial independence.

Conclusions

Current guidelines for the management of acute paediatric asthma exacerbations have substantial deficits in important quality domains and provide limited and inconsistent guidance for severe exacerbations.
Computer-assisted robotic device for upper limb interventions for a patient with an incomplete cervical level spinal cord injury
Authors: Mackenzie Lynette , Tan Emma , Benad Lisa
Published: February 2024

A man in his 50s with an incomplete cervical spinal cord injury underwent a 3-week occupational therapy programme using a computer-assisted robotic device for the upper limbs (Diego) in an acute care spinal injury unit. The patient and their partner reported their experience. Range of motion (ROM), muscle strength, pain, fatigue, independence and occupational performance are reported. Improvements occurred in upper limb ROM (shoulder and elbow), muscle strength (right elbow extensors), fatigue and functional status. Whether the results in this patient with the Diego were the same or better than standard care could not be determined. Preliminary findings suggest that the Diego was feasible for rehabilitation in an acute setting in our patient. However, it may not be suitable for all patients and a large comparative study with other therapies is needed. A limitation in the use of the Diego relates to the initial cost of the device ($A150 000).
Risk factors for development of hyper-reflective foci overlying drusen in eyes with intermediate age-related macular degeneration
Authors: Mahmoudi Alireza , Manafi Navid , Corradetti Giulia , Gupta Nittala Muneeswar , Emamverdi Mehdi , Trejo Corona Stephanie , Wykoff Charles C , Sarraf David , Sadda SriniVas R
Published: February 2024

Aims

The aim of this study is to assess baseline characteristics of drusen preceding the development of intraretinal hyper-reflective foci (IHRF) in eyes with intermediate age-related macular degeneration (AMD).

Methods

In this retrospective case-control study, longitudinal optical coherence tomography (OCT) volume data from eyes with intermediate AMD in a retina clinic population were screened. All drusen that developed overlying IHRF were marked. A random number generator was used to select for further grading three drusen that did not develop IHRF.

Results

Ninety eyes (from 72 patients), including 140 drusen with overlying IHRF and 270 IHRF− drusen, were analysed. Greater drusen height, basal drusen width and overlying ellipsoid zone (EZ) and external limiting membrane disruption were associated with a significantly greater risk for IHRF development (p≤0.001). Regression analysis revealed EZ disruption increased these odds by 4.1 (p≤0.001). Each 10-µm increase in drusen height and width increased the odds by 34% (p≤0.001) and 3% (p: 0.005), respectively. Each 100-µm increase in distance from the fovea decreased the odds by 10% (p: 0.013).

Conclusions

The presence of overlying EZ disruption and a greater drusen height substantially increased the risk for IHRF development, whereas drusen further from the fovea indicated reduced risk. Given the importance of IHRF as a biomarker for AMD progression, these findings may be of value in defining patient populations for future early intervention trials.
Geographical differences in the financial impacts of different forms of tobacco licence fees on small retailers in Scotland
Authors: Valiente Roberto , Tunstall Helena , Kong Amanda Y , Wilson Luke B , Gillespie Duncan , Angus Colin , Brennan Alan , Shortt Niamh K , Pearce Jamie
Published: February 2024

Objective

Retailer licencing fees are a promising avenue to regulate tobacco availability. However, they face strong opposition from retailers and the tobacco industry, who argue significant financial impacts. This study compares the impacts of different forms of tobacco licence schemes on retailers’ profits in Scotland.

Methods

We calculated gross profits from tobacco sales in 179 convenience stores across Scotland using 1 099 697 electronic point-of-sale records from 16 weeks between 2019 and 2022. We estimated different fees using universal, volumetric and separate urban/rural schemes. We identified the point at which 50% of retailers would no longer make a gross profit on tobacco sales for each scheme and modelled the financial impact of 10 incremental fee levels. The financial impact was assessed based on changes in retailers’ tobacco gross profits. Differences by neighbourhood deprivation and urban/rural status were examined.

Results

The gross profit from tobacco per convenience store averaged £15 859/year. Profits were 2.29 times higher in urban (vs rural) areas and 1.59 times higher in high-deprivation (vs low-deprivation) areas, attributable to higher sales volumes. Tobacco gross profit decreased proportionally with increasing fee levels. Universal and urban/rural fees had greater gross profit reductions in rural and/or less deprived areas, where profits were lower, compared with volumetric fees.

Conclusion

The introduction of tobacco licence fees offers a potential opportunity for reducing the availability of tobacco retailers. The likely impact of a tobacco licence fee is sensitive to the type of licence scheme implemented, the level at which fees are set and the retailers’ location in relation to neighbourhood deprivation and rurality.
Modeling the Bifurcation Dynamics of Rumor Propagation in the Spatial Environment
Authors: Zhu Linhe , Chen Xinlin
Published: February 2024

The harm caused by rumors is immeasurable. Studying the dynamic characteristics of rumors can help control their spread. In this paper, we propose a nonsmooth rumor model with a nonlinear propagation rate. First, we utilize the positive invariant regions to prove the boundedness of solutions. Second, we analyze the conditions for the existence of equilibrium points in both the left and right systems. Additionally, we confirm the occurrence of saddle-node bifurcation in the left system. Next, by considering the influence of spatial diffusion, we establish the conditions for Turing instability. Then we discuss the conditions for spatial homogeneous and inhomogeneous Hopf bifurcations in the left and right systems, respectively. We differentiate between supercritical and subcritical bifurcations using the Lyapunov coefficient. Furthermore, we examine the conditions for the existence of discontinuous Hopf bifurcation at the demarcation point. Finally, in the numerical simulation section, we validate our theorems on Turing patterns. We also investigate the impact of parameter changes on rumor propagation and conclude that an increase in the psychological inhibitory factor significantly reduces the rate of rumor propagation, providing an effective strategy for curbing rumors. To that end, we fit actual data to our system and the results are excellent, confirming the validity of the system.
Talk2Data: A Natural Language Interface for Exploratory Visual Analysis via Question Decomposition
Authors: Guo Yi , Shi Danqing , Guo Mingjuan , Wu Yanqiu , Cao Nan , Chen Qing
Published: February 2024

Through a natural language interface (NLI) for exploratory visual analysis, users can directly “ask” analytical questions about the given tabular data. This process greatly improves user experience and lowers the technical barriers of data analysis. Existing techniques focus on generating a visualization from a concrete question. However, complex questions, requiring multiple data queries and visualizations to answer, are frequently asked in data exploration and analysis, which cannot be easily solved with the existing techniques. To address this issue, in this article, we introduce Talk2Data, a natural language interface for exploratory visual analysis that supports answering complex questions. It leverages an advanced deep-learning model to resolve complex questions into a series of simple questions that could gradually elaborate on the users’ requirements. To present answers, we design a set of annotated and captioned visualizations to represent the answers in a form that supports interpretation and narration. We conducted an ablation study and a controlled user study to evaluate the Talk2Data’s effectiveness and usefulness.
Catalyst-Specific Accelerated Stress Tests in Proton Exchange Membrane Low-Temperature Electrolysis for Intermittent Operation
Authors: Alia Shaun M. , Reeves Kimberly S. , Yu Haoran , Park Jae Hyung , Kariuki Nancy N. , Kropf A. Jeremy , Myers Deborah J. , Cullen David A.
Published: February 2024

Device-level stress tests are developed that focus on anode catalyst layer degradation and future anticipated operating conditions, including intermittent load and reduced platinum group metal content. Square-wave cycles with an upper load limit of 2.5 A cm‒2 are utilized to screen commercial iridium (Ir) materials. Performance losses are primarily due to decreasing kinetics and are accompanied by catalyst migration into the membrane, worsening catalyst/ionomer integration, and weakening of the catalyst/membrane interface. For ruthenium-containing catalysts, the in situ performances are higher but durabilities lower than Ir baselines, and any performance advantage is lost within the test. Increased loss is likely due to the higher dissolution rate; microscopy confirmed greater degrees of ruthenium migration. For Ir metal or mixed oxides, ex situ activity improvements generally did not translate to in situ performance. The durability, however, is significantly lower and the loss rate increased from 3 (oxide) to 9 (metal) μV cycle‒1. These results are consistent with historical findings in literature, rationalize the continued use of iridium oxide as a baseline catalyst, and demonstrate that traditional catalyst development approaches may not improve device-level durability when focused on low-cost applications. A shift in focus may therefore be more effective at improving catalyst utilization and lessening load requirements.
Effects of exogenous lactate on lipid, protein, and glucose metabolism—a randomized crossover trial in healthy males
Authors: Pedersen Mette G. B. , Rittig Nikolaj , Bangshaab Maj , Berg-Hansen Kristoffer , Gopalasingam Nigopan , Gormsen Lars C. , Søndergaard Esben , Møller Niels
Published: February 2024

Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.
Characterization of Gold Nanoparticles Synthesized with Zingiber zerumbet Extracts
Authors: Liao Wayne C. , Liao Collin S. , Lin Yu-Chen , Lien Ching-Yi
Published: February 2024

Gold nanoparticles have been used as drug carriers and imaging reagents. The plant extract-capped gold nanoparticles provide better properties than chemically synthesized gold nanoparticles. In this study, Zingiber zerumbet extract-mediated green production of gold nanoparticles (Z. zerumbet@Au NPs) was established. Based on the UV-visible spectroscopy and transmission electron microscope (TEM) results, most Z. zerumbet@Au NPs were spherical. When more Z. zerumbet extracts were added, more spherical nanoparticles were formed. The hydrodynamic size changed slightly along with time, and the average size was approximately 170 nm. Capping of Z. zerumbet extract on the surface of gold nanoparticles was confirmed by Fourier transform infrared spectroscopy (FTIR). In general, phenolic compounds or flavonoid compounds were considered to be the reducing agent. However, zerumbone was identified as the reducing agent in this study. The resulting oxidized products were characterized by high-performance liquid chromatography-mass spectrometry (HPLC-MS). As a result, the solvent was proven to be involved in nanoparticle synthesis. Overall, Z zerumbet@Au NPs showed great potential to be used in cosmetic- or biomedicine-related fields.
An EIRP Measurement Method of High-Power Microwave Systems Based on Near-Field Testing
Authors: Hu Xianggang , Su Jiancang , Zhang Mingtao , Li Xi , Ma Dingkun , Gong Jingang , Cheng Kewei , Liu Jia , Zhang Jiande , Li Rui , Cheng Jie , Wu Shaotong
Published: February 2024

The equivalent isotropic radiated power (EIRP) of high-power microwave (HPM) systems is a core-evaluating indicator. In practical testing, locating a suitable test site for the far-field method becomes challenging due to the requisite antenna separation. The conventional near-field method necessitates the extraction of the antenna’s near-field distribution, resulting in a testing system of intricate complexity and diminished efficiency. Therefore, the traditional near-field method cannot be directly applied in HPM systems. In the present study, a new EIRP measurement method for HPM systems based on near-field testing was proposed. First, a monitoring antenna of a considerable scale is positioned within the near-field vicinity of the HPM antenna to capture radiation power, thereby deriving its equivalent input power. Subsequently, according to the EIRP definition and the measured gain of the HPM antenna, the EIRP of the HPM system can be acquired. Theoretical research on this measurement method was conducted, the electromagnetic simulation model was constructed, and a comprehensive analysis through simulation was undertaken. A measurement system was developed and verified experimentally. The results demonstrate the precision of this approach in determining the EIRP of the HPM system, thereby serving as a valuable tool for assessing the power-handling capability of the HPM antenna. The test error is ±0.5 dB.
Nanoparticle Delivery in Microvascular after Cerebral Ischemia: A Simulation Study
Authors: Chen Peiqian , Dong Bing , Yao Weiwu
Published: February 2024

Nanodrug delivery systems have been used in the diagnosis and treatment of ischemic stroke. However, the delivery mechanisms of nanoparticles within microvascular after cerebral ischemia have not been systematically revealed. This study aims to investigate the binding of different nanoparticles to the walls of ischemic brain microvascular through numerical simulations. In this study, 3D models of cerebral microvascular based on ischemic pathological changes are constructed. After building the mesh of microvascular, computational fluid dynamics is used to simulate blood flow and nanoparticle delivery. The simulation results show that the total amount of binding nanoparticles with small size is higher than that with large size. The large-sized nanoparticles are more easily delivered to the stenosis. The density of the nanoparticles has no significant effect on delivery. Furthermore, the study finds that the presence of red blood cells can significantly enhance the delivery efficiency of nanoparticles. In addition to evaluating the forces exerted on the nanoparticles, the impact of the binding affinity of the modified ligand on nanoparticles to the target receptor on delivery is investigated. In summary, selecting suitable nanoparticles according to different targets will improve the delivery efficiency of nanodrugs. The microvascular delivery model of nanoparticles proposed in this study may be helpful in the design of nanoparticles for diagnosis and treatment of cerebral ischemia.
A SWOT Analysis of Hospitals’ and HMO Representatives’ Opinions regarding Hospital at Home in Israel
Authors: Harel Neta , Magnezi Racheli
Published: February 2024

Purpose. To examine attitudes regarding acute hospital at home (AHaH). Materials and Methods. A SWOT (strengths, weaknesses, opportunities, and threats) questionnaire was developed to interview 14 managers from health management organizations (HMOs) and hospitals. A mixed‐method (qualitative/quantitative) analysis was used. Results. AHaH was provided by hospital or HMO staff or outsourced (private suppliers). Differences in service pertained mainly to on‐site testing and imaging tools. All agreed that AHaH is favorable for patient outcomes and experience and that AHaH promotes medical service and clinical development. Barriers expressed were as follows: choosing the right patient; burden for caregivers and family; unclear financial incentive for providers; insufficient standardization, risk management, and quality control (expressed mainly by hospital representatives); and limited on‐site testing, imaging, and telemonitoring (mainly expressed by HMO representatives). Conclusions. To increase use of AHaH, further development of on‐site testing, imaging, telemonitoring, standards, and financial planning is needed. Research regarding quality and quantity, mid‐ and long‐term medical implications, caregiver implications, and long‐term systemic financial implications is required. Evaluating the fit between AHaH service provider (hospital/outsourced/HMO), patient group, and diagnosis is advised.
Supplementary Figure 7 from Longitudinal Position and Cancer Risk in the United States Revisited
Authors: Niu Jin , Brown Charlotte , Law Michael , Colacino Justin A. , Ritov Ya'acov
Published: February 2024

Supplementary Figure 7 shows the linear approximation result of incidence by relative position for four of the most prevalent cancers, with 95% bootstrap confidence band.
Complexities in Adjuvant Endocrine Therapy for Breast Cancer in Female-to-Male Transgender Patients
Authors: Sato Shoko , Imada Sae , Hayami Ryosuke , Arai Kazumori , Kosugi Rieko , Tsuneizumi Michiko , Matsunuma Ryoichi
Published: February 2024

Introduction: Managing breast cancer in female-to-male (FtM) transgender patients is complicated and challenging. Androgens play a crucial role in the development of secondary sexual identity in FtM transgender patients, but their effectiveness in breast cancer remains unclear. Furthermore, the considerations for adjuvant endocrine therapy in this population are highly intricate and warrant thorough discussion. Case Presentation: We describe the case of a 44-year-old FtM transgender diagnosed with breast cancer 3 years after initiating androgen receptor agonist therapy as part of his gender identity transition. After mastectomy, adjuvant endocrine therapy was initiated, consisting of a combination of an aromatase inhibitor and a gonadotropin-releasing hormone agonist, along with a cross-sex hormone. Conclusion: Estradiol levels were significantly reduced, and male-typical levels of sex hormones were attained.
Inspiratory Muscle Dysfunction Mediates and Predicts a Disease Continuum of Hypercapnic Failure in Chronic Obstructive Pulmonary Disease
Authors: Spiesshoefer Jens , Herkenrath Simon D. , Treml Marcel , Pietzke-Calcagnile Anja , Hagmeyer Lars , Regmi Binaya , Matthes Sandhya , Young Peter , Boentert Matthias , Randerath Winfried J.
Published: February 2024

Introduction: Advanced chronic obstructive pulmonary disease (COPD) is associated with chronic hypercapnic failure. The present work aimed to comprehensively investigate inspiratory muscle function as a potential key determinant of hypercapnic respiratory failure in patients with COPD. Methods: Prospective patient recruitment encompassed 61 stable subjects with COPD across different stages of respiratory failure, ranging from normocapnia to isolated nighttime hypercapnia and daytime hypercapnia. Arterialized blood gas analyses and overnight transcutaneous capnometry were used for patient stratification. Assessment of respiratory muscle function encompassed body plethysmography, maximum inspiratory pressure (MIP), diaphragm ultrasound, and transdiaphragmatic pressure recordings following cervical magnetic stimulation of the phrenic nerves (twPdi) and a maximum sniff manoeuvre (Sniff Pdi). Results: Twenty patients showed no hypercapnia, 10 had isolated nocturnal hypercapnia, and 31 had daytime hypercapnia. Body plethysmography clearly distinguished patients with and without hypercapnia but did not discriminate patients with isolated nocturnal hypercapnia from those with daytime hypercapnia. In contrast to ultrasound parameters and transdiaphragmatic pressures, only MIP reflected the extent of hypercapnia across all three stages. MIP values below −48 cmH2O predicted nocturnal hypercapnia (area under the curve = 0.733, p = 0.052). Conclusion: In COPD, inspiratory muscle dysfunction contributes to progressive hypercapnic failure. In contrast to invasive tests of diaphragm strength only MIP fully reflects the pathophysiological continuum of hypercapnic failure and predicts isolated nocturnal hypercapnia.
Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey
Authors: Sigg Silvan , Arnold Winfried , Grossmann Nico Christian , Baumeister Philipp , Fankhauser Christian Daniel , Wenzel Mike , Mattei Agostino , Würnschimmel Christoph
Published: February 2024

Introduction: The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD). Methods: In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into “adherent” (aRT performed) and “non-adherent” groups (aRT not performed). Results: Of 55 patients receiving a recommendation for aRT (7.5% of all RP patients), 24 (44%) were non-adherent. Baseline tumour characteristics were comparable among the groups. “Fear of radiation damage” was the most common reason for rejection, followed by “lack of information,” “feeling that the treating physician does not support the recommendation” and “the impression that aRT is not associated with improved oncological outcome.” Salvage radiotherapy was performed in 25% of non-adherent patients. Conclusion: High rates of non-adherence to aRT after RP were observed, and reasons for this phenomenon are most likely multifactorial. Multidisciplinary and individualized patient counselling might be a key for increasing adherence rates.
Psychosocial Burden in People with Atopic Dermatitis: Effects of a Substance-Free Basic Skincare in a Randomized Health Care Study
Authors: Braren-von Stülpnagel Catharina , Augustin Matthias , Sommer Rachel , Westphal Lukas
Published: February 2024

Introduction: Atopic dermatitis (AD) is a physical, emotional, and social burden for patients. Most suffer from itching, pain, and dry skin as well as sleep disturbances, experienced stigmatization, anxiety, or depression. Therefore, it is important to consider the psychosocial well-being and also stigmatization in the treatment of people with AD. The aims of this study were to compare clinical and psychosocial parameters between patients with a different severity of AD and to analyse the effect of an omega-6-fatty-acid-skin therapy. Methods: Adult patients with clinically confirmed AD were asked about quality of life, stigmatization, and well-being after dermatological diagnosis. A second examination took place after 2–5 weeks. Meanwhile, after randomization, half of the patients used an omega-6-fatty-acid-skin therapy. Results: Seventy-nine patients were included in the study. The use of omega-6-fatty-acid-skin therapy resulted in a significant reduction in the severity of xerosis cutis compared to patients using another basic therapy. In addition, the health-related quality of life of all patients improved significantly in both groups (F = 7.56; p = 0.008), and no significant difference was found between the groups over time in the patient-reported outcomes. Conclusion: Basic therapy for AD leads to relevant improvements in clinical status as well as quality of life. Patients using omega-6-fatty-acid-skin therapy experience greater improvement in xerosis cutis compared to free-choice basic therapy.