bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant regeneration of the oculomotor nerve: implications for neurosurgeons
Authors: Weber Eric D. , Newman Steven A.
Published: December 2007

✓Aberrant regeneration of cranial nerve III, otherwise known as oculomotor synkinesis, is an uncommon but well-described phenomenon most frequently resulting from trauma, tumors, and aneurysms. Its appearance usually follows an oculomotor palsy, but it can also occur primarily without any preceding nerve dysfunction. It is vital that neurosurgeons recognize this disorder because it may be the only sign of an underlying cavernous tumor or PCoA aneurysm. The tumor most often implicated is a cavernous or parasellar meningioma, but any tumor that causes compression or disruption along the course of the oculomotor nerve may cause primary or secondary misdirection. The most common clinical signs of oculomotor synkinesis consist of elevation of the upper eyelid on attempted downward gaze or adduction, adduction of the eye on attempted upward or downward gaze, and constriction of the pupil on attempted adduction. The authors present the largest series of patients with oculomotor synkinesis, including those in whom it developed after neurosurgical intervention, to illustrate various presentations. In addition, the various mechanisms that contribute to synkinesis are reviewed. Last, the treatment strategies for both oculomotor palsies and synkinesis are discussed.
Cancer Antigen 125 in Ovarian Cancer Surveillance: A Decision Analysis Model
Authors: Hopkins M. Laura , Coyle D. , Le T. , Fung M. Fung Kee , Wells G.
Published: December 2007

We used decision analysis techniques with Markov cohort modeling to examine the role of cancer antigen 125 (CA-125) in follow-up surveillance strategies among patients with advanced ovarian cancer. Utilities were derived from a societal perspective. Using quality-adjusted life years (QALYs) as the outcome variable, the value of CA-125 monitoring for asymptomatic women with ovarian cancer was found to be reduced as compared with a strategy that includes CA-125 testing. Decisions to include CA-125 in surveillance strategies for ovarian cancer patients should be made after discussion with full disclosure of the preference-sensitive nature of CA-125. The model demonstrates that preferences and perspective can influence decisions in cancer care.
Symptom Clusters in Cancer Patients: A Review of the Literature
Authors: Fan G. , Filipczak L. , Chow Edward
Published: December 2007

Cancer patients often experience multiple symptoms, and those symptoms can independently predict changes in patient function, treatment failures, and post-therapeutic outcomes. Symptom clusters are defined as two or more concurrent symptoms that are related and may or may not have a common cause. The purpose of the present study was to review, in cancer patients, common symptom clusters and their predictors. Using medline, embase, Cochrane Central, and cinahl, we conducted a literature search on symptom clusters in cancer patients. Studies that investigated predetermined clusters were not included. We identified seven individual studies and one group of five studies validating the M.D. Anderson Symptom Inventory. These studies had been published between 1997 and 2006. Two of the seven individual studies and the group of five studies that had validated the M.D. Anderson Symptom Inventory included patients with any cancer type; three studies included breast cancer patients only; and two studies included lung cancer patients only. A gastrointestinal cluster consisting of nausea and vomiting was the single cluster common to two of the studies. The severity of this cluster increased when patients were treated with chemotherapy. No common clusters were found in the lung and breast cancer patient populations. However, breast cancer patients experienced more symptom cluster involvement while undergoing chemotherapy. We noted methodology disparities among the papers with regard to assessment tools used, statistical analyses, and populations. Research on symptom clusters is still in an early stage. Multiple symptoms clearly affect prognosis, quality of life, and functional status. The study of symptom clusters is important for its implications regarding patient management, and a consensus on appropriate research methodology is vital.
Interrupted Time Series Analysis of Bar/Tavern Closing Hours and Violent Crime
Authors: Rosen Erika M. , Trangenstein Pamela J. , Fullem Patrick L. , Yeh Jih-Cheng , Jernigan David H. , Xuan Ziming
Published: April 2024

Importance

It is well established that alcohol outlets (ie, places that sell alcohol) attract crime, particularly during late-night hours.

Objective

To evaluate the association of Maryland Senate Bill 571 (SB571), which reduced the hours of sale for bars/taverns in 1 Baltimore neighborhood from 6 am to 2 am to 9 am to 10 pm, with violent crime within that neighborhood.

Design, Setting, and Participants

This controlled interrupted time series analysis compared the change in violent crime density within an 800-ft buffer around bars/taverns in the treatment neighborhood (ie, subject to SB571) and 3 control areas with a similar mean baseline crime rate, alcohol outlet density, and neighborhood disadvantage score in the City of Baltimore between May 1, 2018, and December 31, 2022. The interrupted time series using Poisson regression with overdispersion adjustment tested whether the violent crime density differed before vs after the policy change in the treatment neighborhood and whether this difference was localized to the treatment neighborhood.

Exposure

Statutory reduction of bar/tavern selling hours from 20 to 13 hours per day in the treatment neighborhood.

Main Outcomes and Measures

The primary outcome was all violent crime, including homicide, robbery, aggravated and common assault, and forcible rape. Secondary outcomes were homicides and assaults. All violent crime measures summed the monthly incidents within 800 ft of bars/taverns from 8 pm to 4 am. For each outcome, a level change estimated the immediate change (first month after implementation), and a slope change estimated the sustained change after implementation (percent reduction after the first month). These level and slope changes were then compared between the treatment and control neighborhoods.

Results

The treatment neighborhood included 13 bars/taverns (mean [SD] population, 528.3 [291.6] residents), and the control neighborhoods included 52 bars/taverns (mean [SD] population per census block, 809.0 [416.0] residents). There was a 14% immediate level decrease in density of all violent crimes the month after implementation of SB571; further, compared with the control neighborhoods, the slope of all violent crime density decreased by 29% per year in the treatment neighborhood after SB571 implementation (annualized incidence rate ratio, 0.71; 95% CI, 0.52-0.97; P = .03). Similar results were seen for homicides and assaults. Several sensitivity analyses supported the robustness of these results.

Conclusions and Relevance

This study’s findings suggest that alcohol policies that reduce hours of sale could be associated with a reduction in violent crimes. Given these findings, SB571 may serve as a model for other cities looking to create safer neighborhoods.
Use of Recommended Neurodiagnostic Evaluation Among Patients With Drug-Resistant Epilepsy
Authors: Spotnitz Matthew , Ekanayake Cameron D. , Ostropolets Anna , McKhann Guy M. , Choi Hyunmi , Ottman Ruth , Neugut Alfred I. , Hripcsak George , Natarajan Karthik , Youngerman Brett E.
Published: April 2024

Importance

Interdisciplinary practice parameters recommend that patients with drug-resistant epilepsy (DRE) undergo comprehensive neurodiagnostic evaluation, including presurgical assessment. Reporting from specialized centers suggests long delays to referral and underuse of surgery; however, longitudinal data are limited to characterize neurodiagnostic evaluation among patients with DRE in more diverse US settings and populations.

Objective

To examine the rate and factors associated with neurodiagnostic studies and comprehensive evaluation among patients with DRE within 3 US cohorts.

Design, Setting, and Participants

A retrospective cross-sectional study was conducted using the Observational Medical Outcomes Partnership Common Data Model including US multistate Medicaid data, commercial claims data, and Columbia University Medical Center (CUMC) electronic health record data. Patients meeting a validated computable phenotype algorithm for DRE between January 1, 2015, and April 1, 2020, were included. No eligible participants were excluded.

Exposure

Demographic and clinical variables were queried.

Main Outcomes and Measures

The proportion of patients receiving a composite proxy for comprehensive neurodiagnostic evaluation, including (1) magnetic resonance or other advanced brain imaging, (2) video electroencephalography, and (3) neuropsychological evaluation within 2 years of meeting the inclusion criteria.

Results

A total of 33 542 patients with DRE were included in the Medicaid cohort, 22 496 in the commercial insurance cohort, and 2741 in the CUMC database. A total of 31 516 patients (53.6%) were women. The proportion of patients meeting the comprehensive evaluation main outcome in the Medicaid cohort was 4.5% (n = 1520); in the commercial insurance cohort, 8.0% (n = 1796); and in the CUMC cohort, 14.3% (n = 393). Video electroencephalography (24.9% Medicaid, 28.4% commercial, 63.2% CUMC) and magnetic resonance imaging of the brain (35.6% Medicaid, 43.4% commercial, 52.6% CUMC) were performed more regularly than neuropsychological evaluation (13.0% Medicaid, 16.6% commercial, 19.2% CUMC) or advanced imaging (3.2% Medicaid, 5.4% commercial, 13.1% CUMC). Factors independently associated with greater odds of evaluation across all 3 data sets included the number of inpatient and outpatient nonemergency epilepsy visits and focal rather than generalized epilepsy.

Conclusions and Relevance

The findings of this study suggest there is a gap in the use of diagnostic studies to evaluate patients with DRE. Care setting, insurance type, frequency of nonemergency visits, and epilepsy type are all associated with evaluation. A common data model can be used to measure adherence with best practices across a variety of observational data sources.
Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders
Authors: Cummings Jeffrey , Lanctot Krista , Grossberg George , Ballard Clive
Published: April 2024

Importance

Neuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care.

Observations

Consensus definitions have evolved for psychosis, agitation, apathy, depression, and disinhibition in NDDs. Psychosocial interventions may reduce mild behavioral symptoms in patients with NDD, and pharmacotherapy is available for NPSs in NDDs. Brexpiprazole is approved for treatment of agitation associated with Alzheimer disease dementia, and pimavanserin is approved for treatment of delusions and hallucinations associated with psychosis of Parkinson disease. Trials are being conducted across several of the NDDs, and a variety of mechanisms of action are being assessed for their effect on NPSs.

Conclusions and Relevance

Detection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.
Semantic Variant of Primary Progressive Aphasia With Glycine Receptor α1 Autoantibodies
Authors: Chen Yufei , Wei Cuibai
Published: April 2024

This case report describes a 54-year-old woman with naming deficits, comprehension impairment, and memory loss. Initial physical and neurological examination results were unremarkable.
TACE inhibition: a promising therapeutic intervention against AATF‐mediated steatohepatitis to hepatocarcinogenesis
Authors: Srinivas Akshatha N. , Suresh Diwakar , Vishwanath Prashant M. , Satish Suchitha , Santhekadur Prasanna K. , Koka Saisudha , Kumar Divya P.
Published: April 2024

Metabolic dysfunction‐associated steatohepatitis‐driven hepatocellular carcinoma (MASH‐HCC) is a global clinical challenge for which there is a limited understanding of disease pathogenesis and a subsequent lack of therapeutic interventions. We previously identified that tumor necrosis factor‐alpha (TNF‐α) upregulated apoptosis antagonizing transcription factor (AATF) in MASH. Here, we investigated the effect of TNF‐α converting enzyme (TACE) inhibition as a promising targeted therapy against AATF‐mediated steatohepatitis to hepatocarcinogenesis. A preclinical murine model that recapitulates human MASH‐HCC was used in the study. C57Bl/6 mice were fed with chow diet normal water (CD) or western diet sugar water (WD) along with a low dose of carbon tetrachloride (CCl4; 0.2 μL·g−1, weekly) for 24 weeks. TACE activity, TNF‐α levels, and AATF expression were measured. The mice were treated with the TACE inhibitor Marimastat for 12 weeks, followed by analyses of liver injury, fibrosis, inflammation, and oncogenic signaling. In vitro experiments using stable clones of AATF control and AATF knockdown were also conducted. We found that AATF expression was upregulated in WD/CCl4 mice, which developed severe MASH at 12 weeks and advanced fibrosis with HCC at 24 weeks. WD/CCl4 mice showed increased TACE activity with reduced hepatic expression of sirtuin 1 (Sirt1) and tissue inhibitor of metalloproteinase 3 (Timp3). The involvement of the SIRT1/TIMP3/TACE axis was confirmed by the release of TNF‐α, which upregulated AATF, a key molecular driver of MASH‐HCC. Interestingly, TACE inhibition by Marimastat reduced liver injury, dyslipidemia, AATF expression, and oncogenic signaling, effectively preventing hepatocarcinogenesis. Furthermore, Marimastat inhibited the activation of JNK, ERK1/2, and AKT, which are key regulators of tumorigenesis in WD/CCl4 mice and in AATF control cells, but had no effect on AATF knockdown cells. This study shows that TACE inhibition prevents AATF‐mediated inflammation, fibrosis, and oncogenesis in MASH‐HCC, offering a potential target for therapeutic intervention.
Synthesis of Inorganic Solids Using the Deep Eutectic Solvent (DES) Route
Authors: Rain Mahmudul Islam , Zaikina Julia V.
Published: April 2024

The search for sustainable and environmentally friendly approaches to material synthesis has fueled significant interest in using alternative reaction media, such as ionic liquids. Deep eutectic solvents (DESs) are a promising alternative to ionic liquids due to their low cost, environmental friendliness, and versatile physicochemical properties. This article provides a “close‐up” examination of the synthesis of inorganic materials using type III DES as a reaction medium. The type III DES is an eutectic mixture of choline chloride [(CH
3
)
3
NCH
2
CH
2
OH]
+
Cl
−
and an organic compound, where H‐bonding and ionic interactions lead to the considerable depression of the DESs melting points, making them liquid at around room temperature. The article introduces the fundamental concepts of DESs, including DES types, typical DES components, and resulting solvent properties, emphasizing their distinctive ability to dissolve inorganic precursors, metal coordination environments in DES, and variation in thermal stability. Here, we focus on key synthesis strategies via combustion and precipitation routes, the latter includes solution, solvothermal, and microwave‐assisted synthesis or antisolvent addition techniques. The versatility and solvation properties of DES offer exceptional opportunities for the design and fabrication of diverse compounds, ranging from metal nanoparticles to bulk materials with examples among oxide perovskites, spinels, vanadates, and sulfides. Furthermore, the article explores the specific advantages of DES route in facilitating the synthesis of these materials, such as enhanced precursor solubility, control over morphology, growth, and particle size. The aim of this article is to provide researchers with an understanding of the synthesis of inorganic materials using DESs and stimulate further exploration of novel routes toward materials synthesis in a sustainable manner as well as elucidation of reaction mechanism in DES synthesis routes.
[MoCu]‐Dependent Carbon Monoxide Dehydrogenases
Authors: Gillett David L , Grinter Rhys , Greening Chris
Published: April 2024

[MoCu]‐dependent carbon monoxide dehydrogenases (Mo‐CODH) catalyze the hydroxylation of CO, which produces CO
2
and consumes H
2
O in the process. Aerobic carbon monoxide oxidizing bacteria and archaea use Mo‐CODH to generate energy by providing the respiratory chain with CO‐derived electrons, and aerobic CO‐oxidizers that possess the genes for CO
2
fixation can also use CO as a carbon source. Due to the pervasive nature of CO in the atmosphere as a trace gas, and the numerous marine and terrestrial environments enriched in CO due to its production during the decomposition of organic matter, aerobic CO‐oxidizers are widespread and significantly contribute to the biogeochemical cycle of CO. Mo‐CODH has been structurally characterized by both X‐ray crystallography and cryo‐EM. Structural and biochemical characterization of the purified Mo‐CODH enzyme has focused on bacteria that mediate carboxydotrophic growth such as
Afipia carboxidovorans
, which were isolated from environments with elevated concentrations of CO. Only recently has a Mo‐CODH enzyme capable of oxidizing CO to subatmospheric levels been isolated and characterized, from
Mycobacterium smegmatis,
providing the first insights into structural features that enable high‐affinity CO oxidation. In all aerobic CO oxidizers, CO oxidation occurs at a unique [MoSCu] dimetallic site within the active site of Mo‐CODH, through a mechanism that has been the subject of several computational and biochemical studies. Two [2Fe–2S] clusters facilitate the transport of electrons from the active site to a FAD cofactor, which then donates electrons to an electron carrier. Quinones are believed to be the primary physiological electron acceptor of Mo‐CODH, which can be transported from the cell membrane through the cytoplasm to the soluble Mo‐CODH complex by the CoxG shuttle protein.
Cyanobacterial Zur: Zinc‐Sensing Transcriptional Regulators
Authors: Mikhaylina Alevtina , Scanlan David J , Blindauer Claudia A
Published: April 2024

Zur (zinc uptake regulator) proteins are the most widespread bacterial zinc‐sensing transcriptional regulators, being encoded in the majority of sequenced bacterial genomes. They work predominantly as transcriptional repressors of zinc uptake genes when zinc in a bacterium's environment is abundant. Zinc scarcity in turn leads to de‐repression of these genes, which leads to increased zinc uptake. More recently, several Zur proteins have also been shown to work as activators of transcription, but the mechanism(s) for this type of regulation are not fully understood.

Several 3D structures of Zur proteins are available, including those from the actinobacterium
Streptomyces coelicolor,
pathogenic
Mycobacterium tuberculosis
and
Xanthomonas campestris
, and the marine cyanobacterium
Synechococcus
sp. WH8102. The SynZur protein from the latter photosynthetic organism is the focus of this entry. In contrast to many other bacteria which harbor at least two zinc‐sensing regulators, SynZur is the sole zinc‐sensing transcription factor in this cyanobacterium. Like many other Zur proteins, it regulates the transcription of the
znuABC
genes, which encode ABC‐type zinc uptake systems located at the inner membrane. Uniquely, however, SynZur also activates transcription of a bacterial metallothionein (
bmtA
). The latter small cysteine‐rich proteins have a high capacity to bind up to four zinc ions and are normally regulated by repressors of the SmtB family, in response to zinc excess. The ability to upregulate production of a zinc storage protein upon encountering ‘luxury’ zinc appears to enable
Synechococcus
sp. WH8102 and related oligotrophic strains to populate ecological niches that are poor in inorganic nutrients but may experience episodic rises in zinc levels.
Evaluating mFARS in pediatric Friedreich's ataxia: Insights from the FACHILD study
Authors: Rummey Christian , Perlman Susan , Subramony Sub. H. , Farmer Jennifer , Lynch David R.
Published: April 2024

Objectives

Friedreich ataxia (FRDA) is a rare genetic disorder caused by mutations in the FXN gene, leading to progressive coordination loss and other symptoms. The recently approved omaveloxolone targets this condition but is limited to patients over 16 years of age, highlighting the need for pediatric treatments due to the disorder's early onset and more rapid progression in children. This population also experiences increased non‐neurological complications; the FACHILD study aimed to augment and expand the knowledge about the natural history of the disease and clinical outcome assessments for trials in children in FRDA.

Methods

The study enrolled 108 individuals aged 7–18 years with a confirmed FRDA diagnosis, with visits occurring from October 2017 to November 2022 across three institutions. Several measures were introduced to minimize the impact of the COVID‐19 pandemic, including virtual visits. Outcome measures centered on the mFARS score and its subscores, and data were analyzed using mixed models for repeated measures. For context and to avoid misinterpretation, the analysis was augmented with data from patients enrolled in the Friedreich's Ataxia Clinical Outcome Measures Study.

Results

Results confirmed the general usefulness of the mFARS score in children, but also highlighted issues, particularly with the upper limb subscore (FARS B). Increased variability, limited homogeneity across study subgroups, and potential training effects might limit mFARS application in clinical trials in pediatric populations.

Interpretation

The FARS E (Upright Stability) score might be a preferred outcome measure in this patient population.
Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization
Authors: Tan Yuxuan , Yao Huojie , Lin Chuhang , Lai Zhengtian , Li Haiying , Zhang Jing , Fu Yingyin , Wu Xiaomei , Yang Guang , Feng Liping , Jing Chunxia
Published: April 2024

Objective

Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co‐occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods.

Methods

Bidirectional two‐sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function trait data sets from the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR‐BMA) was performed to adjust for possible competing risk factors. A sensitivity data set, which included data from patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions.

Results

A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD) as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR‐BMA results showed that RA and AITD were independent risk factors in their bidirectional causality, even in the presence of other competing risk factors (adjusted P < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them.

Conclusion

Our results illustrate the significant bidirectional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in patients with RA deserves further attention, and vice versa.
Higher Dietary Inflammatory Index and Increased Mortality Rate of Adults With Hyperuricemia: Findings From the National Health and Nutritional Examination Survey (2001–2018)
Authors: Zhou Mengmeng , Cai Bin , Xiao Qingqing , Zou Hejian , Zeng Xiaofeng , Zhao Jiuliang , Zhu Xiaoxia
Published: April 2024

Objective

This study aimed to assess the association between Dietary Inflammatory Index (DII) score and death among adults with hyperuricemia.

Methods

We collected data from the 2001 to 2018 cohorts of the National Health and Nutritional Examination Survey. Death information was obtained based on death certificate records from the National Death Index through December 31, 2019. The associations between DII score and all‐cause, cardiovascular disease (CVD), and cancer death were investigated by using Cox proportional hazards regression models.

Results

We enrolled 7,786 participants with hyperuricemia in this study. The DII score ranged from −4.42 to 4.61. Higher DII score was significantly associated with higher levels of body mass index, glycohemoglobin, glucose, low‐density lipoprotein–cholesterol, and C‐reactive protein (all P < 0.05). During 67,851 person‐years of follow‐up, deaths of 1,456 participants were identified, including 532 CVD deaths and 246 cancer deaths. After adjusting for potential variables, significant higher risk of all‐cause (hazard ratio [HR] 1.18, 95% confidence interval [95% CI] 1.03–1.36, P = 0.01) and CVD (HR 1.30, 95% CI 1.03–1.63, P = 0.02) death was observed for individuals with higher DII scores. Considering the DII score as a continuous variable, the risk of all‐cause and CVD death increases 5% (HR 1.05, 95% CI 1.01–1.08) and 8% (HR 1.08, 95% CI 1.02–1.15) with each one‐unit increment in DII score, respectively. Subgroup analysis indicated that the association between DII score and all‐cause death among participants with hyperuricemia was more significant in males.

Conclusion

DII score is found to be positively associated with all‐cause and CVD death of adults with hyperuricemia. Controlling the intake of proinflammatory food might be a potential strategy to reduce the mortality rate.
Needs Assessment of Musculoskeletal Ultrasound Training in North American Pediatric Rheumatology Fellowship Programs
Authors: Perron Megan Mariko , Ziniel Sonja I. , Curran Megan , Bloom Jessica L. , Vega‐Fernandez Patricia , Benham Heather , Torralba Karina , De Ranieri Deirdre , Lin Clara ,   the Ultrasound School of North American Rheumatologists (USSONAR)
Published: April 2024

Objective

Musculoskeletal ultrasound (MSUS) is widely used in adult rheumatology practice for diagnosis of arthritis and procedural guidance; however, it is not yet common practice in pediatric rheumatology. MSUS is advantageous to the pediatric population because it lacks radiation and eliminates need for sedation. This study aims to assess interest in, access to, and barriers to MSUS training in pediatric rheumatology fellowship programs in North America.

Methods

A survey was developed by pediatric rheumatology providers with experience in medical and/or MSUS education and distributed via REDCap anonymously in March 2022 (Supplementary Material). Eligible participants included current and recently graduated (<1 year) pediatric rheumatology fellows at a North American program. Descriptive statistics and bivariate analyses using design‐based Pearson chi‐squared tests were performed.

Results

Overall response rate was 78% (88/113), and 75% reported some form of MSUS training during fellowship. Only 36% indicated their program had a formal MSUS curriculum. Of those with MSUS training, 23% reported adult‐only MSUS education. Eighty‐four percent felt MSUS would be beneficial to their career. Major barriers to MSUS training included lack of MSUS‐trained faculty, lack of time, and lack of hands‐on MSUS sessions. Those who had access to MSUS training were significantly more interested in MSUS than those without (P = 0.0036).

Conclusion

This study demonstrates that North American pediatric rheumatology fellows have a strong interest in learning MSUS, but they face significant challenges in accessing MSUS training (lack of MSUS‐trained faculty, time, and access to hands‐on training). MSUS should be incorporated into fellowship curriculum; however, implementation remains a challenge.
Comparative Effectiveness of a Second Tumor Necrosis Factor Inhibitor Versus a Non–Tumor Necrosis Factor Biologic in the Treatment of Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis
Authors: Mannion Melissa L. , Amin Shahla , Balevic Stephen , Chang Min‐Lee , Correll Colleen K. , Kearsley‐Fleet Lianne , Hyrich Kimme L. , Beukelman Timothy ,   for the Childhood Arthritis and Rheumatology Research Alliance Registry Investigators and the UK Juvenile Idiopathic Arthritis Biologics Register Investigators
Published: April 2024

Objective

The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non‐TNFi biologic following discontinuation of a TNFi for patients with polyarticular‐course juvenile idiopathic arthritis (pJIA).

Methods

Using the Childhood Arthritis and Rheumatology Research Alliance Registry, patients with pJIA who started receiving a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on the index date and a visit six months after the index date. Outcome measures included Clinical Juvenile Arthritis Disease Activity Score with a maximum of 10 active joints (cJADAS10), cJADAS10 inactive disease (ID; ≤2.5) and cJADAS10 minimal disease activity (MiDA; ≤5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aORs) were calculated using propensity score quintiles to compare outcomes at six months following second biologic initiation.

Results

There were 216 patients included, 84% initially received etanercept, and most patients stopped receiving it because of its ineffectiveness (74%). A total of 183 (85%) started receiving a second TNFi, and 33 (15%) started receiving a non‐TNFi. Adalimumab was the most common second biologic received (71% overall, 84% of second TNFi), and tocilizumab was the most common non‐TNFi second biologic received (9% overall, 58% of non‐TNFi). There was no difference between receiving TNFi versus non‐TNFi in cJADAS10 ID (29% vs 25%; aOR 1.23, 95% confidence interval [CI] 0.47–3.20) or at least MiDA (43% vs 39%; aOR 1.11, 95% CI 0.47–2.62) at six months.

Conclusion

Most patients with pJIA started receiving TNFi rather than non‐TNFi as their second biologic, and there were no differences in disease activity at six months.

image
Adaptive fixed‐time anti‐synchronization and synchronization control for Liu‐Chen‐Liu chaotic systems with actuator faults
Authors: Wang Huanqing , Chai Ge , Kang Shijia
Published: April 2024

In this paper, the fixed‐time anti‐synchronization and synchronization fault‐tolerant control problem is considered for two identical Liu‐Chen‐Liu chaotic systems with uncertain parameters. With the help of fixed‐time stability theory and adaptive backstepping method, we propose two novel adaptive controllers. In the control scheme proposed in this paper, the adaptive backstepping technique is used to deal with the unknown parameters contained in the chaotic systems. Besides, the piecewise functional method is used to solve the singularity problem in the controller design process. The designed controllers achieve anti‐synchronization and synchronization of two identical Liu‐Chen‐Liu chaotic systems within the preset time interval. Simulation results are conducted to show the effectiveness of two proposed adaptive controllers.
A Spider Leg‐Inspired mm‐Scale Soft Exoskeleton Enabled by Liquid via Hydration and Charge Transport
Authors: Valdur Kadri‐Ann , Tamm Tarmo , Fiorello Isabella , Aabloo Alvo , Must Indrek , Sinibaldi Edoardo , Mazzolai Barbara
Published: April 2024

In organisms, liquid as a continuum intertwines architected components (organs), including nervous, vascular, and musculoskeletal systems. In this regard, spiders exhibit remarkable embodiments where hemolymph, which infuses the animal, simultaneously enables muscle activation and exoskeleton compliance. Previous works on spider‐inspired artificial systems have focused on disentangled aspects, such as pressurization and flexible structures, yet organism‐like liquid‐mediated physical intelligence integrating control, distribution of resources, actuation, and support is still to be demonstrated. Here a spider‐leg‐inspired soft exoskeleton integrating a muscular system is shown, enabled by the contained liquid through hydration for compliance conditioning and charge transport for muscle activation. A two‐photon polymerized 0.8 mm‐diameter exoskeleton is reported that contains an electrolyte solution and is actuated via contraction of an ionic electroactive polymer muscle operated at 0–1 V. The exoskeleton features reversible bending and compliant interaction with natural entities such as anthers, spider webs, and pollen grains. The reported technology demonstrator, which functionally intertwines muscularization, vascularization, and innervation via liquid, supports the development of liquid‐enabled systems based on embodied energy and multi‐material design, particularly for bioinspired soft robotics.
Facile Fabrication of Heterogeneous Olfactory Sensing Array via Thermal Manipulation of A Single Sr─Fe─O Perovskite Precursor
Authors: Xu Feng , Chen Ming , Cui Yaoxuan , Qian Libin , Wang Jin , Han Zhao , Lu Yanli , Wang Di
Published: April 2024

The electronic nose aims to emulate the olfactory capabilities of osmatic animals, utilizing olfactory sensing array with different sensing characteristics to perceive odors. However, the separate precursors and preparation methods of sensing materials pose challenges in the fabrication of an olfactory sensing array. In this work, the customization of the surface crystal phase of Sr─Fe─O materials (SFO) is demonstrated through the control of annealing temperature, enabling the simple fabrication of an olfactory sensing array using a single precursor. Significantly, the SFO materials exhibit diverse proportions of surface crystal phases, showcasing varied selective characteristics toward volatile organic compounds (VOCs). The materials also demonstrate remarkable responsiveness, linearity, and response/recovery times. Furthermore, this study unraveles the intricate gas‐sensor mechanism through first principle calculations, revealing that Fe spin‐down d band center of Sr3Fe2O7, located near the Fermi level, significantly enhances the binding strength of intermediates, leading to a higher response specifically to certain VOCs. Integrating these materials into a unified device, the sensor array quantitatively and discriminatively detected different VOCs. The results indicate that SFO materials hold tremendous potential as a promising and easily manufacturable olfactory material system.
Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells
Authors: Søgaard Ane Bretschneider , Skovbo Frederik , Tvilum Anne , Hansson Rikke F. , Zelikin Alexander N.
Published: April 2024

Receptors are lipid bilayer‐resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non‐genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell‐specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody‐drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody‐drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor‐engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio‐orthogonal and thus afford a dedicated route of communication with the chemically engineered cells.
Highly Conductive Quasi‐1D Hexagonal Chalcogenide Perovskite Sr8Ti7S21 with Efficient Polysulfide Regulation in Lithium‐Sulfur Batteries
Authors: Yang Dawei , Han Yanbing , Li Mengyao , Li Canhuang , Bi Wei , Gong Qianhong , Zhang Jie , Zhang Jinglu , Zhou Yingtang , Gao Han , Arbiol Jordi , Shi Zhifeng , Zhou Guangmin , Cabot Andreu
Published: April 2024

Lithium‐sulfur batteries (LSBs) are regarded as one of the most promising candidates for next‐generation energy storage systems. However, the commercialization of LSBs is still hindered by several technical issues, including the notorious polysulfide migration from the cathode to the anode and the sluggish sulfur conversion kinetics. Herein, a quasi‐1D hexagonal chalcogenide perovskite, Sr8Ti7S21, is demonstrated as an efficient sulfur host able to overcome these limitations. Experimental results and density functional theory calculations show Sr8Ti7S21 to offer strong lithium polysulfides (LiPS) binding through multiple bond formation. Besides, Sr8Ti7S21 effectively facilitates the kinetics of the LiPS redox reaction. As a result, S@Sr8Ti7S21‐based cathodes exhibit excellent initial capacities up to 1315 mAh g−1 at 0.2C, impressive cycling stability with an average capacity decay rate of 0.08% per cycle over 400 cycles at 1C, and a high areal capacity of 6.58 mAh cm−2 under a high sulfur loading of 6.5 mg cm−2. This work reveals the potential capabilities and promising prospects of chalcogenide perovskites in advancing LSBs technology.
Multifunctional Nanovaccine Sensitizes Breast Cancer to Immune Checkpoint Therapy
Authors: Peres Carina , Matos Ana I. , Carreira Bárbara , Moura Liane I. F. , Kleiner Ron , Vaskovich‐Koubi Daniella , Reshef Keren , Dulberg Shai , Verdial Mafalda , Conniot João , Afonso Marta B. , Acúrcio Rita C. , Basto Afonso P. , Mensurado Sofia , Silva‐Santos Bruno , Santos Susana Constantino Rosa , Viana Ana S. , Silva Liana C. , Rodrigues Cecília M. P. , Préat Véronique , Graça Luís , Madi Asaf , Satchi‐Fainaro Ronit , Florindo Helena F.
Published: April 2024

Breast cancer is the primary cause of cancer‐related death in women worldwide. Breast cancer subtypes are characterized by different gene expression patterns, which drive their prognostic factors and therapeutic options. Among them, triple‐negative breast cancer (TNBC) is one of the deadliest due to its aggressiveness, high rate of early recurrence and distant metastases, and limited therapeutic options. Despite the recent approval of monoclonal antibodies targeting programmed cell death protein 1 (PD‐1) or its ligand (PD‐L1) for the treatment of TNBC patients with a locally recurrent unresectable or metastatic tumor expressing PD‐L1, their response rate is very modest. It is reported that polymeric nanoparticle (NP)‐based cancer vaccines, co‐entrapping tumor‐associated antigens, Toll‐like receptor ligands and small interfering RNA (siRNA) targeting the expression of the immunosuppressive cytokine transforming growth factor (TGF)‐β1 by dendritic cells, sensitized TNBC to the agonist immune checkpoint OX40, inhibiting tumor growth and increasing overall survival. This anti‐tumor immune‐mediated effect is also observed in a luminal type of mammary cancer similar to human disease. Therefore, these synergistic anticancer effects of αOX40 and the antigen‐specific adaptive immunity induced by nanovaccine‐mediated TGF‐β silencing may guide the development of novel combination regimens able to improve the response rate to this aggressive tumor.
Unveiling the Electro‐Chemo‐Mechanical Failure Mechanism of Sodium Metal Anodes in Sodium–Oxygen Batteries by Synchrotron X‐Ray Computed Tomography
Authors: Zhang Xia , Zhang Shenghang , Lu Jie , Tang Fengcheng , Dong Kang , Yu Zhenjiang , Hilger André , Osenberg Markus , Markötter Henning , Wilde Fabian , Zhang Shu , Zhao Jingwen , Xu Gaojie , Manke Ingo , Sun Fu , Cui Guanglei
Published: April 2024

Rechargeable sodium–oxygen batteries (NaOBs) are receiving extensive research interests because of their advantages such as ultrahigh energy density and cost efficiency. However, the severe failure of Na metal anodes has impeded the commercial development of NaOBs. Herein, combining in situ synchrotron X‐ray computed tomography (SXCT) and other complementary characterizations, a novel electro‐chemo‐mechanical failure mechanism of sodium metal anode in NaOBs is elucidated. It is visually showcased that the Na metal anodes involve a three‐stage decay evolution of a porous Na reactive interphase layer (NRIL): from the initially dot‐shaped voids evolved into the spindle‐shaped voids and the eventually‐developed ruptured cracks. The initiation of this three‐stage evolution begins with chemical‐resting and is exacerbated by further electrochemical cycling. From corrosion science and fracture mechanics, theoretical simulations suggest that the evolution of porous NRIL is driven by the concentrated stress at crack tips. The findings illustrate the importance of preventing electro‐chemo‐mechanical degradation of Na anodes in practically rechargeable NaOBs.
Rapid and Noise‐Resilient Mapping of Photogenerated Carrier Lifetime in Halide Perovskite Thin Films
Authors: Vidon Guillaume , Scrivanti Gabriele , Soret Etienne , Harada Nao , Chouzenoux Emilie , Pesquet Jean‐Christophe , Guillemoles Jean‐François , Cacovich Stefania
Published: April 2024

Halide perovskite materials offer significant promise for solar energy and optoelectronics yet understanding and enhancing their efficiency and stability require addressing lateral inhomogeneity challenges. While photoluminescence imaging techniques are employed for the measurement of their opto‐electronic and transport properties, going further in terms of precision requires longer acquisition times. Prolonged exposure of perovskites to light, given their high reactivity, can substantially alter these layers, rendering the acquired data less meaningful for analysis. In this paper, a method to extract high‐quality lifetime images from rapidly acquired, noisy time‐resolved photoluminescence images is proposed. This method leverages concepts of the field of constrained reconstruction and includes the Huber loss function and a specific form of total variation regularization. Through both simulations and experiments, it is demonstrated that the approach outperforms conventional pointwise methods. Optimal acceleration and optimization parameters tailored for decay time imaging of perovskite materials, offering new perspectives for accelerated experiments crucial in degradation process characterization are identified. Importantly, this methodology holds the potential for broader applications: it can be extended to explore additional beam‐sensitive materials, and other imaging characterization techniques and employed with more complex physical models to treat time‐resolved decays.
Mucus and Biofilm Penetrating Nanoplatform as an Ultrasound‐Induced Free Radical Initiator for Targeted Treatment of Helicobacter pylori Infection
Authors: Fan Jinjie , Dong Yuze , Sun Yue , Ji Yalan , Feng Jie , Yan Peijuan , Zhu Yingnan
Published: April 2024

Helicobacter pylori (H. pylori) infection is closely associated with the development of various gastric diseases. The effectiveness of current clinical antibiotic therapy is hampered by the rise of drug‐resistant strains and the formation of H. pylori biofilm. This paper reports a sonodynamic nanocomposite PtCu3‐PDA@AIPH@Fucoidan (PPAF), which consists of dopamine‐modified inorganic sonosensitizers PtCu3, alkyl radicals (R•) generator AIPH and fucoidan, can penetrate the mucus layer, target H. pylori, disrupt biofilms, and exhibit excellent bactericidal ability. In vitro experiments demonstrate that PPAF exhibits excellent acoustic kinetic properties, generating a significant amount of reactive oxygen species and oxygen‐independent R• for sterilization under ultrasound stimulation. Simultaneously, the produced N2 can enhance the cavitation effect, aiding PPAF nanoparticles in penetrating the gastric mucus layer and disrupting biofilm integrity. This disruption allows more PPAF nanoparticles to bind to biofilm bacteria, facilitating the eradication of H. pylori. In vivo experiments demonstrate that ultrasound‐stimulated PPAF exhibited significant antibacterial efficacy against H. pylori. Moreover, it effectively modulated the expression levels of inflammatory factors and maintained gastrointestinal microbiota stability when compared to the antibiotic treatment group. In summary, PPAF nanoparticles present a potential alternative to antibiotics, offering an effective and healthy option for treating H. pylori infection.
Stabilization of Lattice Oxygen Evolution Reactions in Oxophilic Ce‐Mediated Bi/BiCeO1.8H Electrocatalysts for Efficient Anion Exchange Membrane Water Electrolyzers
Authors: Jo Seunghwan , Jeon Jeong In , Shin Ki Hoon , Zhang Liting , Lee Keon Beom , Hong John , Sohn Jung Inn
Published: April 2024

The lattice oxygen mechanism (LOM) offers an efficient reaction pathway for oxygen evolution reactions (OERs) in energy storage and conversion systems. Owing to the involvement of active lattice oxygen enhancing electrochemical activity, addressing the structural and electrochemical stabilities of LOM materials is crucial. Herein, a heterostructure (Bi/BiCeO1.8H) containing abundant under‐coordinated oxygen atoms having oxygen nonbonding states is synthesized by a simple electrochemical deposition method. Given the difference in reduction potentials between Bi and Ce, partially reduced Bi nanoparticles and surrounding under‐coordinated oxygen atoms are generated in BiCeO1.8H. It is found that the lattice oxygen can be activated as a reactant of the OER when the valence state of Bi increases to Bi5+, leading to increased metal–oxygen covalency and that the oxophilic Ce3+/4+ redox couple can maintain the Bi nanoparticles and surrounding under‐coordinated oxygen atoms by preventing over‐oxidation of Bi. The anion exchange membrane water electrolyzer with Bi/BiCeO1.8H exhibits a low cell voltage of 1.79 V even at a high practical current density of 1.0 A cm−2. Furthermore, the cell performance remains significantly stable over 100 h with only a 2.2% increase in the initial cell voltage, demonstrating sustainable lattice oxygen redox.