bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study
Authors: Rabe KF , Vermeire PA , Soriano JB , Maier WC
Published: July 2002

Asthma management guidelines provide recommendations for the optimum control of asthma. This survey assessed the current levels of asthma control as reported by patients, which partly reflect the extent to which guideline recommendations are implemented. Current asthma patients were identified by telephone by screening 73,880 households in seven European countries. Designated respondents were interviewed on healthcare utilization, symptom severity, activity limitations and asthma control. Current asthma patients were identified in 3,488 households, and 2,803 patients (80.4%) completed the survey. Forty-six per cent of patients reported daytime symptoms and 30% reported asthma-related sleep disturbances, at least once a week. In the past 12 months, 25% of patients reported an unscheduled urgent care visit, 10% reported one or more emergency room visits and 7% reported overnight hospitalization due to asthma. In the past 4 weeks, more patients had used prescription quick-relief medication (63%) than inhaled corticosteroids (23%). Patient perception of asthma control did not match their symptom severity; approximately 50% of patients reporting severe persistent symptoms also considered their asthma to be completely or well controlled. The current level of asthma control in Europe falls far short of the goals for long-term asthma management. Patients' perception of asthma control is different from their actual asthma control.
Paracetamol sales and atopic disease in children and adults: an ecological analysis
Authors: Newson RB , Shaheen SO , Chinn S , Burney PG
Published: July 2002

The authors recently observed that frequent paracetamol use was positively associated with asthma and rhinitis in young adults. Therefore, an ecological analysis was performed to measure international associations between paracetamol sales and atopic disease prevalences in children and adults. Published data from the International Study of Asthma and Allergies in Childhood (ISAAC) on the prevalence of four atopic symptoms in 13-14-yr-olds (112 centres) and 67-yr-olds (66 centres) in 1994/1995, and European Community Respiratory Health Survey (ECRHS) data on the prevalence of asthma symptoms, diagnosed asthma and rhinitis (44 centres), prevalence of atopy, mean bronchial responsiveness and mean total immunoglobulin E levels (34 centres) in young adults in 1991/1992, were used. Their associations with national 1994/1995 per capita paracetamol sales were measured using linear regression. Paracetamol sales were high in English-speaking countries, and were positively associated with asthma symptoms, eczema and allergic rhinoconjunctivitis in 13-14-yr-olds, and with wheeze, diagnosed asthma, rhinitis and bronchial responsiveness in adults. The prevalence of wheeze increased by 0.52% in 13-14-yr-olds and by 0.26% in adults (p<0.0005) for each gram increase in per capita paracetamol sales. These ecological findings require cautious interpretation, but raise the possibility that variation in paracetamol usage may explain some of the variation in atopic disease prevalence between countries.
Diagnostic accuracy of protected catheter sampling in ventilator-associated bacterial pneumonia
Authors: Bregeon F , Papazian L , Thomas P , Carret V , Garbe L , Saux P , Drancourt M , Auffray JP
Published: July 2002

The aim of this study was to assess the accuracy of protected telescoping catheter performed using: 1) protected distal aspiration, or 2) protected mini-bronchoalveolar lavage for the diagnosis of ventilator-associated bacterial pneumonia. Twenty-seven patients who died after receiving mechanical ventilation for at least 72 h were included in a comparative prospective post-mortem study. The two microbiological sampling procedures were performed immediately after death. Surgical pneumonectomies and biopsies were performed within 30 min of death at the bedside for histological examination. The results of the two techniques were compared with histological post-mortem lung examination or biopsies. Histological examination of the parenchyma showed signs of pneumonia in 14 cases. Lung tissue culture was positive in nine of these 14 cases. When ventilator-associated bacterial pneumonia was defined by the association of histological signs and positive lung tissue culture the sensitivity was 78% for both sampling techniques, specificity was 86% for mini-bronchoalveolar lavage and 100% for protected distal aspiration (at a threshold of 1 x 10(3) cfu x mL(-1)). Both techniques protected the distal aspiration and mini-bronchoalveolar lavage, and provided good specificity with an acceptable sensitivity for the diagnosis of ventilator-associated bacterial pneumonia.
Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer
Authors: Reinmuth N , Brandt B , Kunze WP , Junker K , Thomas M , Achatzy R , Scheld HH , Semik M
Published: July 2002

The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.
Relationship between supramaximal flow during cough and mortality in motor neurone disease
Authors: Chaudri M.B. , Liu C. , Hubbard R. , Jefferson D. , Kinnear W.J.
Published: July 2002

The main function of cough is clearance of intrathoracic airways. A normal cough is characterized by a transient increase in expiratory flow above the maximal flow-volume loop envelope, known as cough “spikes”. They may be absent in patients with motor neurone disease. The relationship between cough pattern, pulmonary function and survival was studied.

Fifty-three patients were recruited (25 bulbar). Vital capacity, maximal inspiratory and expiratory mouth pressures and cough flow/volume curves were performed on all patients, and the presence or absence of spikes were recorded. The primary endpoints were mortality or initiation of ventilatory support over a period of 18 months.

Thirty-five patients died over the 18-month period of the study (including the six who were started on noninvasive ventilation). Twelve of the 24 patients with spikes died compared to 23 out of 29 patients without spikes (p<0.05). Patients without spikes were more likely to be bulbar on clinical grounds (p<0.0001) and had poorer lung function.

The results showed an association between the absence of cough spikes and increased mortality. However the main determinants of survival in motor neurone disease are age, vital capacity and inspiratory mouth pressure, and it remains to be shown whether regular monitoring of cough conveys any additional advantage.
Survey of flexible fibreoptic bronchoscopy in the United Kingdom
Authors: Smyth C.M. , Stead R.J.
Published: July 2002

The practice of flexible bronchoscopy is not standardized. Current guidelines are concerned primarily with safety aspects of the procedure. In view of this, and the authors' own observations of individual variation in preparation and technique, a national survey of bronchoscopic procedure was performed to assess physicians' methods.

A structured questionnaire was mailed to 547 consultant physicians in adult respiratory medicine. Physicians' routines of patient preparation, drug therapy, sampling methods, and experience of complications with the flexible bronchoscope were assessed.

A 60% response (328 physicians) was obtained. Patient consent was obtained by a junior doctor in 31% of replies. 205 (63%) physicians gave benzodiazepine sedation, 46 (14%) used opioid, and 38 (12%) administered both. Ninety-four (29%) physicians prescribed an antimuscarinic agent, and 235 (74%) gave antibiotics to patients with mechanical heart valves. Only 22% of physicians monitored electrocardiogram and 10% monitored blood pressure during all procedures. Marked variance was noted in sampling routines of suspected lung tumours. Physicians who used fluoroscopic guidance for transbronchial lung biopsy reported a significantly lower incidence of pneumothorax requiring drain insertion over the previous 12 months compared to those who did not (2.68 of 1000versus9.17 of 1000, (p<0.03)), but no difference in the total incidence of pneumothorax. Only 87 (27%) of responders had performed transbronchial needle aspiration sampling over the previous 12 months.

The preparation and practice of flexible bronchoscopy varies greatly for each physician. Use of radiographical screening for performing transbronchial lung biopsy was associated with a lower likelihood of pneumothorax requiring chest tube drainage.
Health-related quality of life in obstructive sleep apnoea
Authors: Lacasse Y. , Godbout C. , Sériès F.
Published: July 2002

The identification of the areas of quality of life (QoL) most likely to be affected by obstructive sleep apnoea (OSA) would be an important step in the evaluation of the impact of the disease and its treatment modalities. The objective of this study was to describe the impact of OSA on patients' QoL.

A list of 186 items potentially related to QoL of patients with OSA was constructed. From this list, consecutive patients were asked, at the time of the diagnosis, to identify the most significant items and to grade their importance on a 5‐point scale. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score=frequency×importance).

One hundred patients (82 male; mean age: 51 yrs) were interviewed. The items having the most important impact on QoL clustered into five domains: 1) daytime symptoms; 2) nocturnal symptoms; 3) limitation of activities; 4) emotions; and 5) interpersonal relationships.

The impact of obstructive sleep apnoea on quality of life is not limited to excessive daytime sleepiness. Obstructive sleep apnoea significantly contributes to the impairment of all domains of what is usually referred to as “health-related quality of life”.
Once-daily tobramycin in the treatment of adult patients with cystic fibrosis
Authors: Whitehead A. , Conway S.P. , Etherington C. , Caldwell N.A. , Setchfield N. , Bogle S.
Published: July 2002

The aim of this study was to test the equivalence of once- and thrice-daily dosing with tobramycin by comparing efficacy and safety in adult patients with cystic fibrosis.

Sixty adult patients with an acute respiratory exacerbation were randomized to receive either 10 mg·kg−1tobramycin once-daily or 3.3 mg·kg−1tobramycin thrice-daily. Primary efficacy and safety endpoints were defined as changes in respiratory function and changes in renal function and hearing.

Both groups showed a significant increase in respiratory function without a clinically significant change in renal function. For changes in forced vital capacity % predicted and serum potassium and magnesium levels, equivalence was demonstrated. For the variables forced expiratory volume in one second and forced mid-expiratory flow % pred and serum creatinine levels, there was insufficient power to demonstrate equivalence. One patient in each group showed bilateral impairment in pure tone audiogram after treatment.

This study demonstrated significant clinical improvement with both once- and thrice-daily tobramycin dosing. Equivalence between the two regimens was shown for some, but not all primary endpoints. Once-daily dosing should be used with careful monitoring of safety and efficacy until large multicentre studies confirm these encouraging results.
European Community Respiratory Health Survey calibration project of dosimeter driving pressures
Authors: Ward R.J. , Ward C. , Johns D.P. , Skoric B. , Abramson M. , Walters E.H.
Published: July 2002

Two potential sources of systematic variation in output from Mefar dosimeters, the system used in the European Community Respiratory Health Survey (ECRHS) study have been evaluated: individual nebulizer characteristics and dosimeter driving pressure.

Output variation from 366 new nebulizers produced in two batches for the second ECRHS were evaluated, using a solute tracer method, at a fixed driving pressure. The relationship between dosimeter driving pressure was then characterized and between-centre variation in dosimeter driving pressure was evaluated in an Internet-based survey.

A systematic difference between nebulizers manufactured in the two batches was identified. Batch one had a mean±sd output of 7.0±0.8 mg·s−1and batch two, 6.3±0.7 mg·s−1(p<0.005). There was a wide range of driving pressures generated by Mefar dosimeters as set, ranging between 70–245 kPa, with most outside the quoted manufacturer's specification of 180±5%. Nebulizer output was confirmed as linearly related to dosimeter driving pressure (coefficient of determination (R2)=0.99, output=0.0377×driving pressure–0.4151). The range in driving pressures observed was estimated as consistent with a variation of about one doubling in the provocative dose causing a 20% fall in forced expiratory volume in one second.

Systematic variation has been identified that constitutes potentially significant confounders for between-centre comparisons of airway responsiveness in the European Community Respiratory Health Survey, with the dosimeter driving pressure representing the most serious issue. This work confirms the need for appropriate quality control of both nebulizer output and dosimeter driving pressure, in laboratories undertaking field measurements of airway responsiveness. In particular, appropriate data on driving pressures need to be collected and factored into between-centre comparisons. Comprehensive collection of such data to optimize quality control is practicable and has been instigated by the organizing committee for the European Community Respiratory Health Survey II.
Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer
Authors: Brock C.S. , Lee S.M.
Published: July 2002

The generation of new blood vessels, angiogenesis, is important for tumour proliferation and metastasis. This involves a number of interacting processes and factors, such as growth factors and the receptor tyrosine kinases, matrix metalloproteinases and integrins.

Studies have shown that tumour vascularity and the overexpression of growth factors and their receptors are of independent prognostic importance in different cancers, including lung cancer.

The present article provides a background to angiogenesis and describes the potential targets for anti-angiogenic and vascular targeting strategies in cancer, focusing specifically on carcinoma of the lung. It also describes the anti-angiogenic drugs presently under phase I, II and III investigation and highlights some of the problems associated with the standard methodologies for assessing tumour response and drug efficacy using these agents.
Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease
Authors: Gosker H.R. , van Mameren H. , van Dijk P.J. , Engelen M.P.K.J. , van der Vusse G.J. , Wouters E.F.M. , Schols A.M.W.J.
Published: July 2002

The aim of this study was to examine the nature of fibre-type redistribution in relation to fibre metabolic profile in the vastus lateralis in chronic obstructive pulmonary disease (COPD) and COPD subtypes.

Fifteen COPD patients (eight with emphysema stratified by high-resolution computed tomography) and 15 healthy control subjects were studied. A combination of myofibrillar adenosine triphosphatase staining and immunohistochemistry was used to identify pure, as well as hybrid fibre types. For oxidative capacity, fibres were stained for cytochromecoxidase and succinate dehydrogenase activities, and glycogen phosphorylase for glycolytic capacity.

The proportion of type‐I fibres in COPD patients was markedly lower (16%versus42%), especially in emphysema, and the proportion of hybrid fibres was higher (29%versus16%) compared to controls. The proportion of fibres staining positive for oxidative enzymes was lower in COPD patients, which correlated with the proportion of type‐I fibres. In COPD oxidative capacity was lower within IIA fibres.

The authors conclude that fibre-type transitions are involved in the fibre-type redistribution in chronic obstructive pulmonary disease. Low oxidative capacity is closely related to the proportion of type‐I fibres, but an additional reduction of oxidative enzyme activity is present within IIA fibres. Fibre-type abnormalities may be aggravated in emphysema.
Role of tyrosine phosphatase in the modulation of pulmonary vascular tone
Authors: Huang X.L. , El Kebir D. , De Buys Roessingh A.S. , Schneider J.C. , Jacob L. , Mercier J.C. , Dall'Ava-Santucci J. , Dinh-Xuan A.T.
Published: July 2002

In the vascular system, synthesis of the potent vasodilator nitric oxide (NO) is tightly regulated by the constitutively expressed endothelial NO synthase (eNOS). Activity of eNOS is controlled by Ca2+/calmodulin and various seryl/threonyl protein kinases. Less is known about the importance of phosphorylation and dephosphorylation of tyrosyl residues. Therefore the role of tyrosine phosphatase on the modulation of isolated rat pulmonary artery tone has been assessed. Inhibition of tyrosine phosphatase by sodium orthovanadate (SOV, 1×10−6 M) significantly: 1) increased phenylephrine-induced vasoconstriction and 2) decreased endothelium-dependent relaxation to acetylcholine, but had no effect on endothelium-independent relaxation to the NO donor, sodium nitroprusside. In phenylephrine-precontracted pulmonary arterial rings, SOV (1×10−7–1×10−5 M) had no effect on vascular tone but significantly relaxed rings which were pretreated with the NO-synthase inhibitor,Nω‐nitro‐l‐arginine-methyl ester (l‐NAME). SOV-induced relaxation in the presence of l‐NAME was, however, abolished by glibenclamide.

In conclusion, inhibition of tyrosine phosphatase altered pulmonary vascular tone by increasing vasoconstrictor response to phenylephrine and decreasing endothelium-dependent relaxation to acetylcholine. Furthermore, the tyrosine phosphatase inhibitor, sodium orthovanadate, exhibited original vasodilator properties which were only observed when nitric oxide synthesis was inhibited. Thus a new pathway involving the inhibitory effect of nitric oxide on a glibenclamide-sensitive diffusible relaxing factor, that might play an important role in the control of pulmonary vascular tone is described.
Perspectives on Medical School Admission for Black Students Among Premedical Advisers at Historically Black Colleges and Universities
Authors: Weiss Jasmine , Nguementi Tiako Max Jordan , Akingbesote Ngozi D. , Keene Danya , Balasuriya Lilanthi , Sharifi Mona , Genao Inginia , Latimore Darin
Published: October 2024

Importance

There remains a lack of representation of Black physicians in the physician workforce despite decades of national efforts to increase diversity. Historically Black Colleges and Universities (HBCUs) contribute to increasing representation in the workforce in the US. There is limited literature exploring the experiences of HBCU premedical students navigating the journey to medical school.

Objective

To examine barriers to and facilitators of medical school matriculation among Black students by exploring the perspectives of premedical student advisers at HBCUs.

Design, Setting, and Participants

In this qualitative study, HBCU advisers participated in a focus group in October 2019 or in semistructured interviews from January 2020 to March 2021. Using purposive sampling, premedical student advisers were recruited from different educational backgrounds and geographic locations and conducted 1-on-1 interviews. Data analysis was performed from March 2021 to March 2022.

Main Outcomes and Measures

The main outcome was the experiences of HBCU premedical students navigating to medical school from the perspective of premedical advisers. An inductive approach to generate codes from the interviews and the focus groups was applied by reviewing transcripts and noting concepts and themes associated with advising strategies and student experiences.

Results

Among the 26 participants, 18 (69.2%) were female, 13 (50.0%) had a doctorate degree, and 8 (30.8%) had more than 10 years of experience as advisers. Participants described 3 major themes: (1) the complex institutional relationship dynamics between undergraduate HBCUs and medical schools, (2) concerns about preferential treatment for students from predominantly white undergraduate schools when accessing clinical shadowing opportunities, and (3) the “it takes a village mindset” emphasizing family and peer involvement.

Conclusions and Relevance

In this qualitative study, barriers to medical school matriculation included concerns for the preferential treatment of students from predominantly white institutions when engaging with medical schools and a lack of access to clinical opportunities for HBCU students. The findings suggest that medical schools should continue to build collaborative partnerships with HBCUs to ensure equitable access to opportunities that prepare students for medical school.
Cognitive status and demographics modify the association between subjective cognition and amyloid
Authors: Bolton Corey J. , Khan Omair A. , Liu Dandan , Wilhoite Sydney , Dumitrescu Logan , Peterson Amalia , Blennow Kaj , Zetterberg Henrik , Hohman Timothy J. , Jefferson Angela L. , Gifford Katherine A.
Published: October 2024

Objective

This study examined the effect of cognitive status, education, and sex on the association between subjective cognitive decline (SCD) and Alzheimer's disease (AD) biomarkers in non‐demented older adults.

Methods

Vanderbilt Memory and Aging Project participants (n = 129), dementia or stroke free, completed fasting lumbar puncture, SCD assessment, and cognitive assessment. Cerebrospinal fluid (CSF) biomarkers for AD were analyzed. Linear regression models related SCD to CSF AD biomarkers and follow‐up models assessed interactions of SCD × cognitive status, sex, reading level, and education on AD biomarkers.

Results

In main effect models, higher SCD was associated with more amyloidosis (p‐values <0.004). SCD was not associated with tau, p‐tau, or neurofilament light (NFL) levels (p‐values >0.38). SCD score interacted with cognitive status (p < 0.02), sex (p = 0.03), and education (p‐values <0.005) on amyloidosis. In stratified models, higher SCD was associated with more amyloid in cognitively unimpaired (p‐values <0.003), men (p = 0.0003), and higher education. No SCD score × reading‐level interaction was found (p‐values >0.51) though SCD related to amyloid markers in the higher reading‐level group (p‐values <0.004).

Interpretation

Higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD‐related brain changes prior to objective cognitive impairment, in men, and those with higher quantity and quality of education and highlight the importance of considering these factors.
Association between atherosclerotic disease and cervical artery dissection in a population‐based cohort of older people
Authors: Kahan Joshua , Zhang Cenai , Liberman Ava L. , Segal Alan Z. , Murthy Santosh B. , Kim Jiwon , Kamel Hooman , Merkler Alexander E.
Published: October 2024

Objectives

Many cases of cervical artery dissection are considered “spontaneous.” Recent data suggest that while cervical artery dissection may proportionally explain more strokes in young patients, hospitalization for dissection increases with age, suggesting a potential role of acquired vascular disease. In this study, we hypothesized that traditional vascular risk factors and comorbidities are associated with cervical artery dissection.

Methods

We performed a retrospective cohort study using administrative claims data from a 5% sample of Medicare beneficiaries. Exposures of interest included traditional vascular risk factors and comorbidities: coronary artery disease, hyperlipidemia, hypertension, diabetes mellitus, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, atrial fibrillation, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of cervical artery dissection. Marginal structural Cox models were used to characterize the association between the exposures and outcomes, adjusted for time‐dependent confounding.

Results

Among 2,256,710 eligible Medicare beneficiaries, 730 (0.03%) developed cervical artery dissection. The following exposures were found to be significantly associated with the development of cervical artery dissection: hypertension (HR 1.84 [95% CI: 1.40–2.41]), alcohol use (HR 1.83 [1.52–2.21]), atrial fibrillation (HR 1.80 [1.53–2.11]), tobacco use (HR 1.80 [1.52–2.13]), coronary artery disease (HR 1.56 [1.33–1.82]), and valvular heart disease (HR 1.23 [1.05–1.45]).

Interpretation

In a large cohort of older people, several traditional vascular risk factors and comorbidities were associated with subsequent cervical artery dissection. Further studies exploring the role of such factors in the development of cervical artery dissection are warranted.
Q‐Learning Based Adaptive Kalman Filtering With Adaptive Window Length
Authors: Tang Kun , Luan Xiaoli , Ding Feng , Liu Fei
Published: October 2024

In this article, we propose an adaptive Kalman filtering with adaptive window length based on Q‐learning for dynamic systems with unknown model information. The iteration step length of the Q‐function is quantitatively adjusted through the influence function. The adaptive Kalman filtering algorithm is used to set an appropriate weight matrix for the Q‐function to estimate unknown model parameters. One numerical example and a practice‐oriented case are given to illustrate the effectiveness of the proposed method. It is shown that this filtering can provide state estimates of best accuracy among all the compared methods when the model mismatch and noise statistical characteristics change.
Impact of Senescent Cell‐Derived Extracellular Vesicles on Innate Immune Cell Function
Authors: Chen Yung‐Yi , Sullivan Jack , Hanley Shaun , Price Joshua , Tariq Mohammad A. , McIlvenna Luke C. , Whitham Martin , Sharma‐Oates Archana , Harrison Paul , Lord Janet M. , Hazeldine Jon
Published: October 2024

Extracellular vesicles (EVs) are components of the senescence‐associated secretory phenotype (SASP) that influence cellular functions via their cargo. Here, the interaction between EVs derived from senescent (SEVs) and non‐senescent (N‐SEVs) fibroblasts and the immune system is investigated. Via endocytosis, SEVs are phagocytosed by monocytes, neutrophils, and B cells. Studies with the monocytic THP‐1 cell line find that pretreatment with SEVs results in a 32% (p < 0.0001) and 66% (p < 0.0001) increase in lipopolysaccharide (LPS)‐induced tumor necrosis factor‐alpha (TNF‐α) production when compared to vehicle control or N‐SEVs respectively. Interestingly, relative to vehicle control, THP‐1 cells exposed to N‐SEVs exhibit a 20% decrease in TNF‐α secretion (p < 0.05). RNA sequencing reveals significant differences in gene expression in THP‐1 cells treated with SEVs or N‐SEVs, with vesicle‐mediated transport and cell cycle regulation pathways featuring predominantly with N‐SEV treatment, while pathways relating to SLITS/ROBO signaling, cell metabolism, and cell cycle regulation are enriched in THP‐1 cells treated with SEVs. Proteomic analysis also reveals significant differences between SEV and N‐SEV cargo. These results demonstrate that phagocytes and B cells uptake SEVs and drive monocytes toward a more proinflammatory phenotype upon LPS stimulation. SEVs may therefore contribute to the more proinflammatory immune response seen with aging.
Strategic Defect Engineering Enabled Efficient Oxygen Evolution Reaction in Reconstructed Metal‐Organic Frameworks
Authors: Zhang Yin‐Qiang , Liu Ming , Zhang Le‐Tian , Lu Nan , Wang Xuemin , Li Zhi‐Gang , Zhang Xing‐Hao , Li Na , Bu Xian‐He
Published: October 2024

Metal‐organic frameworks (MOFs) have emerged as promising pre‐catalysts for oxygen evolution reaction (OER) due to their marvelous structural reconstruction process in strongly alkaline media. However, targeting design MOF structures to achieve excellent OER performance of reconstructed products is a challenge. Here, a strategic defect engineering is used to promote the OER performance of reconstructed products. Briefly, modified linkers with monocarboxylic acids (ferrocene carboxylic acid, FcCA) are incorporated into MOF (NiBDC‐FcCA), leading to its stepwise reconstruction into Fe‐doped Ni(OH)2 and NiOOH during the OER process, with the oxygen vacancy and strategic doping of metal Fe persisting throughout the multi‐step reconstruction. Benefiting from the synergistic interaction of oxygen vacancies and Fe doping, NiBDC‐FcCA delivers the extremely enhanced current density at 1.6 V versus reversible hydrogen electrode by ≈9 times compared with that of NiBDC. Moreover, the optimized NiBDC‐FcCA/Fe foam exhibits excellent OER catalytic activity and stability with a low overpotential of 250 mV at 200 mA cm−2 and negligible activity decay after 1200 h at 1 A cm−2. Density function theory calculations reveal that Fe doping weakens the interaction of oxygen intermediate with Ni sites, favoring the formation of OOH* to accelerate the OER process.
In Situ Crystallized Ceria‐Vesicle Nanohybrid Therapeutic for Effective Treatment of Inflammatory Intraocular Disease
Authors: Zhao Jiawei , Wang Yingjie , Zhang Yiquan , Guo Xinyu , Bao Han , Tao Yong
Published: October 2024

Posterior uveitis is a leading cause of vision impairment and blindness globally due to its detrimental effects on the choroid and retina. The condition is worsened by oxidative stress, which heightens inflammation and perpetuates a cycle of damage that current treatments only temporarily relieve. To address this, a novel treatment involving the in situ crystallization of ultrasmall cerium oxide nanoparticles (≈3 nm) on mesenchymal stem cell (MSC) extracellular vesicles (EVs) for the management of primed mycobacterial uveitis (PMU) is developed. This nanohybrid leverages the individual and synergistic effects of its components for a comprehensive therapeutic approach. The cerium oxide nanoparticles act as a nanozyme to reduce inflammation and scavenge excessive reactive oxygen species (ROS), while the MSC EVs, with their biocompatibility, modulate inflammatory cell infiltration and alleviate tissue damage. This synergistic system offers a promising new treatment strategy for ocular diseases characterized by oxidative stress and inflammation.
Next‐Generation Approaches for Biomedical Materials Evaluation: Microfluidics and Organ‐on‐a‐Chip Technologies
Authors: Li Yuxuan , Sun Ke , Shao Yi , Wang Cheng , Xue Feng , Chu Chenglin , Gu Zhongze , Chen Zaozao , Bai Jing
Published: October 2024

Biological evaluation of biomedical materials faces constraints imposed by the limitations of traditional in vitro and animal experiments. Currently, miniaturized and biomimetic microfluidic technologies and organ‐on‐chip systems have garnered widespread attention in the field of drug development. However, their exploration in the context of biomedical material evaluation and medical device development remains relatively limited. In this review, a summary of existing biological evaluation methods, highlighting their respective advantages and drawbacks is provided. The application of microfluidic technologies in the evaluation of biomedical materials, emphasizing the potential of organ‐on‐chip systems as highly biomimetic in vitro models in material evaluation is then focused. Finally, the challenges and opportunities associated with utilizing organ‐on‐chip systems to evaluate biomedical materials in the field of material evaluation are discussed. In conclusion, the integration of advanced microfluidic technologies and organ‐on‐chip systems presents a potential paradigm shift in the biological assessment of biomedical materials, offering the prospective of more accurate and predictive in vitro models in the development of medical devices.
Inflammation‐Targeted Biomimetic Nano‐Decoys via Inhibiting the Infiltration of Immune Cells and Effectively Delivering Glucocorticoids for Enhanced Multiple Sclerosis Treatment
Authors: Yang Yiling , Zhao Yuzhen , Liu Huixian , Wu Xinyun , Guo Mingming , Xie Li , Wang Guangsheng , Shi Jinjin , Yu Wenyan , Dong Gang
Published: October 2024

Excessive infiltration of neutrophil and inflammatory cytokines accumulation as well as the inadequate delivery of drugs to the targeted site are key pathological cascades in multiple sclerosis (MS). Herein, inflammation‐targeting biomimetic nano‐decoys (TFMN) is developed that inhibit the infiltration of immune cells and effectively deliver glucocorticoids to lesions for enhanced MS treatment. Nano‐decoys encapsulated with the glucocorticoid methylprednisolone (MPS) are prepared by coating neutrophil membrane (NM) on nanoparticles formed by the self‐assembly of tannic acid and poloxamer188/pluronic68. Benefiting from the natural inflammation‐targeting ability of activated neutrophil membranes, TFMN can target the lesion site and prevent neutrophils infiltration by adsorbing and neutralizing elevated neutrophil‐related cytokines, subsequently modulating the inflammatory microenvironment in experimental autoimmune encephalomyelitis mice. TFMN exhibits a strong antioxidant capacity and scavenged excessive reactive oxygen species to enhance neuronal protection. Furthermore, at the inflammation site, perforin, discharged by cytotoxic T‐lymphocytes, triggered the controlled release of MPS within the TFMN through perforin‐formed pores in the NM. Simultaneously, this mechanism protected neurons from perforin‐induced toxicity. The MPS liberated at the targeted site achieves optimal drug accumulation, thereby enhancing therapeutic efficacy. In conclusion, the innovative system shows potential for integrating various therapeutic agents, offering a novel strategy for CNS disorders.
“Osteo‐Organogenesis Niche” Hyaluronic Acid Engineered Materials Directing Re‐Osteo‐Organogenesis via Manipulating Macrophage CD44‐MAPK/ERK‐ETV1/5‐MRC1 Axis
Authors: Han Zongpu , Lin Yixiong , Guo Xinyu , Xu Jieyun , Gao Xiaomeng , Yang Ruihan , Zhao Yuan , Gui Mixiao , Zhang Linjun , Guo Yuanlong , Chen Zetao
Published: October 2024

The strategy of re‐organogenesis provides an optimal framework for restoring complex organ structures and functions in adult damage. While the focus has often been on restoring organogenesis stem cells, there is limited investigations of reverting the environmental niche to support this approach. The guiding principle of “Nature selects the fittest to survive” drives the intricate dynamic changes in cellular events within the niche environment, especially through immune surveillance. The extracellular matrix (ECM) serves as the “self‐associated molecular patterns” of the niche, containing extensive data on cell‐niche reaction data and acting as the active tuner of immune surveillance. In this study, hyaluronic acid (HA) is identified as a unique component of the ECM in cranial osteo‐organogenesis. Mechanistically, HA activates the Cluster of Differentiation 44 (CD44)‐Mitogen‐Activated Protein Kinase (MAPK)/Extracellular Signal‐Regulated Kinase (ERK)‐Ets Variant 1/5 (ETV1/5)‐ Mannose Receptor C‐Type 1 (MRC1) axis in macrophages, establishing a distinct immune surveillance during osteo‐organogenesis. Furthermore, HA is utilized as a novel engineered material for an “Osteo‐organogenesis niche”, restoring immune surveillance and synergistically regulating stem cells to achieve re‐osteo‐organogenesis in cranial defects of rats. Taken together, the study unveils a previously unknown strategy for leveraging re‐organogenesis by utilizing “organogenesis niche” ECM engineered materials to manipulate immune surveillance, thereby comprehensively regulating stem cells and other tissue cells effectively for re‐organogenesis.
Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells
Authors: Wang Xiang‐Yu , Yan Yi , Guo Xiao‐Ru , Lu An , Jiang Lin‐Xia , Zhu Yuan‐Jun , Shi Yu‐Jie , Liu Xiao‐Yan , Wang Jian‐Cheng
Published: October 2024

Insufficient activation of stimulator of interferon genes (STING) signaling pathway in tumor‐associated dendritic cells limits the efficiency of tumor immunotherapy. Herein, the “three‐in‐one” IAHA‐LaP/siPTPN6 NPs containing lanthanum ions (La3+), cGAMP, and PTPN6 siRNA are developed for triple amplification of the STING pathway. In vitro results demonstrate that La3+ significantly promotes cGAMP‐mediated activation of the STING pathway by enhancing the phosphorylation of STING, TBK1, IRF3, and NF‐κB p65. Moreover, the IAHA‐LaP/siPTPN6 NPs further significantly enhance the phosphorylation of STING and NF‐κB p65 and augment K63‐linked ubiquitination of STING protein via siPTPN6‐mediated downregulation of SHP‐1 protein. Furthermore, NPs improve the secretion of IFNβ (2.4‐fold), IL‐6 (1.5‐fold), and TNF‐α (1.4‐fold), thereby promoting DCs maturation compared to the mixture of La3+ and cGAMP. In vivo results show that the IAHA‐LaP/siPTPN6 NPs remarkably inhibit primary tumor growth by increasing the percentage of mature DCs in tumor‐draining lymph nodes, polarizing M2/M1 phenotype in TME, and promoting the infiltration of CD8+T cells into tumors. Moreover, these NPs dramatically prevent the growth of distal tumor by inducing systemic anti‐tumor immunity and generating a long‐term anti‐tumor memory for protection against tumor recurrence in mice bearing bilateral B16F10. These IAHA‐LaP/siPTPN6 NPs may offer a promising platform for robust anti‐tumor immune responses.
Netrin1‐Enriched Exosomes From Genetically Modified ADSCs as a Novel Treatment for Diabetic Limb Ischemia
Authors: Jiang Yihong , Hu Jiateng , Cui Chaoyi , Peng Zhaoxi , Yang Sen , Lei Jiahao , Li Bo , Yang Xinrui , Qin Jinbao , Yin Minyi , Liu Xiaobing , Ye Kaichuang , Xu Zhijue , Zhang Xing , Lu Xinwu
Published: October 2024

Diabetic limb ischemia (DLI) is a frequent complication of diabetes and the leading cause of non‐traumatic amputation. Traditional treatments like stent placement and bypass surgery may not suit all patients. Exosome transplantation has emerged as a promising therapy. Netrin1, a protective cardiovascular factor, has an unclear role in DLI. This study investigates the role of Netrin1 in DLI patients and evaluates the therapeutic potential of exosomes derived from Netrin1‐overexpressing adipose‐derived stem cells (N‐ADSCs). The expression of Netrin1 is significantly decreased in both endothelial cells and serum of DLI patients, highlighting its potential as a biomarker or therapeutic target. In vitro, Netrin1‐enriched exosomes (N‐Exos) promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation, and increased resistance to apoptosis under high glucose conditions. These protective effects are mediated through PI3K/AKT/eNOS and MEK/ERK pathways, and N‐Exos further facilitated macrophage polarization from M1 to M2. In vivo, N‐Exos demonstrates superior therapeutic effects over ADSC exosomes (Exos), including enhanced angiogenesis, improved collateral artery remodeling, reduced inflammation, and muscle protection. Collectively, these findings identify Netrin1 as a critical factor in DLI and underscore its significance in disease progression and therapeutic strategies. N‐Exos offers a promising non‐cellular therapeutic approach for the treatment of DLI.
Solid Additive Engineering for Next‐generation Organic Photovoltaics
Authors: Hu Dingqin , Tang Hua , Chen Chen , Lee Duu‐Jong , Lu Shirong , Li Gang , Hsu Hsien‐Yi , Laquai Frédéric
Published: October 2024

Solution‐processed bulk heterojunction (BHJ) organic solar cells (OSCs) have emerged as a promising next‐generation photovoltaic technology. In this emerging field, there is a growing trend of employing solid additives (SAs) to fine‐tune the BHJ morphology and unlock the full potential of OSCs. SA engineering offers several significant benefits for commercialization, including the ability to i) control film‐forming kinetics to expedite high‐throughput fabrication, ii) leverage weak noncovalent interactions between SA and BHJ materials to enhance the efficiency and stability of OSCs, and iii) simplify procedures to facilitate cost‐effective production and scaling‐up. These features make SA engineering a key catalyst for accelerating the development of OSCs. Recent breakthroughs have shown that SA engineering can achieve an efficiency of 19.67% in single‐junction OSCs, demonstrating its effectiveness in promoting the commercialization of organic photovoltaic devices. This review provides a comprehensive overview of significant breakthroughs and pivotal contributions of emerging SAs, focusing on their roles in governing film‐forming dynamics, stabilizing phase separation, and addressing other crucial aspects. The rationale and design rules for SAs in highly efficient and stable OSCs are also discussed. Finally, the remaining challenges are summarized, and perspectives on future advances in SA engineering are offered.
Ultrahigh Elastic Energy Storage in Nanocrystalline Alloys with Martensite Nanodomains
Authors: Dang Pengfei , Li Cheng , Yang Yuanchao , Zhou Yumei , Xu Yangyang , Ding Xiangdong , Sun Jun , Xue Dezhen
Published: October 2024

Elastic materials that store and release elastic energy play pivotal roles in both macro and micro mechanical systems. Uniting high elastic energy density and efficiency is crucial for emerging technologies such as artificial muscles, hopping robots, and unmanned aerial vehicle catapults, yet it remains a significant challenge. Here, a nanocrystalline structure embedded with elliptical martensite nanodomains in ferroelastic alloys was utilized to enable high yield strength, large recoverable strain, and low energy dissipation simultaneously. As a result, the designed Ti–Ni–V alloys demonstrate ultrahigh energy density (>40 MJ m−3) with ultrahigh efficiency (>93%) and exceptional durability. This concept, which combines nano‐sized embryos to minimize energy dissipation of psuedo‐elasticity and employs a fine‐grained structure to enhance yield strength, can be applied to other ferroelastic materials. Furthermore, it holds promise for the development of phase transformation‐involved functionalities such as high‐performance dielectric energy storage, ultralow‐hysteresis magnetostrain, and high‐efficiency solid‐state caloric cooling.
A Frustrated Antipolar Phase Analogous to Classical Spin Liquids
Authors: Bastien Gaël , Repček Dalibor , Eliáš Adam , Kancko Andrej , Courtade Quentin , Haidamak Tetiana , Savinov Maxim , Bovtun Viktor , Kempa Martin , Carva Karel , Vališka Michal , Doležal Petr , Kratochvílová Marie , Barnett Sarah A. , Proschek Petr , Prokleška Jan , Kadlec Christelle , Kužel Petr , Colman Ross H. , Kamba Stanislav
Published: October 2024

The study of magnetic frustration in classical spin systems is motivated by the prediction and discovery of classical spin liquid states. These uncommon magnetic phases are characterized by a massive degeneracy of their ground state implying a finite magnetic entropy at zero temperature. While the classical spin liquid state is originally predicted in the Ising triangular lattice antiferromagnet in 1950, this state has never been experimentally observed in any triangular magnets. The discovery of an electric analogue of classical spin liquids on a triangular lattice of uniaxial electric dipoles in EuAl12O19 is reported here. This new type of frustrated antipolar phase is characterized by a highly‐degenerate state at low temperature implying an absence of long‐range antiferroelectric order, despite short‐range antipolar correlations. Its dynamics are governed by a thermally activated process, slowing down upon cooling toward a complete freezing at zero temperature.
Catalytic Strategies for the Selective Synthesis of α‐ and β‐Functionalized Amines via Hydrofunctionalization of Enamides
Authors: Sun Rui , Yang Xiao
Published: October 2024

α‐ and β‐Functionalized amines are two classes of important compounds, whose structural units are widely present in approved drugs. The hydrofunctionalization of enamides is the most direct and efficient method for constructing these two types of compounds. Regioselectivity is the focus of this conversion, and is largely influenced by the catalytic mode. Therefore, to selectively synthesize α‐ or β‐functionalized amines, the progress in the catalytic hydrofunctionalization of enamides over the past decade is reviewed, and the catalytic pathways for this process discussed in detail. This account aims to objectively evaluate the effects of various catalytic pathways on the regioselectivity of hydrofunctionalization, to provide a new perspective on the selection of catalytic methods and the design of catalytic pathways for the selective synthesis of α‐ or β‐functionalized amines.
Solving Max‐Cut Problem Using Spiking Boltzmann Machine Based on Neuromorphic Hardware with Phase Change Memory
Authors: Kang Yu Gyeong , Ishii Masatoshi , Park Jaeweon , Shin Uicheol , Jang Suyeon , Yoon Seongwon , Kim Mingi , Okazaki Atsuya , Ito Megumi , Nomura Akiyo , Hosokawa Kohji , BrightSky Matthew , Kim Sangbum
Published: October 2024

Efficiently solving combinatorial optimization problems (COPs) such as Max‐Cut is challenging because the resources required increase exponentially with the problem size. This study proposes a hardware‐friendly method for solving the Max‐Cut problem by implementing a spiking neural network (SNN)‐based Boltzmann machine (BM) in neuromorphic hardware systems. To implement the hardware‐oriented version of the spiking Boltzmann machine (sBM), the stochastic dynamics of leaky integrate‐and‐fire (LIF) neurons with random walk noise are analyzed, and an innovative algorithm based on overlapping time windows is proposed. The simulation results demonstrate the effective convergence and high accuracy of the proposed method for large‐scale Max‐Cut problems. The proposed method is validated through successful hardware implementation on a 6‐transistor/2‐resistor (6T2R) neuromorphic chip with phase change memory (PCM) synapses. In addition, as an expansion of the algorithm, several annealing techniques and bias split methods are proposed to improve convergence, along with circuit design ideas for efficient evaluation of sampling convergence using cell arrays and spiking systems. Overall, the results of the proposed methods demonstrate the potential of energy‐efficient and hardware‐implementable approaches using SNNs to solve COPs. To the best of the author's knowledge, this is the first study to solve the Max‐Cut problem using an SNN neuromorphic hardware chip.