bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring high-dose heparin levels by ACT and HMT during extracorporeal circulation: diagnostic accuracy of three compact monitors
Authors: Giavarina Davide , Carta Mariarosa , Fabbri Alessandro , Manfredi Jacopo , Gasparotto Edoardo , Soffiati Giuliano
Published: July 2002

The correct monitoring of heparin therapy and its reversal determines the successful conduct of cardiovascular surgery with extracorporeal circulation (ECC). The activated coagulation time (ACT) and the heparin management test (HMT) are the most frequently used tests in the operating room. Three compact monitors for ACT or HMT are here evaluated. Forty samples were obtained, at 10-min intervals, from eight patients during ECC. The ACT or HMT was immediately performed using: Hemochron Junior™ ACT, CoaguCeck™ Pro (ACT) and Rapid Point Coag (HMT). Data were compared between them and with the heparin levels, measured as anti-Xa. The simple least squares linear regression among, respectively, Hemochron Junior ACT, CoaguCeck Pro ACT, Rapid Point Coag HMT and anti-Xa activity were i= 452.3, s= 15.2, Sy/x= 37.5, r= 0.18; i= 411.9, s= 22.1, Sy/x= 48.7, r= 0.21 and i= 479.4, s= 9.0, Sy/x= 9.3; r= 0.41. CoaguCeck Pro ACT results were above the upper detection limit (500 s) in 37 of 40 determinations. The comparison between ACT Hemocron and HMT Rapid Point Coag shows i= 35.7, s= 0.9, Sy/x= 35.4, r= 0.68, with a bias of 29.0 s (CI: 17.9-40.1), 95% of agreement between -41.5 s (CI: -60.7 to -22.3) and 99.5 s (CI: 80.4-118.7). Taking a concentration of 2.0 U/ml of heparin to discriminate between high- and low-risk conditions, receiver-operator characteristic (ROC) curve was used to rank the performance of the methods. Areas under the ROC curve± SE for Hemochron Junior ACT and Rapid Point Coag HMT were 0.629± 0.097 and 0.543± 0.096. The results obtained by HMT appear similar to those obtained by the ACT for monitoring high-dose heparin therapy in patients undergoing ECC. HMT appeared to perform better than ACT in measuring the heparin effect, while the ROC analysis gives a little more accuracy for ACT. Neither of the two methods is able to achieve enough evidence of diagnostic accuracy. Since these tests are widely used, and there are no laboratory alternatives, a real comparison with the outcome of the patients should be helpful for an evidence-based evaluation of these point-of-care tests.
The Guy's Neurological Disability Scale in patients with multiple sclerosis: a clinical evaluation of its reliability and validity
Authors: Rossier Philippe , Wade Derick T
Published: July 2002

Objective: To establish reliability and validity of the Guy's Neurological Disability Scale (GNDS) for the assessment of patients with multiple sclerosis (MS) and to investigate whether it can be used by postal questionnaire.

Design: An observational study assessing one group of 22 patients using the GNDS face-to-face, repeating the assessment two or three weeks later with other tests; and assessing a second group of 21 patients first using a postal version of the GNDS and then seeing them face-to-face.

Setting: Patients in the community attending a day centre or a voluntary support group.

Subjects: Patients with multiple sclerosis.

Measures: The GNDS was the primary measure, and was compared with the Barthel Index, the Expanded Disability Status Scale (EDSS), the Short Orientation Concentration and Memory Test, the Nine-hole Peg Test, the Rivermead Mobility Index, the Hospital Anxiety and Depression Scale, the Fatigue Severity Scale, visual acuity assessment, swallowing 50 ml of water, and a clinical assessment of dysarthria.

Results: The test–retest reliability of the GNDS total score ( r = 0.972) and each of its components ( r varied from 0.685 to 0.987) was good. When compared with the EDSS or the Barthel, the GNDS had good validity (respectively r = 0.636 and r = –0.757). The validity was also measured for the different areas of the GNDS by comparison with corresponding indices or test. The results varied from good to excellent ( r from –0.557 to 0.910). The results were only a little less reliable when a postal questionnaire was used.

Conclusion: The GNDS is a valid and reliable tool for the assessment of MS patients. The test–retest correlation varies from good to excellent. It can be used as postal questionnaire even if, as expected, the intervieweradministered method shows slightly better results.
Association between hypermobility and congenital limb defi ciencies
Authors: Hassoon Ali , Kulkarni Jai
Published: July 2002

Objective: To determine the prevalence of hypermobility in individuals with congenital limb deficiencies and whether congenital limb loss is associated with increased laxity in the remaining joints.

Study design: All data were collected during the individuals' visits to the prosthetic clinic.

Setting: The subjects were evaluated at the Subregional Disablement Services Centre at University Hospital of South Manchester, UK.

Subjects: Forty-five individuals with congenital limb deficiencies were studied (male/female 27: 18; ages 6–31 years).

Outcome measure: A modified version of the nine-point Beighton Score for hypermobility was used, using the presently accepted criteria for diagnosing hypermobility. Any individual who scored 3 or more points was considered to have joint hypermobility.

Result: Of the 45 individuals with congenital limb deficiencies, 71% had at least one hypermobile joint, whereas 38% had three or more features of hypermobility, with female/male ratio of 2.75: 1.

Conclusion: Our results show an increase in joint hypermobility (laxity) in individuals born with congenital limb deficiencies compared with the prevalence of this condition in the general population. As joint hypermobility may predispose individuals to low back pain, joint effusion, recurrent joint dislocation and ligament rupture, it is useful to identify those individuals with hypermobility.
Effects of one-point and four-point canes on balance and weight distribution in patients with hemiparesis
Authors: Laufer Yocheved
Published: July 2002

Objective: To examine the effects of one-point and four-point canes on postural sway and on the distribution of weight between the lower extremities and the walking aids in hemiparetic patients.

Setting: Flieman Geriatric Rehabilitation Hospital, Haifa, Israel.

Subjects: Thirty hemiparetic patients following a unilateral stroke, with moderate functional impairment, and 20 age-matched healthy subjects.

Intervention: Subjects were tested on two forceplates, which were placed at a 30° angle from each other with the heel end of the plates separated by 3 cm. Each subject was tested under three conditions: with no cane, with a one-point cane, and with a four-point cane. Testing time was 30 seconds, and order of testing was randomized.

Outcome measures: Weight borne by the lower extremities and by the walking aids expressed as a percentage of overall body weight, and Sway Index indicating vertical pressure ‘uctuations over both feet.

Results: In both subject groups, the one-point cane did not reduce sway signi”cantly in comparison with no cane, while the four-point cane reduced sway signi”cantly in comparison with both no cane and one-point cane. Neither cane type affected weight-bearing on the paretic leg, while signi”cantly reducing weight-bearing on the uninvolved extremity. Mean percentage of body weight on the four-point cane was signi”cantly higher than on the one-point cane

Conclusions: A four-point cane increases stability of moderately involved hemiparetic patients during stance more than a one-point cane. The noted shift of weight toward the walking aid does not adversely affect weight-bearing on the paretic limb.
A randomized controlled trial of exercise to improve mobility and function after elective knee arthroplasty. Feasibility, results and methodological difficulties
Authors: Frost H , Lamb S E , Robertson S
Published: July 2002

Objective: To assess the feasibility of comparing two types of exercise regime aiming to improve mobility and function following knee arthroplasty.

Design: A single-blind randomized controlled trial.

Subjects: Patients with primary, unilateral knee osteoarthritis undergoing elective knee joint replacement.

Intervention: Home-based traditional exercise group (TEG) or home-based functional exercise group (FEG) following discharge from hospital.

Outcome measures: These included goniometry; a knee-specific pain score, leg extensor power and a walking test. Patients were followed up at three, six and 12 months after surgery.

Results: Forty-seven patients met the study criteria, 24 were randomized to the TEG and 23 to the FEG. There were marked improvements in mobility, leg extensor power and pain in the year after surgery (MANOVA p < 0.001). There were no statistically significant differences between the two exercise groups. Knee flexion decreased during the follow-up period and had not recovered by 12 months. Retention of patients was a problem, with nearly 50% lost to follow-up at 12 months. These patients were assessed as having low motivation during inpatient rehabilitation ( p < 0.05).

Conclusions: There were trends in favour of the FEG that were of clinical relevance. A definitive study would need a sample size of at least 100 patients in each arm. It is essential to develop strategies to combat loss to follow-up.
Beyond the 10-m time: A pilot study of timed walks in lower limb amputees
Authors: Hatfield Alison G
Published: July 2002

Objective: To investigate in a pilot study the use of extended walking times as an objective method of distinguishing differences in outcome in lower limb amputees.

Setting: Sixteen lower limb amputees attending the prosthetic clinic.

Method: Patients were asked to walk 100 m, turning every 20 m, using their usual walking aids and prostheses at their chosen walking speed. Demographic details and modified Stanmore/Harold Wood mobility grades, walking aids used and discomfort were recorded. Time to walk each 20 m up to 100 m was recorded. Statistical analysis was carried out using the Spearman rank order correlation coefficient.

Results: There was a wide age range and differing causes of amputation. Five out of 16 subjects failed to complete 100 m and these had the slowest 20 and 40-m times. The mean time to walk 40 m was 41 seconds for those who were able to complete 100 m and 144 seconds for those who could not complete 100 m. All those with modified Stanmore/Harold Wood mobility grades less than four failed to complete 100 m. There was a high correlation between 20-, 40-, 60-, 80 and 100-m times and mobility grades, which was statistically significant, and between 20-, 40-, 60-, 80 and 100-m times.

Conclusion: Forty-metre walking time can differentiate between those of mobility grades 4b–6 and those with lower mobility grades who are unable to walk significantly outside.
Depression after stroke: a review of the evidence base to inform the development of an integrated care pathway. Part 1: Diagnosis, frequency and impact
Authors: Turner-Stokes Lynne , Hassan Nibras
Published: July 2002

Background: Depression is a common complication of stroke, leading to increased morbidity and mortality. It can impede the process of rehabilitation, and has been associated with poorer outcomes and increased length of stay in hospital. This systematic review was undertaken as a preliminary step to explore the available evidence on which to base an integrated care pathway (ICP) for the management of post-stroke depression (PSD) in a rehabilitation setting. It is divided into two parts.

Aims and objectives: In part 1 we review the frequency of depression in stroke and its impact on functional recovery. Also the different methods for diagnosis and measurement.

Methods: Data sources comprised a computer-aided search of published studies on depression in stroke and references to literature used in reviews.

Main findings: PSD is common and is associated with cognitive, functional and social deficits which potentially limit the outcome from rehabilitation. However, diversity of assessment tools and diagnostic criteria confound assimilation of the available literature. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale and Zung Self-rating Depression Scale were most commonly used and have demonstrable validity in stroke patients but tend to exclude those with aphasia. Instruments developed specifically to include aphasic patients, such as the Stroke Aphasic Depression Scale, are promising but have yet to be fully evaluated.

Conclusions: Further work is required to adapt and evaluate instruments to measure depression in the context of stroke. Development of an integrated care pathway may help to establish a more consistent approach to assessment and diagnosis of PSD.
Sensitivity of different ADL measures to apraxia and motor impairments
Authors: Donkervoort Mireille , Dekker Joost , Deelman Betto G
Published: July 2002

Objective: To determine whether speci”cally designed activities of daily living (ADL) observations can measure disability due to apraxia with more sensitivity than the Barthel ADL Index, a conventional functional scale.

Design: Cross-sectional study.

Setting: Rehabilitation centres and nursing homes.

Subjects: One hundred and six left hemisphere stroke patients with apraxia, hospitalized in rehabilitation centres and nursing homes.

Measures: ADL observations, Barthel ADL Index, an apraxia test, Motricity Index, Functional Motor Test.

Results: Multivariate analyses showed that the speci”c ADL observations were associated with severity of apraxia (and not with motor impairments). The Barthel ADL Index was associated with motor impairments (and not with severity of apraxia).

Conclusion: The assessment of disability in stroke patients with apraxia cannot rely only on the Barthel ADL Index. In addition, the speci”c ADL observation procedure is needed to measure disability due to apraxia.
Reviewing the impact of metals and PAHs on macroinvertebrates in urban watercourses
Authors: Beasley Gary , Kneale Pauline
Published: July 2002

Pollution-free stream water and sediments are crucial to support healthy stream flora and fauna, but urban surface runoff impairs water quality and leaves a legacy of pollution in the sediments. Pollution in sediments influences the development of macroinvertebrates, the lowest members of the food chain, leading to modification of the whole ecological structure. This review focuses on the sources and impacts of zinc, nickel, copper and oil derivative polycyclic aromatic hydrocarbon (PAH) contaminants on macroinvertebrates in urban streams. Land use, and the connectivity of the runoff and sediment are seen to have an effect on the ecological integrity of the watercourse but case examples are sparse. The literature indicates that while reduced species diversity has been identified at a number of sites the dynamics are neither well understood nor well modelled. The literature evidence is compared with field evidence from a study of 62 source areas in headwater catchments with residential, urban, industrial and motorway land uses. From the review and field results it is evident that there is still an important need for process-based field measurements of urban water quality parameters. It is suggested that forecasting the ecological status of watercourses would benefit from data on sediment chemistry and the interaction effects of metals and PAHs.
Inhibition of salivary enzymes by cigarette smoke and the protective role of glutathione
Authors: Zappacosta B , Persichilli S , Mordente A , Minucci A , Lazzaro D , Meucci E , Giardina B
Published: July 2002

Tobacco smoke is involved in the pathogenesis of several diseases regarding different body systems, mainly cardiovascular and respiratory in addition to its local toxic effect in the oral cavity. The noxious effects of smoke compounds justify the high incidence of periodontal diseases, caries, and neoplastic diseases of oral tissues in smokers. Some toxic components of tobacco smoke, unsaturated and saturated aldehydes, could interact with thiol rich compounds, leading to structural and functional modification of these molecules. Previous papers have demonstrated an in vitro significant decrease of some enzymatic activities, both in plasma and in saliva, following external addition of aldehydes or exposure to cigarette smoke (CS). Furthermore, the same studies underlined the protective effect exerted by the addition of glutathione (GSH) against the damaging role of smoke aldehydes. In this study some salivary enzymes (lactic dehydrogenase [LDH], aspartate aminotransferase [AST] and amylase), and total GSH were measured in 20 volunteers smokers, before and just after smoking a single cigarette. All enzymatic activities showed a significant inhibition following a single cigarette, probably due to the interaction between smoke aldehydes and–SH groups of the enzyme molecules. Moreover, the percentage of the enzymatic inhibition showed a negative correlation with the basal level of salivary GSH. Our results emphasize that not only one cigarette is sufficient to impair the salivary enzymatic activities but also strengthen the proposed protective role of GSH against the noxious biochemical effects of CS.
Molybdenum in rat tissue
Authors: Pandey R , Kumar R , Singh S P , Srivastava S P
Published: July 2002

Male rats were given 50 mg/kg molybdenum (Mo; as sodium molybdate) in drinking water for eight consecutive doses. The feeding of Mo was associated with an increased concentration of Mo in body tissues. The highest concentrations of metal were found in the kidney while it was least in blood cells. The accumulation was considered to be significant.
Defining, explaining and understanding hormesis
Authors: Kitchin K T
Published: July 2002

A problem that hormesis has in being more scientifically accepted is (1) proving that only one mechanism accounts for both the ‘beneficial’ and ‘toxic’ parts of the biphasic dose-response curve and (2) giving substantial evidence against the interpretation that ‘hormesis’ is the sum of many different mechanisms which add up to either ‘beneficial’ or ‘toxic’ in two different parts of the dose-response curve. Hormesis may consist of a initial beneficial dose region where several mechanisms are operating (just for the sake of argument let us say 3 mechanisms) and the overall sum of these 3 mechanisms is ‘beneficial’ to the organism. At higher, toxic, doses, many more mechanisms are operating (just for the sake of argument let us say 8 mechanisms) and the sum of all these 8 mechanisms puts the organism in the ‘toxic’ part of the biphasic dose-response curve.
The role of dopamine in manganese-induced oxidative injury in rat pheochromocytoma cells
Authors: Seth K , Agrawal A K , Date I , Seth P K
Published: July 2002

Reactive dopamine (DA) metabolites have been implicated in both Parkinson's disease and manganese (Mn) neurotoxicity. Rat PC12 and genetically modified PC12 (PC12M) cells capable of producing higher DA content, on exposure to MnCl2 (10¡ 6 M) for 72 hours, exhibited a significant decrease in glutathione content. Activity of antioxidant enzyme catalase was also inhibited following 24 and 72-hour MnCl2 exposure. MnCl2 caused a concentration dependent (10¡ 7 to 10¡3 M) loss in mitochondrial activity after 24 and 72 hours and an impaired DNA synthesis after 72 hours with changes being more marked in PC12M cells. The results indicate that the free-radical-mediated toxicity of Mn at cellular level involves down-regulation of anti oxidants in normal and DA-rich PC12 cells. PC12M cells appeared to be more sensitive than PC12 cells.
The analysis of repeated multivariate binary quality of life data: a hierarchical model approach
Authors: Ribaudo H J , Thompson S G
Published: July 2002

Many quality of life measuring instruments consist of a number of questions that are answered on ordinal scales. Often these responses are then totalled to give a summary score for each quality of life domain within the instrument. This, however, may lose valuable information about individual aspects of patient quality of life and also can have little intuitive meaning. Here we present an alternative analysis, in which dichotomized individual items of the questionnaire are analyzed. We first show how a hierarchical logistic regression model for repeated binary data can be extended to the multivariate case. We then use such a model for analyzing the prevalence of six symptoms in a palliative treatment trial in non-small-cell lung cancer. The analysis provides information about the correlations between symptoms, both between and within person. If appropriate, it also permits the estimation of a treatment effect common to all symptoms. Methods for model checking are discussed. We conclude that this methodology can provide a more intuitive and informative analysis of quality of life data than that obtained by considering summary scores.
Voluntary Active Euthanasia and the Nurse: a comparison of Japanese and Australian nurses
Authors: Tanida Noritoshi , Asai Atsushi , Ohnishi Motoki , Nagata Shizuko K , Fukui Tsuguya , Yamazaki Yasuji , Kuhse Helga
Published: July 2002

Although euthanasia has been a pressing ethical and public issue, empirical data are lacking in Japan. We aimed to explore Japanese nurses’ attitudes to patients’ requests for euthanasia and to estimate the proportion of nurses who have taken active steps to hasten death. A postal survey was conducted between October and December 1999 among all nurse members of the Japanese Association of Palliative Medicine, using a self-administered questionnaire based on the one used in a previous survey with Australian nurses in 1991. The response rate was 68%. A total of 53% of the respondents had been asked by patients to hasten their death, but none had taken active steps to bring about death. Only 23% regarded voluntary active euthanasia as something ethically right and 14% would practice it if it were legal. A comparison with empirical data from the previous Australian study suggests a significantly more conservative attitude among Japanese nurses.
Financing Sustainable Development: Crises of Legitimacy
Authors: Najam Adil
Published: July 2002

This year presents us with two important opportunities to influence the direction of sustainable development financing - the UN Summit on Financing for Development and the World Summit on Sustainable Development. We may ultimately remember both as missed opportunities. We need to take a fresh look at the entire system of financing for development and reorient it towards a sustainable development orientation. This requires focusing on questions of legitimacy, accountability and capacity. Such action would challenge the now entrenched orientation of the regime as a ‘financing’ regime. It will require a re-examination of the institutions that are entrusted with the agenda and will find nearly all lacking in necessary capacities. An expanded institutional framework that incorporates intermediary and local non-government organizations (NGOs) would be absolutely critical. Finally, institutions (at all levels) will need to be invested in with a different set of performance metrics; measures which gauge the ability of institutions to deliver on their developmental goals, rather than focus only on financial accounting.
Estimation of Tax Benefit of US Nonprofit Hospitals
Authors: Plummer Elizabeth , Socal Mariana P. , Bai Ge
Published: September 2024

Importance

Nonprofit hospitals are under increasing scrutiny to justify the generous tax benefit they receive due to their tax-exempt status. Quantifying the value of the tax benefit they receive at the federal, state, and local levels is critical for designing informed public health policies and ensuring nonprofit hospitals’ taxpayer accountability.

Objective

To estimate the financial benefit that nonprofit hospitals derive from their tax-exempt status and assess how the benefit is distributed across state and local communities.

Design, Setting, and Participants

Using methodologies and measures consistent with current tax law and practice and data from 2021 Medicare Cost Reports, this study calculated the total financial benefit from nonprofit hospitals’ tax-exempt status for all US nonprofit hospitals with the required Cost Reports data.

Main Outcomes and Measures

Nonprofit hospitals’ total tax benefit, which equals the sum of federal and state income tax, sales tax, property tax, the fair market value of charitable contributions from donors, savings from tax exemptions on issued bonds, and federal unemployment tax.

Results

A total of 2927 US nonprofit hospitals received a $37.4 billion total tax benefit in 2021 from federal income tax ($11.5 billion; 31%), sales tax ($9.1 billion; 24%), property tax ($7.8 billion; 21%), state income tax ($3.7 billion; 10%), charitable contributions ($3.2 billion; 8%), bond financing ($2.1 billion; 6%), and federal unemployment tax ($200 million; <1%). Tax benefit varied substantially across states, from $25 098 (Delaware) to $159 464 (Massachusetts) per hospital bed and from $19 (Alabama) to $275 (Massachusetts) per capita. Tax benefit was highly concentrated, with 7% (n = 212) of hospitals accounting for half of the total amount.

Conclusion and Relevance

This study highlights the wide variation of nonprofit hospitals’ tax benefit across states, its high concentration among a small number of hospitals, and the primary role played by state and local taxes. Policy efforts to strengthen nonprofit hospitals’ taxpayer accountability are likely to be more effective when pursued at the local level. The detailed standardized estimation road map can be used by various stakeholders to estimate tax benefit for external valuation and reporting purposes, updated as laws change, and improved upon as better data sources become available.
Potential Health Hazards of Cryptocurrency Mining
Authors: Willis Mary D. , Casey Joan A. , Buonocore Jonathan J.
Published: September 2024

This Viewpoint discusses the need for research on and mitigation strategies for the potential community and population health effects of cryptocurrency mining, an energy-intensive and noise-producing industry.
Determinants of Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma With Nodal Metastases
Authors: Ebrahimi Ardalan , Gupta Ruta , McDowell Lachlan , Magarey Matthew J. R. , Smith Paul N. , Schulte Klaus-Martin , Perriman Diana M. , Veness Michael , Porceddu Sandro , Low Tsu-Hui Hubert , Fowler Allan , Clark Jonathan R.
Published: September 2024

Importance

The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE).

Objective

To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease.

Design, Setting, and Participants

This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients.

Exposure

Curative intent surgery ± adjuvant radiotherapy.

Main Outcomes and Measures

Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis.

Results

Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors.

Conclusions and Relevance

The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.
CT45A1‐mediated MLC2 (MYL9) phosphorylation promotes natural killer cell resistance and outer cell fate in a cell‐in‐cell structure, potentiating the progression of microsatellite instability‐high colorectal cancer
Authors: Teng Hao‐Wei , Huang Hsiang‐Yueh , Lin Chun‐Chi , Twu Yuh‐Ching , Yang Wen‐Hao , Lin Wen‐Chun , Lan Hsin‐Yi , Lin Yen‐Yu , Hwang Wei‐Lun
Published: September 2024

Patients with microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) have high tumor mutation burden and tumor immunogenicity, exhibiting a higher response rate to immunotherapy and better survival. However, a portion of MSI‐H CRC patients still experience adverse disease outcomes. We aimed to identify the tumor‐autonomous regulators determining these heterogeneous clinical outcomes. The Cancer Genome Atlas (TCGA) dataset was used to identify regulators in MSI‐H CRC patients with unfavorable outcomes. Stable CRC tumor clones expressing targeted regulators were established to evaluate migratory and stemness properties, immune cell vulnerability, and cell‐in‐cell (CIC) structure formation. RNA‐sequencing (RNA‐seq) was used to identify enriched biological pathways in stable CRC tumor clones. Clinicopathological characterization of formalin‐fixed paraffin‐embedded (FFPE) MSI‐H CRC specimens was performed to explore the underlying mechanisms involved. We showed that cancer/testis antigen family 45 member A1 (CT45A1) expression was upregulated in MSI‐H CRC patients with poor survival outcomes. CT45A1‐expressing microsatellite stable (MSS) CRC cells showed enhanced migratory ability. However, CT45A1‐expressing MSI‐H CRC cells, but not MSS CRC cells, showed higher resistance to natural killer (NK) cell cytotoxicity and served as outer cells in homotypic CIC structures, preventing exogenous or therapeutic antibody access to inner CRC cells. Inactivating RHO‐ROCK/MLCK‐MLC2 signaling with small‐molecule inhibitors or short‐hairpin RNAs (shRNAs) targeting myosin light chain kinase (MYLK) abolished NK cell resistance and reduced the outer cell fate of CT45A1‐expressing MSI‐H CRC cells. In MSI‐H CRC patients, CT45A1‐positive tumors exhibited increased MLC2 phosphorylation, increased outer cell fate, and decreased survival. We demonstrated that CT45A1 potentiates the advanced progression of MSI‐H CRC, and targeting MLC2 phosphorylation may enhance immunotherapy efficacy in CT45A1‐positive MSI‐H CRC patients.
Programmable Multi‐Responsive Nanocellulose‐Based Hydrogels With Embodied Logic
Authors: Arsuffi Beatriz , Siqueira Gilberto , Nyström Gustav , Titotto Silvia , Magrini Tommaso , Daraio Chiara
Published: September 2024

Programmable materials are desirable for a variety of functional applications that range from biomedical devices, actuators and soft robots to adaptive surfaces and deployable structures. However, current smart materials are often designed to respond to single stimuli (like temperature, humidity, or light). Here, a novel multi‐stimuli‐responsive composite is fabricated using direct ink writing (DIW) to enable programmability in both space and time and computation of logic operations. The composite hydrogels consist of double‐network matrices of poly(N‐isopropylacrylamide) (PNIPAM) or poly(acrylic acid) (PAA) and sodium alginate (SA) and are reinforced by a high content of cellulose nanocrystals (CNC) (14 wt%) and nanofibers (CNF) (1 wt%). These composites exhibit a simultaneously tunable response to external stimuli, such as temperature, pH, and ion concentration, enabling precise control over their swelling and shrinking behavior, shape, and mechanical properties over time. Bilayer hydrogel actuators are designed to display bidirectional bending in response to various stimuli scenarios. Finally, to leverage the multi‐responsiveness and programmability of this new composite, Boolean algebra concepts are used to design and execute NOT, YES, OR, and AND logic gates, paving the way for self‐actuating materials with embodied logic.
Integrating Ultrathin Perovskite Nanosheets for Rigid yet Fatigue‐Resistant Elastomers
Authors: Jin Xiaolin , Chen Wentao , Xiao Zhenhua , Wang Jingyu , Yang Wenqi , Cui Shuming , Yao Shenglin , Jiang Zhenyu , Tang Liqun , Sun Taolin
Published: September 2024

The development of rigid yet fatigue‐resistant elastomers possess a critical challenge, necessitating materials capable of enduring substantial mechanical loads while maintaining structural integrity through cycles of deformations. Despite soft materials achieving a fatigue threshold of ∼1000 J m−2, their modulus, typically ∼1 MPa, restricts their applications. This study presents a breakthrough in designing rigid, fatigue‐resistant elastomers by controlling nanosheet orientation within the network using a shear force strategy. The elastomers achieve a high fatigue threshold of 1900 J m−2 while maintaining a high elastic modulus of 8 MPa. These superior mechanical properties are attributed to the synergistic effects of microscale alignment of nanosheets and robust interfacial bonding between the polymer chains and nanosheets at the nanoscale. When the nanosheet volume fraction is below the percolation threshold, well‐dispersed nanosheets transfer load effectively through strong interfacial bonding with the polymer, significantly suppressing fatigue crack propagation. Conversely, above the percolation threshold, agglomerated nanosheets create defects in the matrix, reducing load‐bearing capacity. The innovative elastomers demonstrate potential for a wide range of applications, including automotive components, actuators, and stretchable electronic devices, where high mechanical stability and load‐bearing capacity are essential.
SiOx Based Anodes for Advanced Li‐Ion Batteries: Recent Progress and Perspectives
Authors: Xie Guijuan , Tan Xu , Shi Zezhong , Peng Yi , Ma Yuan , Zhong Yiren , Wang Faxing , He Jiarui , Zhu Zhi , Cheng Xin‐Bing , Wang Gaojun , Wang Tao , Wu Yuping
Published: September 2024

SiOx with high theoretical capacity is regarded as a promising high‐performance anode material for lithium‐ion batteries. The main problem is the dramatic volume expansion after lithiation and the inherent poor conductivity. Tackling these problems, extensive strategies are proposed for SiOx‐based anode materials in order to pursue high initial Coulombic efficiency, high reversible capacity, and long cycle stability. In this review, the lithium storage mechanism, merits, and disadvantages of SiOx will be introduced in detail. Significant progress about SiOx in recent years and their detailed strategies are summarized. Finally, challenges and potential solutions in the development and application of SiOx are proposed. This review aims to offer a reference for the research of anode materials associated with SiOx and offer a good guide for the further improvements of SiOx anode materials.
A Peptide‐Drug Conjugate‐Based Nanoplatform for Immunometabolic Activation and In Situ Nerve Regeneration in Advanced‐Stage Alzheimer's Disease
Authors: Liu Peixin , Zhang Tongyu , Wu Yuxing , Chen Qinjun , Sun Tao , Jiang Chen
Published: September 2024

The formidable protection of physiological barriers and unclear pathogenic mechanisms impede drug development for Alzheimer's disease (AD). As defenders of the central nervous system, immune‐metabolism function, and stemness of glial cells remain dormant during degeneration, representing a significant challenge for simultaneously targeting and modulating. Here, a modular nanoplatform is presented composed of peptide‐drug conjugates and an inflammation‐responsive core. The nanoplatform is transported through the blood‐brain barrier via transcytosis and disassembles in the oxidative stress microenvironment upon intravenous administration. The released drug‐conjugated modules can specifically target and deliver hydroxychloroquine (HCQ) and all‐trans retinoic acid (ATRA) to microglia and astrocytes, respectively. The immune function of chronic tolerant microglia is activated by metabolic modulation, and reactive astrocytes trans‐differentiate into functional neurons. In a transgenic mouse model, nanoplatform reduces levels of toxic proteins and inflammation while increasing neuronal density. This results in the amelioration of learning and memory decline. The modular nanoplatform provides design principles for multi‐cellular targeting and combination nano‐therapy for inflammation‐related diseases.
Design and Additive Manufacturing of Polyethylene‐Based Hierarchical Composites by Selective Laser Sintering
Authors: Yang Muxuan , Bu Jinyu , Shen Naifu , Liu Shan , Xu Weinan
Published: September 2024

Selective laser sintering (SLS) is gaining increasing importance in polymer additive manufacturing. It has many unique advantages compared with extrusion or photopolymerization based technologies. However, one of the main challenges for SLS is the limited types of compatible polymer microparticles. This study develops a versatile material platform for the scalable synthesis of polyethylene (PE) and its composite microparticles for SLS 3D printing. The incorporation of metal oxide nanoparticles inside PE microparticles by in situ sol‐gel chemistry as well as blending with carbon black for enhanced laser absorption is found to have significant impacts on the printability and physical properties of printed structures. Importantly, this study also demonstrates that post‐printing processing can substantially enhance the mechanical properties and introduce new functionalities to 3D PE structures. Thermal annealing improves the mechanical strength and modulus by more than ten times. Electrochemical deposition of copper on the 3D PE composite structures significantly enhances the electrical conductivity and mechanical properties, which can be utilized to fabricate 3D hierarchical metallic structures with broad applications.
Chirality‐Assisted Spin‐Decoupled Metasurface Implemented by Simple Geometrical Rotation
Authors: Huang Yuanqing , Zhang Zhengping , He Chong , Wang Xiong , Zhu Weiren
Published: September 2024

Metasurfaces are distinguished by their ability to flexibly manipulate electromagnetic waves across multiple degrees of freedom. Designing metasurfaces with spin‐multiplexing often involve complex processes with multiple parameters to fine‐tune, posing significant challenges for achieving high accuracy. Here, a chirality‐assisted spin‐decoupled metasurface via solely simple geometrical rotation is theoretically proposed and experimentally demonstrated. In the meta‐atom design, a dual‐layered rectangular copper patch with a twist angle is used for enhancing circular dichroism through circular reflection patterns. A parallel cross structure is also introduced to independently control circularly polarized waves with specific handedness. Theoretical analysis and simulations demonstrate the robust decoupling capabilities of this meta‐atom design. Moreover, the theoretical deductions indicate that circular polarization decoupling can be achieved merely by rotating the meta‐atom structure, significantly reducing the complexity of designing circular polarization decoupling metasurfaces. To validate the practicality of the approach, a metasurface with lens and holographic imaging functionalities across two circular polarization channels is designed. Simulation and experimental results show excellent agreement with the theoretical predictions. This innovative method for circular polarization decoupling opens up promising new avenues for engineering applications in fields such as remote sensing, information encryption, and communication systems.
Enhanced Machine Condition Monitoring Based on Triboelectric Nanogenerator (TENG): A Review of Recent Advancements
Authors: Mehamud Idiris , Björling Marcus , Marklund Pär , An Rong , Shi Yijun
Published: September 2024

Intelligent machine condition monitoring is desirable to enable Industry 4.0 and 5.0 to create sustainable products and services via the integration of automation, data exchange, and human–machine interface. In the past decades, huge progress has been achieved in establishing sustainable machine condition monitoring systems via various sensing technologies. Yet, the dependence on external power sources or batteries for sensing and data communication remains a challenge. In addition, energy harvesting and sensing are dynamically growing research fields introducing various working mechanisms and designs for improved performance, flexibility, and integrability. Recently, triboelectric nanogenerators (TENG) have been applied as a new technology for energy harvesting and sensing to monitor machine performance. This manuscript presents the potential application of TENG for self‐powered sensors and energy harvesting technology for machine condition monitoring, where the developmental aspects of TENG‐based devices including the robustness of design and device integration to machine elements are reviewed. For better comparison, the performance of various reported devices is summarized. Simultaneously, the advanced results achieved in employing TENGs for various condition analysis techniques and self‐powered wireless communication for machine condition monitoring are discussed. Finally, the challenges, and key strategies for utilizing TENGs for machine condition monitoring in the future, are presented.
Time is money: An analysis of cost drivers in ambulatory sinus surgery
Authors: Lerner David K. , Phung Chau , Workman Alan D. , Patel Saawan , Pennington Glenn , Stetson Robert , Douglas Jennifer E. , Kohanski Michael A. , Palmer James N. , Adappa Nithin D.
Published: September 2024

Background

Functional endoscopic sinus surgery (FESS) is one of the most commonly performed otolaryngologic procedures and is associated with significant cost variability.

Methods

We performed a retrospective analysis of all inflammatory sinus surgeries at a single tertiary care medical center from July 2021 to July 2023. The electronic medical record was reviewed for patient factors and cost variables for each procedure, and multivariable analysis was performed.

Results

A total of 221 patients were included in analysis with a mean age of 48.2 years. There was a 44.8% incidence (n = 99) of nasal polyps and 31.2% (n = 69) of cases were revision surgeries. The average total cost for the surgical encounter was $8960.31 (standard deviation $1967.97). Operating room time represented $4912.46 (54.8% of all costs), while average operating room supply costs were $1296.06 (14.5%) and recovery room costs were $919.48 (10.3%). Total costs were significantly associated with length of surgery ($7.83/min, p = 0.04), in addition to presence of nasal polyps ($531.96, p = 0.04). There was no significant association between total costs and the remaining clinical and demographic factors.

Conclusions

Costs associated with ambulatory FESS for inflammatory sinus disease vary across patients and this cost variability is predominantly driven by time efficiency within the operating room, as well as supply utilization and nasal polyposis to a lesser degree. As a result, operating room efficiency represents a primary target for cost‐related interventions. Additionally, our data provide a framework for surgeons and hospitals to make evidence‐based decisions on intraoperative equipment in a tradeoff between efficiency and supply costs. Our findings indicate that an approach focused on streamlining efficiency across the entire ambulatory surgery encounter will have the greatest impact on reducing healthcare expenses for both the patient and the health system.
Microwave‐to‐Optical Conversion and Amplification in Cavity Optomagnonics System
Authors: Yan Ye‐Ting , Wang Da‐Wei , Yang Junya , Zhou Ling
Published: September 2024

A scheme to construct microwave‐to‐optical conversion and amplification using a hybrid cavity optomagnonics system is presented. A yttrium iron garnet (YIG) sphere with nonlinearity couples to optical transverse‐electric (TE) and transverse‐magnetic (TM) whispering gallery modes and a microwave mode. It is shown that the TM classical mode can control the quantum signals input from the microwave mode transmission into the optical TE mode. Due to the nonlinearity of the YIG sphere as well as effective magnon‐optical nondegenerate parametric amplification form interaction, the microwave quantum signals can be amplified and transmitted into the optical TE mode. The current system can function well as a quantum transistor, which is important for constructing a quantum circuit using a cavity optomagnonics system.
Chemical Recording of Pump‐Specific Drug Efflux in Living Cells
Authors: Sun Xuege , Chen Ying , Yang Chen , Yang Song , Lin Wei , Quan Baiyi , Pan Xuanzhen , Ding Qiang , Chen Xing , Wang Chu , Qin Wei
Published: September 2024

Drug efflux—a process primarily facilitated by efflux pumps such as multidrug resistance proteins (MRPs)—plays a pivotal role in cellular resistance to chemotherapies. Conventional approaches to assess drug efflux are predominantly conducted in vitro and often lack pump specificity. Here we report the bioorthogonal reporter inhibiting efflux (BRIEF) strategy, which enables the recording of pump‐specific drug efflux in living cells. In BRIEF, a specific substrate is engineered as a bioorthogonal efflux probe (BEP) for specific pumps. The cellular concentration and protein labeling level of the probe can be augmented when the test drug is transported by the same pumps. Serendipitously, we discovered that per‐O‐acetylated unnatural monosaccharides, initially designed for metabolic glycan labeling, are exported by some MRPs. Using Ac4GlcNAl as a BEP, we studied the structure‐efflux relationship of flavonoids and identified small molecules, including tannic acid, cholesterol and gallic acid, as novel MRP substrates in high‐throughput screening. Tannic acid, known for anti‐tumor and anti‐SARS‐CoV‐2 properties, showed increased efficacy upon MRP inhibition. Additionally, BRIEF was adapted to assess p‐glycoprotein‐mediated efflux using Rhodamine 123 as a BEP, leveraging its light‐activatable proximity labeling ability. BRIEF provides a versatile approach to investigate drug efflux and enhance chemotherapy strategies.
Enantioselective Construction of Oxindoles Bearing a Quaternary Carbon via Ni−Al Bimetal‐Catalyzed Formyl C−H Alkylation
Authors: Wang Haorui , Li Jiang‐Fei , Xu Mengying , Zhou Qi‐Lin , Xu Weiwei , Ye Mengchun
Published: September 2024

Enantioselective transition metal‐catalyzed C−H alkylation emerges as one of the most atom‐ and step‐economical routes to chiral quaternary carbons, while big challenges still remain with acyl C−H alkylations. Herein, we use a Ni−Al bimetallic catalyst to facilitate a highly regioselective and highly enantioselective C−H alkylation of formamides with alkenes, constructing various oxindoles bearing a chiral quaternary carbon in up to 94 % yield and up to 95 % ee.