bluuebunny/crossref_metadata_2025 huggingface dataset:
Antithrombin prevents endotoxin-induced hypotension by inhibiting the induction of nitric oxide synthase in rats
Authors: Isobe Hirotaka , Okajima Kenji , Uchiba Mitsuhiro , Harada Naoaki , Okabe Hiroaki
Published: July 2002

Antithrombin (AT) prevents Escherichia coli–induced hypotension in animal models of sepsis, and it further reduces the mortality of patients with septic shock. In the present study, we examined whether AT may prevent the endotoxin (ET)-induced hypotension by promoting the endothelial release of prostacyclin (PGI2) in rats. Intravenous administration of AT (250 U/kg) prevented both hypotension and the increases in plasma levels of NO2−/NO3− in rats given ET. Lung expression of messenger RNA (mRNA) for tumor necrosis factor-α (TNF-α) was transiently increased after ET administration, followed by the increases in lung tissue levels of TNF-α. Both the lung activity of the inducible form of nitric oxide synthase (iNOS) and the lung expression of iNOS mRNA in animals administered ET were gradually increased after the TNF-α mRNA expression had peaked. Administration of AT significantly inhibited these increases. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor Trp49-modified AT, which is not capable of promoting the endothelial release of PGI2, showed any effects on these changes induced by ET. Administration of antirat TNF-α antibody produced effects similar to those induced by AT. Indomethacin pretreatment abrogated the effects induced by AT. Iloprost, a stable derivative of PGI2, produced effects similar to those of AT. These findings suggested that AT prevents the ET-induced hypotension by inhibiting the induction of iNOS through inhibiting TNF-α production. These effects of AT could be mediated by the promotion of endothelial release of PGI2 and might at least partly explain the therapeutic effects for septic shock.
Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide
Authors: Nagai Yoshinori , Shimazu Rintaro , Ogata Hirotaka , Akashi Sachiko , Sudo Katsuko , Yamasaki Hidetoshi , Hayashi Shin-Ichi , Iwakura Yoichiro , Kimoto Masao , Miyake Kensuke
Published: July 2002

RP105 is a B-cell surface molecule that has been recently assigned as CD180. RP105 ligation with an antibody induces B-cell activation in humans and mice, leading to proliferation and up-regulation of a costimulatory molecule, B7.2/CD86. RP105 is associated with an extracellular molecule, MD-1. RP105/MD-1 has structural similarity to Toll-like receptor 4 (TLR4)/MD-2. TLR4 signals a membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS). MD-2 is indispensable for TLR4-dependent LPS responses because cells expressing TLR4/MD-2, but not TLR4 alone, respond to LPS. RP105 also has a role in LPS responses because B cells lacking RP105 show hyporesponsiveness to LPS. Little is known, however, regarding whether MD-1 is important for RP105-dependent LPS responses, as MD-2 is for TLR4. To address the issue, we developed mice lacking MD-1 and generated monoclonal antibodies (mAbs) to the protein. MD-1–null mice showed impairment in LPS-induced B-cell proliferation, antibody production, and B7.2/CD86 up-regulation. These phenotypes are similar to those of RP105-null mice. The similarity was attributed to the absence of cell surface RP105 on MD-1–null B cells. MD-1 is indispensable for cell surface expression of RP105. A role for MD-1 in LPS responses was further studied with anti–mouse MD-1 mAbs. In contrast to highly mitogenic anti-RP105 mAbs, the mAbs to MD-1 were not mitogenic but antagonistic on LPS-induced B-cell proliferation and on B7.2 up-regulation. Collectively, MD-1 is important for RP105 with respect to B-cell surface expression and LPS recognition and signaling.
Using observation checklists to validate speaking-test tasks
Authors: O’Sullivan Barry , Weir Cyril J. , Saville Nick
Published: July 2002

Test-task validation has been an important strand in recent revision projects for University of Cambridge Local Examinations Syndicate (UCLES) examinations. This article addresses the relatively neglected area of validating the match between intended and actual test-taker language with respect to a blueprint of language functions representing the construct of spoken language ability. An observation checklist designed for both a priori and a posteriori analysis of speaking task output has been developed. This checklist enables language samples elicited by the task to be scanned for these functions in real time, without resorting to the laborious and somewhat limited analysis of transcripts. The process and results of its development, implications and further applications are discussed.
The criterion validity of four vocabulary tests compared with a language sample
Authors: Ukrainetz Teresa A. , Blomquist Carol
Published: July 2002

This study provided empirical evidence of the validity of four vocabulary tests: Peabody Picture Vocabulary Test-III (PPVT-3), Expressive Vocabulary Test (EVT), Receptive One-Word Picture Vocabulary Test (ROWPVT), and Expressive One-Word Picture Vocabulary Test-Revised (EOWPVT-R) against a 150- utterance language sample for 28 normally-developing pre-school children. Systematic Analysis of Language Transcripts (SALT) standard scores on number of different words, total number of words, and mean length of utterance were used to provide evidence of convergent and discriminant criterion validity. Performance on the vocabulary tests showed significant weak to moderate correlations with the semantic measure, and the predicted lower relationship with the non-semantic measures. Despite this, individual score analysis showed considerable variation, indicating caution predicting conversational language performance from standardized tests.
Delayed discharges from Oxford city hospitals: who and why?
Authors: Carter Nicholas D , Wade Derick T
Published: July 2002

Objective: To determine the extent and characteristics of discharge delays of younger patients from acute hospital beds in Oxford, England.

Design: Three-month prospective analysis of patients deemed to have delayed discharge.

Measures: The primary measure was the number of days from the patient being no longer in need of acute medical inpatient care to eventual discharge. Additional assessments included demographic data, primary diagnosis, Motricity Index, Short Orientation-Memory-Concentration Test (SOMC), Barthel Index and contextual data.

Setting: The major acute hospitals serving the county of Oxfordshire (560 000 people).

Subjects: Fifty patients aged 18–70 years identi”ed by referrals, delayed discharge lists and ward visits whose discharge from hospital had been delayed.

Results: The mean (standard deviation, SD) delay period was 36.1 (26.8) days. The mean prevalence and incidence of discharge delays for each three-day period was 19.7 (SD 1.7) and one (SD 1.7) respectively. Most (88%, n = 44) had a primary neurological diagnosis. Twenty-four (48%) patients had Motricity Index scores of less than 50% in one or more limbs and 16 (32%) in two or more limbs. Twenty-six (52%) patients had cognitive impairment (SOMC <18/28). Thirty-nine (78%) patients had a Barthel Index score of less than 15/20 and 24 (48%) of less than 10/20. The period of discharge delay did not correlate with SOMC, Motricity or Barthel Index scores. Only nine had appropriate accommodation available.

Conclusion: Patients whose discharge is delayed were common; most had a neurological disability and cognitive impairment; and accommodation was unsuitable or absent for most. Reorganizing services to give patients access to specialized disability services might both improve the care of these patients and increase the ef”ciency of the health service.
Defining hormesis
Authors: Calabrese E J , Baldwin L A
Published: July 2002

Much confusion surrounds the concept of hormesis and what its biological meaning represents. This paper provides a definition of hormesis that addresses its historical foundations, quantitative features, and under-lying evolutionary and toxicologically based mechanistic strategies. Hormesis should be considered an adaptive response characterized by biphasic dose responses of generally similar quantitative features with respect to amplitude and range of the stimulatory response that are either directly induced or the result of compensatory biological processes following an initial disruption in homeostasis. Given the limited magnitude of the stimulatory response (i.e., usually 30–60% greater than controls at maximum), heightened study design and replication requirements are often necessary to ensure reliable judgments on causality. Even though hormesis is considered an adaptive response, the issue of beneficial/harmful effects should not be part of the definition of hormesis, but reserved to a subsequent evaluation of the biological and ecological context of the response.
Why the professional-Client Ethic is Inadequate in Mental Health Care
Authors: Leung Wai-Ching
Published: July 2002

Patients who are subject to compulsory care constitute a substantial proportion of the work-load of mental health professionals, particularly psychiatric nurses. This article examines the traditional ‘beneficence-autonomy’ approach to ethics in compulsory psychiatric care and evaluates it against the reality of daily practice. Risk to the public has always been an important but often unacknowledged consideration. Inequalities exist among ethnic and socio-economic groups and there is a lack of agreement on what constitutes mental disorder. Two major changes in compulsory psychiatric care - community orders and care for patients with untreatable severe personality disorders - further challenge the traditional ethical approach. There are also important human rights implications. The simple patient-health professional relationship no longer provides an adequate framework for mental health professionals on which to base their ethical decisions. The public and organizations may have different perspectives and their interests are becoming increasingly important. Mental health professionals, particularly psychiatric nurses, may face ethical dilemmas because of these different perspectives.
Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: A Preliminary Report
Authors: Lee Jung-Hee , Lee Je-Hwan , Ahn Jin-Hee , Bahng Hyeseung , Kim Tae-Won , Kang Yoon-Koo , Lee Kyoo-Hyung , Kim Jin-Cheon , Yu Chang-Sik , Kim Jong-Hoon , Ahn Seung-Do , Kim Woo-Kun , Kim Sang-Hee , Lee Jung-Shin
Published: July 2002

PURPOSE: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer.

PATIENTS AND METHODS: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m2/d and leucovorin 20 mg/m2/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles.

RESULTS: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v 70% at 4 years; P = .043). Twenty-three recurrences occurred in arm I and 38 in arm II (P = .047). Overall survival was not significantly different between arms I and II (84% v 82% at 4 years; P = .387).

CONCLUSION: Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.
Prognostic Factors for Survival in Adult Patients With Cerebral Low-Grade Glioma
Authors: Pignatti Francesco , van den Bent Martin , Curran Desmond , Debruyne Channa , Sylvester Richard , Therasse Patrick , Áfra Denes , Cornu Philippe , Bolla Michel , Vecht Charles , Karim Abul B.M.F.
Published: July 2002

PURPOSE: To identify prognostic factors for survival in adult patients with cerebral low-grade glioma (LGG), to derive a prognostic scoring system, and to validate results using an independent data set.

PATIENTS AND METHODS: European Organization for Research and Treatment of Cancer (EORTC) trial 22844 and EORTC trial 22845 are the largest phase III trials ever carried out in adult patients with LGG. The trials were designed to investigate the dosage and timing of postoperative radiotherapy in LGG. Cox analysis was performed on 322 patients from EORTC trial 22844 (construction set), and the results were validated on 288 patients from trial 22845 (validation set). Patients with pilocytic astrocytomas were excluded from this prognostic factor analysis.

RESULTS: Multivariate analysis on the construction set showed that age ≥ 40 years, astrocytoma histology subtype, largest diameter of the tumor ≥ 6 cm, tumor crossing the midline, and presence of neurologic deficit before surgery were unfavorable prognostic factors for survival. The total number of unfavorable factors present can be used to determine the prognostic score. Presence of up to two of these factors identifies the low-risk group, whereas a higher score identifies high-risk patients. The validity of the multivariate model and of the scoring system was confirmed in the validation set.

CONCLUSION: In adult patients with LGG, older age, astrocytoma histology, presence of neurologic deficits before surgery, largest tumor diameter, and tumor crossing the midline were important prognostic factors for survival. These factors can be used to identify low-risk and high-risk patients.
High‐throughput detection of RNA modifications at single base resolution
Authors: Ron Keren , Kahn Joshua , Malka‐Tunitsky Nofar , Sas‐Chen Aldema
Published: November 2024

RNA is modified by > 170 chemical modifications that affect its structure and function. Accordingly, RNA modifications have been implicated in regulation of gene expression and cellular outcomes in a variety of species spanning the phylogenetic tree. The study of RNA modifications is accelerated by generation of high‐throughput methods for detecting RNA modifications at single base resolution. Here, we review recent advancement in next generation sequencing based approaches for detection of 14 distinct RNA modifications present in rRNA, tRNA and mRNA. We further outline the molecular and computational principles underlying currently available methods.
Supported bridge position in one‐stop coronary and craniocervical CT angiography: A randomized clinical trial
Authors: Zhou Heng , Yan Cheng , Ji Min , Shi Zhang , Yang Chun , Zeng Mengsu
Published: November 2024

Objective

The routine patient arm position differs between coronary CT angiography (CTA) and craniocervical CTA protocols. To investigate the clinical feasibility of supported bridge position (SBP) in combined coronary and craniocervical CTA.

Methods

Prospective enrollment included patients with suspected coronary artery disease (CAD) or craniocervical artery disease (CCAD) from February 2022 to November 2022. Patients were divided into three groups: coronary or craniocervical CTA according to CAD or CCAD using standard position (group 1), combined CTA with naturally arm‐down position (group 2) and SBP (group 3). Statistical analysis of objective image quality, such as noise and contrast‐to‐noise ratio (CNR), subjective image quality, patient position and radiation dose was performed among the three groups.

Results

Two hundred and one patients (median age, 67 years; 138 men) were included. In terms of CNR for cardiac segment, group 1 and group 3 had no statistical difference, both significantly higher than group 2 (group 1, 12.56 ± 2.05; group 2, 10.4 ± 2.43; group 3, 11.94 ± 2.22; P < 0.05). Subjective image evaluation revealed no statistically significant differences among the three groups of coronary arteries (P > 0.05). Additionally, the lateral project value of scout images at the heart level indicated a significant difference (119.48 ± 12.19, 182.34 ± 25.09, and 140.58 ± 19.68 of patients, for group 1, group 2, and group 3, respectively, P < 0.05). No statistical differences were observed in between group 1 and group 3 (cardiac scan, 15.77 [15.07–16.37] mGy vs. 14.88 [12.19–18.81] mGy; craniocervical scan, 7.85 [7.69–8.01] mGy vs. 7.88 [7.88–7.89] mGy; all P > 0.05). However, group 2 had a higher dose (19.54 [16.86–22.85] mGy and 10.87 [10.86–10.87] mGy, for cardiac and craniocervical scans, respectively).

Conclusions

In comparison with a naturally arm‐down position, SBP, which aligns the humerus bones with the spinal column, can provide diagnostic image quality at routine dose level of standard position CTA.
Attention 3D UNET for dose distribution prediction of high‐dose‐rate brachytherapy of cervical cancer: Intracavitary applicators
Authors: Gautam Suman , Osman Alexander F. I. , Richeson Dylan , Gholami Somayeh , Manandhar Binod , Alam Sharmin , Song William Y.
Published: November 2024

Background

Formulating a clinically acceptable plan within the time‐constrained clinical setting of brachytherapy poses challenges to clinicians. Deep learning based dose prediction methods have shown favorable solutions for enhancing efficiency, but development has primarily been on external beam radiation therapy. Thus, there is a need for translation to brachytherapy.

Purpose

This study proposes a dose prediction model utilizing an attention‐gating mechanism and a 3D UNET for cervical cancer high‐dose‐rate intracavitary brachytherapy treatment planning with tandem‐and‐ovoid/ring applicators.

Methods

A multi‐institutional data set consisting of 77 retrospective clinical brachytherapy plans was utilized in this study. The data were preprocessed and augmented to increase the number of plans to 252. A 3D UNET architecture with attention gates was constructed and trained for mapping the contour information to dose distribution. The trained model was evaluated on a testing data set using various metrics, including dose statistics and dose‐volume indices. We also trained a baseline UNET model for a fair comparison.

Results

The attention‐gated 3D UNET model exhibited competitive accuracy in predicting dose distributions similar to the ground truth. The average values of the mean absolute errors were 0.46 ± 11.71 Gy (vs. 0.47 ± 9.16 Gy for a baseline UNET) in CTVHR, 0.55 ± 0.67 Gy (vs. 0.70 ± 1.54 Gy for a baseline UNET) in bladder, 0.42 ± 0.46 Gy (vs. 0.49 ± 1.34 Gy for a baseline UNET) in rectum, and 0.31 ± 0.65 Gy (vs. 0.20 ± 3.76 Gy for a baseline UNET) in sigmoid. Our results showed that the mean individual differences in ΔD2cc for bladder, rectum, and sigmoid were 0.38 ± 1.19 (p = 0.50), 0.43 ± 0.71 (p = 0.41), and −0.47 ± 0.79 (p = 0.30) Gy, respectively. Similarly, the mean individual differences in ΔD1cc for bladder, rectum, and sigmoid were 0.09 ± 1.21 (p = 0.36), 0.20 ± 0.95 (p = 0.24), and −0.21 ± 0.59 (p = 0.30) Gy. The mean individual differences for ΔD90, ΔV100%, ΔV150%, and ΔV200% of the CTVHR were −0.45 ± 2.42 (p = 0.26) Gy, 0.55 ± 9.42% (p = 0.78), 0.82 ± 4.21% (p = 0.81), and −0.80 ± 10.48% (p = 0.36), respectively. The model requires less than 5 s to predict a full 3D dose distribution for a new patient plan.

Conclusion

Attention‐gated 3D UNET revealed a promising capability in predicting voxel‐wise dose distributions compared to 3D UNET. This model could be deployed for clinical use to predict 3D dose distributions for near real‐time decision‐making before planning, quality assurance, and guiding future automated planning, making the current workflow more efficient.
National Institute of Health and Care Excellence Clinical Criteria for the Diagnosis of Knee Osteoarthritis: A Prospective Diagnostic Accuracy Study in Individuals With Type 2 Diabetes
Authors: King Lauren K. , Stanaitis Ian , Hung Vivian , Koppikar Sahil , Waugh Esther J. , Lipscombe Lorraine , Hawker Gillian A.
Published: November 2024

Objective

The National Institute of Health and Care Excellence (NICE) criteria for osteoarthritis (OA) obviate the need for physical examination or imaging, and their use may improve timely diagnosis of OA. However, they have not been validated.

Methods

Within a larger study of individuals with type 2 diabetes, participants with and without self‐reported knee pain underwent assessment of the NICE criteria for knee OA by questionnaire (index test) and clinical evaluation for established or possible knee OA by a rheumatologist (reference standard). We calculated the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) of the NICE criteria and modified NICE criteria without the stiffness criterion.

Results

Our study included 96 participants: the mean ± SD age was 65.4 ± 8.3 years and 52% were women. Individuals who fulfilled the NICE criteria for knee OA (55.2%) included a spectrum of pain severity on an 11‐point pain numeric rating scale with a median score of 5 (range 1–9). Rheumatologist assessment identified 56 participants (58.3%) with symptomatic knee OA. The sensitivity, specificity, LR+, and LR− of the NICE criteria for symptomatic knee OA were 0.84 (95% confidence interval [CI] 0.74–0.94), 0.85 (95% CI 0.74–0.96), 5.6, and 0.19, respectively. For the modified NICE criteria, these were 0.89 (95% CI 0.82–0.97), 0.85 (95% CI 0.74–0.96), 5.93, and 0.13.

Conclusion

The NICE criteria have high sensitivity and specificity for detecting symptomatic knee OA in a population with type 2 diabetes. We found that a modified version, omitting the stiffness criterion, performed similarly. These criteria should be validated in other settings and populations.
Immunosuppressive Drugs in Early Systemic Sclerosis and Prevention of Damage Accrual
Authors: Baron Murray , Nikpour Mandana , Hansen Dylan , Proudman Susanna , Stevens Wendy ,   the Australian Scleroderma Interest Group and the Canadian Scleroderma Research Group, Wang Mianbo
Published: November 2024

Objective

Organ damage in patients with systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by receiving immunosuppressive drugs (ISs). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC‐DI), has allowed us to investigate whether receiving ISs may reduce global organ damage accrual in patients with early SSc.

Methods

This was a retrospective study of patients with two or less years of disease duration in Canadian and Australian cohorts with SSc. Patients with either limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) were observed separately and divided into groups who were either ever or never exposed to ISs. The SCTC‐DI was the outcome, and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation model.

Results

In the cohort with lcSSc, there were 210 patients, of whom 34% were exposed to ISs at some time. Exposure to ISs was associated with lower damage scores. In the cohort with dcSSc, there were 192 patients, of whom 76% were exposed to ISs at some time. Exposure to ISs was not associated with damage scores.

Conclusion

In this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of receiving ISs on damage accrual in patients with lcSSc. We were unable to determine such an effect in patients with dcSSc, but unknown confounders may have been present, and prospective studies of patients with dcSSc receiving ISs should include the SCTC‐DI to determine the possible effect of ISs on damage accrual.
Oral Glucocorticoids for Skin Fibrosis in Early Diffuse Systemic Sclerosis: A Target Trial Emulation Study From the European Scleroderma Trials and Research Group Database
Authors: Mongin Denis , Matucci‐Cerinic Marco , Walker Ulrich A. , Distler Oliver , Becvar Radim , Siegert Elise , Ananyeva Lidia P. , Smith Vanessa , Alegre‐Sancho Juan Jose , Yavuz Sule , Limonta Massimiliano , Riemekasten Gabriela , Rezus Elena , Vonk Madelon , Truchetet Marie‐Elise , Del Galdo Francesco , Courvoisier Delphine S. , Iudici Michele ,   the EUSTAR Collaborators
Published: November 2024

Objective

The objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc).

Methods

We performed an emulated randomized trial comparing the changes from baseline to 12 ± 3 months of the modified Rodnan skin score (mRSS: primary outcome) in patients with early dcSSc receiving either oral glucocorticoids (≤20 mg/day prednisone equivalent) combined with immunosuppression (treated) or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary end points were the difference occurrence of progressive skin or lung fibrosis and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups.

Results

We matched 208 patients (mean age 49 years; 33% male; 59% anti‐Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12 ± 3 months was similar in the two groups (decrease of 2.7 [95% confidence interval {95% CI} 1.4–4.0] in treated vs 3.1 [95% CI 1.9–4.4] in control, P = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between‐group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups.

Conclusion

We did not find any significant benefit of adding low‐dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.
Evaluating Meaningful Changes in Patient‐Reported Outcome Measurement Information System–Fatigue Scores from Three Phase 3 Clinical Trials of Sarilumab for Patients With Rheumatoid Arthritis
Authors: Bingham Clifton O. , Molina Emily , Praestgaard Amy , Fiore Stefano , Cella David
Published: November 2024

Objective

The aim of this study was to evaluate changes in fatigue measured by Patient‐Reported Outcome Measurement Information System (PROMIS)‐Fatigue scores in patients with rheumatoid arthritis (RA) who received sarilumab and to assess the proportion of patients achieving clinically meaningful change.

Methods

Data from three phase 3 randomized controlled trials of patients with RA who received sarilumab—MOBILITY, TARGET, and MONARCH—were evaluated. The 10 RA‐relevant items from the 13‐item Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue were scored in the PROMIS T score metric. Mean changes in 10‐item PROMIS‐Fatigue T score (PROMIS‐Fatigue 10a) were compared, proportions of patients reporting meaningful within‐person change thresholds were assessed, and results were visualized using empirical cumulative distribution function (eCDF) curves.

Results

Patients with RA reported high baseline fatigue. Using PROMIS‐Fatigue 10a, at week 24, patients receiving 150 or 200 mg sarilumab every other week in MOBILITY and TARGET had rapidly and significantly improved mean levels of fatigue compared to those who received placebo. When compared to patients who received adalimumab in MONARCH, patients who received sarilumab had a trend toward increased improvement. eCDF curves showed separation between active treatment versus placebo with both sarilumab doses and across the score range for improvement. Higher proportions of patients reported three‐, five‐, and seven‐point improvements in PROMIS‐Fatigue scores in groups who received active treatment.

Conclusion

Substantial proportions of patients with RA who received sarilumab reported meaningful change in fatigue measured by PROMIS‐Fatigue 10a over time. This study demonstrates the ability to convert FACIT‐Fatigue score onto the PROMIS T score metric, the rapid reduction in fatigue with biologic therapies, and the use of novel eCDF curves to show individual patient‐level change.
Advanced 2D Nanomaterials for Phototheranostics of Breast Cancer: A Paradigm Shift
Authors: Parihar Arpana , Gaur Kritika , Sarbadhikary Paromita
Published: November 2024

Breast cancer is the leading cause of women's deaths and associated comorbidities. The advanced and targeted strategies against breast cancer have gained considerable attention due to their potential enhanced therapeutic efficacy over conventional therapies. In this context, phototherapies like photodynamic therapy (PDT) and photothermal therapy (PTT) have shown promise as an effective and alternative strategy due to reduced side effects, noninvasiveness, and spatiotemporal specificity. With the advent of nanotechnology, several types of nanomaterials that have shown excellent prospects in increasing the efficacy of photo therapies have been exploited in cancer treatment. In recent years, 2D nanomaterials have stood out promising because of their unique ultrathin planar structure, chemical, physical, tunable characteristics, and corresponding remarkable physiochemical/biological properties. In this review, the potential and the current status of several types of 2D nanomaterials such as graphene‐based nanomaterials, Mxenes, Black phosphorous, and Transition Metal Dichalcogenides for photo/thermo and combination‐based imaging and therapy of breast cancer have been discussed. The current challenges and prospects in terms of translational potential in future clinical oncology are highlighted.
Ferrocene‐Based Nickel Metal–Organic Framework Nanosheets as Efficient, Long‐Cycle Cathode Catalyst for Li‐CO2 Battery
Authors: Chen Haixia , Li Xijuan , Liu Zhixin , Xu Yunyun , Yan Yige , Li Peng , Chang Kun , Huang Xianli , He Jianping , Wang Tao
Published: November 2024

Li‐CO2 batteries, as a novel type of secondary battery, show great potential for energy conversion and storage. However, challenges such as large electrode polarization and poor cycling performance, stemming from difficulties in decomposing discharge products, limit their practical application. Here, Ferrocene‐based nickel metal–organic framework (Ni‐Fc) nanosheets structure to act as cathode catalysts, prepared via a one‐pot solvothermal reaction. X‐ray absorption fine structure (XAFS) analysis shows that Ni metal forms abundant catalytic active centers with O coordination of carboxylic acid groups in ferrocene units. The Ni‐Fc‐based battery demonstrates a high discharge capacity of 18636 mAh g−1 and exhibits a cycle life exceeding 2000 h at a current of 200 mA g−1. Density functional theory (DFT) calculations indicate that the stronger interaction of Ni‐Fc with discharge intermediates and enhanced Li adsorption accelerate battery reaction kinetics. This study introduces novel catalyst design concepts aimed at achieving high‐performance CO2 reduction and oxidation, thereby advancing Li‐CO2 batteries toward practical application.
3D Bimetallic Platinum‐Nickel Electrodes for Electro‐Oxidation of Glycerol at Ambient Conditions
Authors: Angizi Shayan , Nankali Mahdis , Foroozan Amir , Park Jihyeon , Yelekli Kirici Ecem , Noor Navid , Fefer Michael , Terazono Yuichi , Higgins Drew
Published: November 2024

Partial electro‐oxidation using renewable electricity offers a sustainable route for valorizing glycerol, a major by‐product of biofuel production. This study introduces a bimetallic electrode with nanostructured platinum dendrites on nickel foam (Pt/NiF), achieving a peak geometric current density of 235 mA cm−2 and a Pt‐mass normalized current density of 3.71 for glycerol electro‐oxidation at 0.92 V versus a reversible hydrogen electrode (RHE) in 3 m KOH electrolyte containing 1 m glycerol, outperforming most previously reported Pt‐containing catalysts. The Pt/NiF electrode demonstrates over 92% cumulative selectivity toward C3 products, with 64% selectivity for lactic acid at 0.65 V versus RHE over 5 h of testing. This research also highlights the role of chemical oxidation pathways (isomerization and rearrangements) in converting glycerol to lactic acid. After 5 h at 0.65 V versus RHE, the Pt/NiF electrode maintains 35% of its initial current density, plateauing at 12.2 mA cm−2 (0.15 ), with performance loss likely due to surface poisoning by carbon‐based reaction intermediates/byproducts or passivating platinum (hydr)oxide species. These findings pave the way for developing low‐platinum group metal catalysts with high glycerol oxidation affinity and highlight the importance of considering chemical transformations during catalyst evaluation and reactor design.
Large Scale Ultrafast Manufacturing of Wireless Soft Bioelectronics Enabled by Autonomous Robot Arm Printing Assisted by a Computer Vision‐Enabled Guidance System for Personalized Wound Healing
Authors: Kim Jihyun , Jeong Seol‐Ha , Thibault Brendan Craig , Soto Javier Alejandro Lozano , Tetsuka Hiroyuki , Devaraj Surya Varchasvi , Riestra Estefania , Jang Yeongseok , Seo Jeong Wook , Rodríguez Rafael Alejandro Cornejo , Huang Lucia L. , Lee Yuhan , Preda Ioana , Sonkusale Sameer , Fiondella Lance , Seo Jungmok , Pirrami Lorenzo , Shin Su Ryon
Published: November 2024

A Customized wound patch for Advanced tissue Regeneration with Electric field (CARE), featuring an autonomous robot arm printing system guided by a computer vision‐enabled guidance system for fast image recognition is introduced. CARE addresses the growing demand for flexible, stretchable, and wireless adhesive bioelectronics tailored for electrotherapy, which is suitable for rapid adaptation to individual patients and practical implementation in a comfortable design. The visual guidance system integrating a 6‐axis robot arm enables scans from multiple angles to provide a 3D map of complex and curved wounds. The size of electrodes and the geometries of power‐receiving coil are essential components of the CARE and are determined by a MATLAB simulation, ensuring efficient wireless power transfer. Three heterogeneous inks possessing different rheological behaviors can be extruded and printed sequentially on the flexible substrates, supporting fast manufacturing of large customized bioelectronic patches. CARE can stimulate wounds up to 10 mm in depth with an electric field strength of 88.8 mV mm−1. In vitro studies reveal the ability to accelerate cell migration by a factor of 1.6 and 1.9 for human dermal fibroblasts and human umbilical vein endothelial cells, respectively. This study highlights the potential of CARE as a clinical wound therapy method to accelerate healing.
Polymer‐ and Lipid‐Based Nanostructures Serving Wound Healing Applications: A Review
Authors: Cetin Fatma N. , Mignon Arn , Van Vlierberghe Sandra , Kolouchova Kristyna
Published: November 2024

Management of hard‐to‐heal wounds often requires specialized care that surpasses the capabilities of conventional treatments. Even the most advanced commercial products lack the functionality to meet the needs of hard‐to‐heal wounds, especially those complicated by active infection, extreme bleeding, and chronic inflammation. The review explores how supramolecular nanovesicles and nanoparticles—such as dendrimers, micelles, polymersomes, and lipid‐based nanocarriers—can be key to introducing advanced wound healing and monitoring properties to address the complex needs of hard‐to‐heal wounds. Their potential to enable advanced functions essential for next‐generation wound healing products—such as hemostatic functions, transdermal penetration, macrophage polarization, targeted delivery, and controlled release of active pharmaceutical ingredients (antibiotics, gaseous products, anti‐inflammatory drugs, growth factors)—is discussed via an extensive overview of the recent reports. These studies highlight that the integration of supramolecular systems in wound care is crucial for advancing toward a new generation of wound healing products and addressing significant gaps in current wound management practices. Current strategies and potential improvements regarding personalized therapies, transdermal delivery, and the promising critically evaluated but underexplored polymer‐based nanovesicles, including polymersomes and proteinosomes, for wound healing.
Mitochondrial‐Targeting Mesoporous Polydopamine Nanoparticles for Reducing Kidney Injury Caused by Depleted Uranium
Authors: Li Wenrun , Shen Li , Fu Shiyan , Li Yong , Huang Feng , Li Qi , Lin Qinyang , Liu Hongjia , Wang Qiuchi , Chen Liyi , Tan Huanhuan , Li Juan , Zhao Yazhen , Ran Yonghong , Hao Yuhui
Published: November 2024

Depleted uranium (DU), when accidentally released from the nuclear industry, can enter the human body and cause kidney damage, as DU induces oxidative damage and apoptosis through mitochondrial pathways and inflammatory reactions. The existing nanoparticles used to treat DU injury have low bioavailability and poor targeting. In this study, mesoporous polydopamine (MPDA), poly‐(ethylene glycol) (PEG), and triphenylphosphonium (TPP) are combined to develop a novel mitochondrion‐targeting bifunctional nanoparticle, MPDA–PEG–TPP, and confirm that it can protect the kidneys from DU. This study demonstrates the high selectivity of MPDA–PEG–TPP for uranyl in uranyl chelate assays and its promising efficiency in uranyl sequestration from the kidneys, lungs, and femurs, following immediate or delayed administration of MPDA–PEG–TPP nanoparticles. In vitro assays confirm its efficiency in removing reactive oxygen species and targeting the mitochondria. In addition, in vitro and in vivo assays confirm that MPDA–PEG–TPP can reduce mitochondrial dysfunction and ameliorate kidney injury. These results suggest that MPDA–PEG–TPP is a valuable agent for ameliorating the DU‐induced kidney injury.
Biocooperative Regenerative Materials by Harnessing Blood‐Clotting and Peptide Self‐Assembly
Authors: Padilla‐Lopategui Soraya , Ligorio Cosimo , Bu Wenhuan , Yin Chengcheng , Laurenza Domenico , Redondo Carlos , Owen Robert , Sun Hongchen , Rose Felicity R.A.J. , Iskratsch Thomas , Mata Alvaro
Published: November 2024

The immune system has evolved to heal small ruptures and fractures with remarkable efficacy through regulation of the regenerative hematoma (RH); a rich and dynamic environment that coordinates numerous molecular and cellular processes to achieve complete repair. Here, a biocooperative approach that harnesses endogenous molecules and natural healing to engineer personalized regenerative materials is presented. Peptide amphiphiles (PAs) are co‐assembled with blood components during coagulation to engineer a living material that exhibits key compositional and structural properties of the RH. By exploiting non‐selective and selective PA‐blood interactions, the material can be immediately manipulated, mechanically‐tuned, and 3D printed. The material preserves normal platelet behavior, generates and provides a continuous source of growth factors, and promotes in vitro growth of mesenchymal stromal cells, endothelial cells, and fibroblasts. Furthermore, using a personalized autologous approach to convert whole blood into PA‐blood gel implants, bone regeneration is shown in a critical‐sized rat calvarial defect. This study provides proof‐of‐concept for a biocooperative approach that goes beyond biomimicry by using mechanisms that Nature has evolved to heal as tools to engineer accessible, personalized, and regenerative biomaterials that can be readily formed at point of use.
Regulating the Local Spin States in Spinel Oxides to Promote the Activity of Li‐CO2 Batteries
Authors: Liu Yingqi , Wu Xinru , Qu Haotian , Lu Gongxun , Chen Yanli , Lu Bingyi , Song Yanze , Zhou Guangmin , Cheng Hui‐Ming
Published: November 2024

Due to the high energy barrier, slow reaction kinetics, and complex reaction environments of Li‐CO2 batteries, the development of durable and efficient catalysts is essential. Transition metal oxides are promising for their availability, stability, and 3d electronic features, with spin states playing an important role in CO2 activation. In this study, the local spin states are regulated by incorporating Ni into Co3O4 and its impact on activity in Li‐CO2 batteries is explored. The results show that Ni atoms with high spin states in Ni0.1Co2.9O4 facilitate electron transfer from the catalyst to the unoccupied orbitals of CO2, providing sufficient active sites for the nucleation and growth of small Li2CO3 crystals. These small crystals have a low decomposition barrier, leading to improved battery efficiency. Therefore, Ni0.1Co2.9O4 shows superior catalytic performance with an overpotential of 0.72 V and an energy efficiency of ≈70% after 500 h. This work provides insights into the relationship between spin states and CO2 reactions, highlighting a promising avenue for developing high‐performance metal‐CO2 batteries.
Inducing Efficient and Multiwavelength Circularly Polarized Emission From Perovskite Nanocrystals Using Chiral Metasurfaces
Authors: Fiuza‐Maneiro Nadesh , Mendoza‐Carreño Jose , Gómez‐Graña Sergio , Alonso Maria Isabel , Polavarapu Lakshminarayana , Mihi Agustín
Published: November 2024

Chiral nano‐emitters have recently received great research attention due to their technological applications and the need for a fundamental scientific understanding of the structure‐property nexus of these nanoscale materials. Lead halide perovskite nanocrystals (LHP NCs) with many interesting optical properties have anticipated great promise for generating chiral emission. However, inducing high anisotropy chiral emission from achiral perovskite NCs remains challenging. Although chiral ligands have been used to induce chirality, their anisotropy factors (glum) are low [10−3 to 10−2]. Herein, the generation of high anisotropy circularly polarized photoluminescence (CPL) from LHP NCs is demonstrated using chiral metasurfaces by depositing nanocrystals on top of prefabricated resonant photonic structures (2D gammadion arrays). This scalable approach results in CPL with glum to a record high of 0.56 for perovskite NCs. Furthermore, the differences between high‐index dielectric chiral metasurfaces and metallic ones are explored for inducing chiral emission. More importantly, the generation of simultaneous multi‐wavelength circularly polarized light is demonstrated by combining dielectric and metallic chiral metasurfaces.
Light‐Manipulated Millimeter‐Scale Swimming Robot for Precise Navigation
Authors: Qin Huanqi , He Cong , Zhang Jiahao , Wen Chunyu , Wang Dalei , Liu Wei , Dai Chaoqing
Published: November 2024

Micro‐swimming robots have been increasingly emphasized in the fields of targeted drug delivery and water surface cleaning, which mainly use open external structures or external environments to assist navigation, but there are still salient problems, such as the difficulty of stable capture and poor navigation accuracy. Theoretically, a light‐driven swimming robot can have a symmetrical embedded structure to constrain surface tension gradient forces and thermophoretic forces in a wide range of directions and convert them into precise directional forces. Therefore, a sustained‐capture swimming robot is developed with precise navigation consisting of TiO2/polypyrrole (PPy) composites containing a symmetric inner truncated‐cone hole structure and realized multiple controllable motion patterns. Excitingly, the capture motion of the TiO2/PPy inner truncated‐cone hole structure robot “TPHR” can be accurately controlled by programmable automation, with capture travel speeds of up to ≈23.64 mm s−1. Its excellent kinematic performance stems from the high photothermal conversion efficiency (≈47.83%) of the composite and the synergistic effect between thermo‐capillary and thermo‐convective flows. Furthermore, a patterning precision movement, water surface oil‐cleaning microstructure assembly, etc. are realized, reflecting the engineering application value of TPHR. This structure provides a novel strategy for the development of micro‐swimming robots with stable capture and sustainable motion.
3D Printed Biodegradable Soft Actuators from Nanocellulose Reinforced Gelatin Composites
Authors: Müller Oliver , Poulin Alexandre , Aeby Xavier , Emma Roberto , Kanno Ryo , Nagai Toshiaki , Shintake Jun , Nyström Gustav
Published: November 2024

Eco‐friendly materials are increasingly important for several applications due to growing environmental concerns, including in robotics and medicine. Within robotics, silicone‐based soft grippers are recently developed owing to their high adaptability and versatility allowing to deal with various objects. However, the soft grippers are difficult to recycle and may cause increased environmental impact. Here biodegradable soft pneumatic actuators reinforced by cellulose nanofibrils (CNF) distributed in a matrix of gelatin are presented. The results show that adding CNF enables 3D printability and provides tunable mechanical properties for the actuators. The actuator performance, with a bending angle of 80° and a blocked force of 0.1 N at 15 kPa, is comparable to state‐of‐the‐art mold‐casted pneumatic actuators from conventional silicone materials while being exclusively composed of non‐toxic, biodegradable materials and fabricated by additive manufacturing techniques. Moreover, the actuators exhibit self‐healing ability and enable object manipulation when formed in a gripper configuration. The mold‐free approach and achieved functionalities establish new opportunities for soft‐robotics, across various fields including healthcare, packaging, or even environmental monitoring. The performance of the gripper shows that CNF can be used in the creation of eco‐friendly high‐performance soft robots and contribute to the advancement of sustainable and green robotics.
Role of Polymer‐Iodine Complexes on Solid‐Liquid Polysulfide Phase Transitions and Rate Capability of Lithium Sulfur Batteries
Authors: Nishshanke Maleesha M. , Jovanović Petar , Panda Manas R. , Abedin Md. Joynul , McNamara Declan , Hill Matthew R. , Bhattacharya Joydipto , Kamal Chinnathambi , Shaibani Mahdokht , Majumder Mainak
Published: November 2024

Lithium–sulfur (Li–S) batteries are considered as a viable technology offering energy‐dense electrochemical energy storage systems. However, the inherently slow reaction kinetics manifested in the slow charge and discharge characteristics constrain their real‐world applications. Here, it is reported that polyiodide species held within a complex polar network of polyvinylpyrrolidone (PVP) accelerate the rate‐limiting solid‐liquid phase transitions both in the reduction and oxidation steps during battery cycling. Density functional theory calculations support a mechanism in which a combination of enhanced binding of polysulfides and additional energy states in the PVP‐iodine‐polysulfide complexes accelerates the reaction pathways mediated by inter‐valance polyiodide reactions within the working voltage of Li–S batteries. These studies show that PVP‐iodine (PVP‐I) complexes enhance the rate capability of cells with practical sulfur loadings delivering a high areal capacity of ≈7 mAh cm−2 at the practical 0.5C rate. This advantage is demonstrated in one of the highest‐rate pouches reported in Li–S literature, attaining energy densities of 215 and 156 Wh kg at 0.1C and 0.3C, respectively. The results demonstrate a subtle but powerful shift in the design of molecular binder systems, which have functional roles above and beyond the role of simply holding the active materials together.