bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo Human Single‐Chain Fragment Variable Phage Display‐Assisted Identification of Galectin‐3 as a New Biomarker of Atherosclerosis
Authors: Hemadou Audrey , Fontayne Alexandre , Laroche‐Traineau Jeanny , Ottones Florence , Mondon Philippe , Claverol Stéphane , Ducasse Éric , Sanchez Stéphane , Mohamad Sarah , Lorenzato Cyril , Duonor‐Cerutti Martine , Clofent‐Sanchez Gisèle , Jacobin‐Valat Marie‐Josée 
Published: September 2021

Background
Atherosclerosis is a complex pathology in which dysfunctional endothelium, activated leucocytes, macrophages, and lipid‐laden foam cells are implicated, and in which plaque disruption is driven by many putative actors. This study aimed to identify accurate targetable biomarkers using new in vivo approaches to propose tools for improved diagnosis and treatment.

Methods and Results

Human scFv (single‐chain fragment variable) selected by in vivo phage display in a rabbit model of atherosclerosis was reformatted as scFv fused to the scFv‐Fc (single‐chain fragment variable fused to the crystallizable fragment of immunoglobulin G format) antibodies. Their reactivity was tested using flow cytometry and immunoassays, and aorta sections from animal models and human carotid and coronary artery specimens. A pool of atherosclerotic proteins from human endarterectomies was co‐immunoprecipitated with the selected scFv‐Fc followed by mass spectrometry for target identification. Near‐infrared fluorescence imaging was performed in
Apoe
−/−
mice after injection of an Alexa Fluor 647–labeled scFv‐Fc‐2c antibody produced in a baculovirus system with 2 additional cysteine residues (ie, 2c) for future coupling to nano‐objects for theranostic applications. One scFv‐Fc clone (P3) displayed the highest cross‐reactivity against atherosclerotic lesion sections (rabbit, mouse, and human) and was chosen for translational development. Mass spectrometry identified galectin‐3, a β‐galactoside‐binding lectin, as the leader target. ELISA and immunofluorescence assays with a commercial anti‐galectin‐3 antibody confirmed this specificity. P3 scFv‐Fc‐2c specifically targeted atherosclerotic plaques in the
Apoe
−/−
mouse model.

Conclusions
These results provide evidence that the P3 antibody holds great promise for molecular imaging of atherosclerosis and other inflammatory pathologies involving macrophages. Recently, galectin‐3 was proposed as a high‐value biomarker for the assessment of coronary and carotid atherosclerosis.
Insights From the Ventricular Fibrillation Waveform Into the Mechanism of Survival Benefit From Bystander Cardiopulmonary Resuscitation
Authors: Bessen Brooke , Coult Jason , Blackwood Jennifer , Hsu Cindy H. , Kudenchuk Peter , Rea Thomas , Kwok Heemun 
Published: September 2021

Background
The mechanism by which bystander cardiopulmonary resuscitation (CPR) improves survival following out‐of‐hospital cardiac arrest is unclear. We hypothesized that ventricular fibrillation (VF) waveform measures, as surrogates of myocardial physiology, mediate the relationship between bystander CPR and survival.

Methods and Results

We performed a retrospective cohort study of adult, bystander‐witnessed patients with out‐of‐hospital cardiac arrest with an initial rhythm of VF who were treated by a metropolitan emergency medical services system from 2005 to 2018. Patient, resuscitation, and outcome variables were extracted from emergency medical services and hospital records. A total of 3 VF waveform measures (amplitude spectrum area, peak frequency, and median peak amplitude) were computed from a 3‐second ECG segment before the initial shock. Multivariable logistic regression estimated the association between bystander CPR and survival to hospital discharge adjusted for Utstein elements. Causal mediation analysis quantified the proportion of survival benefit that was mediated by each VF waveform measure. Of 1069 patients, survival to hospital discharge was significantly higher among the 814 patients who received bystander CPR than those who did not (0.52 versus 0.43, respectively;
P
<0.01). The multivariable‐adjusted odds ratio for bystander CPR and survival was 1.6 (95% CI, 1.2, 2.1), and each VF waveform measure attenuated this association. Depending on the specific waveform measure, the proportion of mediation varied: 53% for amplitude spectrum area, 31% for peak frequency, and 29% for median peak amplitude.

Conclusions
Bystander CPR correlated with more robust initial VF waveform measures, which in turn mediated up to one‐half of the survival benefit associated with bystander CPR. These results provide insight into the biological mechanism of bystander CPR in VF out‐of‐hospital cardiac arrest.
Termination Based on Event Accrual in Per Protocol Versus Intention to Treat in the ROCKET AF Trial
Authors: Carnicelli Anthony P. , Hellkamp Anne S. , Mahaffey Kenneth W. , Singer Daniel E. , Breithardt Günter , Halperin Jonathan L. , Hankey Graeme J. , Piccini Jonathan P. , Becker Richard C. , Nessel Christopher C. , Berkowitz Scott D. , Fox Keith A. A. , Califf Robert M. , Patel Manesh R. 
Published: September 2021

Background
In event‐driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial to determine the effect of primary efficacy‐event tracking in the per‐protocol cohort during the on‐treatment period versus the intention‐to‐treat (ITT) cohort during the ITT period.

Methods and Results

ROCKET AF was terminated after accruing 429 primary efficacy events (stroke or systemic embolism) in the per‐protocol cohort during the on‐treatment period for noninferiority. We identified the date on which 429 events occurred in the ITT cohort during the ITT period. We performed noninferiority and superiority analyses based on hypothetical study termination on this date. ROCKET AF would have terminated 226 days earlier if events were tracked during the ITT period. Similar to the main trial findings, rivaroxaban would have met noninferiority versus warfarin for the primary efficacy end point (hazard ratio [HR], 0.77; 95% CI, 0.62–0.96;
P
<0.001). In contrast to the main trial findings, rivaroxaban would have met superiority for the primary efficacy end point (HR, 0.82; 95% CI, 0.68–0.99;
P
=0.038). In both termination scenarios, rivaroxaban was associated with a lower risk of intracranial hemorrhage and similar risk of other safety end points.

Conclusions
Clinical trial termination based on event accrual in the ITT cohort versus the per‐protocol cohort may have important implications on trial results depending on rates of study drug discontinuation and event rates off treatment.
Comparative Treatment Outcome in T3N0 Glottic Cancer With and Without Vocal Fold Fixation Receiving Radiation Therapy and Concurrent Low-Dose Intra-Arterial Cisplatin Infusion
Authors: Ono Takeharu , Tanaka Norimitsu , Chitose Shun-ichi , Tanoue Syuichi , Kurita Takashi , Sueyoshi Shintarou , Fukahori Mioko , Miyata Yusaku , Muraki Koichiro , Tsuji Chiyoko , Ogo Etsuyo , Hattori Chikayuki , Sato Kiminobu , Abe Toshi , Umeno Hirohito 
Published: September 2021

Objectives: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. Methods: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. Results: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). Conclusions: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.
Pharmacist-led interventions for people living with severe and persistent mental illness: A systematic review
Authors: Ng Ricki , El-Den Sarira , Stewart Victoria , Collins Jack C , Roennfeldt Helena , McMillan Sara S , Wheeler Amanda J , O’Reilly Claire L 
Published: September 2021

Objective: People living with severe and persistent mental illness experience poorer physical health, often due to medication and preventable lifestyle factors, and exacerbated by barriers to accessing healthcare services. Pharmacists are well-positioned to improve the physical and mental health of this population. However, little is known about pharmacists’ current practices when providing services to this population nor the impact of pharmacist-led interventions on consumer health outcomes. We undertook a systematic review to identify, describe and assess the effectiveness of pharmacist-led interventions for supporting people living with severe and persistent mental illness and the impact on consumer outcomes. Methods: MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Scopus, Cochrane Library, International Pharmaceutical Abstracts and ProQuest Dissertations and Theses were searched between January 1990 and April 2020. Full-text studies exploring pharmacist-led interventions in any setting for people living with severe and persistent mental illness were included. A risk of bias assessment was conducted. Results: A total of 37 studies were included. More than half of the pharmacist interventions were multifaceted. The most common components of pharmacist-led interventions included education and/or patient counselling, providing recommendations to healthcare professionals and conducting medication reviews. Multifaceted interventions demonstrated improvements in clinical outcomes, whereas single interventions focused mostly on consumer-reported outcomes. The methodological quality of included studies was moderate-to-high risk of bias and there was considerable heterogeneity in the study design, interventions described, and outcomes reported. Conclusion: There is evidence that pharmacist-led interventions improve consumer-reported and clinical outcomes for people living with severe and persistent mental illness. Pharmacists are capable and have a role in supporting people living with severe and persistent mental illness, either individually or as interprofessional collaborators with other healthcare professionals. Future research should attempt to better understand which particular intervention components have the greatest impact and also evaluate the implementation and long-term sustainability of such interventions.
Twin Peaks 2.0: Avoiding Influence Over an Australian Financial Regulator Assessment Authority
Authors: Schmulow Andrew , Mazzola Paul , de Zilva Daniel 
Published: September 2021

AbstractGlobally, financial system regulators are susceptible to deliberate and inadvertent influence by the industry that they oversee and, hence, are also susceptible to acting to benefit the industry rather than the public interest – a phenomenon known as ‘regulatory capture’. Australia, arguably, has an optimal model of financial system regulation (a ‘Twin Peaks’ model) comprising separate regulators for prudential soundness on the one hand, and market conduct and consumer protection on the other. However, the current design of the Twin Peaks model has not been sufficient to prevent and address prolonged and systemic misconduct that culminated in a public Royal Commission of Inquiry into misconduct in the industry. Subsequent to the Royal Commission and other inquiries, the Department of Treasury has proposed legislation to establish an Assessment Authority to assess the effectiveness of the Twin Peaks regulators. The proposal includes enquiries by an Assessment Authority into the regulators’ independence, so as to identify instances of, and thereby mitigate, their capture. As with all financial system regulators, the Assessment Authority itself may be susceptible to regulatory capture, either by the Twin Peaks regulators, or by the financial industry. Thus, this paper poses the question: how can the new Assessment Authority be optimally constituted by legislation, and operated, to effectively oversee the effectiveness of the regulators, but itself remain insulated from the influence of the regulators and industry? We analyse the primary sources of influence over financial system regulators that the Assessment Authority will likely face and recommend ways in which a robust design of the Assessment Authority can mitigate those sources of influence. In doing so, we adopt an inter-disciplinary approach, drawing upon not only regulatory theory but also for the first time in relation to this question, organisational psychology. Our findings address gaps in the proposed legislation currently before Federal Parliament and propose methods by which those gaps may be filled, in order to ensure that this important reform to Australia’s financial regulatory regime has the greatest chance of success.
3D Real IR MR Findings in Acoustic Neuromas: Altered Perilymph Metabolism
Authors: Shi Suming , Guo Ping , Li Wenquan , Wang Wuqing 
Published: September 2021

Objectives This study aimed to investigate the perilymph metabolism by analyzing the 3D real IR MR findings in acoustic neuroma (AN) after intravenous administration of gadolinium (Gd). Methods Eleven patients (6 men and 5 women) diagnosed with AN were included, and 3D real IR MRI was performed 4 hours after intravenous Gd injection. The signal intensity and details of inner ear, tumor, and internal auditory canal (IAC) by MRI were analyzed. Results Four patients had tumors confined to the IAC, and 5 had tumors that extended to the cerebellopontine angle cistern. The signal intensity of the cochlea, vestibule, and IAC fundus was conspicuously enhanced in 3D real IR images than the control side. One patient had a tumor in the cochlea, in which the signal intensity of the semicircular canal and vestibule was increased. One patient had an intravestibular tumor in which the signal intensity of the semicircular canal was increased and the cochlea had endolymphatic hydrops in the affected ear. Conclusions The synchronously increased signal intensity in the inner ear and IAC may indicate that IAC may serve as a channel for removal of the perilymph in the inner ear; the blockage by the tumor may have changed the hydrodynamics of the perilymph to cause a longer retention of Gd in the inner ear.
“Be free together rather than confined together”: A qualitative exploration of how relationships changed in the early COVID-19 pandemic
Authors: Vowels Laura M. , Francois-Walcott Rachel R. R. , Perks Rhia E. , Carnelley Katherine B. 
Published: September 2021

Due to the COVID-19 pandemic, many couples are staying at home together for an extended period. This is likely to impact couples as they navigate their responsibilities while maintaining a healthy relationship during uncertain times. We conducted qualitative research to investigate participants’ perception on how relationships changed considering COVID-19 and social distancing measures. Data were collected through open-ended surveys ( n = 200) which were completed weekly for 5 weeks and by semi-structured interviews ( n = 48). Overall, 28.6% of relationships had gotten better, 28.6% worse, 29.9% stayed the same, and 8.0% were mixed. Both methods highlighted similar themes (communication, space, togetherness, sharing responsibilities, quality time, and support networks) including 15 sub-themes in the interviews. The study provides a unique insight into the impact of COVID-19 on relationships and provides techniques that have been identified by couples to increase relationship satisfaction for their own and others’ relationships.
Potential benefit of GnRH-agonist treatment before uterine artery embolization for large fibroids: MRI prediction of fibroid volume reduction
Authors: Lee Woo Jin , Kim Man-Deuk , Han Kyunghwa , Won Ye Ryung , Alqahtani Abdulrahman , Moon Sungmo , An Hyeongsu 
Published: September 2021

Background Signal intensity (SI) of predominant fibroid (F1) on T2-weighted (T2W) images is useful for predicting the volume reduction response after gonadotropin-releasing hormone (GnRH)-agonist treatment. Few studies have been published regarding when and how to use GnRH agonist before UAE. Purpose To investigate magnetic resonance imaging (MRI) prediction of volume reduction rate (VRR) of large fibroids after GnRH-agonist treatment before uterine artery embolization (UAE) as well as the efficacy of UAE based on MRI. Material and Methods Data from 30 patients with a large fibroid and MRI results both before and after GnRH-agonist treatment were retrospectively analyzed. Indications for GnRH-agonist treatment are fibroids with a maximum diameter ≥10 cm or pedunculated submucosal fibroids ≥8 cm. GnRH agonist (3.75 mg leuprolide acetate) was administered subcutaneously once per month 2–6 times. SI of F1 on T2W imaging was measured: the SI was referenced to the SI of the rectus abdominis muscle (F/R). Results Mean maximum fibroid diameter was 11.1 ± 1.9 cm (range = 8.0–15.5 cm). Mean number of GnRH-agonist injections before UAE was 2.8 (range = 2–6). For predicting VRR ≥50% and <30%, the optimal cut-off values of F/R were 2.58 (sensitivity 80%, specificity 80%) and 1.69 (sensitivity 100%, specificity 70%), respectively. Of the 30 patients, fibroid infarction was complete in 29 (96.7%). Conclusion SI of F1 on T2W imaging is useful for predicting the volume reduction response after GnRH-agonist treatment. After GnRH-agonist treatment for large fibroids, UAE is effective to achieve complete infarction of fibroids.
Nickel nanoparticles induce hepatotoxicity via oxidative and nitrative stress-mediated apoptosis and inflammation
Authors: Iqbal Shabnoor , Jabeen Farhat , Peng Cheng , Shah Muhammad Ajmal , Ijaz Muhammad Umar , Rasul Azhar , Ali Shujat , Rauf Abdur , Batiha Gaber ES , Kłodzińska Ewa 
Published: September 2021

Nickel nanoparticles (Ni NPs) are utilized extensively in various industrial applications. However, there are increasing concerns about potential exposure to Ni NPs and consequent health effects. The aim of this study was to assess Ni NPs-induced liver toxicity in Sprague Dawley rats. Twenty-five rats were exposed to Ni NPs via intraperitoneal injection at doses of 15, 30, and 45 mg/kg per body weight for 28 days. Results from ICP-MS analysis showed an increase in the concentration of Ni NPs in a dose-dependent manner. The liver dysfunction was indicated by considerable production of ALT, AST, ALP, LDH, and TB in Ni NPs-treated rats. Histological examination demonstrated liver injuries (inflammatory cells, congestion, necrosis, and pyknosis) in exposed rats with dose-dependent severity of pathologies by semi-quantitative histograding system. To explore the toxicological pathways, we examined oxidative stress biomarkers and detected Ni NPs significantly elevated the levels of MDA and LPO while decreasing the levels of CAT and GSH. All the changes in biomarkers were recorded in a dose-dependent relationship. In addition, we found upregulated NF-kβ indicating activation of inflammatory cytokines. ELISA results of serum revealed a remarkable increase of nitrative stress markers (iNOS and NO), ATPase activity, inflammatory cytokine (IL-6, IL-1β, and TNF-α), and apoptotic mediators (caspase-3 and caspase-9) in Ni NPs-treated groups than the control. In summary, the result of this study provided evidence of hepatotoxicity of Ni NPs and insightful information about the involved toxic pathways, which will help in health risk assessment and management, related preventive measures for the use of Ni-NPs materials.
Acrylamide impairs the developmental potential of germinal vesicle oocytes by inducing mitochondrial dysfunction and autophagy/apoptosis in mice
Authors: Gao Ji-Guang , Yang Jian-Ke , Zhu Lei , Xu Cheng , Nie Liu-Wang 
Published: September 2021

Background: Acrylamide (ACR), an important endogenous contaminant in carbohydrate-rich foods, has been involved in various negative effects on multiple organ networks, including the reproductive system. Previous studies have reported that ACR affects oocyte quality and fertility. Purpose: This study aimed to explore the toxic effects and regulatory mechanisms of ACR on mouse germinal vesicle (GV) oocytes. Research Design: In this study, adult female mice were exposed to ACR at 10 mg/kg/day/body weight through their drinking water continuously for 4 weeks. Study Sample and Data Analysis: The mitochondrial function, autophagy/apoptosis, and development potential of GV oocytes were investigated. Results: The results showed that ACR reduced the oocyte diameter, sperm-binding ability, parthenogenetic activation and in vitro fertilization (IVF) rate, and development potential of pre-implantation embryos. We also found that ACR exposure disrupted chromatin configuration, mitochondrial distribution, and membrane potential (Δφm) of oocytes. Actin filament expression was significantly reduced in both the membrane and cytoplasm of mouse oocytes. Moreover, ACR exposure increased LC3-positive signals, early apoptosis rate, aberrant ATG3, ATG5, LC3, Beclin1, and mTOR mRNA expression. Conclusions: These results suggest that ACR exposure can affect the developmental potential of GV oocytes by inducing mitochondrial dysfunction, actin filament assembly, and autophagy/apoptosis.
Single dose of atezolizumab plus chemotherapy in active psoriasis with advanced non-small cell lung cancer
Authors: Wong Pui Yee , How Soon Hin , Ismail Irnani , Hassan Radhiana 
Published: September 2021

Introduction Immunotherapy has been recognized as the standard of care in addition to chemotherapy in the treatment of advanced non-small cell lung cancer. Most immunotherapy trials, however, exclude patients with autoimmune disease owing to concerns of disease exacerbation. Case report We report a case of a patient with advanced non-small cell lung cancer and underlying active psoriasis who experienced a remarkable response, without developing psoriasis flares, following treatment with a single dose of atezolizumab and first-line chemotherapy. Management and outcome The patient remained asymptomatic 10 months since treatment discontinuation, without disease progression, despite having received only a single dose of atezolizumab and six cycles of chemotherapy. Discussion Little is known about the optimum duration required to achieve a durable response with immunotherapy. Patients with autoimmune disease are commonly excluded from immunotherapy trials owing to a higher risk of autoimmune disease flares or immune-related adverse events. The remarkable outcome observed in this case offers some insights into the possible durable response with limited doses of immunotherapy and a safer approach for administering immunotherapy in patients with autoimmune disease. Initiating chemotherapy to induce remission in active autoimmune disease prior to administering immunotherapy could potentially be an ideal approach that facilitates the use of immunotherapy in this patient population.