bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapeutic early-phase clinical trials and malignant gliomas: A single-center experience and comprehensive immunophenotyping of circulating leukocytes
Authors: Simonelli Matteo , Persico Pasquale , Capucetti Arianna , Carenza Claudia , Franzese Sara , Lorenzi Elena , Dipasquale Angelo , Losurdo Agnese , Giordano Laura , Pessina Federico , Navarria Pierina , Politi Letterio S , Mavilio Domenico , Locati Massimo , Della Bella Silvia , Santoro Armando , Bonecchi Raffaella 
Published: November 2021

Abstract

Background
Immunotherapeutic early-phase clinical trials (ieCTs) increasingly adopt large expansion cohorts exploring novel agents across different tumor types. High-grade glioma (HGG) patients are usually excluded from these trials.

Methods
Data of patients with recurrent HGGs treated within multicohort ieCTs between February 2014 and August 2019 (experimental group, EG) at our Phase I Unit were retrospectively reviewed and compared to a matched control group (CG) of patients treated with standard therapies. We retrospectively evaluated clinical, laboratory, and molecular parameters through univariate and multivariate analysis. A prospective characterization of circulating leukocyte subpopulations was performed in the latest twenty patients enrolled in the EG, with a statistical significance cutoff of P &lt; .1.

Results
Thirty HGG patients were treated into six ieCTs. Fifteen patients received monotherapies (anti-PD-1, anti-CSF-1R, anti-TGFβ, anti-cereblon), fifteen patients combination regimens (anti-PD-L1 + anti-CD38, anti-PD-1 + anti-CSF-1R). In the EG, median progression-free survival and overall survival (OS) from treatment initiation were 1.8 and 8.6 months; twelve patients survived more than 12 months, and two of them more than 6 years. Univariate analysis identified O6-methylguanine DNA methyltransferase (MGMT) promoter methylation and total protein value at six weeks as significantly correlated with a better outcome. Decreased circulating neutrophils and increased conventional dendritic cells levels lead to significantly better OS.

Conclusions
A subgroup of EG patients achieved remarkably durable disease control. MGMT promoter methylation identifies patients who benefit more from immunotherapy. Monitoring dynamic changes of innate immune cell populations may help to predict clinical outcomes.
Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats
Authors: Bagdas Deniz , Rupprecht Laura E , Nunes Eric J , Schillinger Emma , Immanuel Judah J , Addy Nii A 
Published: November 2021

Abstract

Introduction
Tobacco product flavors may change the sensory properties of nicotine, such as taste and olfactory cues, which may alter nicotine reward and aversion and nicotine taking behavior. The hedonic or aversive value of a taste stimulus can be evaluated by examining affective orofacial movements in rodents.

Aims and Methods
We characterized taste responses to various oral nicotine concentrations using the taste reactivity test in rats. We also evaluated the impact of menthol and benzaldehyde (cherry, almond) flavorants on both ingestive and aversive responses to oral nicotine. Adult Sprague-Dawley rats (n = 5–10 per sex per group) were implanted with intraoral catheters and received 20 infusions (200 µl/ea). Nicotine (1–100 µg/mL) was evaluated in taste reactivity test to determine taste responses to nicotine. Later, the effects of menthol (50 µg/mL) and benzaldehyde (100 µg/mL) on the taste responses to nicotine were determined.

Results
Nicotine at low concentrations (3 µg/mL in males, 1 µg/mL in females) elicited significantly greater ingestive responses compared with water, whereas higher nicotine concentrations (≥30 µg/mL in males, ≥10 µg/mL in females) elicited significant aversive reactions. Thus, intraoral nicotine induced both hedonic and aversive responses in a concentration- and sex-dependent manner. Females were more sensitive to nicotine’s concentration. The addition of menthol or benzaldehyde significantly increased the hedonic responses to nicotine, and significantly decreased the aversive nicotine responses.

Conclusions
Oral nicotine induces both hedonic and aversive taste responses, which may represent liking and disliking. Menthol and benzaldehyde can alter the orosensory experience of nicotine, which may influence nicotine’s abuse liability.

Implications
Our work represents a model to study impact of flavors on oral nicotine liking and disliking responses in rats. Moreover, our findings show that menthol and benzaldehyde alter the orosensory experience of nicotine, suggesting that both could influence nicotine’s abuse liability.
Antipseudomonal Versus Narrow-Spectrum Agents for the Treatment of Community-Onset Intra-abdominal Infections
Authors: Worden Lacy J , Dumkow Lisa E , VanLangen Kali M , Beuschel Thomas S , Jameson Andrew P 
Published: November 2021

Abstract

Background
Antipseudomonal antibiotics are often used to treat community-acquired intra-abdominal infections (CA-IAIs) despite common causative pathogens being susceptible to more narrow-spectrum agents. The purpose of this study was to compare treatment-associated complications in adult patients treated for CA-IAI with antipseudomonal versus narrow-spectrum regimens.

Methods
This retrospective cohort study included patients &gt;18 years admitted for CA-IAI treated with antibiotics. The primary objective of this study was to compare 90-day treatment-associated complications between patients treated empirically with antipseudomonal versus narrow-spectrum regimens. Secondary objectives were to compare infection and treatment characteristics along with patient outcomes. Subgroup analyses were planned to compare outcomes of patients with low-risk and high-risk CA-IAIs and patients requiring surgical intervention versus medically managed.

Results
A total of 350 patients were included: antipseudomonal, n=204; narrow spectrum, n=146. There were no differences in 90-day treatment-associated complications between groups (antipseudomonal 15.1% vs narrow spectrum 11.3%, P=.296). In addition, no differences were observed in hospital length of stay, 90-day readmission, Clostridiodes difficile, or mortality. In multivariate logistic regression, treatment with a narrow-spectrum regimen (odds ratio [OR], 0.75; 95% confidence interval, 0.39–1.45) was not independently associated with the primary outcome. No differences were observed in 90-day treatment-associated complications for (1) patients with low-risk (antipseudomonal 15% vs narrow spectrum 9.6%, P=.154) or high-risk CA-IAI (antipseudomonal 15.8% vs narrow spectrum 22.2%, P=.588) or (2) those who were surgically (antipseudomonal 8.5% vs narrow spectrum 9.2%, P=.877) or medically managed (antipseudomonal 23.1 vs narrow spectrum 14.5, P=.178).

Conclusions
Treatment-associated complications were similar among patients treated with antipseudomonal and narrow-spectrum antibiotics. Antipseudomonal therapy is likely unnecessary for most patients with CA-IAI.
Invertibility conditions for field transformations with derivatives: Toward extensions of disformal transformation with higher derivatives
Authors: Babichev Eugeny , Izumi Keisuke , Tanahashi Norihiro , Yamaguchi Masahide 
Published: November 2021

Abstract
We discuss a field transformation from fields ψa to other fields ϕi that involves derivatives, $\phi _i = \bar{\phi }_i(\psi _a, \partial _\alpha \psi _a, \ldots ;x^\mu )$, and derive conditions for this transformation to be invertible, primarily focusing on the simplest case that the transformation maps between a pair of fields and involves up to their first derivatives. General field transformation of this type changes the number of degrees of freedom; hence, for the transformation to be invertible, it must satisfy certain degeneracy conditions so that additional degrees of freedom do not appear. Our derivation of necessary and sufficient conditions for invertible transformation is based on the method of characteristics, which is used to count the number of independent solutions of a given differential equation. As applications of the invertibility conditions, we show some non-trivial examples of the invertible field transformations with derivatives, and also give a rigorous proof that a simple extension of the disformal transformation involving a second derivative of the scalar field is not invertible.
pH-responsive delivery of H2 through ammonia borane-loaded mesoporous silica nanoparticles improves recovery after spinal cord injury by moderating oxidative stress and regulating microglial polarization
Authors: Liu Yi , Wang Yeying , Xiao Bing , Tang Guoke , Yu Jiangming , Wang Weiheng , Xu Guohua , Ye Xiaojian 
Published: November 2021

Abstract
Imbalance of oxidative and inflammatory regulation is the main contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury (SCI). As an emerging biosafe strategy for protecting against oxidative and inflammatory damage, hydrogen (H2) therapy is a promising approach for improving the microenvironment to allow neural regeneration. However, achieving release of H2 at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H2. Thus, we assembled SiO2@mSiO2 mesoporous silica nanoparticles and loaded them with ammonia borane (AB), which has abundant capacity and allows controllable release of H2 in an acid-dependent manner. The release of H2 from AB/SiO2@mSiO2 was satisfactory at pH 6.6, which is approximately equal to the microenvironmental acidity after SCI. After AB/SiO2@mSiO2 were intrathecally administered to rat models of SCI, continuous release of H2 from these nanoparticles synergistically enhanced neurofunctional recovery, reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction. Furthermore, in the subacute phase of SCI, microglia were markedly polarized toward the M2 phenotype by H2 via inhibition of TLR9 expression in astrocytes. In conclusion, H2 delivery through AB/SiO2@mSiO2 has the potential to efficiently treat SCI through comprehensive modulation of the oxidative and inflammatory imbalance in the microenvironment.
Preparation of EGCG decorated, injectable extracellular vesicles for cartilage repair in rat arthritis
Authors: Song Changwei , Xu Shibo , Chang Linna , Zhao Xingjun , Mei Xifan , Ren Xiuli , Chen Zhenhua 
Published: November 2021

Abstract
Arthritis is a kind of chronic inflammatory autoimmune disease, which can destroy joint cartilage and bone, leading to joint pain, joint swelling, and limited mobility. Traditional therapies have many side effects or focus too much on anti-inflammation while neglecting joint repair. In this experiment, we combined Epigallocatechin gallate (EGCG) with extracellular vesicles derived from macrophages to treat rheumatoid arthritis. Sustained-release resulted in a significant decrease in chondrocyte expression of hypoxia-inducible factor 1-alpha, a decrease in apoptosis-related proteins Cytochrome C, Caspase-3, Caspase-9, and Bax. Molecular biological analysis showed that extracellular vesicles-encapsulated EGCG (EVs-EGCG) more significantly upregulated type II collagen expression by about 1.8-fold than EGCG alone, which was more beneficial for arthritis repair. Animal experiments revealed that these EGCG-coated extracellular vesicles significantly reduced swelling, decreased synovial hyperplasia, repaired cartilage, and attenuated arthritis-related pathology scores in arthritic rats. Measurement data showed that EVs-EGCG treatment reduced joint swelling by approximately 39.5% in rheumatoid rats. In vitro studies have shown that this EVs-EGCG can increase the expression of cartilage type II collagen and reduce apoptosis of chondrocytes. Moreover, it was demonstrated in vivo experiments to reduce cartilage destruction in rheumatoid arthritis rats, providing a solution for the treatment of rheumatoid arthritis.
Purinergic signalling in systemic sclerosis
Authors: Höppner Jakob , Bruni Cosimo , Distler Oliver , Robson Simon C , Burmester Gerd R , Siegert Elise , Distler Jörg H W 
Published: November 2021

Abstract
SSc is a chronic autoimmune rheumatic disease that involves numerous organs and presents major management challenges. The histopathologic hallmarks of SSc include vasculopathy, fibrosis and autoimmune phenomena involving both innate and adaptive immune systems. Purinergic signalling is a pathway that may be implicated in the pathophysiology of several of these disease manifestations. Extracellular purines are potent signalling mediators, which have been shown to be dysregulated in SSc. As examples, purines can exacerbate vasculopathy and provoke platelet dysfunction; as well as contributing to immune dysregulation. Elements of purinergic signalling further promote organ and tissue fibrosis in several disease models. Here, we provide an overview of extracellular purine metabolism in purinergic signalling and link disorders of these to the molecular pathology of SSc. We also discuss targeting the purinergic signalling and explore the translational applications for new therapeutic options in SSc.
Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum
Authors: Di Matteo Andrea , Duquenne Laurence , Cipolletta Edoardo , Nam Jacqueline L , Garcia-Montoya Leticia , Wakefield Richard J , Mahler Michael , Mankia Kulveer , Emery Paul 
Published: November 2021

AbstractObjectivesTo investigate whether anti-CCP2-positive at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis (CCP2+ at-risk) develop US subclinical synovitis before inflammatory arthritis and if US subclinical synovitis can be predicted.MethodsFirst, US scans of CCP2+ at-risk individuals who developed inflammatory arthritis (‘progressors’) were reviewed for subclinical synovitis prior to inflammatory arthritis development. Patients in whom the pre-progression US scan was negative but the scan was conducted &gt;6 months before progression were excluded. Subsequently, regression analyses were performed to identify predictors of US synovitis in CCP2+ at-risk individuals without baseline US abnormalities who had one or more longitudinal US scan and a complete dataset.ResultsUS subclinical synovitis was detected in one or more scan in 75 of 97 progressors (77.3%) {median time to inflammatory arthritis development from first evidence of US synovitis 26.5 weeks [interquartile range (IQR) 7–60]}, in whom one or more scan was available, excluding those with a negative scan &gt;6 months from inflammatory arthritis development (n = 38). In 220 CCP2+ at-risk individuals with normal baseline US scans, who had one or more longitudinal US scan and a complete dataset, US synovitis was detected in 69/220 (31.4%) [median time to first developing US synovitis 56.4 weeks (IQR 33.0–112.0)]. In the multivariable analysis, only anti-CCP3 antibodies were predictive for the development of US synovitis [odds ratio 4.75 (95% CI 1.97, 11.46); P &lt; 0.01].ConclusionsIn anti-CCP2+ at-risk individuals, a stage of subclinical synovitis usually precedes the development of inflammatory arthritis. Anti-CCP2+/CCP3+ individuals without clinical or US subclinical synovitis may represent the optimal window of opportunity for intervention to prevent joint disease.
Association between insomnia patients’ pre-treatment characteristics and their responses to distinctive treatment sequences
Authors: Edinger Jack D , Beaulieu-Bonneau Simon , Ivers Hans , Guay Bernard , Bélanger Lynda , Simmons Bryan , Morin Charles M 
Published: November 2021

AbstractStudy ObjectivesIt is common to provide insomnia patients a second treatment when the initial treatment fails, but little is known about optimal treatment sequences for different patient types. This study examined whether pre-treatment characteristics/traits predict optimal treatment sequences for insomnia patients.MethodsA community sample of 211 adults (132 women; Mage = 45.6 ± 14.9 years) with insomnia were recruited. Patients were first treated with behavioral therapy (BT) or zolpidem (Zol). Non-remitting BT recipients were randomized to a second treatment with either Zol or cognitive therapy; non-remitting Zol recipients underwent BT or Trazodone as a second treatment. Remission rates were assessed at the end of the first and second 6-week treatments. We then compared the remission rates of dichotomous groups formed on the basis of gender, age, pretreatment scores on SF36 and Multidimensional Fatigue Scale, the presence/absence of psychiatric/medical comorbidities or pain disorders, and mean subjective sleep duration and efficiency within and across treatment sequences.ResultsLower remission rates were noted for those: with a pain disorder, poor mental health perceptions, high MFI fatigue scores, and lower sleep times and efficiencies. Patients with a pain disorder responded best to the BT-to-Zol sequence, whereas patients with more mental impairment, severe fatigue, short sleep, and low sleep efficiency responded poorly to treatment starting with BT.ConclusionsPain, fatigue, poor mental health status, and subjective sleep duration and efficiency all affect response to different insomnia treatment sequences. Findings may guide clinicians in matching insomnia treatments to their patients.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT01651442, Protocol version 4, April 20, 2011, registered June 26, 2012, https://clinicaltrials.gov/ct2/show/NCT01651442?rslt=With&type=Intr&cond=Insomnia&cntry=US&state=US%3ACO&city=Denver&age=12&draw=2&rank=1.
Obstructive sleep apnea is an independent risk factor for severe COVID-19: a population-based study
Authors: Rögnvaldsson Kristján Godsk , Eyþórsson Elías Sæbjörn , Emilsson Össur Ingi , Eysteinsdóttir Björg , Pálsson Runólfur , Gottfreðsson Magnús , Guðmundsson Gunnar , Steingrímsson Vilhjálmur 
Published: November 2021

Abstract

Study Objectives
Obstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities.

Methods
Included were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali – The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting.

Results
A total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4–3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2–3.2) when adjusted for demographic characteristics and various comorbidities.

Conclusions
OSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.
The case for prioritizing implementation strategy fidelity measurement: benefits and challenges
Authors: Akiba Christopher F , Powell Byron J , Pence Brian W , Nguyen Minh X B , Golin Carol , Go Vivian 
Published: November 2021

Abstract
Implementation strategies are systematic approaches to improve the uptake and sustainability of evidence-based interventions. They frequently focus on changing provider behavior through the provision of interventions such as training, coaching, and audit-and-feedback. Implementation strategies often impact intermediate behavioral outcomes like provider guideline adherence, in turn improving patient outcomes. Fidelity of implementation strategy delivery is defined as the extent to which an implementation strategy is carried out as it was designed. Implementation strategy fidelity measurement is under-developed and under-reported, with the quality of reporting decreasing over time. Benefits of fidelity measurement include the exploration of the extent to which observed effects are moderated by fidelity, and critical information about Type-III research errors, or the likelihood that null findings result from implementation strategy fidelity failure. Reviews of implementation strategy efficacy often report wide variation across studies, commonly calling for increased implementation strategy fidelity measurement to help explain variations. Despite the methodological benefits of rigorous fidelity measurement, implementation researchers face multi-level challenges and complexities. Challenges include the measurement of a complex variable, multiple data collection modalities with varying precision and costs, and the need for fidelity measurement to change in-step with adaptations. In this position paper, we weigh these costs and benefits and ultimately contend that implementation strategy fidelity measurement and reporting should be improved in trials of implementation strategies. We offer pragmatic solutions for researchers to make immediate improvements like the use of mixed methods or innovative data collection and analysis techniques, the inclusion of implementation strategy fidelity assessment in reporting guidelines, and the staged development of fidelity tools across the evolution of an implementation strategy. We also call for additional research into the barriers and facilitators of implementation strategy fidelity measurement to further clarify the best path forward.
Care Coordination: A Concept Analysis
Authors: Anderson Amanda , Hewner Sharon 
Published: November 2021

ABSTRACT:
Care coordination is both a well-known concept discussed in a wide range of multidisciplinary health care literature and a familiar nursing role in clinical practice; however, the definition of care coordination lacks role clarity across disciplines and within the nursing profession. Despite variations, defining factors of care coordination practice exist; however, role ambiguity limits the effective implementation of evidence-based care coordination in practice and policy. Following Walker and Avant's eight-step concept analysis method, we aim to further clarify care coordination as a concept and practice role and examine the value that nursing brings to its implementation.