bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience of hospital-initiated medication changes in older people with multimorbidity: a multicentre mixed-methods study embedded in the OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial
Authors: Thevelin Stefanie , Pétein Catherine , Metry Beatrice , Adam Luise , van Herksen Anniek , Murphy Kevin , Knol Wilma , O'Mahony Denis , Rodondi Nicolas , Spinewine Anne , Dalleur Olivia 
Published: March 2022

BackgroundA patient-centred approach to medicines optimisation is considered essential. The OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial evaluated the effectiveness of medication review with shared decision-making (SDM) in older people with multimorbidity. Beyond evaluating the clinical effectiveness, exploring the patient experience facilitates a better understanding of contextual factors and mechanisms affecting medication review effectiveness.ObjectiveTo explore experiences of hospital-initiated medication changes in older people with multimorbidity.MethodsWe conducted a multicentre mixed-methods study, embedded in the OPERAM trial, combining semi-structured interviews and the Beliefs about Medicines Questionnaire (BMQ) with a purposive sample of 48 patients (70–94 years) from four European countries. Interviews were analysed using the Framework approach. Trial implementation data on SDM were collected and the 9-item SDM questionnaire was conducted with 17 clinicians.ResultsPatients generally displayed positive attitudes towards medication review, yet emphasised the importance of long-term, trusting relationships such as with their general practitioners for medication review. Many patients reported a lack of information and communication about medication changes and predominantly experienced paternalistic decision-making. Patients’ beliefs that ‘doctors know best’, ‘blind trust’, having limited opportunities for questions, use of jargon terms by clinicians, ‘feeling too ill’, dismissive clinicians, etc highlight the powerlessness some patients felt during hospitalisation, all representing barriers to SDM. Conversely, involvement of companions, health literacy, empathetic and trusting patient-doctor relationships, facilitated SDM. Paradoxical to patients’ experiential accounts, clinicians reported high levels of SDM. The BMQ showed that most patients had high necessity and low concern beliefs about medicines. Beliefs about medicines, experiencing benefits or harms from medication changes, illness perception, trust and balancing advice between different healthcare professionals all affected acceptance of medication changes.ConclusionTo meet patients’ needs, future medicines optimisation interventions should enhance information exchange, better prepare patients and clinicians for partnership in care and foster collaborative medication reviews across care settings.
Associations between household air pollution and early child development among children aged 36–59 months in Bangladesh
Authors: Rana Juwel , Luna-Gutiérrez Patricia , Haque Syed Emdadul , Ignacio Nazif-Muñoz José , Mitra Dipak Kumar , Oulhote Youssef 
Published: March 2022

BackgroundHousehold air pollution (HAP) from solid fuel use (SFU) for cooking may impact child health in low-resources countries. This study examined the associations between HAP and early childhood development (ECD) outcomes among children under 5 years of age in Bangladesh and explored potential effect modification by sex and urbanicity.MethodsThe study sample consisted of 9395 children aged 36–59 months in the households from the Bangladesh Multiple Indicator Cluster Survey 2019. SFU and levels of exposure to SFU (unexposed, moderately exposed and highly exposed) were used as proxies of HAP exposure. We estimated the covariate-adjusted prevalence ratios (aPRs) and 95% CIs for the associations between HAP and ECD outcomes using multilevel mixed-effects Poisson regression models with a robust variance estimator.Results81.4% of children were exposed to SFU, and the prevalence of developmental delay (in Early Childhood Development Index) was 25.3%. Children exposed to SFU were 1.47 times more likely to have developmental delays (95% CI: 1.25, 1.73; p<0.001) compared with children with no SFU exposure. SFU was significantly associated with developmental delay in socioemotional (aPR: 1.17; 95% CI: 1.01, 1.36; p=0.035) and learning-cognitive (aPR: 1.90; 95% CI: 1.39, 2.60; p<0.001) domains. Similarly, children moderately exposed and highly exposed to HAP had higher prevalence of developmental delays than unexposed children. We did not observe effect modification by sex or urbanicity.ConclusionPublic health policies should promote the use of clean cooking fuels and cookstoves to reduce the high burden of HAP exposure in low-resource countries for helping younger children to meet their developmental milestones.
Quantum gravitational corrections to the entropy of a Reissner–Nordström black hole
Authors: Campos Delgado Ruben 
Published: March 2022

AbstractStarting from an effective action for quantum gravity, we calculate the quantum gravitational corrections to the Wald entropy of a four dimensional non-extremal Reissner–Nordström (RN) black hole in the limit of small electric charge, generalising a previous calculation carried out by Calmet and Kuipers (Phys Rev D 104(6):066012, 2021) for a Schwarzschild black hole. We show that, at second order in the Ricci curvature, the RN metric receives quantum corrections which shift the classical position of the event horizon. We apply the Wald entropy formula by integrating over the perimeter of the quantum corrected event horizon. We then compute the quantum gravitational corrections to the temperature and the pressure of the black hole.
An Engel condition with two generalized derivations on Lie ideals of prime rings
Authors: Liu Cheng-Kai 
Published: March 2022

Let [Formula: see text] be a prime ring, let [Formula: see text] be a noncentral Lie ideal of [Formula: see text] and let [Formula: see text] be two generalized derivations of [Formula: see text]. In this paper, we characterize the structure of [Formula: see text] and all possible forms of [Formula: see text] and [Formula: see text] such that [Formula: see text] for all [Formula: see text], where [Formula: see text] are fixed positive integers. With this, several known results can be either deduced or generalized. In particular, we give a Lie ideal version of the theorem obtained by Lee and Zhou in [An identity with generalized derivations, J. Algebra Appl. 8 (2009) 307–317] and describe a more complete version of the theorem recently obtained by Dhara and De Filippis in [Engel conditions of generalized derivations on left ideals and Lie ideals in prime rings, Comm. Algebra 48 (2020) 154–167].
Suppression of Endothelial Cell FAK Expression Reduces Pancreatic Ductal Adenocarcinoma Metastasis after Gemcitabine Treatment
Authors: Roy-Luzarraga Marina , Reynolds Louise E. , de Luxán-Delgado Beatriz , Maiques Oscar , Wisniewski Laura , Newport Emma , Rajeeve Vinothini , Drake Rebecca J.G. , Gómez-Escudero Jesús , Richards Frances M. , Weller Céline , Dormann Christof , Meng Ya-Ming , Vermeulen Peter B. , Saur Dieter , Sanz-Moreno Victoria , Wong Ping-Pui , Géraud Cyrill , Cutillas Pedro R. , Hodivala-Dilke Kairbaan 
Published: March 2022

Abstract

Despite substantial advances in the treatment of solid cancers, resistance to therapy remains a major obstacle to prolonged progression-free survival. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with a high level of liver metastasis. Primary PDAC is highly hypoxic, and metastases are resistant to first-line treatment, including gemcitabine. Recent studies have indicated that endothelial cell (EC) focal adhesion kinase (FAK) regulates DNA-damaging therapy–induced angiocrine factors and chemosensitivity in primary tumor models. Here, we show that inducible loss of EC-FAK in both orthotopic and spontaneous mouse models of PDAC is not sufficient to affect primary tumor growth but reduces liver and lung metastasis load and improves survival rates in gemcitabine-treated, but not untreated, mice. EC-FAK loss did not affect primary tumor angiogenesis, tumor blood vessel leakage, or early events in metastasis, including the numbers of circulating tumor cells, tumor cell homing, or metastatic seeding. Phosphoproteomics analysis showed a downregulation of the MAPK, RAF, and PAK signaling pathways in gemcitabine-treated FAK-depleted ECs compared with gemcitabine-treated wild-type ECs. Moreover, low levels of EC-FAK correlated with increased survival and reduced relapse in gemcitabine-treated patients with PDAC, supporting the clinical relevance of these findings. Altogether, we have identified a new role of EC-FAK in regulating PDAC metastasis upon gemcitabine treatment that impacts outcome.

Significance:
These findings establish the potential utility of combinatorial endothelial cell FAK targeting together with gemcitabine in future clinical applications to control metastasis in patients with pancreatic ductal adenocarcinoma.
A Phase 1/2 Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma
Authors: Wagner Michael J. , Zhang Yuzheng , Cranmer Lee D. , Loggers Elizabeth T. , Black Graeme , McDonnell Sabrina , Maxwell Shannon , Johnson Rylee , Moore Roxanne , Hermida de Viveiros Pedro , Aicher Lauri , Smythe Kimberly S. , He Qianchuan , Jones Robin L. , Pollack Seth M. 
Published: March 2022

Abstract

Purpose:
Leiomyosarcoma and liposarcoma frequently express PD-L1 but are generally resistant to PD-1/PD-L1 inhibition (immune checkpoint inhibitor). Trabectedin is FDA approved for leiomyosarcoma and liposarcoma. This study aimed to evaluate the safety and efficacy of trabectedin with anti–PD-L1 antibody avelumab in patients with advanced leiomyosarcoma and liposarcoma.

Patients and Methods:
A single-arm, open-label, Phase 1/2 study tested avelumab with trabectedin for advanced leiomyosarcoma and liposarcoma. The phase I portion evaluated safety and feasibility of trabectedin (1, 1.2, and 1.5 mg/m2) with avelumab at standard dosing. Primary endpoint of the phase II portion was objective response rate (ORR) by RECIST 1.1. Correlative studies included T-cell receptor sequencing (TCRseq), multiplex IHC, and tumor gene expression.

Results:
33 patients were evaluable: 24 with leiomyosarcoma (6 uterine and 18 non-uterine) and 11 with liposarcoma. In Phase 1, dose-limiting toxicities (DLT) were observed in 2 of 6 patients at both trabectedin 1.2 and 1.5 mg/m2. The recommended Phase 2 dose (RP2D) was 1.0 mg/m2 trabectedin and 800-mg avelumab. Of 23 patients evaluable at RP2D, 3 (13%) had partial response (PR) and 10 (43%) had stable disease (SD) as best response. Six-month PFS was 52%; median PFS was 8.3 months. Patients with PR had higher Simpson Clonality score on TCRseq from peripheral blood mononuclear cells versus those with SD (0.182 vs. 0.067, P = 0.02) or progressive disease (0.182 vs. 0.064, P = 0.01).

Conclusions:
Although the trial did not meet the primary objective response rate endpoint, PFS compared favorably with prior studies of trabectedin warranting further investigation.
Therapeutic Targeting of Stromal-Tumor HGF-MET Signaling in an Organotypic Triple-Negative Breast Tumor Model
Authors: Singh Sunil , Lamichhane Astha , Rafsanjani Nejad Pouria , Heiss Jacob , Baumann Hannah , Gudneppanavar Ravindra , Leipzig Nic D. , Konopka Michael , Luker Gary D. , Tavana Hossein 
Published: March 2022

Abstract

The tumor microenvironment (TME) promotes proliferation, drug resistance, and invasiveness of cancer cells. Therapeutic targeting of the TME is an attractive strategy to improve outcomes for patients, particularly in aggressive cancers such as triple-negative breast cancer (TNBC) that have a rich stroma and limited targeted therapies. However, lack of preclinical human tumor models for mechanistic understanding of tumor–stromal interactions has been an impediment to identify effective treatments against the TME. To address this need, we developed a three-dimensional organotypic tumor model to study interactions of patient-derived cancer-associated fibroblasts (CAF) with TNBC cells and explore potential therapy targets. We found that CAFs predominantly secreted hepatocyte growth factor (HGF) and activated MET receptor tyrosine kinase in TNBC cells. This tumor–stromal interaction promoted invasiveness, epithelial-to-mesenchymal transition, and activities of multiple oncogenic pathways in TNBC cells. Importantly, we established that TNBC cells become resistant to monotherapy and demonstrated a design-driven approach to select drug combinations that effectively inhibit prometastatic functions of TNBC cells. Our study also showed that HGF from lung fibroblasts promotes colony formation by TNBC cells, suggesting that blocking HGF-MET signaling potentially could target both primary TNBC tumorigenesis and lung metastasis. Overall, we established the utility of our organotypic tumor model to identify and therapeutically target specific mechanisms of tumor–stromal interactions in TNBC toward the goal of developing targeted therapies against the TME.

Implications:
Leveraging a state-of-the-art organotypic tumor model, we demonstrated that CAFs-mediated HGF-MET signaling drive tumorigenic activities in TNBC and presents a therapeutic target.
Angels with Guns: A Memoir on Guy Brett (and David Medalla)
Authors: Bois Yve-Alain 
Published: March 2022

Abstract
In this memoir—which is part diary, part scrapbook—Yve-Alain Bois sifts through his nearly half-a-century correspondence with the British art critic Guy Brett to recount their friendship and evoke the numerous exhibitions the latter curated as well as the many books and catalogues he wrote, from his publications on Kinetic art and Helio Oiticica in the 1960s to his pioneering forays into contemporary art in the global South from the 1970s on. (Four short texts previously published by Bois on Brett's work are interspersed in the narrative). Particular attention is given to the Filipino artist David Medalla and the Brazilian artist Lygia Clark, whom Brett championed all his life and whose work and tribulations are discussed throughout.
Cattleya mireileiana, a new species of Orchidaceae (Laeliinae) from the Southern Espinhaço Complex, Minas Gerais State, Brazil
Authors: MENEZES EULER DA LUZ FERNANDES , GIORDANI SAMUEL CUNHA OLIVEIRA , MENDES JONE CLEBSON RIBEIRO 
Published: March 2022

This study describes and illustrates Cattleya mireileiana (Orchidaceae: Laeliinae), a new species endemic to the Southern Espinhaço Complex near Diamantina, Minas Gerais State, Brazil, where it was found in a few isolated rocky outcrops, sharing habitat with Cattleya rupestres. It is close to three other species: Cattleya bradei, C. briegeri, and C. cruziana. However, the new species differs in the number of nodes present in the pseudobulb components, the size of the diameter, the scent of the flowers and the time of flowering. In addition, its flowers have two unique chromatic characteristics that distinguish it from all other species with yellow flowers in the Parviflorae series: the color of the carinae and the whitish area at the base of the petals and sepals. We provide a detailed morphological description, a distribution map, in situ photographs, and compare it with similar species. We assessed its state of conservation as data deficient (DD), as the only know population consists of at least 150 mature individuals and is outside of an environmentally protected area.
Systemic Steroids for Otolaryngology–Head and Neck Surgery Disorders: An Evidence‐Based Primer for Clinicians
Authors: McCoul Edward D. , Megwalu Uchechukwu C. , Joe Stephanie , Gray Raluca , O'Brien Daniel C. , Ference Elisabeth H. , Lee Victoria S. , Patel Prayag S. , Figueroa‐Morales Marco A. , Shin Jennifer J. , Brenner Michael J. 
Published: March 2022

AbstractObjectiveTo offer pragmatic, evidence‐informed guidance on the use of systemic corticosteroids (SCS) for common otolaryngologic disorders.Data SourcesPubMed, Cochrane Library, and American Academy of Otolaryngology–Head and Neck Surgery Foundation clinical practice guidelines.Review MethodsA comprehensive search of published literature through November 2021 was conducted on the efficacy of SCS, alone or in combination with other treatments, for managing disorders in otolaryngology and the subdisciplines. Clinical practice guidelines, systematic reviews, and randomized controlled trials, when available, were preferentially retrieved. Interventions and outcomes of SCS use were compiled to generate summary tables and narrative synthesis of findings.ConclusionsEvidence on the effectiveness of SCS varies widely across otolaryngology disorders. High‐level evidence supports SCS use for Bell's palsy, sinonasal polyposis, and lower airway disease. Conversely, evidence is weak or absent for upper respiratory tract infection, eustachian tube dysfunction, benign paroxysmal positional vertigo, adenotonsillar hypertrophy, or nonallergic rhinitis. Evidence is indeterminate for acute laryngitis, acute pharyngitis, acute sinusitis, angioedema, chronic rhinosinusitis without polyps, Ménière's disease, postviral olfactory loss, postoperative nerve paresis/paralysis, facial pain, and sudden sensorineural hearing loss.Implications for PracticeClinicians should bring an evidence‐informed lens to SCS prescribing to best counsel patients regarding the risks, anticipated benefits, and limited data on long‐term effects. Alternate routes of corticosteroid administration—such as sprays, drops, inhalers, and intralesional injections—may be preferable for many disorders, particularly those that are self‐limited or require a prolonged duration of therapy. Prudent use of SCS reduces the risk of medication‐related adverse effects. Clinicians who are conversant with high‐level evidence can achieve optimal outcomes and stewardship when prescribing SCS.
A Protocol for Propofol‐Infusion Drug‐Induced Sleep Endoscopy
Authors: Lackey Taylor G. , Duffy James R. , Green Katherine K. 
Published: March 2022

AbstractObjectiveThe objective of this study was to outline a protocol utilizing propofol infusion without an initial bolus during drug‐induced sleep endoscopy (DISE). We define normative values for final propofol infusion rate (Pfinal) during DISE and sedation depth values at Pfinal.Study DesignRetrospective chart review.SettingTertiary academic hospital.MethodsA review of patients with obstructive sleep apnea who underwent DISE between 2016 and 2020 was performed. The following patient data were recorded: demographics; DISE procedure details, including Pfinal, time to Pfinal, frequency and cadence of infusion rate changes, depth of sedation as measured by Bispectral Index and SedLine values, and hemodynamics; and polysomnography details including apnea‐hypopnea index severity and minimum oxygen saturation. A mixed linear model adjusted for age and body mass index was performed for the analysis of effects on Pfinal. Pearson correlation coefficients determined the strength of association between depth of sedation measured and pattern of collapse on DISE and Pfinal.ResultsThere were 246 patients who met inclusion criteria. Pfinal resembled a normal distribution (mean ± SD, 156.44 ± 26.69 mcg/kg/min; median, 150 mcg/kg/min). Analysis demonstrated that Pfinal was influenced by male sex, current smoker status, time to Pfinal, and number of propofol dose changes (P < .05). Depth of sedation categories measured differently between Bispectral Index and SedLine (55‐65 vs 45‐55, P < .001). The pattern including severity of collapse on DISE was not associated with Pfinal (P > .05). No patients required intra‐ or postoperative respiratory support beyond oxygen via nasal canula.ConclusionWe describe a propofol slow‐infusion DISE protocol that demonstrates safe and reproducible outcomes.
A Novel External Auditory Canal Squamous Cell Carcinoma Cell Line Sensitive to CDK4/6 Inhibition
Authors: García‐Marín Rocío , Cabal Virginia N. , Fernández‐Cedrón Bermejo Carmen , Riobello Cristina , Suárez‐Fernández Laura , Codina‐Martínez Helena , Navarro‐García Ainhoa , Lorenzo‐Guerra Sara Lucila , García‐Martínez Jorge , Vivanco Blanca , López Fernando , Llorente José Luis , Hermsen Mario A. 
Published: March 2022

AbstractObjectiveTo characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents.Study DesignPreclinical translational research.SettingBiomedical research institute.MethodsThe cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed.ResultsCAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound‐healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next‐generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high‐level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo‐Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC50 of 0.46 µM.ConclusionThis is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio‐ and chemotherapy or other specific signaling pathway inhibitors.
Factors influencing the Sharp score of 1057 patients with rheumatoid arthritis and anemia: a retrospective study
Authors: Sun Yanqiu , Liu Jian , Xin Ling , Wen Jianting , Zhou Qin , Chen Xiaolu , Ding Xiang , Zhang Xianheng 
Published: March 2022

Objective This study examined the relationship of the Sharp score with demographic factors and clinical immune-inflammatory markers in patients with anemia in rheumatoid arthritis (RA). Methods The clinical data of 1057 patients with RA and anemia and 1006 patients with RA without anemia were retrospectively analyzed. Spearman’s correlation coefficient analysis, association rule analysis, and logistic regression were used to study the relationships between the Sharp score and influencing factors in patients with RA and anemia. Results The incidence of anemia was 51.24% (1057/2063), and mild anemia accounted for 81.93% (866/1057) of cases. Spearman’s correlation coefficient and association rule analyses revealed that the Sharp score of patients with RA and anemia was correlated with immune-inflammatory response and anemia. Logistic regression analysis illustrated that advanced age (>60 years), female, low serum iron levels, C-reactive protein positivity, and immunoglobulin A positivity were risk factors for a high Sharp score (>28.25) in patients with RA and anemia. Conclusion The Sharp score is closely related to clinical disease activity and anemia, and it should be considered in the treatment strategy of patients with RA and anemia.