bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria
Authors: Terhorst‐Molawi Dorothea , Hawro Tomasz , Grekowitz Eva , Kiefer Lea , Merchant Kunal , Alvarado Diego , Thomas Lawrence J. , Hawthorne Thomas , Crowley Elizabeth , Heath‐Chiozzi Margo , Metz Martin , Maurer Marcus 
Published: November 2022

AbstractBackgroundChronic inducible urticaria (CIndU) is characterized by mast cell (MC)‐mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism (SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX‐0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose‐dependent plasma tryptase suppression indicative of systemic mast cell ablation.MethodsThis is an open‐label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12‐week follow‐up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI).ResultsAnalysis populations were safety (n = 21) and pharmacodynamics/clinical activity (n = 20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (<limit of detection), and increased soluble SCF through Week 12. Complete responses (negative provocation test) occurred in 95% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD), and all (n = 20/20) showed improvement in urticaria control (UCT ≥ 12). The kinetics of clinical activity mirrored that of MC and tryptase reduction. DLQI‐measured impairment significantly decreased to minimal/none in 93% of patients on study.ConclusionIn CIndU patients, barzolvolimab was well tolerated, demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, and reductions in clinical activity with significant improvements in disease control and quality of life (QoL) demonstrating potential therapeutic effects for MC‐mediated disorders.
Human leukocyte antigen evolutionary divergence influences outcomes of paediatric patients and young adults affected by malignant disorders given allogeneic haematopoietic stem cell transplantation from unrelated donors
Authors: Merli Pietro , Crivello Pietro , Strocchio Luisa , Pinto Rita Maria , Algeri Mattia , Del Bufalo Francesca , Pagliara Daria , Becilli Marco , Carta Roberto , Gaspari Stefania , Galaverna Federica , Quagliarella Francesco , Boz Giulia , Catanoso Maria Luigia , Boccieri Emilia , Troiano Maria , Fleischhauer Katharina , Andreani Marco , Locatelli Franco 
Published: November 2022

SummaryHigh genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9–10/10 HLA‐matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1, using the locus median to stratify patients with ‘high’ or ‘low’ HED. Patients with high HED‐B and ‐DRB1 showed significantly improved disease‐free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED‐B + ‐DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non‐relapse‐mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED‐B + ‐DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA‐DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.
Discovery of novel DNA‐damaging agents through phenotypic screening for DNA double‐strand break
Authors: Zhang Doudou , Shimokawa Takashi , Guo Qianqian , Dan Shingo , Miki Yoshio , Sunada Shigeaki 
Published: November 2022

AbstractDNA double‐strand breaks (DSBs) seriously damage DNA and promote genomic instability that can lead to cell death. They are the source of conditions such as carcinogenesis and aging, but also have important applications in cancer therapy. Therefore, rapid detection and quantification of DSBs in cells are necessary for identifying carcinogenic and anticancer factors. In this study, we detected DSBs using a flow cytometry‐based high‐throughput method to analyze γH2AX intensity. We screened a chemical library containing 9600 compounds and detected multiple DNA‐damaging compounds, although we could not identify mechanisms of action through this procedure. Thus, we also profiled a representative compound with the highest DSB potential, DNA‐damaging agent‐1 (DDA‐1), using a bioinformatics‐based method we termed “molecular profiling.” Prediction and verification analysis revealed DDA‐1 as a potential inhibitor of topoisomerase IIα, different from known inhibitors such as etoposide and doxorubicin. Additional investigation of DDA‐1 analogs and xenograft models suggested that DDA‐1 is a potential anticancer drug. In conclusion, our findings established that combining high‐throughput DSB detection and molecular profiling to undertake phenotypic analysis is a viable method for efficient identification of novel DNA‐damaging compounds for clinical applications.
Pyrrole‐based EGFR inhibitors for the treatment of NCSLC: Binding modes and SARs investigations
Authors: He Jie , Luo Leixuan , Xu Shidi , Yang Feiyi , Zhu Wufu 
Published: November 2022

AbstractThe treatment of advanced non‐small cell lung cancer (NSCLC) has made substantial progress due to the rapid development of small molecule targeted therapy, with dramatically prolonged survival. As an effective drug for the treatment of NSCLC, epidermal growth factor receptor (EGFR) inhibitors are currently experiencing issues like severe adverse events and drug resistance. It is urgent to develop novel types of EGFR inhibitors to overcome the abovementioned limitations. Pyrrole always works well as a probe for the creation of novel medication candidates for hard‐to‐treat conditions like lung cancer. Although the design, synthesis, and biological assays of pyrrole derivatives have been reported, their inhibitory actions against the receptor tyrosine kinase (RTK) EGFR have not been in‐depthly studied. This review highlights the small molecule EGFR inhibitors containing pyrrole heterocyclic pharmacophores in recent years, and the research on their mechanism, biological activity, and structure–activity relationship (SAR).
Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series
Authors: Sundra Tania , Kelty Erin , Rendle David 
Published: November 2022

SummaryBackgroundHyperinsulinaemia‐associated laminitis (HAL) is encountered commonly in equine practice. There are currently no registered medications which specifically target hyperinsulinaemia in horses and ponies. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to limit post‐prandial insulin responses and prevent the development of diet‐induced laminitis.ObjectivesThe objective of the study was to evaluate the efficacy of an SGLT2i, ertugliflozin, in the management of hyperinsulinaemia and laminitis.Study designRetrospective case series.MethodsMedical records of 51 horses and ponies that had presented with laminitis and hyperinsulinaemia and had been treated with oral ertugliflozin at 0.05 mg/kg once daily for a minimum of 30 days were reviewed.ResultsAfter 30 days of treatment with ertugliflozin, there was a reduction in insulin concentrations from a median of >300 μu/ml (IQR: 149, >300) to 43 μu/ml (IQR: 20, 66) (p < 0.001). Modified Obel laminitis scores improved, reducing from a median of 10/12 to 1/12 (p < 0.001). Median serum triglyceride concentrations increased from 0.6 (IQR: 0.4, 0.9) before treatment to 1.4 (IQR: 0.8, 3.7) mmol/L after 30 days of treatment (p < 0.001) before declining, however, none of the horses developed any clinical signs of hyperlipaemia. Ten horses (19%) were reported to have polyuria and polydipsia during treatment, otherwise no adverse clinical effects were identified.Main limitationsThe study was limited by the absence of a control group, the retrospective data collection and the short period of follow‐up.ConclusionsErtugliflozin may be effective in reducing insulin concentrations in horses and ponies with equine metabolic syndrome and its use may hasten recovery from laminitis associated with hyperinsulinaemia.
Theses and dissertations completed in family and consumer sciences: 2021
Authors: Wilmarth Melissa J. , Milstead Morgan 
Published: November 2022

AbstractGraduate student degree completion and research has been collected annually since 1992. This year's data collection began with an e‐mail invitation to 593 institutional contacts at 165 U.S. universities and colleges in June 2022. This e‐mail requested information on family and consumer sciences graduate degrees and research completed in 2021. A total of 150 master's theses, 122 doctoral dissertations, and 664 non‐thesis master's degrees were conferred in 2021 from family and consumer sciences programs. This report presents the submitted information on theses and dissertations categorized into 16 subject‐matter categories by degree level.
Opposing seasonal temperature dependencies of CO2 and CH4 emissions from wetlands
Authors: Li Jinquan , Pei Junmin , Fang Changming , Li Bo , Nie Ming 
Published: November 2022

AbstractWetlands are critically important to global climate change because of their role in modulating the release of atmospheric greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4). Temperature plays a crucial role in wetland GHG emissions, while the general pattern for seasonal temperature dependencies of wetland CO2 and CH4 emissions is poorly understood. Here we show opposite seasonal temperature dependencies of CO2 and CH4 emissions by using 36,663 daily observations of simultaneous measurements of ecosystem‐scale CO2 and CH4 emissions in 42 widely distributed wetlands from the FLUXNET‐CH4 database. Specifically, the temperature dependence of CO2 emissions decreased with increasing monthly mean temperature, but the opposite was true for that of CH4 emissions. Neglecting seasonal temperature dependencies may overestimate wetland CO2 and CH4 emissions compared to the use of a year‐based static and consistent temperature dependence parameter when only considering temperature effects. Our findings highlight the importance of incorporating the remarkable seasonality in temperature dependence into process‐based biogeochemical models to predict feedbacks of wetland GHG emissions to climate warming.
‘It feels like my metabolism has shut down’. Negotiating interactional roles and epistemic positions in a primary care consultation
Authors: Lian Olaug S. , Nettleton Sarah , Grange Huw , Dowrick Christopher 
Published: November 2022

AbstractIntroductionOur aim is to explore the ways in which a patient and a general practitioner (GP) negotiate knowledge claims stemming from different epistemic domains while dealing with a mismatch between experiential and biomedical knowledge during the clinical consultation. We interpret their interaction in relation to the sociocultural context in which their negotiation is embedded and identify factors facilitating their successful negotiation (a medical error is avoided).MethodsBased on a narrative analysis of a verbatim transcript of a complete naturally occurring primary care consultation, we explore the moment‐to‐moment unfolding of talk between the patient and the GP (two women).FindingsThe patient experiences symptoms of what she interprets as a thyroid condition, and indirectly asks for medication. She presents her case by drawing on experiential knowledge (‘it feels like my metabolism has shut down’) and biomedical knowledge (while suggesting a diagnosis and a diagnostic test). The GP informs her that her thyroid blood tests are normal and uses biomedical knowledge to explain why she turns down the patient's request. This stages a potential conflict between the patient's embodied experiential knowledge and the doctor's biomedical knowledge. However, during their encounter, the patient and the GP manage to co‐construct the patient's illness story and make shared decisions about further actions.ConclusionThe transition from potential conflict to consensus is a result of the mutual efforts of two parties: a patient who persistently claims experiential as well as biomedical knowledge while at the same time deferring to the GP's professional knowledge, and a GP who maintains her epistemic authority while also acknowledging the patient's experiential and biomedical knowledge.Patient and Public ContributionOur empirical data are sourced from a data archive and patients were not involved in the design or conduct of the study, but our study is based on a naturally occurring clinical consultation with a patient.
The effect of two different root canal sealers on treatment outcome and post‐obturation pain in single‐visit root canal treatment: A prospective randomized clinical trial
Authors: Coşar Melis , Kandemir Demirci Gözde , Çalışkan Mehmet Kemal 
Published: November 2022

AbstractAimThis randomized clinical trial aimed to evaluate and compare the effect of mineral trioxide aggregate (MTA)‐based bioceramic‐ and resin‐based sealers on the incidence and intensity of post‐obturation pain and treatment outcome in asymptomatic vital molar teeth in single‐visit root canal treatment.MethodologyOne hundred asymptomatic mandibular molar teeth with vital pulp were randomly assigned into two groups according to the sealer used: MTA Fillapex or AH Plus sealer. WaveOne Gold instruments were used for root canal preparations. Root canals were obturated with WaveOne Gold gutta‐percha cones corresponding in size and taper to the last instrument used. MTA Fillapex was used in the first group and AH Plus was used in the second group as the root canal sealer. The effects of age, gender, tooth types and the level of root canal filling on the treatment outcome were evaluated after 1 and 2 years. Postoperative pain at 6, 12, 24, 48, 72 h, 4, 5, 6, 7 and 30 days after root canal treatment was measured with the Numerical Rating Scale. Chi‐square test was used for the treatment outcome and Mann–Whitney U, chi‐Square and Spearman correlation analyses were used for postoperative pain. α = .05 was the level of significance.ResultsTwelve patients did not complete the 2‐year follow‐up and the study finished with 88 patients. In the MTA Fillapex group 41 correct, one short, two extruded, and in the AH Plus group 40 correct, one short and three extruded root canal fillings were detected. No significant differences were observed between the first‐ and second‐year treatment outcomes between the groups (p > .05).There was no association between age, gender, tooth number, root canal filling length and the treatment success in all evaluated teeth (p > .05). The differences between the groups in terms of postoperative pain incidence and intensity at all time‐points were not significant (p > .05). There was no correlation between the age and postoperative pain (p > .05), but pain was statistically higher in women (p < .05).ConclusionsMineral trioxide aggregate Fillapex showed similar success rate and post‐obturation pain incidence and intensity as AH Plus sealer and can be used as a root canal sealer in asymptomatic mandibular molars with irreversible pulpitis.
Imagining the ecosocial within social work
Authors: Thysell Maria , Cuadra Carin Björngren 
Published: November 2022

AbstractAiming to explore how the ecosocial is imagined within social work research, this article engages with understandings of the relationship between the social and ecological realms when responding to the call for sustainability. A theoretical framework offering five possible imaginations of the ecosocial was developed: the holistic; the anthropocentric conflictual; the anthropocentric compatible; the ‘ecocentric’ conflictual; and the ‘ecocentric’ compatible. The material consists of international peer‐reviewed articles referring to the ecosocial. The result reveals that the imagination of the ecosocial is heterogeneous. However, the holistic and anthropocentric compatible imaginations are common, while ‘ecocentric’ and conflictual understandings are rare, which confirms that nurturing social and ecological sustainability does not entail conflicting interests or rivalry but rather the opposite. This implies not only an ongoing widening of the notion of sustainability, in which the idea of limitations is re‐installed, but also a possible re‐definition of ‘the social’ so as to include the non‐human.
Higher risk for influenza‐associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients
Authors: Waldeck Frederike , Boroli Filippo , Zingg Sandra , Walti Laura N. , Wendel‐Garcia Pedro David , Conen Anna , Pagani Jean‐Luc , Boggian Katia , Schnorf Madeleine , Siegemund Martin , Abed‐Maillard Samia , Michot Marc , Que Yok‐Ai , Bättig Veronika , Suh Noémie , Kleger Gian‐Reto , Albrich Werner C. 
Published: November 2022

AbstractBackgroundInfluenza‐associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality.MethodsWe conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR‐confirmed influenza infection and treatment on intensive‐care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in‐hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation.ResultsOne hundred fifty‐eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non‐IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1–67.2]) and days of mechanical ventilation (OR 1.1 [1.1–1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non‐IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU‐mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3–253.4]), influenza A (OR 3.3 [1.4–7.8]), and higher SAPS II score (OR 1.07 [1.05–1.10]) were independent predictors of poor outcome.InterpretationHigh clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.
On Gratitude to Nature
Authors: Lewis Max 
Published: November 2022

ABSTRACTIn this article, I argue that it cannot be fitting to be grateful to nature. I start by arguing that gratitude to someone/something can be fitting even if they do not intentionally benefit one. I then argue that a recent view on which it can be fitting to be grateful to nature faces counterexamples. Finally, I argue that it cannot be fitting to be grateful to nature, because it is fitting to be grateful to someone/something only if they manifest the right kind of goodwill or care toward one. In particular, I argue that it is fitting to be grateful to someone/something only if they manifest a level of final care toward one beyond what can be legitimately expected or demanded of them. However, because nature does not manifest any level of goodwill or care, it cannot be fitting to be grateful to nature. I end by noting that it can still be fitting to be grateful that certain things are true about nature (e.g. that it provides many benefits to humans).
The US Impact on Qatar's Foreign Policy During the Gulf Crisis
Authors: Aljassar Nouf , Rosenson Beth 
Published: November 2022

AbstractThis article explains the Gulf diplomatic crisis and its repercussions by tracing its various stages. It also analyzes the inconsistency of US policy during the Trump administration toward this crisis and how this taught Qatar not to rely entirely on the United States to achieve security. These challenges pushed Qatar to diversify its international alliances and to create a rapprochement with countries in the region, such as Turkey, to achieve military security. Qatar's status as an energy provider to Asia and an alternative to Russian oil and gas, along with its soft power, also strengthened its strategic position. Eventually, the article explains, Qatar was able to strengthen its relationship with the United States once the Biden administration took power. The study concludes that Qatar has become a model for small countries in the region.
Genetic time traveling: sequencing old herbarium specimens, including the oldest herbarium specimen sequenced from kingdom Fungi, reveals the population structure of an agriculturally significant rust
Authors: Bradshaw Michael J. , Carey Julie , Liu Miao , Bartholomew Holly P. , Jurick Wayne M. , Hambleton Sarah , Hendricks Dylan , Schnittler Martin , Scholler Markus 
Published: November 2022

Summary

Sequencing herbarium specimens can be instrumental in answering ecological, evolutionary, and taxonomic inquiries. We developed a protocol for sequencing herbarium specimens of rust fungi (Pucciniales) and proceeded to sequence specimens ranging from 4 to 211 yr old from five different genera.

We then obtained sequences from an economically important biological control agent, Puccinia suaveolens, to highlight the potential of sequencing herbarium specimens in an ecological sense and to evaluate the following hypotheses: (1) The population structure of a plant pathogen changes over time, and (2) introduced pathogens are more diverse in their native range.

Our efforts resulted in sequences from 87 herbarium specimens that revealed a high level of diversity with a population structure that exhibited spatial–temporal patterns. The specimens sequenced from Europe showed more diversity than the ones from North America, uncovering an invasion pattern likely related to its European native host in North America. Additionally, to the best of our knowledge, the specimen from France collected in c. 1811 is the oldest herbarium specimen sequenced from kingdom Fungi.

In conclusion, sequencing old herbarium specimens is an important tool that can be extrapolated to better understand plant–microbe evolution and to evaluate old type specimens to solidify the taxonomy of plant pathogenic fungi.