bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐5 as a pleiotropic cytokine orchestrating airway type 2 inflammation: Effects on and beyond eosinophils
Authors: Buchheit Kathleen M. , Shaw Dominick , Chupp Geoffrey , Lehtimaki Lauri , Heffler Enrico , Finney‐Hayward Tricia , Zangrilli James , Kwiatek Justin , Siddiqui Salman , Roufosse Florence , Thamboo Andrew , West Nicholas , Vichiendilokkul Anna , Hellings Peter W. , Peters Anju , Howarth Peter H. 
Published: October 2024

AbstractInterleukin (IL)‐5 is the key cytokine in the maturation, activation, proliferation, migration and survival of eosinophils, which are key effector cells in many upper and lower airway diseases. Through its effects on eosinophils, IL‐5 indirectly contributes to various pathophysiological processes including tissue damage, repair and remodelling. Understanding the importance of IL‐5 in eosinophil‐associated diseases led to the development of anti‐IL‐5 therapies, which provide clinical benefits across a range of conditions. However, recent evidence suggests that eosinophil‐depletion alone may not account for all of the therapeutic effects of anti‐IL‐5 therapy and that IL‐5 may also contribute to disease independently of its effects on eosinophils. Indeed, evidence from ex vivo studies and targeted therapy in vivo demonstrates that IL‐5 and its inhibition affects a much broader range of cells beyond eosinophils, including epithelial cells, plasma cells, mast cells, basophils, neutrophils, type 2 innate lymphoid cells, T regulatory cells and fibroblasts. This review will provide an update on the evidence supporting the breadth of IL‐5 biology relevant to disease pathogenesis beyond eosinophil‐associated inflammation, where there is a need for additional insight, and the clinical implications of a more central role of IL‐5 in type 2 inflammation.
Notch4 regulatory T cells and SARS‐CoV‐2 viremia shape COVID19 survival outcome
Authors: Benamar Mehdi , Lai Peggy S. , Huang Ching‐Ying , Chen Qian , Oktelik Fatma Betul , Contini Paola , Wang Muyun , Okin Daniel , Crestani Elena , Fong Jason , Fion Tsz Man Chan , Gokbak Merve Nida , Harb Hani , Phipatanakul Wanda , Marri Luca , Vassallo Chiara , Guastalla Andrea , Kim Minsik , Sui Hui‐Yu , Berra Lorenzo , Goldberg Marcia B. , Angelini Claudia , De Palma Raffaele , Chatila Talal A. 
Published: October 2024

AbstractBackgroundImmune dysregulation and SARS‐CoV‐2 plasma viremia have been implicated in fatal COVID‐19 disease. However, how these two factors interact to shape disease outcomes is unclear.MethodsWe carried out viral and immunological phenotyping on a prospective cohort of 280 patients with COVID‐19 presenting to acute care hospitals in Boston, Massachusetts and Genoa, Italy between June 1, 2020 and February 8, 2022. Disease severity, mortality, plasma viremia, and immune dysregulation were assessed. A mouse model of lethal H1N1 influenza infection was used to analyze the therapeutic potential of Notch4 and pyroptosis inhibition in disease outcome.ResultsStratifying patients based on %Notch4+ Treg cells and/or the presence of plasma viremia identified four subgroups with different clinical trajectories and immune phenotypes. Patients with both high %Notch4+ Treg cells and viremia suffered the most disease severity and 90‐day mortality compared to the other groups even after adjusting for baseline comorbidities. Increased Notch4 and plasma viremia impacted different arms of the immune response in SARS‐CoV‐2 infection. Increased Notch4 was associated with decreased Treg cell amphiregulin expression and suppressive function whereas plasma viremia was associated with increased monocyte cell pyroptosis. Combinatorial therapies using Notch4 blockade and pyroptosis inhibition induced stepwise protection against mortality in a mouse model of lethal H1N1 influenza infection.ConclusionsThe clinical trajectory and survival outcome in hospitalized patients with COVID‐19 is predicated on two cardinal factors in disease pathogenesis: viremia and Notch4+ Treg cells. Intervention strategies aimed at resetting the immune dysregulation in COVID‐19 by antagonizing Notch4 and pyroptosis may be effective in severe cases of viral lung infection.
p38α kinase governs muscle strength through PGC1α in mice
Authors: Herrera‐Melle Leticia , Cicuéndez Beatriz , López Juan Antonio , Dumesic Phillip A. , Wilensky Sarah E. , Rodríguez Elena , Leiva‐Vega Luis , Caballero Ainoa , León Marta , Vázquez Jesús , Spiegelman Bruce M. , Folgueira Cintia , Mora Alfonso , Sabio Guadalupe 
Published: October 2024

AbstractAimsSkeletal muscle, with its remarkable plasticity and dynamic adaptation, serves as a cornerstone of locomotion and metabolic homeostasis in the human body. Muscle tissue, with its extraordinary capacity for force generation and energy expenditure, plays a fundamental role in the movement, metabolism, and overall health. In this context, we sought to determine the role of p38α in mitochondrial metabolism since mitochondrial dynamics play a crucial role in the development of muscle‐related diseases that result in muscle weakness.MethodsWe conducted our study using male mice (MCK‐cre, p38αMCK‐KO and PGC1α MCK‐KO) and mouse primary myoblasts. We analyzed mitochondrial metabolic, physiological parameters as well as proteomics, western blot, RNA‐seq analysis from muscle samples.ResultsOur findings highlight the critical involvement of muscle p38α in the regulation of mitochondrial function, a key determinant of muscle strength. The absence of p38α triggers changes in mitochondrial dynamics through the activation of PGC1α, a central regulator of mitochondrial biogenesis. These results have substantial implications for understanding the complex interplay between p38α kinase, PGC1α activation, and mitochondrial content, thereby enhancing our knowledge in the control of muscle biology.ConclusionsThis knowledge holds relevance for conditions associated with muscle weakness, where disruptions in these molecular pathways are frequently implicated in diminishing physical strength. Our research underscores the potential importance of targeting the p38α and PGC1α pathways within muscle, offering promising avenues for the advancement of innovative treatments. Such interventions hold the potential to improve the quality of life for individuals affected by muscle‐related diseases.
Evaluation of Quinoline‐Related Carboxylic Acid Derivatives as Prospective Differentially Antiproliferative, Antioxidative, and Anti‐Inflammatory Agents
Authors: Arabiyat Shereen , Alzoubi Ahmad , Al‐Daghistani Hala , Al‐Hiari Yusuf , Kasabri Violet , Alkhateeb Rema 
Published: October 2024

ABSTRACTThe higher prevalence of cancer and the unmet need for antioxidant/anti‐inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half‐maximal inhibitory concentration (IC50 value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline‐4‐carboxlic and quinoline‐3‐carboxylic acids) exerted impressively appreciable anti‐inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline‐2‐carboxylic acid, quinoline‐4‐carboxylic acid, quinoline‐3‐carboxylic acid, and 1,2‐dihydro‐2‐oxo‐4‐quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline‐2‐carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co‐planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti‐inflammation pharmacologies of quinoline derivatives. Activity‐guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies.
Child–father and child–mother attachment relationships in naturalistic settings
Authors: Trumbell Jill M. , Posada German , Anaya Laura , Kim Geurim , Liu Muqing 
Published: October 2024

AbstractThis study examines paternal and maternal sensitivity as predictors of toddlers' attachment security in two naturalistic contexts. Seventy‐three mostly White middle‐class families participated between 2015 and 2019 when children (49.3% girls) were approximately 29.48 months old. Each child–parent dyad completed a home and playground visit. Findings revealed paternal and maternal sensitivity were significantly associated at home and marginally at the playground. Paternal sensitivity was only predictive of security to the father at the playground, showing a medium effect, while small effects of maternal sensitivity on security to the mother were found in both contexts. Cross‐parent contributions to security were small and limited to the playground. The need to consider the greater ecology of child–parent relationships and suggestions for larger‐scale research are discussed.
Adrenal Vein Sampling for Primary Aldosteronism: Recommendations From the Australian and New Zealand Working Group
Authors: Yang Jun , Bell Damon A. , Carroll Richard , Chiang Cherie , Cowley Diane , Croker Emma , Doery James C. G. , Elston Marianne , Glendenning Paul , Hetherington Julie , Horvath Andrea R. , Lu‐Shirzad Shanshan , Ng Elisabeth , Mather Amanda , Perera Nimalie , Rashid Muddassir , Sachithanandan Nirupa , Shen Jimmy , Stowasser Michael , Swarbrick Michael J. , Tan Hong Lin Evelyn , Thuzar Moe , Young Simon , Chong Winston 
Published: October 2024

ABSTRACTAdrenal vein sampling (AVS) is the current recommended procedure for identifying unilateral subtypes of primary aldosteronism (PA), which are amenable to surgery with the potential for cure. AVS is a technically challenging procedure usually undertaken by interventional radiologists at tertiary centres. However, there are numerous variations in AVS protocols relating to patient preparation, sampling techniques and interpretation which may impact the success of AVS and patient care. To reduce practice variations, improve the success rates of AVS and optimise patient outcomes, we established an Australian and New Zealand AVS Working Group and developed evidence‐based expert consensus recommendations for the preparation, performance and interpretation of AVS. These recommendations can be used by all healthcare professionals in a multidisciplinary team who look after the diagnosis and management of PA.
Evaluation of Multiple Tissue Levels Frequently Upstages Patients With Clinically Localized Thin Primary Cutaneous Melanoma
Authors: Jackett Louise A. , Gullifer James P. , Scolyer Richard A. 
Published: October 2024

ABSTRACTBackgroundBreslow thickness (BT), ulceration, and microsatellitosis are critical prognostic parameters for cutaneous melanoma staging. These parameters can vary depending on the number of tissue levels examined from individual paraffin blocks. We sought to evaluate all prognostic histopathologic parameters in melanoma for their variations between levels, taken at regular intervals, in a single study.MethodsWe analyzed 40 consecutive cases of primary cutaneous (nonacral) melanoma through five hematoxylin and eosin sections, taken at 100 μm intervals, for staging and prognostic parameters.ResultsExamination of additional levels resulted in (a) an increase in BT in 47.5% (19 out of 40) of cases and (b) detection of ulceration in a further 5% (2/40). This resulted in upstaging for 20% (8 out of 40) of patients (15% because of BT, 2.5% because of ulceration, and 2.5% because of BT and ulceration). The upstaging effect was incremental, with approximately 5% of patients upstaged with each additional 100 μm interval (up to 400 μm). Incipient ulceration and epidermal consumption were infrequent (10% of cases); however, when present, ulceration was subsequently observed in half of cases. We encountered no cases where microsatellitosis was detected at deeper levels.ConclusionThe performance of additional tissue levels is a simple and inexpensive procedure that can improve the accuracy of staging for patients with thin (pT1) primary cutaneous melanomas. It may be pertinent for pathologists to consider additional levels for thin melanomas when a BT measurement is close to a staging threshold (e.g., within 0.1–0.3 mm for pT1a vs. pT1b, or pT1b vs. pT2a), or when incipient ulceration is encountered.
Mothers' experiences of stigma and blame: The views of mothers of people who use substances
Authors: O'Dowd Edith , Hunter Simon C. , Canfield Martha 
Published: October 2024

AbstractObjectiveThe objective of this study is to make the distinction between courtesy stigma and parent‐blame, two related but unique forms of judgment, and to explore the consequence of courtesy stigma and parent‐blame.BackgroundHaving a child who uses substances has been linked to numerous adverse mental and physical health implications for family members. Parents, in particular, are at great risk of experiencing negative consequences including courtesy stigma and parent‐blame.MethodWe conducted in‐depth interviews with eight mothers of individuals who use substances. Data were analyzed using thematic analysis.ResultsThree primary themes were identified: the spreading impact of stigma, parent‐blame, and coping with stigma and blame.ConclusionIn this study we were able to distinguish between courtesy stigma and parent‐blame when considering the experiences of mothers of people who use substances. Findings suggest that stigma and blame leave mothers feeling judged and alone when navigating complex family dynamics.ImplicationsFamily support organizations offer accepting spaces that counter judgment and generate a sense of connectedness. Our findings stress the importance of professionals cultivating an awareness of the consequence of stigma and blame when working with mothers of people who use substances.
Parentification and satisfaction of psychological needs in romantic relationships: The mediating role of relational attitudes
Authors: Tolmacz Rami , Hasson Shaked , Cohen Michal , Mikulincer Mario 
Published: October 2024

AbstractObjectiveWe examined the association between adult women's reports of parentification during childhood and the extent to which basic psychological needs are satisfied in romantic relationships. We also explored the mediating role of sense of relational entitlement, pathological concern, and authenticity in relational contexts.BackgroundNegative implications of adults' sense of being parentified as children have been observed in relational feelings, cognitions, and behavior.MethodA convenience sample of 225 Israeli young adult women completed self‐report scales tapping retrospective accounts of parentification, basic psychological needs in romantic relationships, sense of relational entitlement, pathological concern, and relational authenticity. The data were analyzed with Pearson correlations and a mediation analysis.ResultsParentification was associated with lower levels of need satisfaction and authenticity within romantic relationships and higher levels of pathological concern and either a restricted or inflated sense of relational entitlement. An inflated sense of relational entitlement and lack of authenticity mediated the association between women's reports of parentification and the extent to which they feel their personal needs are satisfied in romantic relationships.ConclusionWomen who feel parentified during childhood tend to show negative expectations of relational mutuality and experience difficulties in disclosing their personal needs and wishes to a partner, which seem to lead them to feel that their basic psychological needs are not satisfied in romantic relationships.ImplicationsFindings highlight the problematic nature of feelings of being parentified as children and the importance of helping people who hold these feeling to communicate their relational needs to a romantic partner.
Living With Multiple Sclerosis: The Rainbow of Inspiring Experiences and Resilience in the Face of the Disease
Authors: Zare Leily , Nayeri Nahid Dehghan , Bahramnezhad Fatemeh , Rasti Arezoo 
Published: October 2024

ABSTRACTIntroductionMultiple sclerosis (MS), a leading cause of disability in young adults worldwide, including in Iran, affects their whole life so common care is no longer effective. In this regard, context‐based approaches should be considered for a holistic care delivery that accords with the patients' inputs. We aimed to explore patients' understanding of MS and their personal experiences of living with this disease.MethodsA qualitative descriptive study was conducted. The data were collected through in‐depth, semi‐structured interviews with 17 patients. These patients were selected using a purposive sampling method, and the data were analyzed using a conventional content analysis approach.FindingsThree main categories and nine subcategories were identified: Thunder and Lightning strike in the form of Displeasure, Social wrong beliefs, Experiences of Constraints, Interference with Life Stages and Dark Spots on the Horizon of the Future; Subtle Beam consisting of Extrinsic Light Radiation, Reflection of Individual Effort and Formation of a Rainbow by Resilience and Hope for a Bright Future.ConclusionBy offering multidimensional support, patients reported a shift from fear to a vibrant life. Although research often focuses on the negative aspects of MS, this study recognizes both positive and negative aspects. These findings can contribute to future interventional research.Patient or Public ContributionDuring the explanation of research goals and consent acquisition, participants were reminded that sharing their experiences could provide valuable insights benefiting others coping with or at risk of the same disease. Additionally, during data analysis, codes extracted were reviewed and improved with active participant involvement.
Disrupted Candidacy: A Longitudinal Examination of the Constrained Healthcare‐Access Journeys of National Health Service Workers in Scotland Seeking Supports for Long COVID Illness
Authors: Adams Nicholas Norman , MacIver Emma , Douglas Flora , Kennedy Catriona , Skåtun Diane , Hernandez Santiago Virginia , Torrance Nicola , Grant Aileen 
Published: October 2024

ABSTRACTIntroductionEvidence examines how persons experiencing Long COVID (LC) struggle to secure healthcare for symptoms. However, few studies examine healthcare workers experiencing LC, nor the complex and multiple difficulties faced when seeking and receiving healthcare.MethodsThis study is based on two phases of longitudinally conducted qualitative interviews, 6 months apart, with National Health Service (NHS) workers experiencing LC, from different occupational roles at NHS locales in Scotland (first interviews, n = 50; second interviews, n = 44).ResultsMultiple factors restricted healthcare access, including worries about pressuring the NHS and concerns over LC being legitimised. When healthcare was sought, workers struggled to secure support, referrals and treatment. The following reasons were included: (1) context: the restrictive pandemic healthcare context; (2) illness climate: low GP knowledge surrounding LC and how this could be treated, trends for ascribing symptoms to other causes and reluctance to diagnose LC; (3) sense‐making of LC: healthcare availability linked to occupational role identity. To visualise and examine healthcare barriers, candidacy theory is applied, drawing inferences between healthcare context, illness climate, sense‐making and identities.ConclusionNHS workers' complex journeys represent Disrupted Candidacy, intersecting challenges across candidacy domains, restricting the seeking and receiving of LC healthcare. Findings provide insights into why NHS workers resisted and withdrew from healthcare‐seeking, and the barriers they faced when attempting to secure LC support. This study presents a pathway for future LC illness research to use a modified candidacy theory framework.Patient and Public ContributionThis research focuses on amplifying and learning from lived experiences, and the voices of NHS workers in Scotland experiencing LC. Interviews represent primary data for this study; thus, participants and their healthcare journeys are centred in this research and all aspects of production, reporting and output. Explicit discussions of stakeholder group involvement are highlighted in the methods section.
Effect of temperature and pH value on the stability of magnesium potassium phosphate hexahydrate
Authors: Pang Bo , Zhao Yuanhong , Zhang Guanhua , Guo Jinbo , Liu Runqing 
Published: October 2024

AbstractMagnesium potassium phosphate hexahydrate (MgKPO4·6H2O) was used as solidification matrix to immobilize some radioactive element and some heavy metal ions, the stability of MgKPO4·6H2O under different conditions had become the focus. This work gives new insights on the stability of synthesized MgKPO4·6H2O in the different temperatures and pH values solutions. The solid phase transformed from synthesized MgKPO4·6H2O was characterized by X‐ray diffractometer (XRD), thermal gravity analysis (TG/DSC), Fourier‐transform infrared spectrum (FTIR) and scanning electron microscope (SEM) at different temperature and pH values solution. Results indicated MgKPO4·6H2O had almost no phase transition at the temperature of 50°C and 60°C. Mg3(PO4)2·22H2O appears with the increase of solution temperature. The main phase is MgKPO4·6H2O at the pH of 9 and 12, minor MgHPO4·3H2O formed at the pH of 6, next Mg3(PO4)2·22H2O formed at the pH of 3 and 6. High pH value environment is beneficial for the maintenance of MgKPO4·6H2O. This study is an important guidance for the application of MgKPO4·6H2O crystal.