bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin restriction by miR‐34 protects germline progenitors from cell death during aging
Authors: Perry Noam , Braun Racheli , Ben‐Hamo‐Arad Aya , Kanaan Diana , Arad Tal , Porat‐Kuperstein Lilach , Toledano Hila 
Published: March 2024

AbstractDuring aging, regenerative tissues must dynamically balance the two opposing processes of proliferation and cell death. While many microRNAs are differentially expressed during aging, their roles as dynamic regulators of tissue regeneration have yet to be described. We show that in the highly regenerative Drosophila testis, miR‐34 levels are significantly elevated during aging. miR‐34 modulates germ cell death and protects the progenitor germ cells from accelerated aging. However, miR‐34 is not expressed in the progenitors themselves but rather in neighboring cyst cells that kill the progenitors. Transcriptomics followed by functional analysis revealed that during aging, miR‐34 modifies integrin signaling by limiting the levels of the heterodimeric integrin receptor αPS2 and βPS subunits. In addition, we found that in cyst cells, this heterodimer is essential for inducing phagoptosis and degradation of the progenitor germ cells. Together, these data suggest that the miR‐34—integrin signaling axis acts as a sensor of progenitor germ cell death to extend progenitor functionality during aging.
Public support for and concerns regarding pediatric dose optimization for seizures in emergency medical services: An exception from informed consent (EFIC) trial
Authors: Ward Caleb E. , Adelgais Kathleen M. , Holsti Maija , Jacobsen Kammy K. , Simon Harold K. , Morris Claudia R. , Gonzalez Victor M. , Lerner Gonzalo , Ghaffari Kimia , VanBuren John M. , Lerner E. Brooke , Shah Manish I. ,   the Pediatric Emergency Care Applied Research Network (PECARN) PediDOSE Study Group
Published: March 2024

AbstractBackgroundFederal regulations allow exception from informed consent (EFIC) to study emergent conditions when obtaining prospective consent is not feasible. Little is known about public views on including children in EFIC studies. The Pediatric Dose Optimization for Seizures in EMS (PediDOSE) trial implements age‐based, standardized midazolam dosing for pediatric seizures. The primary objective of this study was to determine public support for and concerns about the PediDOSE EFIC trial. The secondary objective was to assess how support for PediDOSE varied by demographics.MethodsWe conducted a mixed‐methods study in 20 U.S. communities. Participants reviewed information about PediDOSE before completing an online survey. Descriptive data were generated. Univariable and multivariable logistic regression analysis identified factors associated with support for PediDOSE. Reviewers identified themes from free‐text response data regarding participant concerns.ResultsOf 2450 respondents, 79% were parents/guardians, and 20% had a child with previous seizures. A total of 96% of respondents supported PediDOSE being conducted, and 70% approved of children being enrolled without prior consent. Non‐Hispanic Black respondents were less likely than non‐Hispanic White respondents to support PediDOSE with an adjusted odds ratio (aOR) of 0.57 (95% CI 0.42–0.75). Health care providers were more likely to support PediDOSE, with strongest support among prehospital emergency medicine clinicians (aOR 5.82, 95% CI 3.19–10.62). Age, gender, parental status, and level of education were not associated with support of PediDOSE. Common concerns about PediDOSE included adverse effects, legal and ethical concerns about enrolling without consent, and potential racial bias.ConclusionsIn communities where this study will occur, most respondents supported PediDOSE being conducted with EFIC and most approved of children being enrolled without prior consent. Support was lowest among non‐Hispanic Black respondents and highest among health care providers. Further research is needed to determine optimal ways to address the concerns of specific racial and ethnic groups when conducting EFIC trials.
Diet quality and blood pressure among pregnant women with overweight or obesity: A secondary analysis of two randomized controlled trials
Authors: Lynch Sorcha , Killeen Sarah Louise , O'Brien Eileen , Mullane Kate , Hokey Emma , Mealy Grace , McAuliffe Fionnuala M. 
Published: March 2024

AbstractIntroductionMaternal obesity is a significant risk factor for hypertensive disorders of pregnancy. High diet quality may protect against this, yet data regarding the relationship between diet quality and blood pressure among pregnant women with raised body mass index (BMI) is limited.Material and methodsThis is a secondary analysis (n = 543) of women with BMI ≥25 kg/m2 from two randomized controlled trials; PEARS (Pregnancy Exercise and nutrition Research Study with smartphone application support) and ROLO (Randomized cOntrol trial of LOw glycemic index diet to prevent macrosomia in euglycemic women). Blood pressure was measured at 10–18 weeks and 28 weeks of pregnancy. Mean arterial pressure was calculated as (diastolic blood pressure [systolic blood pressure  diastolic blood pressure]). Diet quality was assessed using 3‐day food diaries, and Alternative Healthy Eating Index for Pregnancy (AHEI‐P) scores were generated, quantifying alignment of food intakes with dietary guidelines in first and early third trimesters. The cohort was divided based on AHEI‐P tertiles to explore differences at an alpha significance value of <0.05.ResultsThe mean age of the group was 32.21 ± 4.39 years with a median body mass index (BMI) of 28.13 (IQR 3.47) kg/m2. Mean arterial pressures in the first and third trimesters were 81.07 ± 9.00 mmHg and 82.33 ± 7.53 mmHg, respectively. Rates of elevated blood pressure (≥120/80 mmHg) were 22.33% in trimester 1 and 24.48% in early trimester 3. Mean AHEI‐P scores in trimester 1 and early trimester 3 were 53.90 ± 10.43 and 54.05 ± 10.76, respectively. There was no correlation between AHEI‐P score and blood pressure and no differences in blood pressure between AHEI‐P tertiles at either timepoint (all P‐values <0.05). A higher proportion of those with elevated early third trimester blood pressure had a BMI of ≥30 kg/m2 compared with those with normal blood pressure (40.31% vs 28.64%, P = 0.016).ConclusionsWhile diet remains an important factor in maternal health and wellbeing, we did not find a relationship between diet quality as measured by AHEI‐P and blood pressure among pregnant women with BMI ≥25 kg/m2. High BMI remains a risk factor for hypertensive disorders of pregnancy.
Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma
Authors: Li Xuelei , Gao Fenghua , Meng Xiangrui , Zhang Xiaoyan , Sun Cong , Liu Hengqi , Yu Jingwei , Liu Xia , Han Xue , Li Lanfang , Qiu Lihua , Qian Zhengzi , Zhou Shiyong , Gong Wenchen , Golchehre Zahra , Chavoshzadeh Zahra , Ren Xiubao , Wang Xianhuo , Zhang Huilai 
Published: March 2024

SummaryPrimary gastrointestinal follicular lymphoma (PGI‐FL) is a rare extra‐nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI‐FL and 34 892 nodal FL (N‐FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age‐adjusted average annual incidence of PGI‐FL was 0.111/100000. The median overall survival (OS) for PGI‐FL and N‐FL patients was 207 and 165 months respectively. The 5‐year diffuse large B‐cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1‐, 5‐ and 10‐year OS and disease‐specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI‐FL has increased over the past 40 years, and PGI‐FL has a better prognosis and a lower DLBCL transformation rate than N‐FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high‐risk patients and choosing the optimal individualized treatments.
R2R01: A long‐acting single‐chain peptide agonist of RXFP1 for renal and cardiovascular diseases
Authors: Poirier Bruno , Pasquier Olivier , Chenede Xavier , Corbier Alain , Prigent Philippe , Azam Aurélien , Bernard Carine , Guillotel Michel , Gillot Florence , Riva Laurence , Briand Veronique , Ingenito Raffaele , Gauzy‐Lazo Laurence , Duclos Olivier , Philippo Christophe , Maillere Bernard , Bianchi Elisabetta , Mallart Sergio , Janiak Philip , Illiano Stephane 
Published: March 2024

AbstractBackgroundThe therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half‐life of serelaxin. Optimization of fatty acid‐acetylated single‐chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half‐life.Experimental ApproachCellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01. Increased renal blood flow was used as a translational marker of R2R01 activity. Human mastocytes (LAD2 cells) were used to study potential pseudo‐allergic reactions and CD4+ T‐cells to study immunogenicity. The pharmacokinetics of R2R01 were characterized in rats and minipigs.Key ResultsIn vitro, R2R01 had comparable potency and efficacy to relaxin as an agonist for human RXFP1. In vivo, subcutaneous administration of R2R01 increased heart rate and renal blood flow in normotensive and hypertensive rat and did not show evidence of tachyphylaxis. R2R01 also increased nipple length in rats, used as a chronic model of RXFP1 engagement. Pharmacokinetic studies showed that R2R01 has a significantly extended terminal half‐life. The in vitro assays with LAD2 cells and CD4+ T‐cells showed that R2R01 had low potential for pseudo‐allergic and immunogenic reactions, respectively.Conclusion and implicationsR2R01 is a potent RXFP1 agonist with an extended half‐life that increases renal blood flow in various settings including normotensive and hypertensive conditions. The preclinical efficacy and safety data supported clinical development of R2R01 as a potential new therapy for renal and cardiovascular diseases.
Primary pulmonary histiocytic sarcoma with high PD‐L1 expression benefited from immunotherapy: A case report and bioinformatic analysis
Authors: Lin Yuanjie , Cao Qian , Hong Aonan , Liang Xiao 
Published: March 2024

AbstractHistiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45‐year‐old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD‐L1 expression was 90% positive, and the disease has been well‐controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan‐cancer analysis verified that there was the highest genetic alteration frequency of PD‐L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD‐L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10−4), progress‐free survival (PFS) (p = 4.90 × 10−2) and disease‐specific survival (DSS) (p = 4.90 × 10−2). To our knowledge, this may be the first reported case with high PD‐L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.
Tumor biomarkers in evaluating the severity and prognosis of idiopathic pulmonary arterial hypertension: A comprehensive analysis
Authors: Li Xin , Zhang Yi , Zhang Sicheng , Zhao Qing , Jin Qi , Duan Anqi , Huang Zhihua , Gao Luyang , Wang Yijia , Li Sicong , Zhao Zhihui , Luo Qin , Liu Zhihong 
Published: March 2024

AbstractInflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014–2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163–3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001–1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well‐validated PH biomarkers, CA125 was still of prognostic value in the low‐risk patients (HR: 1.014, 95% CI: 1.004–1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.
Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice
Authors: Weins Andreas Benedikt , Kerzel Sebastian , Schnopp Christina 
Published: March 2024

SummaryAtopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. “Children are not little adults” ‐ this applies in particular to infants with severe atopic dermatitis. Age‐specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment.
Acquired hypothalamic obesity: A clinical overview and update
Authors: Roth Christian L. , McCormack Shana E. 
Published: March 2024

AbstractHypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep–wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin–melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long‐term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.
Student voice in higher education: A negotiated curriculum in the foreign language classroom
Authors: Oruç Eylem 
Published: March 2024

AbstractThe article examines an action research of negotiated curriculum in a university‐level EFL (English as a Foreign Language) classroom. Drawing on critical pedagogy, this study is best suited to action research as negotiated curriculum can be explored with a deeper understanding through action‐oriented research. The research details how negotiated curriculum affects learning and teaching in an EFL classroom. Data collection methods included participant observation, teacher journals, student journals, and minutes of student meetings. The findings revealed that student choice, participation in classroom management, negotiated assessment, collaborative dialogue, and student‐led activities can be considered in a negotiated curriculum. Moreover, it was indicated that the negotiated curriculum contributed to speaking skills, learner engagement, motivation, self‐confidence, and enjoyment.
Social representations of teachers' dropout in the French context: An exploratory study
Authors: Benmbarek Abdelkader , Poplimont Christine , Lo Monaco Grégory 
Published: March 2024

AbstractThis work aims to investigate the causes behind teachers leaving their profession in France, as well as the aspects that influence some teachers to stay in. The phenomenon of teacher dropout and abandonment is increasingly prevalent in OECD countries, particularly affecting new teachers. Taking a social psychological perspective, the research delves into the representational content of teachers' attitudes towards their profession. By distinguishing between teacher dropout and abandonment—the latter being considered an earlier phase, the results suggest that pupils play a central role in preventing teachers' dropout, along with the love and passion for teaching and the discipline they teach. Conversely, lack of consideration, inadequate resources, working conditions and classroom management challenges are identified as aspects contributing to increase teachers' dropout phenomenon. The findings provide an empirical basis for future studies and valuable insights for enhancing initial teacher training programmes. Understanding these phenomena through the lens of social representations provides valuable insights for developing supportive environments that foster teacher retention and well‐being and facilitate intervention and prevention strategies targeting key elements linked to teachers dropping out.
Engaging with the Other
Authors: Cho Hyuk 
Published: March 2024

AbstractThe World Council of Churches (WCC) has recently stated that we live in a “poly‐crisis” world. This context raises questions about finding common ground with people of other faiths or no faith for the common good. How do Christians practise ecumenical diakonia in the public sphere and offer transformative diaconal services in their contexts? To explore these questions, I reflect on the essence of faith in Korean Sŏn Buddhist monk Chinul (知訥, 1158–1210) and that of the contemporary Canadian theologian Douglas John Hall to identify implications for the practice of ecumenical diakonia and its commitment to interreligious dialogue. Chinul and Hall agree that faith encourages reaching out to others. Buddhists and Christians can be companions on the journey of working together across differences for the common good of the world.
Changes in the composition of molecular species of covalently bound and free ceramides [EOS], and their correlation with disease severity in atopic dermatitis
Authors: Kondo A. , Takenaka Y. , Fujiwara A. , Takahashi S. , Kitade‐Miyayama M. , Morifuji M. , Kawashima M. , Ishiguro N. 
Published: March 2024

AbstractCeramides are major constituents of stratum corneum (SC) intercellular lipids involved in skin barrier function. The ratio of molecular species of ceramides and their correlation with disease severity was examined in patients with atopic dermatitis (AD). Thirty‐eight patients with AD and 32 healthy controls (HCs) were assessed for transepidermal water loss, SC collection and clinical assessment. The ceramide content of different molecular species in the samples was quantified using high‐performance liquid chromatography coupled with tandem mass spectrometry. Unsaturated acyl chains of both covalently bound and free ceramides [EOS] were higher in AD lesional skin than those in AD non‐lesional or normal HC skin. The proportion of unsaturated acyl chains (C30:1, C32:1 and C34:1) was higher than other ceramide molecular species among covalently bound and free ceramides [EOS] in patients with AD. The proportion of unsaturated acyl chains in covalently bound ceramides was positively correlated with transepidermal water loss (r = 0.600) when considering the total number of non‐lesional and lesional skin. Additionally, thymus and activation‐regulated chemokine (TARC) showed a positive correlation with unsaturated acyl chains proportion in AD non‐lesional (r = 0.676) and lesional (r = 0.503) skin. Our study is the first to show the increase in unsaturated acyl chains of both covalently bound and free ceramides [EOS] in lesional and non‐lesional skin in AD for each molecular species. This increase is associated with dryness and impaired barrier function, which correlates with TARC levels, a marker for the degree of type 2 inflammation. We speculate that type 2 inflammation exacerbation leads to abnormal epidermal lipid metabolism in the skin of patients with AD.
Dermal papilla cells cultured as spheres improve angiogenesis
Authors: Oppenheimer Florencia Maia , Proietti Cecilia Jazmín , Ceruti Julieta María , Hagelin Karin , Leirós Gustavo José , Balañá María Eugenia 
Published: March 2024

AbstractTissue‐engineered skin represents a helpful strategy for the treatment of deep skin injuries. Nevertheless, these skin substitutes must promote and encourage proper vascularization for a successful graft take. Previous work showed that dermal papilla cells (DPC) favour an earlier neovascularization process of grafted skin substitute contributing to the rapid maturation of the neovascular network, reducing inflammation and favouring extracellular matrix remodelling in nude mice. Based on these results, we studied the influence of DPC and its culture conditions on the different stages of angiogenesis in in vitro models. Here, we showed that DPC cultured as spheres favour the expression of angiogenic factors such as VEGF, FGF2 and angiogenin compared to their monolayer culture. To study the effects of DPC on the different stages of angiogenesis, an in vitro model has been adapted. DPC cultured as spheres significantly enhanced HUVEC migration and tubule formation, indicating the importance of employing physiological culture systems that provide a closer representation of cell behaviour and interactions occurring in vivo. Overall, these results allow us to speculate that the use of DPC spheres in skin substitutes could promote its grafting, vascularization and vascular network maturation through the secretion of angiogenic factors. This approach has great potential to improve clinical outcomes in regenerative medicine and skin wound repair.