bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models
Authors: Iwatake Mayumi , Nagamura-Inoue Tokiko , Doi Ryoichiro , Tanoue Yukinori , Ishii Mitsutoshi , Yukawa Hiroshi , Matsumoto Keitaro , Tomoshige Koichi , Nagayasu Takeshi , Tsuchiya Tomoshi 
Published: April 2024

BackgroundResearchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion.ObjectiveTo develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment.MethodsdUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed.ResultsIncreased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin β1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs.ConclusionWe developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.
Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies
Authors: Shao Chenyi , Xia Nana , Zhen Yan , Zhang Xueliang , Yan Ninghui , Guo Qiang 
Published: April 2024

ObjectivesInterstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS).MethodsHere, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately.ResultsPeripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age &gt; 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count &lt; 148 cells/μL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count &lt; 533.2 cells/μL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells &lt; 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes &lt; 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin &gt; 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS.ConclusionsPatients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD
Co-designing an intervention using the COM-B model to change an eating behaviour in people living with achalasia
Authors: Kalantari Melika , Hollywood Amelia , Lim Rosemary , Hashemi Majid 
Published: April 2024

BackgroundAchalasia is a rare motility disorder affecting the oesophagus, leading to difficulties with eating and drinking. Participants in previous studies reported that they needed more social, clinical and behavioural support in the long-term management of achalasia. This study, therefore aimed to 1) identify the most challenging eating behaviour for people living with achalasia and 2) co-design a behaviour change intervention to help address the challenges they experience.MethodsThis study used a qualitative approach involving online focus groups. The COM-B model was the theoretical framework, with behaviour change techniques (BCTs) as the active ingredients that target a mixture of capability, opportunity and/or motivation. Three focus groups were undertaken to obtain a range of input from different people living with achalasia. Participants in this study identified the target behaviour, prioritised the different BCTs which most resonated with them to design an intervention and decided on the mode of delivery. The research team analysed the techniques that helped participants with their eating behaviour using the COM-B model as a framework to create the intervention.ResultsThe 24 participants in this study identified “eating in a social setting” as the target behaviour for the intervention. A workbook that can be personalised by the individual was the most suitable intervention. The workbook structure aligns with the constructs of the COM-B model. It includes reflection, activities and goal-setting sections based on what was indicated to be useful for the majority of the participants. Key techniques to overcome the challenges with eating in a social setting included social support, regulation to reduce negative emotions, goals and planning.ConclusionUsing a focus group approach with the COM-B model as the theoretical framework, the participants in this study developed an intervention to support people living with achalasia. In order to achieve long-term behaviour change, engagement with a personalised workbook could facilitate eating in a social setting. Future work will need to pilot the workbook to ensure it can support people to improve their quality of life and complement the ongoing care they receive from health services.
Optimizing clinical outcomes in polypharmacy through poly-de-prescribing: a longitudinal study
Authors: Garfinkel Doron , Levy Yuval 
Published: April 2024

ObjectivesTo evaluate polypharmacy in older people to determine whether the number of medications de-prescribed correlates with the extent of improvement in quality of life (QoL) and clinical outcomes.DesignA prospective longitudinal cohort study of polypharmacy in people living in a community in Israel.SettingParticipants aged 65 years or older who took at least six prescription drugs followed up for at least 3 years (range 3–10 years) after poly-de-prescription (PDP) recommendations.InterventionsPDP recommended at first home visit using the Garfinkel algorithm. Annual follow-up and end-of-study questionnaires used to assess clinical outcomes, QoL, and satisfaction from de-prescribing. All medications taken, complications, hospitalizations, and mortality recorded. In total, 307 participants met the inclusion criteria; 25 incomplete end-of-study questionnaires meant 282 participants for subjective analysis. Participants divided into two subgroups: (i) those who discontinued more than 50% of the drugs (PDP group) or (ii) those who discontinued less than 50% of the drugs (non-responders, NR).Main outcome measuresObjective: 3-year survival rate and hospitalizations. Subjective: general satisfaction from de-prescribing; change in functional, mental, and cognitive status; improved sleep quality, appetite, and continence; and decreased pain.ResultsMean age: 83 years (range 65–99 years). Mean number of drugs at baseline visit: 9.8 (range 6–20); 6.7 ± 2.0 de-prescribed in the PDP group (n = 146) and 2.2 ± 2.1 in the NR group (n = 161) (p &lt; 0.001).No statistical difference between the groups in the 3-year survival rate and hospitalizations, but a significant improvement in functional and cognitive status and, in general, satisfaction from the intervention in the PDP group compared to the NR group. Improvement usually evident within the first 3 months and persists for several years.ConclusionPoly-de-prescribing in the older population has beneficial effects on several clinical outcomes with no detrimental effect on the rate of hospitalization and survival. The extent of improvement correlates with the extent of de-prescribing. Applying the Garfinkel algorithm globally may improve QoL in millions of patients, a clinical and economic win–win situation.
PAM-1: an antimicrobial peptide with promise against ceftazidime-avibactam resistant Escherichia coli infection
Authors: Han Yijia , Zhang Yi , Zhang Xiaodong , Huang Zeyu , Kong Jingchun , Wang Xiuxiu , Chen Lijiang , Wang Yue , Cao Jianming , Zhou Tieli , Shen Mo 
Published: April 2024

IntroductionAntibiotic misuse and overuse have led to the emergence of carbapenem-resistant bacteria. The global spread of resistance to the novel antibiotic combination ceftazidime-avibactam (CZA) is becoming a severe problem. Antimicrobial peptide PAM-1 offers a novel approach for treating infections caused by antibiotic-resistant bacteria. This study explores its antibacterial and anti-biofilm activities and mechanisms against CZA-resistant Escherichia. Coli (E. coli), evaluating its stability and biosafety as well.MethodsThe broth microdilution method, growth curve analysis, crystal violet staining, scanning electron microscopy, and propidium iodide staining/N-phenyl-1-naphthylamine uptake experiments were performed to explore the antibacterial action and potential mechanism of PAM-1 against CZA-resistant E. coli. The biosafety in diverse environments of PAM-1 was evaluated by red blood cell hemolysis, and cytotoxicity tests. Its stability was further assessed under different temperatures, serum concentrations, and ionic conditions using the broth microdilution method to determine its minimum inhibitory concentration (MIC). Galleria mellonella infection model and RT-qPCR were used to investigate the in vivo antibacterial and anti-inflammatory effects.Results and discussionIn vitro antibacterial experiments demonstrated that the MICs of PAM-1 ranged from 2 to 8 μg/mL, with its effectiveness sustained for a duration of 24 h. PAM-1 exhibited significant antibiofilm activities against CZA-resistant E. coli (p &lt; 0.05). Furthermore, Membrane permeability test revealed that PAM-1 may exert its antibacterial effect by disrupting membrane integrity by forming transmembrane pores (p &lt; 0.05). Red blood cell hemolysis and cytotoxicity tests revealed that PAM-1 exerts no adverse effects at experimental concentrations (p &lt; 0.05). Moreover, stability tests revealed its effectiveness in serum and at room temperature. The Galleria mellonella infection model revealed that PAM-1 can significantly improve the survival rate of Galleria mellonella (&gt;50%)for in vivo treatment. Lastly, RT-qPCR revealed that PAM-1 downregulates the expression of inflammatory cytokines (p &lt; 0.05). Overall, our study findings highlight the potential of PAM-1 as a therapeutic agent for CZA-resistant E. coli infections, offering new avenues for research and alternative antimicrobial therapy strategies.
MIR4435-2HG as a possible novel predictive biomarker of chemotherapy response and death in pediatric B-cell ALL
Authors: Torres-Llanos Yulieth , Zabaleta Jovanny , Cruz-Rodriguez Nataly , Quijano Sandra , Guzmán Paula Carolina , de los Reyes Iliana , Poveda-Garavito Nathaly , Infante Ana , Lopez-Kleine Liliana , Combita Alba Lucía 
Published: April 2024

Introduction: Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. There are few tools available to identify at the time of diagnosis whether the patient will respond to induction therapy. Our goal was to identify predictive biomarkers of treatment response, which could also serve as prognostic biomarkers of death, by identifying methylated and differentially expressed genes between patients with positive minimal residual disease (MRD+) and negative minimal residual disease (MRD-).Methods: DNA and RNA were extracted from tumor blasts separated by immunomagnetic columns. Illumina MethlationEPIC and mRNA sequencing assays were performed on 13 bone marrows from Hispanic children with B-cell ALL. Partek Flow was used for transcript mapping and quantification, followed by differential expression analysis using DEseq2. DNA methylation analyses were performed with Partek Genomic Suite and Genome Studio. Gene expression and differential methylation were compared between patients with MRD−/− and MRD+/+ at the end of induction chemotherapy. Overexpressed and hypomethylated genes were selected and validated by RT-qPCR in samples of an independent validation cohort. The predictive ability of the genes was assessed by logistic regression. Survival and Cox regression analyses were performed to determine the association of genes with death.Results:DAPK1, BOC, CNKSR3, MIR4435-2HG, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in MRD+/+ patients. Overexpression was also validated by RT-qPCR. DAPK1, BOC, ASCL2, and CNKSR3 can predict refractoriness, but MIR4435-2HG is the best predictor. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. Finally, MIR4435-2HG overexpression, together with MRD+, are associated with poorer survival, and together with overexpression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype.Conclusion:MIR4435-2HG is a potential predictive biomarker of treatment response and death in children with B-cell ALL.
Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats
Authors: Fauser Mareike , Payonk Jan Philipp , Weber Hanna , Statz Meike , Winter Christine , Hadar Ravit , Appali Revathi , van Rienen Ursula , Brandt Moritz D. , Storch Alexander 
Published: April 2024

IntroductionDeep brain stimulation (DBS) is a highly effective treatment option in Parkinson’s disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.MethodsIn our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation.ResultsSTN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches.DiscussionOur data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson’s disease.
A study of the impact of staggered boards on corporate financialization: from the perspective of board governance
Authors: Cao Chongyan , Zhang Yutong 
Published: April 2024

IntroductionThe objective of this study is to assess the influence of staggered boards on corporate financialization and the role that incentive and supervision mechanisms play in this process.MethodsWe employ a total of 20,647 panel data samples of Chinese A-share listed companies over the period 2011-2020 to empirically test the impact of staggered boards on corporate financialization in the Chinese context.ResultsThe results indicate that implementing staggered boards significantly increases levels of corporate financialization. On the one hand, the implementation of a staggered board structure can exacerbate the speculative mindset and profit-driven behavior among board members, leading management to prioritize financial investments for personal gain. On the other hand, a staggered board system may also amplify managerial laziness, potentially incentivizing them to rely heavily on financial investments in order to swiftly achieve performance targets with minimal effort. Furthermore, both managerial ownership and audit supervision are found to be critical factors in mitigating this positive impact and preventing excessive financial investment behavior.DiscussionThis paper offers guidance on comprehending the applicability of staggered board provisions and mitigating financial risks in enterprises.
Are cash incentives always king? A randomized controlled trial evaluating hedonic versus cash incentives (TEH-C)
Authors: Finkelstein Eric Andrew , Chow Michelle Tian Nee , Gandhi Mihir 
Published: April 2024

IntroductionPhysical inactivity is a risk factor for obesity and non-communicable diseases. Despite myriad health and non-health benefits resulting from physical activity (PA), most individuals do not meet PA recommendations. Providing an incentive for meeting activity goals may increase activity levels. Classical economists argue that cash is the best incentive. Behavioral economists have posited that hedonic (pleasurable) incentives (e.g., massages, restaurant meals) may be superior to cash when incentives are offered over multiple time periods. To date, no studies have directly compared the effectiveness of cash versus hedonic incentives in promoting PA across multiple time periods.MethodsWe conducted a two-arm, parallel, 4-month randomized controlled trial with healthy adults in Singapore where participants were randomized to either cash or hedonic incentives. Participants could earn up to SGD50 (≈USD37) in cash or hedonic incentives each month they met the study’s step target of 10,000 steps daily on at least 20/25 days out of the first 28 days of a month. The primary objective was to compare the mean proportion of months that participants met the step target between the two arms.ResultsBy month 4, participants in the cash (N = 154) and hedonic incentive (N = 156) arms increased their mean daily steps by 870 (p &lt; 0.001) and 1,000 steps (p &lt; 0.001), respectively. The mean proportion of months the step target was achieved was 90.53 and 88.34 for participants in the cash and hedonic incentive arms respectively, but differences across arms were small and not statistically significant for this or any outcome assessed.ConclusionOur findings suggest that both cash and hedonic incentives are effective at promoting physical activity but that neither strategy is clearly superior.Clinical trial registration: ClinicalTrials.gov, NCT 04618757 registered on November 6, 2020.
Exploring active ageing in a community-based living environment: an ethnographic study in the Western Norway context
Authors: Førsund Elise , Torrado Vidal Juan Carlos , Fæø Stein Erik , Reithe Haakon , Patrascu Monica , Husebo Bettina S. 
Published: April 2024

BackgroundAge-friendly environments intend to promote active ageing by facilitating social, mental, and physical participation. This could potentially delay the onset of chronic complex conditions, enabling people to live longer independently at home, and prevent loneliness. This study investigates a community-based living environment in Norway called Helgetun and aims to explore how it can facilitate active ageing.MethodWe chose an ethnographic approach consisting of observation, informal conversations, and in-depth semi-structured interviews with 15 residents (11 female, 4 male, ages 62–84). We analysed the data using reflexive thematic analysis.ResultWe developed three themes on facilitating active ageing in this living environment: maintaining self-identity, experiencing growth and development, and feeling a sense of belonging. These themes were related to physical activity levels, social engagement, and overall satisfaction with the living environment. Maintaining self-identity concerned getting a new role in life as well as access to meaningful activities. Experiencing growth and development involved being exposed to new activities, learning new skills, and experiencing mastery. Lastly, feeling a sense of belonging meant feeling safe and part of a group, as well as receiving social support and help. This feeling of social connectedness and safety was reflected in their experience with the COVID-19 pandemic, in which most felt relatively unaffected, suggesting that this way of living could increase reliance among this age group.ConclusionHaving a flexible structure, adapting to the core needs and individual resources of the residents, can facilitate active ageing in community-based living environments. Our findings contribute to the growing evidence that these environments increase social and physical engagement, whilst reducing social isolation and loneliness. These findings may be particularly relevant in a Norwegian context—where older adults are less dependent on family for care—and are meant as grounding points for policymakers to reflect upon designing future senior living.