bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Organ Stewardship
Authors: Shupe Eli 
Published: December 2024

AbstractI present a bipartite model of organ stewardship that places it at the intersection of resource stewardship and gift stewardship. Though both forms of stewardship are grounded in relationships of trust, they are importantly distinct, as are the duties they confer. This bipartite model of organ stewardship functions as a beneficial instrument for understanding and resolving conflicts among transplant stakeholders. As proof of concept, I apply the bipartite model of organ stewardship to a controversial case of conditional organ donation, showing that we can better understand the underlying moral conflict if we recognize that it involves a tension between resource and gift stewardship. Then, demonstrating that the model can do more than just explanatory work, I use it to resolve the long‐standing debate over whether organ transplant recipients are organ stewards. Although some transplant recipients are gift stewards, I argue, none are resource stewards, and they therefore do not owe anything to members of the transplant team.
Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia
Authors: Bibikova Elena , Parsa Sara , Floren Muskan , Law Brian , Clevenger Tracy , Cheung Jean , De Jesus Gary , Burke Kathleen , Gulrajani Michael , Yamaguchi Kyoko , Do Phuong , Dougherty Brian , Whitston David , Brock Graham , Munugalavadla Veerendra , Frigault Melanie M. , Hartmann Tanja N. , Byrd John C. , Furman Richard R. , Brown Jennifer R. , Covey Todd , Mortlock Andrew 
Published: December 2024

ABSTRACTContemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B‐cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second‐generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment‐naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18). Peripheral blood mononuclear cells (PBMCs) from the two groups of patients were profiled at baseline (BL) and at a second timepoint (T2) by RNA‐seq and flow cytometry. Our findings show a correlation between acquired resistance to acalabrutinib and upregulation of integrin alpha‐4 (ITGA4; CD49d), the BCR surface receptor CD79B, and oncogenes such as MYC, LAG3, and MCL1 in CLL cells. High surface expression of CD49d and CD79b prior to acalabrutinib therapy was associated with increased risk of disease progression on acalabrutinib in patients with CLL. When stratified by pretreatment CD49d surface expression, the CD49dhi group (defined as ≥ 30% CD49d+ cells at baseline) showed reduced acalabrutinib‐induced lymphocytosis and higher levels of tumor proliferation markers such as CD38 and Ki‐67 compared with the CD49dlo group (defined as < 30% CD49d+ cells at baseline). In summary, CD49d and CD79b are useful predictive markers for CLL progression on acalabrutinib.Trial Registration: ClinicalTrials.gov identifier: NCT02029443
Different Role of PET‐CT Evaluation in Newly Diagnosed Follicular Lymphoma Upon Rituximab‐Based Chemotherapy and Chemo‐Free Immunotherapy
Authors: Wang Nan , Huang Xin‐Yun , Jiang Xu‐Feng , Wang Li , Cheng Shu , Xu Peng‐Peng , Dong Lei , Ou‐Yang Bin‐Shen , Mu Rong‐Ji , Li Chen , Zhao Yan , Feng Yan , Dou Hong‐Jing , Zheng Zhong , Zhao Wei‐Li 
Published: December 2024

ABSTRACTNewly diagnosed follicular lymphoma (FL) patients usually received first‐line rituximab‐based immunochemotherapy (R‐chemo). Recently, rituximab plus lenalidomide (R2) emerged as an alternative chemo‐free immunotherapy. We performed a comparative analysis of positron emission tomography/computed tomography (PET/CT) in FL undergoing R‐chemo or R2. With data of sequential PET/CT at the baseline, interim, and end‐of‐induction, treatment responses and survival outcomes were analyzed using Deauville scores at the interim and end‐of‐induction. Additionally, correlations between interim Deauville scores and baseline PET/CT parameters were explored. Conclusively, we revealed that Deauville 1–3 at the interim and end‐of‐induction showed lower disease progression within 24 months (POD24) and superior progression‐free survival (PFS) in R‐chemo and R2 cohorts. Also, patients with interim Deauville 1–3 exhibited reduced POD24 and favorable PFS as compared to those with interim Deauville 4–5/end‐of‐induction Deauville 1–3. Furthermore, total lesion glycolysis of baseline PET‐CT surpassed standardized uptake value and total metabolic tumor volume in predicting interim Deauville 1–3, with different optimal cutoffs of 2600 and 600 mL in the R‐chemo and R2 cohort. These findings underscored the potential of PET‐CT‐adapted strategies to achieve durable remission in FL undergoing rituximab‐based immunochemotherapy or immunotherapy.
Decreasing Patient Wait Time by Process Level Interventions in an Oncology Daycare Unit: A Quasi‐Experimental Study
Authors: Radheshyam Avani , Ramani Vinod K. , Mhaske Manohar , Naik Radhehsyam 
Published: December 2024

ABSTRACTIntroductionThe DMAIC approach is a five‐phase improvement cycle which enables the advancement of pre‐existing processes and was implemented as part of the “lean” process improvement initiative. The present study aims to improve the work efficiency of chemotherapy daycare unit (CDU) at a cancer hospital. The objectives include studying the process flow of the CDU, estimating the patient wait time (PWT) before infusion at the CDU, and implementing new measures to improve its functioning.MethodsIn this quasi‐experimental study, PWT of the CDU process was assessed and its work efficiency was analyzed using other parameters of functioning. The research team implemented a planning system using “lean” methods for reducing the patient contact points in the hospital, streamlining the workflow of patient services at CDU and reducing the laboratory waiting time. The patient satisfaction survey enabled measuring the quality of care at CDU.ResultsThe study methodology was “lean‐DMAIC,” which enabled an improvement in the activities performed by the CDU staff. The mean difference in PWT between the two groups (pre‐ and postintervention) was 13.93 min, which is a significant (p < 0.001) reduction (19%) in the mean PWT values. Although the patient satisfaction survey did not show significant results for the general questionnaire conducted on study subjects (95 patients each in the pre‐ and postintervention groups), the intervention‐specific questionnaire on the cohort of 20 patients showed a significant mean difference (µ = 4.2 ± 0.3 and 4.8 ± 0.2, p < 0.001) between the pre‐ and postintervention groups.ConclusionThe results of the study implicate the potential of revising the process flow for a subset of oncology patients, and its impact on the efficiency of CDU. Adopting a lean technique in the study resulted in an improvised work approach and an anticipative growth in revenue generation.
Prevalence of Diabetic Foot Ulcer and Determinant Factors Among Adult Diabetic Patients Who Attend the Diabetic Follow‐Up at Adwa General Hospital, Ethiopia, 2019: A Cross‐Sectional Study
Authors: Mekonen Haftea Hagos , Gebru Tsegu Hailu 
Published: December 2024

ABSTRACTBackground and AimsDiabetic foot ulcers are the main complication of diabetes mellitus. There is limited information on the prevalence and factors of diabetic foot ulcers in Ethiopia, particularly to the study setting. The study aimed to assess the prevalence of diabetic foot ulcers and determinant factors among adult diabetic patients who attend the diabetic follow‐up at Adwa General Hospital, Ethiopia, 2019.MethodsAn institutional‐based cross‐sectional study was conducted. The data was collected using face to face interviews, direct observation, and a patient's records reviews. Data were cleaned, entered, and analyzed using SPSS version 23. Bivariate and multivariable logistic regression was used to identify factors associated with a diabetic foot ulcer. Finally, p < 0.05 in multivariable logistic regression was used to declare statistical significance.ResultsThe prevalence of diabetic foot ulcer was 13%. Being a rural residence (AOR = 7.180, 95% CI: 2.663–19.359), oral hypoglycemic medication (AOR = 2.521, 95% CI: 1.001–6.349), medication nonadherence (AOR = 4.480, 95% CI: 1.954–10.269), poor diabetic foot self‐care practice (AOR = 4.350, 95% CI: 1.378–13.731), lost to follow‐up (AOR = 4.838, 95% CI: 1.828–12.801), neuropathy (AOR = 4.938, 95% CI: 1.565–15.580), and alcohol drink (AOR = 4.178, 95% CI: 1.592–10.966) were the determinant factors.ConclusionThe prevalence of diabetic foot ulcer was high. Being a rural residence, oral hypoglycemic medication, medication nonadherence, poor diabetic foot self‐care practice, lost to follow‐up, neuropathy, and alcohol drinks were the determinants of diabetic foot ulcer. Health education on diabetic foot self‐care practice, alcohol drink, and the other determinants are important to prevent diabetic foot ulcer.
A Study of Quadratic Buoyancy‐Driven Magnetohydrodynamic Stagnation‐Point Flow With Radiative Heat, Thermophoresis, and Arrhenius Energy Over a Stretching Surface
Authors: Das Utpal Jyoti , Patgiri Indushri 
Published: December 2024

ABSTRACTThe motivation of this study is to explore the magnetohydrodynamic flow of the Newtonian fluid model, focusing on the effects of thermophoresis and nonlinear convection on the viscous fluid in a stretchy sheet embedded in permeable media. This work aims to study the flow behavior, including the novel effects of radiative heat in the energy equation and energy activation in the concentration equation. Through proper similarity variables, governing equations are transformed to dimension‐free form. The nonlinear dimension‐free equations are solved via the bvp4c tool. The study of stagnation‐point flow for a viscous nanofluid towards a stretchable area offers a comprehensive understanding of the relationships between fluid dynamics, heat transportation, and material properties. The flow behavior of several physical factors is studied graphically for temperature, velocity, and concentration boundary layer. Moreover, skin friction, mass, and heat transmission rates are important in this investigation. The impact of skin friction, heat, and mass transmission rates are represented in a table. From observation, it is highlighted that the permeability parameter reduces fluid velocity and the heat transport rate. Magnetic parameter enhances skin friction. Heat and mass transfer rates decrease by 0.39% and 0.21%, respectively, whereas skin friction rises by 6.19% when M is increased by 0.5 from 0.5 to 1. The heat transfer rate increases by 0.06% when the activation energy is increased by 0.2 from 0.4 to 0.6, but the mass transfer rate declines by 39.8%. Eckert number and radiation parameters enhance the fluid's temperature. The concentration boundary layer reduces for increasing chemical reactions and Schmidt numbers. This research helps design efficient systems and processes for engineering and commercial uses incorporating fluid motion and heat exchange.
The Role of Periodic Mixing on Thermal Energy Extraction From an L‐Shaped Heater Covered by Porous Layer
Authors: Tarek Nehila , Ismael Muneer 
Published: December 2024

ABSTRACTIn this numerical study, a technical solution is proposed to maximize heat transfer within a square cavity by integrating an L‐shaped porous layer in the lower right part of the cavity, covering an L‐shaped heat sink heated to a set temperature. Additionally, a thin bar undergoes a periodic sinusoidal motion with an amplitude of Vbar and a period of ωbar. The finite element method is used to solve the governing dimensionless nonlinear equations, with a mesh test supported by numerical and experimental validations. The study focuses on the effects of bar displacement amplitude (Vbar = 0.1–0.4), displacement period (ωbar = 1/3–1), Reynolds number (Re = 50, 100, and 200), Darcy number (Da = 10−2 and 10−4), and porosity (ε = 0.75–0.95) on the average Nusselt number, streamlines, and isotherms distribution. The numerical results show that increasing the bar displacement amplitude, Darcy number, and Reynolds number can significantly enhance the overall heat transfer, while an increase in the porosity of the porous medium has the opposite effect. The bar's sinusoidal motion and the porous medium's presence alter the flow dynamics within the cavity and directly influence heat transfer.
Modeling cancer–microbiome interactions in vitro: A guide to co‐culture platforms
Authors: Moskal Kamil , Khurana Nimisha , Siegert Luisa , Lee Ye Seul , Clevers Hans , Elinav Eran , Puschhof Jens 
Published: December 2024

AbstractThe biology of cancer is characterized by an intricate interplay of cells originating not only from the tumor mass, but also its surrounding environment. Different microbial species have been suggested to be enriched in tumors and the impacts of these on tumor phenotypes is subject to intensive investigation. For these efforts, model systems that accurately reflect human–microbe interactions are rapidly gaining importance. Here we present a guide for selecting a suitable in vitro co‐culture platform used to model different cancer–microbiome interactions. Our discussion spans a variety of in vitro models, including 2D cultures, tumor spheroids, organoids, and organ‐on‐a‐chip platforms, where we delineate their respective advantages, limitations, and applicability in cancer microbiome research. Particular focus is placed on methodologies that facilitate the exposure of cancer cells to microbes, such as organoid microinjections and co‐culture on microfluidic devices. We highlight studies offering critical insights into possible cancer–microbe interactions and underscore the importance of in vitro models in those discoveries. We anticipate the integration of more complex microbial communities and the inclusion of immune cells into co‐culture systems to more accurately simulate the tumor microenvironment. The advent of ever more sophisticated co‐culture models will aid in unraveling the mechanisms of cancer‐microbiome interplay and contribute to exploiting their potential in novel diagnostic and therapeutic strategies.
Silicone Loss During Histological Preparation of Breast Implant Tissue From Capsular Contracture, Quantified by Stimulated Raman Scattering Microscopy
Authors: Schmidt Robert W. , de Bakker Erik , Ariese Freek 
Published: December 2024

ABSTRACTBreast augmentations, commonly performed for aesthetic or medical reasons, often use silicone (polydimethylsiloxane [PDMS]) implants. Some patients develop complications like capsular contracture, where scar tissue forms around the implant. Previously, we used stimulated Raman scattering (SRS) microscopy to detect and quantify silicone in stained capsule tissue, finding a correlation between silicone amount and contracture severity. However, we suspected silicone loss during histological preparation, which includes multiple steps like formalin fixation and paraffin embedding. In this study, we assessed silicone loss by comparing adjacent tissue samples from the same capsule: one prepared conventionally and the other snap‐frozen. SRS microscopy revealed that snap‐frozen samples had roughly five times more silicone, indicating significant silicone loss during conventional preparation. Thus, measuring silicone in histologically prepared samples likely underestimates PDMS content.
A Comprehensive Review Highlighting the Prospects of Phytonutrient Berberine as an Anticancer Agent
Authors: Haque Shafiul , Mathkor Darin Mansor , Bhat Sajad Ahmad , Musayev Abdugani , Khituova Lidiya , Ramniwas Seema , Phillips Enosh , Swamy Nitin , Kumar Suneel , Yerer Mukerrem Betul , Tuli Hardeep Singh , Yadav Vikas 
Published: December 2024

ABSTRACT﻿Berberine, an isoquinoline alkaloid derived from various medicinal plants, emerges as a potential therapeutic agent against diverse human diseases. It has particularly shown notable anticancer efficacy against breast, colorectal, lung, prostate, and liver cancer. Berberine results in inhibition of cancer cell proliferation, induction of apoptosis, and suppressing angiogenesis, positioning it as a versatile, multitargeted therapeutic tool against cancer. Notably, berberine enhances the effectiveness of conventional chemotherapeutic drugs, mitigating associated drug resistance. Mechanistically, it has been shown to exert its efficacy by targeting molecules like nuclear factor‐kappa B (NF‐κB), mitogen‐activated protein kinases (MAPKs), and phosphoinositide 3‐kinase (PI3K)/Akt, thereby inhibiting survival pathways and promoting apoptosis of cancer cells. Moreover, berberine influences the expression of tumor suppressor genes, curtails cancer cell migration and invasion, and modulates the tumour microenvironment. Despite promising preclinical evidence, further research is essential to comprehensively elucidate its mechanisms of action and evaluate its safety and efficacy in clinical settings. In the present review, we have highlighted the pharmacokinetics, biosynthesis, and recent research work done pertaining to berberine's strong anticancer activity. We have also emphasised on the research being done on nanoformulations of berberine, which aim to improve its stability and bioavailability.
Anti‐Hyperlipidemic, Antioxidant, Anti‐Inflammatory and Antidiabetic Effect of Brucine Against Streptozotocin‐Induced Diabetic Nephropathy in Rats
Authors: Feng Ling , Gao Lei 
Published: December 2024

ABSTRACTAmong the diabetes‐related complications, diabetic nephropathy is the major complication and it leads to end‐stage renal failure. In the current investigation, we examined the protection of brucine, an alkaloid extracted from the seeds of Strychnos nux vomica plant widely used in traditional Chinese and Indian medicines against diabetic‐induced nephropathy. Male Wistar rats were divided into four groups: control, diabetic rats, diabetic‐induced + 40 mg/kg brucine‐treated rats, and diabetic‐induced + 25 mg/kg metformin‐treated rats. The 35 mg/kg streptozotocin (STZ) was injected into (i.p.) rats to induce diabetes, and then rats were post‐treated with brucine and metformin for 45 days. The food intake, weight gain, fasting blood glucose, HbA1C, insulin, and HOMA‐IR values were measured on initial and after completion of treatment to confirm the induction of diabetes by STZ and the antidiabetic effect of brucine. The rats were euthanized on 45th day, and kidney tissue was isolated to assess the nephroprotective effect of brucine. The antioxidant property of brucine was analyzed by measuring the oxidative stress and antioxidant biomarkers. The lipid profiles in the control and treated rats were measured. To assess the nephroprotective effect of brucine KIM‐1 protein was measured. The anti‐inflammatory property of brucine was assessed by quantifying the levels of pro‐inflammatory cytokines i.e., NF‐κB, TNF‐α, IL‐1β, IL‐6, TGF‐β and to confirm the nephroprotective effect. The histopathological analysis was also performed with H&E staining. Our results suggested that brucine showed potent antidiabetic, antioxidant, antilipidemic, anti‐inflammatory, and nephroprotective properties.
Overexpression of lncRNA LINC00294 Induces Cell Cycle Arrest and Apoptosis in Colorectal Cancer by Regulating the miR‐499a‐5p/LARP4B Axis
Authors: Wang Ke , Nie Yuanhua , Wang Shilong , Chang Dongmin 
Published: December 2024

ABSTRACTIncreasing long noncoding RNAs (lncRNAs) have been found to participate in regulating the progression of colorectal cancer (CRC), which is a common gastrointestinal malignancy. Here, the specific role and mechanisms of lncRNA LINC00294 were investigated in CRC. The expression levels of LINC00294, miR‐499a‐5p, and La‐related protein 4B (LARP4B) in CRC cells (HCT116 and SW620) and tissues were assessed by RT‐qPCR. The viability, proliferation, cell cycle, and apoptosis of HCT116 and SW620 cells were determined by CCK‐8, EdU, and flow cytometry assays. Protein levels of cell cycle and cell apoptosis markers were measured by western blot analysis. FISH assay was performed to evaluate the subcellular localization of LINC00294 in CRC cells. Luciferase reporter assay, RNA pull‐down assay, as well as RIP assay verified the interactions between miR‐499a‐5p and LINC00294 (or LARP4B). The xenograft model was established in mice to investigate the function of LINC00294 in vivo. LINC00294 presented a decreased expression level in CRC cells and tissues. LINC00294 overexpression suppressed the cell proliferative capacity, promoted cell cycle arrest, and induced cell apoptosis in CRC HCT116 and SW620 cells. LINC00294 interacted with miR‐499a‐5p, and miR‐499a‐5p targeted LARP4B. MiR‐499a‐5p was upregulated while LARP4B was downregulated in CRC cells. In rescue assays, LARP4B knockdown reversed the inhibition of LINC00294 overexpression on malignant phenotypes of HCT116 and SW620 cells. In the xenograft model, LINC00294 overexpression inhibited tumor growth in vivo. LINC00294 exerted an antitumor function in CRC by forming a LINC00294/miR‐499a‐5p/LARP4B regulatory network.
Cx43 Regulates Nicotine‐Induced Proliferation and Migration of Distal Pulmonary Artery Smooth Muscle Cells by the ERK1/2 Signaling Pathway
Authors: Hou Xiaomin , Xu Xinrong , Dong Lin , Li Yanhua , Liang Ruifeng , Zhang Mingsheng , Nie Jisheng , Shi Yiwei , Qin Xiaojiang 
Published: December 2024

ABSTRACTPulmonary hypertension is a progressive disease associated with remodeling of the pulmonary vasculature. Excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) play important roles in nicotine‐induced vascular injury. Connexin 43 (Cx43) is involved in intracellular communication and regulation of the pulmonary vasculature. However, the role of Cx43 and the potential mechanisms in PASMCs proliferation and migration induced by nicotine remains not very clear. In this study, we used both in vitro and in vivo models to explore the crucial role of Cx43 in pulmonary artery remodeling in nicotine treatment Tagln‐Cre; Cx43+/+ and Cx43 heterozygous (Tagln‐Cre; Cx43flox/+) or Cx43 Homozygous (Tagln‐Cre; Cx43flox/flox) deletion mice, and further explore the mechanism. We found that nicotine exposure led to modifications in the morphology and ultrastructure of pulmonary arteries in Tagln‐Cre; Cx43+/+ mice. Nicotine increased the Cx43 expression of pulmonary arteries and promoted the proliferation and migration of PASMCs of Tagln‐Cre; Cx43+/+ mice in a concentration‐dependent manner by promoting ERK1/2 phosphorylation. Compared with the Tagln‐Cre; Cx43+/+ mice, the Tagln‐Cre; Cx43flox/+ mice were protected against increased ERK1/2 phosphorylation induced by nicotine. These results demonstrated that the downregulation of Cx43 reduced nicotine‐induced proliferation and migration of distal PASMCs by inhibiting ERK1/2 phosphorylation.