bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
Authors: Najafi Haniyeh , Abolmaali Samira Sadat , Heidari Reza , Valizadeh Hadi , Tamaddon Ali Mohammad , Azarpira Negar 
Published: July 2022

Abstract
Background
Mesenchymal-based therapy has been utilized as a practical approach in the treatment of renal ischemia/reperfusion (I/R) injury. However, low cell retention and survival in the ischemic site have remained challenging issues. To bridge this gap, the integrin receptor-binding RGD peptide-functionalized, s-nitroso-n-acetyl penicillamine (SNAP)-loaded hydrogel was used to transplant Wharton's jelly-mesenchymal stem cells (WJ-MSCs).

Methods
Apart from physicochemical and rheological characterizations that confirmed entangled interlocking β-sheets with nanofibrous morphology, real-time RT-PCR, ROS production, serum biomarker concentrations, and histopathological alterations were explored in a mouse model to assess the therapeutic efficacy of formulations in the treatment of renal I/R injury.

Results
The RGD-functionalized Fmoc-diphenylalanine (Fmoc-FF + Fmoc-RGD) hydrogel supported the spread and proliferation of WJ-MSCs in vivo. Notably, intralesional injection of nitric oxide donor combined with the embedded WJ-MSCs caused superior recovery of renal I/R injury compared to free WJ-MSCs alone in terms of histopathological scores and renal function indices. Compared to the I/R control group, oxidative stress and inducible nitric oxide synthase (iNOS) expression biomarkers showed a significant decline, whereas endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression exhibited a significant increment, indicating regeneration of the injured endothelial tissue.

Conclusion
The findings confirmed that the hydrogels containing WJ-MSCs and nitric oxide donors can promote the regeneration of renal I/R injuries by increasing angiogenic factors and cell engraftment.
Adipose-derived stromal cells reverse insulin resistance through inhibition of M1 expression in a type 2 diabetes mellitus mouse model
Authors: Chen Lee-Wei , Chen Pei-Hsuan , Tang Chia-Hua , Yen Jui-Hung 
Published: July 2022

Abstract
Background
Adipose tissue inflammation is considered as one of the major mechanisms underlying the pathogenesis of insulin resistance and complications in diabetes. Here, we aimed to study the effects of adipose-derived stromal cells on diabetes-induced insulin resistance and M1 cytokine expression.

Methods
Stromal vascular fractions (SVFs) purified from the inguinal adipose tissue of diabetic mice were treated with plasma from either nondiabetic (Lepr+/+) or diabetic (Leprdb/db) mice and injected into the inguinal white adipose tissue of Leprdb/db mice.

Results
We found that diabetic plasma treatment induced, whereas nondiabetic plasma suppressed TNF-α, IL-1β, and dipeptidyl peptidase 4 (DPP4) mRNA expression in SVFs in vitro. Importantly, the injection of nondiabetic plasma-treated SVFs significantly decreased TNF-α, IL-6, IL-1β, CCL2, and IL-33 and induced IL-10 mRNA expression in adipose tissue of Leprdb/db mice in vivo. Furthermore, we observed that nondiabetic plasma-treated SVFs increased mRNA expression of Foxp3 in adipose tissue macrophages and Foxp3 in adipose CD4+ T cells, decreased CD11b+CD11c+ cells in adipose tissue, and suppressed mRNA expression of ICAM-1, FCM3, IL-6, IL-1β, iNOS, TNF-α, and DPP4 as well as protein expression of DPP4 and phosphorylated JNK and NF-κB in the liver of Leprdb/db mice. Moreover, we found that nondiabetic plasma-treated SVFs increased Akt activation following insulin administration and attenuated glucose intolerance in Leprdb/db mice.

Conclusions
Our results demonstrate that nondiabetic plasma inhibits M1 but increases M2 cytokine expression in adipose tissue of diabetic mice. Most importantly, our findings reveal that nondiabetic plasma-treated SVFs are capable of mitigating diabetes-induced plasma DPP4 activity, liver inflammation, and insulin resistance and that may be mediated through suppressing M1 cytokines but increasing IL-10 and Tregs in adipose tissue. Altogether, our findings suggest that adipose stromal cell-based therapy could potentially be developed as an efficient therapeutic strategy for the treatment of diabetes.
Transplantation of insulin-producing cells derived from human mesenchymal stromal/stem cells into diabetic humanized mice
Authors: Ghoneim Mohamed A. , Gabr Mahmoud M. , Refaie Ayman F. , El-Halawani Sawsan M. , Al-issawi Mohga M. , Elbassiouny Batoul L. , Kader Mai A. Abd El , Ismail Amani M. , Zidan Mona F. , Karras Mary S. , Magar Raghda W. , Khater Sherry M. , Ashamallah Sylvia A. , Zakaria Mahmoud M. , Kloc Malgorzata 
Published: July 2022

Abstract
Background
The purpose of this study was to investigate allogenic immune responses following the transplantation of insulin-producing cells (IPCs) differentiated from human adipose tissue-derived stem cells (hAT-MSCs) into humanized mice.

Methods
hAT-MSCs were isolated from liposuction aspirates obtained from HLA-A2-negative healthy donors. These cells were expanded and differentiated into IPCs. HLA-A2-positive humanized mice (NOG-EXL) were divided into 4 groups: diabetic mice transplanted with IPCs, diabetic but nontransplanted mice, nondiabetic mice transplanted with IPCs and normal untreated mice. Three million differentiated cells were transplanted under the renal capsule. Animals were followed-up to determine their weight, glucose levels (2-h postprandial), and human and mouse insulin levels. The mice were euthanized 6–8 weeks posttransplant. The kidneys were explanted for immunohistochemical studies. Blood, spleen and bone marrow samples were obtained to determine the proportion of immune cell subsets (CD4+, CD8+, CD16+, CD19+ and CD69+), and the expression levels of HLA-ABC and HLA-DR.

Results
Following STZ induction, blood glucose levels increased sharply and were then normalized within 2 weeks after cell transplantation. In these animals, human insulin levels were measurable while mouse insulin levels were negligible throughout the observation period. Immunostaining of cell-bearing kidneys revealed sparse CD45+ cells. Immunolabeling and flow cytometry of blood, bone marrow and splenic samples obtained from the 3 groups of animals did not reveal a significant difference in the proportions of immune cell subsets or in the expression levels of HLA-ABC and HLA-DR.

Conclusion
Transplantation of IPCs derived from allogenic hAT-MSCs into humanized mice was followed by a muted allogenic immune response that did not interfere with the functionality of the engrafted cells. Our findings suggest that such allogenic cells could offer an opportunity for cell therapy for insulin-dependent diabetes without immunosuppression, encapsulation or gene manipulations.

Graphical Abstract
The Rural Opioid Initiative Consortium description: providing evidence to Understand the Fourth Wave of the Opioid Crisis
Authors: Jenkins Richard A. , Whitney Bridget M. , Nance Robin M. , Allen Todd M. , Cooper Hannah L. F. , Feinberg Judith , Fredericksen Rob , Friedmann Peter D. , Go Vivian F. , Jenkins Wiley D. , Korthuis P. Todd , Miller William C. , Pho Mai T. , Rudolph Abby E. , Seal David W. , Smith Gordon S. , Stopka Thomas J. , Westergaard Ryan P. , Young April M. , Zule William A. , Delaney Joseph A. C. , Tsui Judith I. , Crane Heidi M. ,   the Rural Opioid Initiative
Published: July 2022

Abstract
Objective
To characterize and address the opioid crisis disproportionately impacting rural U.S. regions.

Methods
The Rural Opioid Initiative (ROI) is a two-phase project to collect and harmonize quantitative and qualitative data and develop tailored interventions to address rural opioid use. The baseline quantitative survey data from people who use drugs (PWUD) characterizes the current opioid epidemic (2018–2020) in eight geographically diverse regions.

Results
Among 3,084 PWUD, 92% reported ever injecting drugs, 86% reported using opioids (most often heroin) and 74% reported using methamphetamine to get high in the past 30 days; 53% experienced homelessness in the prior 6 months; and 49% had ever overdosed. Syringe service program use varied by region and 53% had ever received an overdose kit or naloxone prescription. Less than half (48%) ever received medication for opioid use disorder (MOUD).

Conclusions
The ROI combines data across eight rural regions to better understand drug use including drivers and potential interventions in rural areas with limited resources. Baseline ROI data demonstrate extensive overlap between opioid and methamphetamine use, high homelessness rates, inadequate access to MOUD, and other unmet needs among PWUD in the rural U.S. By combining data across studies, the ROI provides much greater statistical power to address research questions and better understand the syndemic of
infectious diseases and drug use in rural settings including unmet treatment
needs.
The use of gels in localized dechlorination treatments of metallic cultural heritage objects
Authors: Fontaine Clémence , Lemoine Stéphane , Pelé-Meziani Charlène , Guilminot Elodie 
Published: July 2022

Abstract
Gels were used to perform localized dechlorination treatments on ferrous or copper alloy archaeological objects. Agar gel (3%w) was used as a medium for the electrolyte, a 1%w KNO3 solution. Localized electrolysis with gel was carried out using the same parameters as immersion electrolysis. To determine the end of treatment, two tools were validated: determining the quantity of chlorides present in the gels by XRF and monitoring the oxygen consumption of an object before and after treatment. This study shows that the technique results in the efficient extraction of chlorides. In the case of the stabilization of composite objects or for the localized treatment of copper objects, the use of a localized electrolytic gel treatment is a new effective solution proposed to conservators.
Insights on conducting digital patient and public involvement in dementia research during the COVID-19 pandemic: supporting the development of an “E-nabling digital co-production” framework
Authors: Molinari-Ulate Mauricio , Woodcock Rebecca , Smith Isabelle , van der Roest Henriëtte G. , Franco-Martín Manuel A. , Craven Michael P. 
Published: July 2022

AbstractBackgroundThe rapid transition to digital working, accelerated due to the response to the COVID-19 pandemic, has impacted the involvement of patients and public in research. This paper presents experiences of engaging in digital Patient and Public Involvement (e-PPI) in dementia research since the lockdowns, offering recommendations regarding future digital and hybrid working. Furthermore, it introduces a co-produced framework for researchers, PPI coordinators and public contributors to identify and discuss challenges and opportunities provided by e-PPI.MethodsTwo online workshops and one individual interview were performed with a group of researchers and PPI coordinators with experience in PPI in dementia research, and with an existing dementia PPI group having some experience of working online during the pandemic. The project was constructed as a PPI activity, with the MindTech Involvement Team (PPI group) involved in the entire process, and a collaborative data analysis process was adopted.ResultsAfter refinement of the coding structure, the MindTech Involvement Team and Project Leaders identified four main themes, resulting in the ‘E-nabling Digital Co-production' Framework. During this framework development, different positions were expressed, associated with the transition to digital working. Two main themes were shared by the participating groups regarding e-PPI: wider potential reach without geographical constraints, and the perception of more business-like sessions with reduced opportunities for social interactions and communication. Specifically for dementia research, whilst e-PPI may allow public contributors to attend more meetings, potentially mutually supportive environments provided by face-to-face meetings could be diminished, with carers experiencing a possible reduction in informal respite opportunities.ConclusionsThrough involving public contributors, researchers, and PPI coordinators with a focus on digital PPI in dementia research, we were able to further refine and co-produce the ‘E-nabling Digital Co-production' Framework. Demonstrating potential for analysis of benefits and limitations within e-PPI, it was possible to identify both general insights and those specific to dementia research. However, the most significant contribution of the framework is the potential to support local journeys of co-production in ongoing digital and hybrid public involvement activities.
The effects of subacute exposure to a water-soluble cannabinol compound in male mice
Authors: Bailey Melissa M. , Emily Mills Mariah C. , Haas Ashley E. , Bailey Kelly , Kaufmann Robert C. 
Published: July 2022

Abstract
Background
Cannabinol (CBN) is one of the many cannabinoids present in Cannabis sativa and has been explored as a potential treatment for sleeplessness. The purpose of this study was to determine the physiological and behavioral effects of subacute exposure to therapeutic and low pharmacological levels of a mechanically formed, stabilized water-soluble cannabinol nano-emulsion (CBNight™).

Methods
Sixty-two male mice were randomly assigned to one of six treatment groups given CBNight™ at dosages designed to deliver 0mg (control) to 4 mg/kg of CBN daily via oral gavage for 14 days. In-cage behavior was observed at 30 minutes and at 2, 4, 8, and 16 hours after each dose. After 14 days, the mice were sacrificed and necropsied. Organs were weighed and inspected for gross abnormalities, and blood was collected via cardiac puncture for clinical chemistry.

Results
No dosage-dependent adverse effects on behavior, body mass, or blood chemistry were observed, except that the highest doses of CBNight™ were associated with significantly lower eosinophil counts.

Conclusions
The commercially available, water-soluble CBN compound employed in this study does not appear to cause adverse effects in mice; rather, it appears to be well tolerated at pharmacological levels. The findings of eosinopenia at higher doses of CBN and lack of hepatotoxicity at any dosage employed in this study have not been reported to date.
Burosumab Treatment for Autosomal Recessive Hypophosphatemic Rickets Type 1 (ARHR1)
Authors: Bai Xiuying , Levental Mark , Karaplis Andrew C 
Published: July 2022

Abstract

Context
Autosomal recessive hypophosphatemic rickets (ARHR) are rare, heritable renal phosphate-wasting disorders that arise from overexpression of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) leading to impaired bone mineralization (rickets and osteomalacia). Inactivating mutations of Dentin matrix protein 1 (DMP1) give rise to ARHR type 1 (ARHR1). Short stature, prominent bowing of the legs, fractures/pseudofractures, and severe enthesopathy are prominent in this patient population. Traditionally, treatment consists of oral phosphate replacement and the addition of calcitriol but this approach is limited by modest efficacy and potential renal and gastrointestinal side effects.

Objective
The advent of burosumab (Crysvita), a fully humanized monoclonal antibody to FGF23 for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia, offers a unique opportunity to evaluate its safety and efficacy in patients with ARHR1.

Results
Monthly administration of burosumab to 2 brothers afflicted with the disorder resulted in normalization of serum phosphate, healing of pseudofracture, diminished fatigue, less bone pain, and reduced incapacity arising from the extensive enthesopathy and soft tissue fibrosis/calcification that characterizes this disorder. No adverse effects were reported following burosumab administration.

Conclusion
The present report highlights the beneficial biochemical and clinical outcomes associated with the use of burosumab in patients with ARHR1.
The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids
Authors: Hewitt Sylvia C , Wu San-pin , Wang Tianyuan , Ray Madhumita , Brolinson Marja , Young Steven L , Spencer Thomas E , DeCherney Alan , DeMayo Francesco J 
Published: July 2022

Abstract
Endometrial health is affected by molecular processes that underlie estrogen responses. We assessed estrogen regulation of endometrial function by integrating the estrogen receptor α (ESR1) cistromes and transcriptomes of endometrial biopsies taken from the proliferative and mid-secretory phases of the menstrual cycle together with hormonally stimulated endometrial epithelial organoids. The cycle stage–specific ESR1 binding sites were determined by chromatin immunoprecipitation and next-generation sequencing and then integrated with changes in gene expression from RNA sequencing data to infer candidate ESR1 targets in normal endometrium. Genes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal from gene promoters when compared to primary endometrium and was more similar to the proliferative than the mid-secretory phase ESR1 cistrome. Inferred organoid estrogen/ESR1 candidate target genes affected formation of cellular protrusions and chromatin modification. Comparison of signaling effected by candidate ESR1 target genes in endometrium vs organoids reveals enrichment of both overlapping and distinct responses. Our analysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen affects endometrial health and function.
Is the Effect Larger in Group A or B? It Depends: Understanding Results From Nonlinear Probability Models
Authors: Bloome Deirdre , Ang Shannon 
Published: July 2022

Abstract
Demographers and other social scientists often study effect heterogeneity (defined here as differences in outcome–predictor associations across groups defined by the values of a third variable) to understand how inequalities evolve between groups or how groups differentially benefit from treatments. Yet answering the question “Is the effect larger in group A or group B?” is surprisingly difficult. In fact, the answer sometimes reverses across scales. For example, researchers might conclude that the effect of education on mortality is larger among women than among men if they quantify education's effect on an odds-ratio scale, but their conclusion might flip (to indicate a larger effect among men) if they instead quantify education's effect on a percentage-point scale. We illuminate this flipped-signs phenomenon in the context of nonlinear probability models, which were used in about one third of articles published in Demography in 2018–2019. Although methodologists are aware that flipped signs can occur, applied researchers have not integrated this insight into their work. We provide formal inequalities that researchers can use to easily determine if flipped signs are a problem in their own applications. We also share practical tips to help researchers handle flipped signs and, thus, generate clear and substantively correct descriptions of effect heterogeneity. Our findings advance researchers' ability to accurately characterize population variation.
Cell type-specific dynamics underlie cellular growth variability in plants
Authors: Le Gloanec Constance , Collet Loann , Silveira Sylvia R. , Wang Binghan , Routier-Kierzkowska Anne-Lise , Kierzkowski Daniel 
Published: July 2022

ABSTRACT
Coordination of growth, patterning and differentiation is required for shaping organs in multicellular organisms. In plants, cell growth is controlled by positional information, yet the behavior of individual cells is often highly heterogeneous. The origin of this variability is still unclear. Using time-lapse imaging, we determined the source and relevance of cellular growth variability in developing organs of Arabidopsis thaliana. We show that growth is more heterogeneous in the leaf blade than in the midrib and petiole, correlating with higher local differences in growth rates between neighboring cells in the blade. This local growth variability coincides with developing stomata. Stomatal lineages follow a specific, time-dependent growth program that is different from that of their surroundings. Quantification of cellular dynamics in the leaves of a mutant lacking stomata, as well as analysis of floral organs, supports the idea that growth variability is mainly driven by stomata differentiation. Thus, the cell-autonomous behavior of specialized cells is the main source of local growth variability in otherwise homogeneously growing tissue. Those growth differences are buffered by the immediate neighbors of stomata and trichomes to achieve robust organ shapes.
Proteomic analysis of the actin cortex in interphase and mitosis
Authors: Vadnjal Neza , Nourreddine Sami , Lavoie Geneviève , Serres Murielle , Roux Philippe P. , Paluch Ewa K. 
Published: July 2022

ABSTRACT
Many animal cell shape changes are driven by gradients in the contractile tension of the actomyosin cortex, a thin cytoskeletal network supporting the plasma membrane. Elucidating cortical tension control is thus essential for understanding cell morphogenesis. Increasing evidence shows that alongside myosin activity, actin network organisation and composition are key to cortex tension regulation. However, owing to a poor understanding of how cortex composition changes when tension changes, which cortical components are important remains unclear. In this article, we compared cortices from cells with low and high cortex tensions. We purified cortex-enriched fractions from cells in interphase and mitosis, as mitosis is characterised by high cortical tension. Mass spectrometry analysis identified 922 proteins consistently represented in both interphase and mitotic cortices. Focusing on actin-related proteins narrowed down the list to 238 candidate regulators of the mitotic cortical tension increase. Among these candidates, we found that there is a role for septins in mitotic cell rounding control. Overall, our study provides a comprehensive dataset of candidate cortex regulators, paving the way for systematic investigations of the regulation of cell surface mechanics.
This article has an associated First Person interview with the first author of the paper.