bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model
Authors: Guan Jingyan , Li Yibao , Lu Feng , Feng Jingwei 
Published: March 2022

Abstract
Background
Mesenchymal stem cells (MSCs) have therapeutic potential for atopic dermatitis (AD) owing to their immunoregulatory effects. However, the underlying mechanisms associated with the therapeutic efficacy of MSCs on AD are diverse and related to both cell type and delivery method.

Objectives
This study investigated the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin (OVA)-induced AD mouse model.

Methods
AD mice were subcutaneously injected with mouse ADSCs, cortisone, or PBS, and the therapeutic effects were determined by gross and histological examinations and serum IgE levels. Additionally, qPCR, RNA-sequencing analyses of skin samples and co-culture of ADSCs and Th17 cells were conducted to explore the underlying therapeutic mechanisms.

Results
ADSCs treatment attenuated the AD pathology, decreased the serum IgE levels, and decreased mast cells infiltration in the skin of the model mice. Moreover, tissue levels of IL-4R and Th17-relevant products (IL-17A, CCL20, and MMP12) were suppressed in the ADSC- and cortisone-treated groups. Genomics and bioinformatics analyses demonstrated significant enrichment of inflammation-related pathways in the downregulated genes of the ADSC- and cortisone-treated groups, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the proliferation of Th17 cells and the expression of proinflammatory cytokines (IL-17A and RORγT). Furthermore, expression levels of PD-L1, TGF-β, and PGE2 were significantly upregulated in co-cultured ADSCs relative to those in monocultured ADSCs.

Conclusion
ADSCs ameliorate OVA-induced AD in mice mainly by downregulating IL-17 secretion of Th17 cells.
Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells
Authors: Elzarki Adrian Farid , Nandula Seshagiri Rao , Awal Hassan , Simon Gary L. , Sen Sabyasachi 
Published: March 2022

Abstract
Background
To determine the effects of integrase inhibitor (INSTI) in comparison with non-INSTI-based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker.

Methods
Nineteen male subjects, ages 32–61 years with BMI 21.0–36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI-based regimen with 13 subjects or NNRTI (non-INSTI)-based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir–emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood-derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation.

Results
A significant increase in percentage number of progenitor cells, CD133+ cells (p = 0.004), was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population being observed in INSTI group as compared to NNRTI group, by flow cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend toward a decrease in gene expression of inflammatory marker IL6 (p = 0.06) being observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil–Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p = 0.03). Interestingly, urine microalbumin levels were higher in the INSTI group compared to NNRTI group (p = 0.08), while eGFR levels were significantly lower in the INSTI group (p = 0.002). The arterial stiffness measures did not show statistically significant differences between the two groups.

Conclusion
We conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI-based HAART regimen; however, the increased albuminuria along with lower eGFR, noted in INSTI group, is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice.
Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1. ClinicalTrials.gov Identifier: NCT03782142.
Regulation of paternal 5mC oxidation and H3K9me2 asymmetry by ERK1/2 in mouse zygotes
Authors: Chen Baobao , Deng Mingtian , Pan Meng-Hao , Sun Shao-Chen , Liu Honglin 
Published: March 2022

AbstractBackgroundExtracellular-signal-regulated kinase (ERK) direct cell fate determination during the early development. The intricate interaction between the deposition of H3K9me2, de novo 5mC, and its oxides affects the remodeling of zygotic epigenetic modification. However, the role of fertilization-dependent ERK in the first cell cycle during zygotic reprogramming remains elusive.MethodsIn the present study, we used the small molecule inhibitor to construct the rapid ERK1/2 inactivation system in early zygotes in mice. The pronuclear H3K9me2 deposition assay and the pre-implantation embryonic development ability were assessed to investigate the effect of fertilization-dependent ERK1/2 on zygotic reprogramming and developmental potential. Immunofluorescence and RT-PCR were performed to measure the 5mC or its oxides and H3K9me2 deposition, and the expression of related genes.ResultsWe reported that zygotic ERK1/2 inhibition impaired the development competence of pre-implantation embryos. Following the ERK1/2 inhibition, H3K9me2, as well as 5mC and its oxides, were all accumulated abnormally, and the excess accumulation of paternal H3K9me2 and 5mC resulted in reduced asymmetry between parental pronuclei. Furthermore, ERK1/2 inhibition triggered paternal pronuclear localization of the H3K9 methyltransferase G9a and Tet methylcytosine dioxygenase 3 (Tet3). Moreover, the excess localization of G9a antagonized the tight binding of Tet3 to paternal chromatin when ERK1/2 was inhibited.ConclusionsIn conclusion, we propose that zygotic H3K9me2 and 5mC are regulated by fertilization-dependent ERK1/2, which contributes to the development competence of pre-implantation embryos in mice.
Generation of immunodeficient pig with hereditary tyrosinemia type 1 and their preliminary application for humanized liver
Authors: Ren Jilong , Yu Dawei , Wang Jing , Xu Kai , Xu Yanan , Sun Renren , An Peipei , Li Chongyang , Feng Guihai , Zhang Ying , Dai Xiangpeng , Zhao Hongye , Wang Zhengzhu , Han Zhiqiang , Zhu Haibo , Ding Yuchun , You Xiaoyan , Liu Xueqin , Wu Meng , Luo Lin , Li Ziyi , Yang Yong-Guang , Hu Zheng , Wei Hong-jiang , Ge Liangpeng , Hai Tang , Li Wei 
Published: March 2022

Abstract
Background
Mice with humanized livers are important models to study drug toxicology testing, development of hepatitis virus treatments, and hepatocyte transplantation therapy. However, the huge difference between mouse and human in size and anatomy limited the application of humanized mice in investigating human diseases. Therefore, it is urgent to construct humanized livers in pigs to precisely investigate hepatocyte regeneration and human hepatocyte therapy. CRISPR/Cas9 system and somatic cell cloning technology were used to generate two pig models with FAH deficiency and exhibiting severe immunodeficiency (FAH/RAG1 and FAH/RAG1/IL2RG deficiency). Human primary hepatocytes were then successfully transplanted into the FG pig model and constructed two pigs with human liver.

Results
The constructed FAH/RAG1/IL2RG triple-knockout pig models were characterized by chronic liver injury and severe immunodeficiency. Importantly, the FG pigs transplanted with primary human hepatocytes produced human albumin in a time dependent manner as early as 1 week after transplantation. Furthermore, the colonization of human hepatocytes was confirmed by immunochemistry staining.

Conclusions
We successfully generated pig models with severe immunodeficiency that could construct human liver tissues.
Improved capsule routing for weakly labeled sound event detection
Authors: Li Haitao , Yang Shuguo , Wang Wenwu 
Published: March 2022

AbstractPolyphonic sound event detection aims to detect the types of sound events that occur in given audio clips, and their onset and offset times, in which multiple sound events may occur simultaneously. Deep learning–based methods such as convolutional neural networks (CNN) achieved state-of-the-art results in polyphonic sound event detection. However, two open challenges still remain: overlap between events and prone to overfitting problem. To solve the above two problems, we proposed a capsule network-based method for polyphonic sound event detection. With so-called dynamic routing, capsule networks have the advantage of handling overlapping objects and the generalization ability to reduce overfitting. However, dynamic routing also greatly slows down the training process. In order to speed up the training process, we propose a weakly labeled polyphonic sound event detection model based on the improved capsule routing. Our proposed method is evaluated on task 4 of the DCASE 2017 challenge and compared with several baselines, demonstrating competitive results in terms of F-score and computational efficiency.
Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model
Authors: Lv Yi-Qing , Yuan Lin , Sun Yan , Dou Hao-Wen , Su Ji-Hui , Hou Zhi-Pan , Li Jia-Yi , Li Wen 
Published: March 2022

Abstract
Background
Growing evidence suggests an association between Parkinson’s disease (PD) and diabetes mellitus (DM). At the cellular level, long-term elevated levels of glucose have been shown to lead to nigrostriatal degeneration in PD models. However, the underlying mechanism is still unclear. Previously, we have elucidated the potential of type 2 diabetes mellitus (T2DM) in facilitating PD progression, involving aggregation of both alpha-synuclein (α-syn) and islet amyloid polypeptide in the pancreatic and brain tissues. However, due to the complicated effect of insulin resistance on PD onset, the actual mechanism of hyperglycemia-induced dopaminergic degeneration remains unknown.

Methods
We employed the type 1 diabetes mellitus (T1DM) model induced by streptozotocin (STZ) injection in a transgenic mouse line (BAC-α-syn-GFP) overexpressing human α-syn, to investigate the direct effect of elevated blood glucose on nigrostriatal degeneration.

Results
STZ treatment induced more severe pathological alterations in the pancreatic islets and T1DM symptoms in α-syn-overexpressing mice than in wild-type mice, at one month and three months after STZ injections. Behavioral tests evaluating motor performance confirmed the nigrostriatal degeneration. Furthermore, there was a marked decrease in dopaminergic profiles and an increase of α-syn accumulation and Serine 129 (S129) phosphorylation in STZ-treated α-syn mice compared with the vehicle-treated mice. In addition, more severe neuroinflammation was observed in the brains of the STZ-treated α-syn mice.

Conclusion
Our results solidify the potential link between DM and PD, providing insights into how hyperglycemia induces nigrostriatal degeneration and contributes to pathogenic mechanisms in PD.
Drug research and development opportunities in low- and middle-income countries: accelerating traditional medicine through systematic utilization and comprehensive synergy
Authors: Liu Guangqi , Xie Yan , Sun Yinuo , Zhang Kaixuan , Ma Jiyan , Huang Yangmu 
Published: March 2022

Abstract
Background
Though the utilization of traditional medicine has been proposed for modern drug research and development (R&D), limited research has discussed its feasible paths. In this commentary, we summarized key factors for new drug R&D under limited resources by reviewing China’s discovery of artemisinin, and raised suggestions to utilize traditional medicines in low- and middle-income countries (LMICs).

Main text
We suggested that systematic utilization of traditional medicine, outstanding synergy of research units at all levels and timely information-sharing mechanism should be achieved to establish a comprehensive and efficient R&D system, especially under low-resource settings. In the case of artemisinin discovery, Chinese scientists integrated documented traditional medicine experiences and modern approaches to develop drug candidates timely. Due to limited R&D resources, China adopted a collaborative way, motivating nearly all domestic research units at different levels, to develop antimalarial products. Moreover, the excellent synergy among all units through efficient information-sharing mechanisms greatly avoided work repetition and accelerated the R&D process.

Conclusion
Traditional medicines inspires drug discoveries in LMICs, while a comprehensive and efficient R&D system could accelerate its R&D process and save investment. The discovery of artemisinin in China gave a reliable pattern to promote sustainable development of traditional medicines and a good example to realize R&D of traditional medicine under low-resource settings.
Adaptation and validation of the Caregiver Burden Inventory in eating disorders
Authors: Bertelli Sara , Ferrara Paolo , Di Modica Sharon , Bergamelli Emilio , Gambini Orsola , D’Agostino Armando , Destrebecq Anne , Terzoni Stefano 
Published: March 2022

Abstract
Background
Living with people diagnosed with a mental disorder is known to increase the risk of developing high levels of so–called “caregiver burden” in informal caregivers. In–depth analysis of this phenomenon and specific assessment tools for caregivers of patients diagnosed with Eating Disorders (EDs) are lacking. In this study, we aimed to evaluate the psychometric properties of the Caregiver Burden Inventory in EDs and employ this adapted tool in this category of caregivers.

Methods
A cross–sectional study was conducted in the Eating Disorders outpatient unit of an Italian University hospital. Face and content validity were investigated by calculating standard Content Validity Indices (CVI-I and CVI-S) after administering the Inventory to 6 expert nurses with at least 5 years of experience in mental health services assisting people diagnosed with Eating Disorders. Internal consistency was evaluated with Cronbach’s α coefficient for the overall scale and subscales. An exploratory factor analysis (EFA) was performed to explore latent constructs. The adapted CBI was then administered to 62 informal caregivers of ED patients.

Results
The EFA yielded a 5–factor structure. The CVI-S was 97.2%; the Cronbach α coefficient was 0,90 (> 0.74 in each subscale). The median burden level in the experimental population was 40.0 [range = 21 to 54], in a theoretical range from 0 (no burden) to 96 (highest level of burden).

Conclusion
The Caregiver Burden Inventory appears to be a valid and reliable instrument to assess caregiver burden in individuals diagnosed with Eating Disorders. Further research is needed to evaluate this tool’s efficiency in improving individually tailored interventions on families.
Compensation for wind drift prevails for a shorebird on a long-distance, transoceanic flight
Authors: Linscott Jennifer A. , Navedo Juan G. , Clements Sarah J. , Loghry Jason P. , Ruiz Jorge , Ballard Bart M. , Weegman Mitch D. , Senner Nathan R. 
Published: March 2022

Abstract
Background
Conditions encountered en route can dramatically impact the energy that migratory species spend on movement. Migratory birds often manage energetic costs by adjusting their behavior in relation to wind conditions as they fly. Wind-influenced behaviors can offer insight into the relative importance of risk and resistance during migration, but to date, they have only been studied in a limited subset of avian species and flight types. We add to this understanding by examining in-flight behaviors over a days-long, barrier-crossing flight in a migratory shorebird.

Methods
Using satellite tracking devices, we followed 25 Hudsonian godwits (Limosa haemastica) from 2019–2021 as they migrated northward across a largely transoceanic landscape extending > 7000 km from Chiloé Island, Chile to the northern coast of the Gulf of Mexico. We identified in-flight behaviors during this crossing by comparing directions of critical movement vectors and used mixed models to test whether the resulting patterns supported three classical predictions about wind and migration.

Results
Contrary to our predictions, compensation did not increase linearly with distance traveled, was not constrained during flight over open ocean, and did not influence where an individual ultimately crossed over the northern coast of the Gulf of Mexico at the end of this flight. Instead, we found a strong preference for full compensation throughout godwit flight paths.

Conclusions
Our results indicate that compensation is crucial to godwits, emphasizing the role of risk in shaping migratory behavior and raising questions about the consequences of changing wind regimes for other barrier-crossing aerial migrants.
pH-dependent warping behaviors of ancient lacquer films excavated in Shanxi, China
Authors: Wang Kai , Liu Chongwen , Zhou Yihang , Hu Dongbo 
Published: March 2022

Abstract
The ancient lacquer films excavated from Dongshan Han tomb M6 of the Western Han Dynasty in Taiyuan City, Shanxi, China, were found sensitive to pH variation. This paper aims to demonstrate the pH-dependent warping behaviors of the ancient lacquer film and discuss their mechanism. The samples were analyzed by surface analytical techniques including attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray photoelectron spectrometry. The results suggest that the outer layer of the lacquer film is more oxidized than the inner layer and contains more carboxylates, with calcium ions and possibly ammonium cations as counter ions. The carboxylates are speculated to be formed by oxidative cleavages in the urushiol side chains and hydrolysis of glycerides of drying oils. The shrinkage and swelling of the lacquer film can be regulated by the type of cations (H+, Ca2+, Na+) of carboxylates through hydrogen bonds, coordination bonds and static forces. Due to the higher content of carboxylates in the outer part, it shrinks more at low pH causing warping outward and swells more at high pH causing warping inward. This paper may provide an important reference for pH control and help resolve the warping problem during conservation or restoration of ancient lacquerware.
Evaluation of interproximal reduction in individual teeth, and full arch assessment in clear aligner therapy: digital planning versus 3D model analysis after reduction
Authors: Hariharan Amirtha , Arqub Sarah Abu , Gandhi Vaibhav , Da Cunha Godoy Lucas , Kuo Chia-Ling , Uribe Flavio 
Published: March 2022

Abstract
Aim
To evaluate the correspondence between the interproximal reduction (IPR) performed clinically and that programmed in ClinCheck® and further assess which teeth showed an amount of implemented IPR (I-IPR) that corresponds with that programmed in ClinCheck®.

Materials and methods
Pre- (T0) and post-treatment (T1) ClinCheck® digital models for 75 subjects (30 males and 45 females), mean age (38 ± 15) years, were included. To calculate the amount of I-IPR, Ortho Analyzer software (3Shape, Copenhagen, Denmark) was used to measure the mesiodistal widths for the maxillary and mandibular teeth from second premolar to the contralateral second premolar on the initial (T0) and final (T1) STL models. I- IPR performed by tooth was obtained by comparing the mesiodistal width of each tooth at T0 and T1. The amount of programmed IPR (P-IPR) in ClinCheck® was compared to that implemented clinically using the following formula: IPR difference = (P-IPR) − (I-IPR).

Results
Statistically significant differences were observed between the average value of digitally programmed and implemented IPR per tooth for both the maxillary (p < .0001) and mandibular (p < .0001) teeth. The mean P-IPR for the maxillary teeth was 0.28 ± 0.16 mm versus the mean I-IPR of 0.15 ± 0.15 mm. In the mandibular arch, the mean P-IPR was 0.31 ± 0.17 mm, while the I-IPR was 0.17 ± 0.16 mm. The mean I-IPR was consistently lower than the mean P-IPR regardless of teeth and sites (p < 0.0001). The difference between the P-IPR compared to the I-IPR was larger for mandibular anterior teeth than for maxillary anterior teeth (p = 0.0302) and larger for maxillary posterior teeth than mandibular posterior teeth (p = 0.0059).

Conclusion
The amount of implemented-IPR in clear aligner therapy is less than that digitally programmed for most teeth. Regardless of the regions, I-IPR was consistently lower than that programmed. Mandibular anterior teeth and maxillary posterior teeth showed greater discrepancy between P-IPR and I-IPR than the maxillary anterior and mandibular posteriors. Further prospective studies are needed to determine the factors affecting the precision of IPR and the clinical implications of a significantly reduced I-IPR on treatment outcomes.
Motivation to learn by age, education, and literacy skills among working-age adults in the United States
Authors: Yamashita Takashi , Smith Thomas J. , Sahoo Shalini , Cummins Phyllis A. 
Published: March 2022

AbstractThis study highlighted how particular intersections of personal characteristics were related to Motivation to Learn (MtL) among adults. MtL is a prerequisite for adult education and training participation. However, little is known about MtL across subpopulations due to several methodological limitations. This study developed a national profile of MtL by key subpopulations that are defined by combinations of age, gender, education level, and literacy proficiency in the United States. Data were obtained from 2012/2014/2017 Program for International Assessment of Adult Competencies (PIAAC) restricted use file (N = 8400). The alignment optimization (AO) method was employed to estimate subpopulation means of a PIAAC-based latent MtL construct. Subpopulations with younger age, greater educational attainment, and higher literacy proficiency showed significantly greater MtL.
New avenues of sepsis research: obtaining perspective by analyzing and comparing SSCG 2021 and J-SSCG 2020
Authors: Yatabe Tomoaki , Egi Moritoki , Ogura Hiroshi 
Published: March 2022

AbstractRecently, revisions of two sepsis guidelines, namely, the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 and the Surviving Sepsis Campaign Guidelines 2021, were published. Although both guidelines were created in accordance with the Grading of Recommendations, Assessment, Development and Evaluation approach, the evidence-to-decision tables differed between them. In addition, certain recommendations may differ between these guidelines for similar clinical questions because of differences in the “PICO” criteria. Other differences in recommendations between the two guidelines are due to unclear evidence, and these ambiguities may provide the basis for further sepsis research. We hope that these two guidelines will contribute to the creation of new clinical evidence in addition to supporting treatment of patients with sepsis.