bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of HDAC4 by GSK3β leads to downregulation of KLF5 and ASK1 and prevents the progression of intravertebral disc degeneration
Authors: Xiao Lin , Gong Dongping , Liang Loufeng , Liang Anwei , Liang Huaxin , Xu Xiayi , Teng Hongli 
Published: March 2021

Abstract
Background
Intervertebral disc degeneration (IDD) is a major cause of lower back pain. This study aimed at exploring the effects of histone deacetylase 4 (HDAC4) and its upstream and downstream signaling molecules on IDD development.

Methods
A murine IDD model was established by inducing a needle puncture injury to the vertebrate, whereupon we isolated and transfected of nucleus pulposus (NP) cells. Disc height index (DHI) of the mice was determined by X-ray tomography, while the pain experienced by the IDD mice was evaluated by mechanical and thermal sensitivity tests. Next, the interaction between GSK3β and HDAC4 as well as that between HDAC4 and KLF5 acetylation was assessed by co-immunoprecipitation, while the promoter region binding was assessed identified by chromatin immunoprecipitation. By staining methods with TUNEL, Safranin O fast green, and hematoxylin and eosin, the NP cell apoptosis, degradation of extracellular matrix, and morphology of intervertebral disc tissues were measured. Furthermore, mRNA and protein expressions of GSK3β, HDAC4, KLF5, and ASK1, as well as the extent of HDAC4 phosphorylation, were determined by RT-qPCR and Western blotting.

Results
GSK3β was identified to be downregulated in the intervertebral disc tissues obtained from IDD mice, while HDAC4, KLF5, and ASK1 were upregulated. HDAC4 silencing alleviated IDD symptoms. It was also found that GSK3β promoted the phosphorylation of HDAC4 to increase its degradation, while HDAC4 promoted ASK1 expression through upregulating the expression of KLF5. In IDD mice, GSK3β overexpression resulted in increased DHI, inhibition of NP cell apoptosis, alleviation of disc degeneration, and promoted mechanical and thermal pain thresholds. However, HDAC4 overexpression reversed these effects by promoting ASK1 expression.

Conclusion
Based on the key findings of the current study, we conclude that GSK3β can promote degradation of HDAC4, which lead to an overall downregulation of the downstream KLF5/ASK1 axis, thereby alleviating the development of IDD.
The excess costs of childhood food allergy on Canadian families: a cross-sectional study
Authors: Golding Michael A. , Simons Elinor , Abrams Elissa M. , Gerdts Jennifer , Protudjer Jennifer L. P. 
Published: March 2021

Abstract
Background
The impact of childhood food allergy on household costs has not been examined in Canada. The current study sought to examine differences in direct, indirect, and intangible costs among Canadian families with and without a food-allergic child.

Methods
Families with a child with a specialist-diagnosed food allergy (cases) were recruited from two tertiary pediatric allergy clinics in the Province of Manitoba, Canada, and matched, based on age and sex, to families without a food-allergic child (controls). Cost data for the two groups were collected via an adapted version of the Food Allergy Economic Questionnaire (FA-EcoQ). Consideration was given to income, defined as above vs. below the provincial annual median income.

Results
Results from 35 matched case/control pairs revealed that while total household costs did not significantly differ between cases and controls, food-allergic families did incur higher direct costs ($12,455.69 vs. $10,078.93, p = 0.02), which were largely attributed to spending on food. In contrast, cases reported lower, but not statistically significant, total indirect costs compared to controls ($10,038.76 vs. $12,294.12, p = 0.06). Families also perceived their food-allergic child as having poorer quality of life relative to their healthy peers. Lastly, stratification of the analyses by annual income revealed several differences between the higher and lower income groups.

Conclusions
Relative to families without a food-allergic child, food-allergic families incurred higher direct costs across a number of different areas.
Trisomy 5p with bilateral congenital diaphragmatic hernia: a case report
Authors: Nakamura Noriyuki , Ushida Takafumi , Moriyama Yoshinori , Imai Kenji , Nakano-Kobayashi Tomoko , Osuka Satoko , Goto Maki , Kajiyama Hiroaki , Asada Hideyuki , Hayakawa Masahiro , Kotani Tomomi 
Published: March 2021

Abstract
Background
Bilateral congenital diaphragmatic hernia (CDH) is very rare. A few studies have reported the pathogenic role of 5p in CDH.

Case presentation
A 23-year-old primigravida Japanese woman was referred for the following abnormal findings at 33 weeks of gestation: polyhydramnios, macroglossia, talipes equinovarus, and levocardia. A marker chromosome was detected by amniocentesis. Fluorescence in situ hybridization with whole chromosome paint 5 and nucleolus organizer region probes confirmed its origin from chromosome 5 and an acrocentric chromosome. The karyotype of the fetus was diagnosed as 47, XY, +mar. ish +mar(WCP5+). At 39 + 5 weeks, a 2462 g male infant was delivered, with a specific facial configuration. Bilateral CDH, hypoplasia of the corpus callosum, atrial septal defect, and hypothyroidism were also detected in the baby. The karyotype of the peripheral blood was consistent with that of the amniocentesis.

Conclusion
Genes coded on 5p might be associated with the pathogenesis of CDH; however, further investigation is required.
Progress and challenges in developing organoids in farm animal species for the study of reproduction and their applications to reproductive biotechnologies
Authors: Bourdon Guillaume , Cadoret Véronique , Charpigny Gilles , Couturier-Tarrade Anne , Dalbies-Tran Rozenn , Flores Maria-José , Froment Pascal , Raliou Mariam , Reynaud Karine , Saint-Dizier Marie , Jouneau Alice 
Published: March 2021

AbstractWithin the past decades, major progress has been accomplished in isolating germ/stem/pluripotent cells, in refining culture medium and conditions and in establishing 3-dimensional culture systems, towards developing organoids for organs involved in reproduction in mice and to some extent in humans. Haploid male germ cells were generated in vitro from primordial germ cells. So were oocytes, with additional support from ovarian cells and subsequent follicle culture. Going on with the female reproductive tract, spherical oviduct organoids were obtained from adult stem/progenitor cells. Multicellular endometrial structures mimicking functional uterine glands were derived from endometrial cells. Trophoblastic stem cells were induced to form 3-dimensional syncytial-like structures and exhibited invasive properties, a crucial point for placentation. Finally, considering the embryo itself, pluripotent embryonic cells together with additional extra-embryonic cells, could self-organize into a blastoid, and eventually into a post-implantation-like embryo. Most of these accomplishments have yet to be reached in farm animals, but much effort is devoted towards this goal. Here, we review the progress and discuss the specific challenges of developing organoids for the study of reproductive biology in these species. We consider the use of such organoids in basic research to delineate the physiological mechanisms involved at each step of the reproductive process, or to understand how they are altered by environmental factors relevant to animal breeding. We evaluate their potential in reproduction of animals with a high genetic value, from a breeding point of view or in the context of preserving local breeds with limited headcounts.
Early combination of albumin with crystalloids administration might be beneficial for the survival of septic patients: a retrospective analysis from MIMIC-IV database
Authors: Zhou Shiyu , Zeng Zhenhua , Wei Hongxia , Sha Tong , An Shengli 
Published: March 2021

Abstract
Background
Fluid therapy is a cornerstone in the treatment of sepsis. Recently, the guidelines have recommended the combined administration that using crystalloids plus albumin for septic patients, but the optimal timing for albumin combined is still unclear. The objective of this study was to investigate the association of timing of albumin combined with 28-day mortality in patients with sepsis.

Methods
We involved septic patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and these patients were categorized into crystalloids group (crystalloids alone) and early combination group (crystalloids combined albumin at 0–24 h). The primary outcome was 28-day mortality. We used propensity score matching (PSM) to adjust confounding and restricted mean survival time (RMST) analysis was conducted to quantify the beneficial effect on survival due to the combination group.

Results
We categorized 6597 and 920 patients in the “crystalloids alone” and “early combination”, respectively. After PSM, compared to the crystalloids group, the combination group was associated with the increased survival among 28-day (increased survival: 3.39 days, 95% CI 2.53–4.25; P < 0.001) after ICU admission. Patients who received albumin combination at the first 24-h was associated with prolonged LOS in ICU (10.72 days vs. 8.24 days; P < 0.001) but lower risk of 28-day mortality (12.5% vs 16.4%, P = 0.003) than those received crystalloids alone.

Conclusion
In septic patients, receiving albumin combined within the first 24-h after crystalloids administration was associated with an increment of survival in 28 days.
Uniform estimates with data from generalized Lebesgue spaces in periodic structures
Authors: Jang Yunsoo 
Published: March 2021

AbstractWe study various types of uniform Calderón–Zygmund estimates for weak solutions to elliptic equations in periodic homogenization. A global regularity is obtained with respect to the nonhomogeneous term from weighted Lebesgue spaces, Orlicz spaces, and weighted Orlicz spaces, which are generalized Lebesgue spaces, provided that the coefficients have small BMO seminorms and the domains are δ-Reifenberg domains.
A fractional order epidemic model for the simulation of outbreaks of Ebola
Authors: Pan Weiqiu , Li Tianzeng , Ali Safdar 
Published: March 2021

AbstractThe Ebola outbreak in 2014 caused many infections and deaths. Some literature works have proposed some models to study Ebola virus, such as SIR, SIS, SEIR, etc. It is proved that the fractional order model can describe epidemic dynamics better than the integer order model. In this paper, we propose a fractional order Ebola system and analyze the nonnegative solution, the basic reproduction number$R_{0}$R0, and the stabilities of equilibrium points for the system firstly. In many studies, the numerical solutions of some models cannot fit very well with the real data. Thus, to show the dynamics of the Ebola epidemic, the Gorenflo–Mainardi–Moretti–Paradisi scheme (GMMP) is taken to get the numerical solution of the SEIR fractional order Ebola system and the modified grid approximation method (MGAM) is used to acquire the parameters of the SEIR fractional order Ebola system. We consider that the GMMP method may lead to absurd numerical solutions, so its stability and convergence are given. Then, the new fractional orders, parameters, and the root-mean-square relative error$g(U^{*})=0.4146$g(U∗)=0.4146are obtained. With the new fractional orders and parameters, the numerical solution of the SEIR fractional order Ebola system is closer to the real data than those models in other literature works. Meanwhile, we find that most of the fractional order Ebola systems have the same order. Hence, the fractional order Ebola system with different orders using the Caputo derivatives is also studied. We also adopt the MGAM algorithm to obtain the new orders, parameters, and the root-mean-square relative error which is$g(U^{*})=0.2744$g(U∗)=0.2744. With the new parameters and orders, the fractional order Ebola systems with different orders fit very well with the real data.
Proinov type contractions on dislocated b-metric spaces
Authors: Alqahtani Badr , Alzaid Sara S. , Fulga Andreea , Roldán López de Hierro Antonio Francisco 
Published: March 2021

AbstractIn this paper, we improve the Proinov theorem by adding certain rational expressions to the definition of the corresponding contractions. After that, we prove fixed point theorems for these modified Proinov contractions in the framework of dislocated b-metric spaces. We show some illustrative examples to indicate the validity of the main results.
Differentiating IDH status in human gliomas using machine learning and multiparametric MR/PET
Authors: Tatekawa Hiroyuki , Hagiwara Akifumi , Uetani Hiroyuki , Bahri Shadfar , Raymond Catalina , Lai Albert , Cloughesy Timothy F. , Nghiemphu Phioanh L. , Liau Linda M. , Pope Whitney B. , Salamon Noriko , Ellingson Benjamin M. 
Published: March 2021

Abstract
Background
The purpose of this study was to develop a voxel-wise clustering method of multiparametric magnetic resonance imaging (MRI) and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) positron emission tomography (PET) images using an unsupervised, two-level clustering approach followed by support vector machine in order to classify the isocitrate dehydrogenase (IDH) status of gliomas.

Methods
Sixty-two treatment-naïve glioma patients who underwent FDOPA PET and MRI were retrospectively included. Contrast enhanced T1-weighted images, T2-weighted images, fluid-attenuated inversion recovery images, apparent diffusion coefficient maps, and relative cerebral blood volume maps, and FDOPA PET images were used for voxel-wise feature extraction. An unsupervised two-level clustering approach, including a self-organizing map followed by the K-means algorithm was used, and each class label was applied to the original images. The logarithmic ratio of labels in each class within tumor regions was applied to a support vector machine to differentiate IDH mutation status. The area under the curve (AUC) of receiver operating characteristic curves, accuracy, and F1-socore were calculated and used as metrics for performance.

Results
The associations of multiparametric imaging values in each cluster were successfully visualized. Multiparametric images with 16-class clustering revealed the highest classification performance to differentiate IDH status with the AUC, accuracy, and F1-score of 0.81, 0.76, and 0.76, respectively.

Conclusions
Machine learning using an unsupervised two-level clustering approach followed by a support vector machine classified the IDH mutation status of gliomas, and visualized voxel-wise features from multiparametric MRI and FDOPA PET images. Unsupervised clustered features may improve the understanding of prioritizing multiparametric imaging for classifying IDH status.
Immediate and early loading of hydrothermally treated, hydroxyapatite-coated dental implants: a 7-year prospective randomized clinical study
Authors: Arghami Afarin , Simmons David , St. Germain Jeanne , Maney Pooja 
Published: March 2021

Abstract
Background
Existing research on marginal bone stability around hydroxyapatite (HA)-coated implants often lacks adequate long-term follow-up. The purpose of this randomized prospective study was to evaluate the 7-year outcome of patients with immediate and early loaded single-tooth restorations supported by implants with plasma-sprayed, partially HA-coated surfaces. Forty-two patients in need of 50 single implants were treated in in the Postgraduate Periodontics Clinic of Louisiana State University School of Dentistry. Implants were randomly divided into 2 groups: Group A was immediately loaded, and Group B was early loaded. Continuous follow-up with periodic maintenance care and radiographic evaluations was performed. The primary outcome of interest was implant survival, characterized using the Kaplan–Meier method. Secondary study outcome consisted of peri-implant crestal bone level changes. Data on age, sex, bone quality, implant location, length and diameter, and prior augmentation of the site were collected. Multiple regression analyses were conducted to determine whether the independent variables were associated with bone loss.

Results
One implant failed to maintain stability and was removed at 3 weeks. Thirty-four patients (14 males, 20 females with a total of 42 implants) completed the 7-year follow-up visit. Average age of evaluable patients was 52 in Group A and 55 in Group B. No significant difference was observed regarding sex and age distribution between the 2 groups. No significant difference was detected in the distribution of implant locations, types of bone, implant length, implant diameter, and augmentation status of the bone between the 2 groups. After 7 years of functioning for the 42 implants examined, implant survival rate was 100% for Group A and 95.5% for Group B. The results from this study of 50 implants showed that HA-coated Zimmer Tapered Screw-Vent Implants were clinically effective, with an overall cumulative 7-year survival rate of 98.0%. When comparing radiographic bone levels between 2-year and 7-year follow-ups, no significant differences in bone loss were found between Group A and Group B.

Conclusions
After 7 years in function, implants partially coated with plasma-sprayed and hydrothermally treated HA were clinically predictable when restored in occlusion immediately after or 3 weeks after implant placement.
Snow removal maintained a high level of physical activity in patients undergoing hemodialysis in heavy snowfall areas
Authors: Sato Yoichi , Iino Noriaki 
Published: March 2021

Abstract
Background
Physical activity is an essential parameter associated with the prognosis of hemodialysis patients. Physical activity has regional characteristics; for example, snow removal is imperative in snowbelts during the winter. This study investigated the effects of removing snow on the physical activity levels of hemodialysis patients living in a snowbelt.

Methods
This study retrospectively examined 28 patients who underwent hemodialysis (age 69.6 ± 15.4 years, 19 males) in Uonuma Kikan Hospital between December 2019 and March 2020. Physical activity was assessed using the International Physical Activity Questionnaire. Patients were divided into a snow remover group and a non-snow remover group. We examined whether there were differences in physical or mental functioning and physical activity between the two groups. We also investigated the factors that influence high levels of physical activity among hemodialysis patients using multivariate linear regression analysis.

Results
The snow remover group had significantly greater grip strength, higher sit-to-stand test scores and gait speed, and a lower prevalence of frailty than the non-snow remover group. The level of physical activity was also significantly higher in the snow remover group. One of the patients in the snow remover group was frail. The univariate linear regression analysis showed that physical activity was related to age, grip strength, sit-to-stand test score, gait speed, and snow removal. In the multivariate linear regression analysis, snow removal and grip strength were significantly associated with a high level of physical activity.

Conclusions
Among hemodialysis patients living in a snowbelt, the snow remover group had significantly better physical functioning and a higher level of physical activity.
Discrete choice experiments or best-worst scaling? A qualitative study to determine the suitability of preference elicitation tasks in research with children and young people
Authors: Rogers Helen J. , Marshman Zoe , Rodd Helen , Rowen Donna 
Published: March 2021

Abstract
Background
Ordinal tasks are increasingly used to explore preferences for health states. This study aimed to determine the suitability of two ordinal preference elicitation tasks (discrete choice experiments (DCE) and best-worst scaling (BWS)) for use with children and young people to generate health state utility values. The study explored children’s understanding, the relationship between their age and level of understanding, and how many tasks they felt they could complete.

Methods
Children aged 11–16 years were recruited from a secondary school in South Yorkshire, UK. Participants were asked to ‘think aloud’ as they completed a computer-based survey that contained both DCE and BWS tasks relating to dental caries (tooth decay) health states. Health states involved descriptions of the impact of tooth decay on children’s daily lives. One-to-one semi-structured interviews were then held with participants, with use of a topic guide. Qualitative data were transcribed verbatim and analysed thematically.

Results
A total of 33 children (12 male, 21 female) participated, comprising 5–6 children from each school year group. Children expressed a preference for BWS and demonstrated a better understanding of these tasks than DCE. There was no clear relationship between children’s level of understanding and age. Children felt they could manage between 8 and 10 BWS tasks comfortably.

Conclusion
This study suggests that BWS tasks are the most appropriate type of preference elicitation task to value health states for children and young people aged 11–16 years to complete.
Histopathological specialized staining of oral lichen planus-induced fibrotic changes and surgical treatment of associated restricted mouth opening: a case report
Authors: Shudo Atsushi 
Published: March 2021

Abstract
Background
Oral lichen planus is a chronic inflammatory and immune-mediated disease that affects the oral mucosa. Recent findings have suggested that oral lichen planus is often associated with submucosal fibrotic changes. Fibrotic changes in the buccal submucosa may cause restricted mouth opening. This report discusses the histopathological examination (including specialized staining) and surgical treatment for oral lichen planus-induced fibrotic changes.

Case presentation
Here, we describe a 63-year-old woman who had oral lichen planus with fibrotic changes. Her maximum mouth opening distance was approximately 30 mm due to submucosal fibrotic changes, and she exhibited gradual fibrosis progression. Histological examinations were performed to assess the oral lichen planus-induced fibrotic changes. Then, double Z-plasty were performed as treatment for restricted mouth opening. The immunohistochemical staining results were negative for cytokeratin 13 and positive in some layers for cytokeratin 17 and Ki-67/MIB-1. Masson's trichrome staining showed enhanced collagen formation. Postoperative mouth opening training enabled the patient to achieve a mouth opening distance of > 50 mm.

Conclusion
Our findings suggest that histopathological examination with specialized staining can aid in the evaluation of oral lichen planus-induced fibrotic changes, and that Z-plasty is effective for the treatment of restricted mouth opening due to oral lichen planus.