bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of robotic priming of bilateral arm training, mirror therapy, and impairment-oriented training on sensorimotor and daily functions in patients with chronic stroke: study protocol of a single-blind, randomized controlled trial
Authors: Lee Yi-chen , Li Yi-chun , Lin Keh-chung , Yao Grace , Chang Ya-ju , Lee Ya-yun , Liu Chien-ting , Hsu Wan-ling , Wu Yi-hsuan , Chu Ho-ta , Liu Ting-xuan , Yeh Yi-ping , Chang Chieh 
Published: July 2022

AbstractBackgroundCombining robotic therapy (RT) with task-oriented therapy is an emerging strategy to facilitate motor relearning in stroke rehabilitation. This study protocol will compare novel rehabilitation regimens that use bilateral RT as a priming technique to augment two task-oriented therapies: mirror therapy (MT) and bilateral arm training (BAT) with a control intervention: RT combined with impairment-oriented training (IOT).MethodsThis single-blind, randomized, comparative efficacy study will involve 96 participants with chronic stroke. Participants will be randomized into bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT groups and receive 18 intervention sessions (90 min/day, 3 d/week for 6 weeks). The outcomes will include the Fugl-Meyer Assessment, Stroke Impact Scale version 3.0, Medical Research Council scale, Revised Nottingham Sensory Assessment, ABILHAND Questionnaire, and accelerometer and will be assessed at baseline, after treatment, and at the 3-month follow-up. Analysis of covariance and the chi-square automatic interaction detector method will be used to examine the comparative efficacy and predictors of outcome, respectively, after bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT.DiscussionThe findings are expected to contribute to the research and development of robotic devices, to update the evidence-based protocols in postacute stroke care programs, and to investigate the use of accelerometers for monitoring activity level in real-life situations, which may in turn promote home-based practice by the patients and their caregivers. Directions for further studies and empirical implications for clinical practice will be further discussed in upper-extremity rehabilitation after stroke.Trial registrationThis trial was registered December 12, 2018, at www.clinicaltrials.gov (NCT03773653).
Interval Valued Intuitionistic Fuzzy Line Graphs
Authors: Repalle V. N. Srinivasa Rao , Tola Keneni Abera , Ashebo Mamo Abebe 
Published: July 2022

Abstract
Objectives
In the field of graph theory, an intuitionistic fuzzy set becomes a useful tool to handle problems related to uncertainty and impreciseness. We introduced the interval-valued intuitionistic fuzzy line graphs (IVIFLG) and explored the results related to IVIFLG.

Result
Some propositions and theorems related to IVIFLG are proposed and proved, which are originated from intuitionistic fuzzy graphs (IVIG). Furthermore, Isomorphism between two IVIFLGs toward their IVIFGs was determined and verified.
Publication dynamics: what can be done to eliminate barriers to publishing full manuscripts by the postgraduate trainees of a low-middle income country?
Authors: Majid Hafsa , Jafri Lena , Ahmed Sibtain , Abid Muhammad Abbas , Aamir Mohammad , Ijaz Aamir , Khan Aysha Habib , Siddiqui Imran 
Published: July 2022

Abstract
Objectives
This study aimed to determine the publication rate of free paper abstracts presented by the postgraduate (PG) trainees and determine the reasons for non-publication. A mixed methods study was conducted. PG trainees presenting free papers at the at the Pakistan Society of Chemical Pathologist conferences from 2012 to 2018 were included. Three databases were searched to identify if the abstracts were published or not. The PG trainee authors of abstracts not published as full manuscript, were surveyed to determine the barriers and challenges in publishing a manuscript.

Results
The average rate of full manuscript publication was 51.8% (n = 93/177) for the abstracts presented by the PG trainees. Publication rate was higher for oral (n = 73/119, 61.3%) compared to poster presentation (n = 20/58, 34.5%). Most of the manuscripts were published after two years of abstract presentation. The survey showed that the main challenges to publishing an abstract were lack of time, limited scientific writing or submission skills, lack of funding for publication fee, and negative or statistically non-significant results. This reflects a need to arrange workshops/symposia for the PG trainees of low-middle income country (LMIC) to enhance their writing and time management skills and improve the full manuscript publication rate from LMICs.
The G1/S repressor WHI5 is expressed at similar levels throughout the cell cycle
Authors: Tollis Sylvain 
Published: July 2022

Abstract
Objectives
While it is clear that cells need to grow before committing to division at the G1/S transition of the cell cycle, how cells sense their growth rate or size at the molecular level is unknown. It has been proposed that, in budding yeast, the dilution of the Whi5 G1/S transcriptional repressor as cells grow in G1 is the main driver of G1/S commitment. This model implies that Whi5 synthesis is substantially reduced in G1 phase. Recent work has reported that the concentration of Whi5 is size- and time-independent in G1 cells, challenging the dilution model. These results in turn imply that Whi5 must be synthesized in G1 phase, but the cell cycle dependence of WHI5 mRNA expression has not been examined in live cells.

Results description
To address this question, we monitored single WHI5 mRNA molecules in single live cells using confocal microscopy, and quantified WHI5 mRNA copy number in G1, G1/S, and S/G2/M phase cells. We observed that WHI5 mRNA is found in very similar amount irrespective of cell cycle stage. The constant WHI5 mRNA copy number throughout G1 phase rules out alterations in mRNA abundance as a contributing factor for any putative dilution of Whi5.
The investigation of the efficacy and safety of stromal vascular fraction in the treatment of nanofat-treated acne scar: a randomized blinded controlled clinical trial
Authors: Behrangi Elham , Moradi Sepideh , Ghassemi Mohammadreza , Goodarzi Azadeh , Hanifnia Amirreza , Zare Sona , Nouri Maryam , Dehghani Abbas , Seifadini Azadeh , Nilforoushzadeh Mohammad Ali , Roohaninasab Masoumeh 
Published: July 2022

Abstract
Background
Acne is the most common skin disorder which is known as a chronic inflammatory disease with psychological burden and reduced quality of life. Adipose tissue-derived stromal vascular fraction (SVF) is recognized as a source of regenerative cells and improves the quality of skin by increasing collagen content. To date, a few studies have been performed on the therapeutic role of SVF in the treatment of acne scars.

Methods
This randomized, single-blinded clinical trial was performed on 7 patients with acne scars. In all patients, the initial grade of acne (volume, area and depth) was evaluated and ultrasound of the relevant scar was performed to evaluate neocollagenesis. As a spilt face study, for treating the scars, we used nanofat subcutaneously on one side of the face (control group) and combination of nanofat subcutaneously and SVF intradermally on the opposite side (intervention group). The patients were evaluated for severity of acne by visioface after one month, also for thickness of epidermis and dermis by ultrasound after one month and three months.

Results
All of the apparent findings of scars improved in two groups after one month, but these changes were significant just for the group treated with SVF (p value < 0.05). Epidermal, dermal and complete thicknesses during the first month in both control and intervention groups were significantly increased (p value < 0.05) but between the first and third months, there was no significant difference in the variables (p value > 0.05). The findings showed that dermal and complete thicknesses of the skin in the first month were different between two groups significantly (p value: 0.042 and 0.040, respectively).

Conclusion
The use of SVF in the treatment of patients with acne scars accelerates the improvement of volume, area and depth of the scar by increasing collagen content and the dermal thickness, so it can be used as a potentially effective treatment for these patients.
Expansion of mouse castration-resistant intermediate prostate stem cells in vitro
Authors: Xu Yalan , Mu Jie , Zhou Zhixia , Leng Yu , Yu Yali , Song Xiuyue , Liu Aihua , Zhu Hai , Li Jing , Wang Dong 
Published: July 2022

Abstract
Background
Most castration-resistant prostate cancers (CRPCs) have a luminal phenotype with high androgen receptor (AR) and prostate-specific antigen (PSA) expression. Currently, it is difficult to culture castration-resistant luminal cells with AR and PSA expression.

Methods
We formulated a custom-made medium and isolated primary cells from the prostate of adult wild-type (WT) and TRAMP mice. The cells were characterized by immunofluorescence staining, transcriptomic analysis, and qRT-PCR verification. Their self-renewal and differentiation potential in vitro and in vivo were examined. We treated the cells with androgen deprivation and enzalutamide and performed immunofluorescence staining and western blotting to analyze their expression of AR and PSA.

Results
We isolated a novel type of castration-resistant intermediate prostate stem cells (CRIPSCs) from adult WT and TRAMP mice. The mouse CRIPSCs proliferated rapidly in two-dimensional (2D) culture dishes and can be cultured for more than six months. The mouse CRIPSCs expressed luminal markers (AR, PSA, and Dsg4), basal markers (CK5 and p63), Psca, and the intermediate cell marker (Ivl). Transcriptomic analysis showed that the mouse CRIPSCs had upregulated signaling pathways related to cancer development and drug resistance. In the long-term culture, TRAMP CRIPSCs had higher expression of the genes related to stem cells and cancers than WT mice. Both WT and TRAMP CRIPSCs formed organoids in Matrigel. WT CRIPSCs did not form prostate tissues when transplanted in vivo without urogenital sinus mesenchyme (UGM) cells. In contrast, TRAMP CRIPSCs formed prostate ducts in NOG mice without UGM cells and differentiated into luminal, basal, and neuroendocrine cells. Androgens regulated AR translocation between the nucleus and cytoplasm in the mouse CRIPSCs. Treatment of androgen deprivation (ADT) and enzalutamide reduced AR expression in WT and TRAMP CRIPSCs; however, this treatment promoted PSA expression in TRAMP, while not WT CRIPSCs, similar to the clinical observations of CRPC.

Conclusions
Our study established a method for isolating and expanding mouse CRIPSCs in 2D culture dishes. Mouse CRIPSCs had markers of basal and luminal cells, including AR and PSA, and can differentiate into prostate organoids and tissues. TRAMP CRIPSCs had elevated PSA expression upon ADT and enzalutamide treatment. Our method can be translated into clinical settings for CRPC precision medicine.
CCL20/CCR6 axis mediates macrophages to promote proliferation and migration of ESCs by blocking autophagic flux in endometriosis
Authors: Tan Jiahuan , Xu Tenghan , Gou Yanling , Wang Honglin , Liang Zongwen , Cao Yingying , Wang Han , Yu Yangyang , Jiao Na , Zhang Zongfeng 
Published: July 2022

Abstract
Background
Endometriosis (EMs) is a common benign gynecological disease that affects approximately 10% of females of reproductive age. Endometriosis ectopic lesions could recruit macrophages, which in turn facilitates endometriosis progression. Several studies have indicated that CCL20 derived from macrophages activates the expression of CCR6 in several cells and induces cell proliferation and migration. However, the function of the CCL20/CCR6 axis in the interactions between macrophages and endometriotic stromal cells (ESCs) in EMs has yet to be elucidated.

Methods
Ectopic and normal endometrial tissues were collected from 35 ovarian endometriosis patients and 21 control participants for immunohistochemical staining. It was confirmed that macrophages secreted CCL20 to promote CCR6 activation of ESCs during co-culture by ELISA, qRT-PCR and western blot analysis. CCK8 and Edu assays were used to detect cell proliferation, and wound healing and Transwell assay were used to detect cell migration. Autophagic flux was detected by measuring the protein expression levels of LC3 and P62by western blot and analyzing the red/yellow puncta after ESCs were transfected with mRFP-GFP-LC3 double fluorescence adenovirus (Ad‐LC3). Lysosomal function was tested by quantifying the fluorescent intensities of Lyso-tracker and Gal3 and activity of acid phosphatase. In addition, co-IP experiments verified the binding relationship between CCR6 and TFEB. Finally, the suppressive effect of CCL20-NAb on endometriosis lesions in vivo was demonstrated in mice models.

Results
We demonstrated that macrophages secreted CCL20 to promote CCR6 activation of ESCs during co-culture, which further induced the proliferation and migration of ESCs. We observed that the CCL20/CCR6 axis impaired lysosomal function and then blocked the autolysosome degradation process of autophagic flux in ESCs. The combination of CCR6 and TFEB to inhibit TFEB nuclear translocation mediates the role of the CCL20/CCR6 axis in the above process. We also found that co-culture with ESCs upregulated the production and secretion of CCL20 by macrophages. The suppression effect of CCL20-NAb on endometriosis lesions in vivo was demonstrated in mice models.

Conclusions
Our data indicate that macrophages block TFEB-mediated autolysosome degradation process of autophagic flux in ESCs via the CCL20/CCR6 axis, thereby promoting ESC proliferation and migration.
Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway
Authors: Zhang Yi-Lin , Liu Fen , Li Zhi-Bang , He Xiao-Tao , Li Xuan , Wu Rui-Xin , Sun Hai-Hua , Ge Shao-Hua , Chen Fa-Ming , An Ying 
Published: July 2022

AbstractBackgroundHigh glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown.MethodsOsteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways.ResultsWe found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs under high glucose.ConclusionsThe present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals.
Organ-specific extracellular matrix directs trans-differentiation of mesenchymal stem cells and formation of salivary gland-like organoids in vivo
Authors: Tran Olivia N. , Wang Hanzhou , Li Shengxian , Malakhov Andrey , Sun Yuyang , Abdul Azees Parveez A. , Gonzalez Aaron O. , Cao Brian , Marinkovic Milos , Singh Brij B. , Dean David D. , Yeh Chih-Ko , Chen Xiao-Dong 
Published: July 2022

Abstract
Background
Current treatments for salivary gland (SG) hypofunction are palliative and do not address the underlying cause or progression of the disease. SG-derived stem cells have the potential to treat SG hypofunction, but their isolation is challenging, especially when the tissue has been damaged by disease or irradiation for head and neck cancer. In the current study, we test the hypothesis that multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model are capable of trans-differentiating to the SG epithelial cell lineage when induced by a native SG-specific extracellular matrix (SG-ECM) and thus may be a viable substitute for repairing damaged SGs.

Methods
Rat BM-MSCs were treated with homogenates of decellularized rat SG-ECM for one hour in cell suspension and then cultured in tissue culture plates for 7 days in growth media. By day 7, the cultures contained cell aggregates and a cell monolayer. The cell aggregates were hand-selected under a dissecting microscope, transferred to a new tissue culture dish, and cultured for an additional 7 days in epithelial cell differentiation media. Cell aggregates and cells isolated from the monolayer were evaluated for expression of SG progenitor and epithelial cell specific markers, cell morphology and ultrastructure, and ability to form SG-like organoids in vivo.

Results
The results showed that this approach was very effective and guided the trans-differentiation of a subpopulation of CD133-positive BM-MSCs to the SG epithelial cell lineage. These cells expressed amylase, tight junction proteins (Cldn 3 and 10), and markers for SG acinar (Aqp5 and Mist 1) and ductal (Krt 14) cells at both the transcript and protein levels, produced intracellular secretory granules which were morphologically identical to those found in submandibular gland, and formed SG-like organoids when implanted in the renal capsule in vivo.

Conclusions
The results of this study suggest the feasibility of using autologous BM-MSCs as an abundant source of stem cells for treating SG hypofunction and restoring the production of saliva in these patients.
In silico prediction and in vitro validation of the effect of pH on adhesive behaviour of the fused CsgA-MFP3 protein
Authors: Shahryarimorad Keyvan , Alipour Atefeh , Honar Yousof Saeedi , Abtahi Behrouz , Shokrgozar Mohammad Ali , Shahsavarani Hosein 
Published: July 2022

AbstractRecombinant production of mussel foot proteins among marine-inspired proteinaceous adhesive materials has been attracted high attention for medical applications, due to their exceptional versatility potential of hierarchically arranged nanostructures. Various biochemical and proteinous factors such as amyloid CsgA curli protein have been used as a synergistic factor to enhance the constancy of obtained bio-adhesion but their mechanistic interactions have not yet been deeply investigated widely in different pH conditions. To this end, the present study has first sought to assess molecular simulation and prediction by using RosettaFold to predict the 3-dimensional structure of the fused CsgA subunit and the MFP3 protein followed by in vitro verification. It was developed an ensemble of quantitative structure-activity relationship models relying on simulations according to the surface area and molecular weight values of the fused proteins in acidic to basic situations using PlayMolecule (protein preparation app for MD simulations) online databases followed by molecular dynamic simulation at different pHs. It was found that acidic conditions positively affect adhesive strength throughout the chimeric structure based on comparative structure-based analyses along with those obtained in prevailing literature. Atomic force microscopy analysis was confirmed obtained in silico data which showed enhanced adhesive properties of fused protein after self-assembly in low pH conditions. In conclusion, the augmented model for reactivity predictions not only unravels the performance and explain ability of the adhesive proteins but in turn paves the way for the decision-making process for chimeric subunits modifications needed for future industrial production.
Morphological characterization and habitat suitability modeling of the goat population of Benin under climate change scenarios
Authors: Whannou Habib Rainier Vihotogbe , Afatondji Cossi Ulriche , Linsoussi Côme Agossa , Favi Gnimansou Abraham , Nguyen Thanh Thi , Houinato Marcel Romuald Benjamin , Dossa Luc Hippolyte 
Published: July 2022

Abstract
Background
Insufficient knowledge of the genetic and phenotypic diversity in the local Beninese goat population combined with the lack of understanding of its adaptive capacity to ongoing environmental and societal changes hampers the development of strategies for better management and genetic improvement. The objective of this study was to establish the current geographical distribution of goats in Benin based on their morphology and model the potential habitat suitability of the three known main goat phenotypes (i.e., Djallonké goat or Type I, Sahelian goat or Type II, and their Crossbreeds or Type III) under climate change scenarios. Ten qualitative and 26 linear body measurements were taken on 2114 adult female goats sampled across the three vegetation zones of the country. Fifteen ratios were generated from the quantitative variables. The data were analyzed using generalized linear model procedures followed by multiple comparisons of least-squares means and multivariate analytical methods, including canonical discrimination analysis and hierarchical ascendant classification. Each goat was then assigned to one of the three aforementioned main goat phenotypes following its morphological characteristics and according to the a priori cluster membership defined in the previous step. The Maximum Entropy algorithm was used to model the current and future distribution of the three goat phenotypes under climate change scenario using the Representative Conservation Pathways 4.5 and 8.5.

Results
All linear body measurements varied among vegetation zones. In the discriminant function analysis, 71% of the measured individuals were correctly classified in their vegetation zone of origin by seven measured variables and three ratios. The cluster procedure analysis revealed two groups of goats subdivided into the three main phenotypes. The modeling results showed that the currently highly favorable habitats were distributed in the South for Type I, in the North for Type II, and both South and North for Type III. However, under climate change scenarios, the favorable habitats for Type I decreased while those of Types II and III increased.

Conclusions
The results of this study confirm the spatial variation of the goat population in Benin. The habitat suitability model can be used to support decision-making toward better management of goat genetic diversity in Benin.