bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corneal epithelial differentiation of human pluripotent stem cells generates ABCB5+ and ∆Np63α+ cells with limbal cell characteristics and high wound healing capacity
Authors: Vattulainen Meri , Ilmarinen Tanja , Viheriälä Taina , Jokinen Vilma , Skottman Heli 
Published: December 2021

Abstract
Background
Differentiation of functional limbal stem cells (LSCs) from human pluripotent stem cells (hPSCs) is an important objective which can provide novel treatment solutions for patients suffering from limbal stem cell deficiency (LSCD). Yet, further characterization is needed to better evaluate their immunogenicity and regenerative potential before clinical applications.

Methods
Human PSCs were differentiated towards corneal fate and cryopreserved using a clinically applicable protocol. Resulting hPSC-LSC populations were examined at days 10–11 and 24–25 during differentiation as well as at passage 1 post-thaw. Expression of cornea-associated markers including PAX6, ABCG2, ∆Np63α, CK15, CK14, CK12 and ABCB5 as well as human leukocyte antigens (HLAs) was analyzed using immunofluorescence and flow cytometry. Wound healing properties of the post-thaw hPSC-LSCs were assessed via calcium imaging and scratch assay. Human and porcine tissue-derived cultured LSCs were used as controls for marker expression analysis and scratch assays at passage 1.

Results
The day 24–25 and post-thaw hPSC-LSCs displayed a similar marker profile with the tissue-derived LSCs, showing abundant expression of PAX6, ∆Np63α, CK15, CK14 and ABCB5 and low expression of ABCG2. In contrast, day 10–11 hPSC-LSCs had lower expression of ABCB5 and ∆Np63α, but high expression of ABCG2. A small portion of the day 10–11 cells coexpressed ABCG2 and ABCB5. The expression of class I HLAs increased during hPSC-LSCs differentiation and was uniform in post-thaw hPSC-LSCs, however the intensity was lower in comparison to tissue-derived LSCs. The calcium imaging revealed that the post-thaw hPSC-LSCs generated a robust response towards epithelial wound healing signaling mediator ATP. Further, scratch assay revealed that post-thaw hPSC-LSCs had higher wound healing capacity in comparison to tissue-derived LSCs.

Conclusions
Clinically relevant LSC-like cells can be efficiently differentiated from hPSCs. The post-thaw hPSC-LSCs possess functional potency in calcium responses towards injury associated signals and in wound closure. The developmental trajectory observed during hPSC-LSC differentiation, giving rise to ABCG2+ population and further to ABCB5+ and ∆Np63α+ cells with limbal characteristics, indicates hPSC-derived cells can be utilized as a valuable cell source for the treatment of patients afflicted corneal blindness due to LSCD.

Graphical Abstract
The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity
Authors: Klid Sergiy , Algaba-Chueca Francisco , Maymó-Masip Elsa , Guarque Albert , Ballesteros Mónica , Diaz-Perdigones Cristina , Gutierrez Cristina , Vendrell Joan , Megía Ana , Fernández-Veledo Sonia 
Published: December 2021

Abstract
Background
An environment of gestational diabetes mellitus (GDM) can modify the phenotype of stem cell populations differentially according to their placental localization, which can be useful to study the consequences for the fetus. We sought to explore the effect of intrauterine GDM exposure on the angiogenic properties of human amniotic membrane stem cells (hAMSCs).

Methods
We comprehensively characterized the angiogenic phenotype of hAMSCs isolated from 14 patients with GDM and 14 controls with normal glucose tolerance (NGT). Maternal and fetal parameters were also recorded. Hyperglycemia, hyperinsulinemia and palmitic acid were used to in vitro mimic a GDM-like pathology. Pharmacological and genetic inhibition of protein function was used to investigate the molecular pathways underlying the angiogenic properties of hAMSCs isolated from women with GDM.

Results
Capillary tube formation assays revealed that GDM-hAMSCs produced a significantly higher number of nodes (P = 0.004), junctions (P = 0.002) and meshes (P < 0.001) than equivalent NGT-hAMSCs, concomitant with an increase in the gene/protein expression of FGFR2, TGFBR1, SERPINE1 and VEGFA. These latter changes were recapitulated in NGT-hAMSCs exposed to GDM-like conditions. Inhibition of the protein product of SERPINE1 (plasminogen activator inhibitor 1, PAI-1) suppressed the angiogenic properties of GDM-hAMSCs. Correlation analyses revealed that cord blood insulin levels in offspring strongly correlated with the number of nodes (r = 0.860; P = 0.001), junctions (r = 0.853; P = 0.002) and meshes (r = 0.816; P = 0.004) in tube formation assays. Finally, FGFR2 levels correlated positively with placental weight (r = 0.586; P = 0.028) and neonatal adiposity (r = 0.496; P = 0.014).

Conclusions
GDM exposure contributes to the angiogenic abilities of hAMSCs, which are further related to increased cord blood insulin and fetal adiposity. PAI-1 emerges as a potential key player of GDM-induced angiogenesis.
The usefulness of repeated CMR and FDG PET/CT in the diagnosis of patients with initial possible cardiac sarcoidosis
Authors: Mathijssen H. , Tjoeng T. W. H. , Keijsers R. G. M. , Bakker A. L. M. , Akdim F. , van Es H. W. , van Beek F. T. , Veltkamp M. V. , Grutters J. C. , Post M. C. 
Published: December 2021

AbstractBackgroundCardiac sarcoidosis (CS) diagnosis is usually based on advanced imaging techniques and multidisciplinary evaluation. Diagnosis is classified as definite, probable, possible or unlikely. If diagnostic confidence remains uncertain, cardiac imaging can be repeated. The objective is to evaluate the usefulness of repeated cardiac magnetic resonance imaging (CMR) and fluorodeoxyglucose positron emission tomography (FDG PET/CT) for CS diagnosis in patients with an initial “possible” CS diagnosis.MethodsWe performed a retrospective cohort study in 35 patients diagnosed with possible CS by our multidisciplinary team (MDT), who received repeated CMR and FDG PET/CT within 12 months after diagnosis. Imaging modalities were scored on abnormalities suggestive for CS and classified as CMR+/PET+, CMR+/PET−, CMR−/PET+ and CMR−/PET−. Primary endpoint was final MDT diagnosis of CS.ResultsAfter re-evaluation, nine patients (25.7%) were reclassified as probable CS and 16 patients (45.7%) as unlikely CS. Two patients started immunosuppressive treatment after re-evaluation. At baseline, eleven patients (31.4%) showed late gadolinium enhancement (LGE) on CMR (CMR+) and 26 (74.3%) patients showed myocardial FDG-uptake (PET+). At re-evaluation, nine patients (25.7%) showed LGE (CMR+), while 16 patients (45.7%) showed myocardial FDG-uptake (PET+). When considering both imaging modalities together, 82.6% of patients with CMR−/PET+ at baseline were reclassified as possible or unlikely CS, while 36.4% of patients with CMR+ at baseline were reclassified as probable CS. Three patients with initial CMR−/PET+ showed LGE at re-evaluation.ConclusionRepeated CMR and FDG PET/CT may be useful in establishing or rejecting CS diagnosis, when initial diagnosis is uncertain. However, clinical relevance has to be further determined.
Supporting strategic health purchasing: a case study of annual health budgets from general tax revenue and social health insurance in Abia state, Nigeria
Authors: Mbachu Chinyere , Okeke Chinyere , Obayi Chinonso , Gatome-Munyua Agnes , Olalere Nkechi , Ogbonna Ikechi , Uzochukwu Benjamin , Onwujekwe Obinna 
Published: December 2021

Abstract
Background
Tracking general trends in strategic purchasing of health financing mechanisms will highlight where country demands may exist for technical support and where progress in being made that offer opportunities for regional learning. Health services in Abia State, Nigeria are funded from general tax-revenues (GTR), and a new state social health insurance scheme (SSHIS) is proposed to overcome the failings of the GTR and expand coverage of services. This study examined purchasing functions within the GTR and the proposed SSHIS to determine if the failings in GTR have been overcome, identify factors that shape health purchasing at sub-national levels, and provide lessons for other states in Nigeria pursuing a similar intervention.

Methods
Data was collected through document review and key informant interviews. Government documents were retrieved electronically from the websites of different organizations. Hard copies of paper-only files were retrieved from relevant government agencies and departments. Interviews were conducted with seven key personnel of the State Ministry of Health and State Health Insurance Agency. Thematic analysis of data was based on a strategic health purchasing progress tracking framework which delves into the governance arrangements and information architecture needed for purchasing to work well; and the core purchasing decisions of what to buy; who to buy from; and how to buy.

Results
There are differences in the purchasing arrangements of the two schemes. Purchaser-provider split does not exist for the GTR, unlike in the proposed SSHIS. There are no data systems for monitoring provider performance in the GTR-funded system, unlike in the SSHIS. Whereas GTR is based on a historical budgeting system, the SSHIS proposes to use a defined benefit package, which ensures value-for-money, as the basis for resource allocation. The GTR lacks private sector engagement, provider accreditation and contracting arrangements while the SSHIS will accredit and engage private providers through selective contracting. Likewise, provider payment is not linked to performance or adherence to established standards in the GTR, whereas provider payment will be linked to performance in the SSHIS.

Conclusions
The State Social Health Insurance has been designed to overcome many of the limitations of the budgetary allocation to health. This study provides insights into the enabling and constraining factors that can be used to develop interventions intended to strengthen the strategic health purchasing in the study area, and lessons for the other Nigeria states with similar characteristics and approaches.
Water surface object detection using panoramic vision based on improved single-shot multibox detector
Authors: Li Aofeng , Zhu Xufang , He Shuo , Xia Jiawei 
Published: December 2021

AbstractIn view of the deficiencies in traditional visual water surface object detection, such as the existence of non-detection zones, failure to acquire global information, and deficiencies in a single-shot multibox detector (SSD) object detection algorithm such as remote detection and low detection precision of small objects, this study proposes a water surface object detection algorithm from panoramic vision based on an improved SSD. We reconstruct the backbone network for the SSD algorithm, replace VVG16 with a ResNet-50 network, and add five layers of feature extraction. More abundant semantic information of the shallow feature graph is obtained through a feature pyramid network structure with deconvolution. An experiment is conducted by building a water surface object dataset. Results showed the mean Average Precision (mAP) of the improved algorithm are increased by 4.03%, compared with the existing SSD detecting Algorithm. Improved algorithm can effectively improve the overall detection precision of water surface objects and enhance the detection effect of remote objects.
Convergence of a distributed method for minimizing sum of convex functions with fixed point constraints
Authors: Ekkarntrong Nawarat , Arunrat Tipsuda , Nimana Nimit 
Published: December 2021

AbstractIn this paper, we consider a distributed optimization problem of minimizing sum of convex functions over the intersection of fixed-point constraints. We propose a distributed method for solving the problem. We prove the convergence of the generated sequence to the solution of the problem under certain assumption. We further discuss the convergence rate with an appropriate positive stepsize. A numerical experiment is given to show the effectiveness of the obtained theoretical result.
The sub-supersolution method for a nonhomogeneous elliptic equation involving Lebesgue generalized spaces
Authors: Figueiredo Giovany M. , Razani A. 
Published: December 2021

AbstractIn this paper, a nonhomogeneous elliptic equation of the form$$\begin{aligned}& - \mathcal{A}\bigl(x, \vert u \vert _{L^{r(x)}}\bigr) \operatorname{div}\bigl(a\bigl( \vert \nabla u \vert ^{p(x)}\bigr) \vert \nabla u \vert ^{p(x)-2} \nabla u\bigr) \\& \quad =f(x, u) \vert \nabla u \vert ^{\alpha (x)}_{L^{q(x)}}+g(x, u) \vert \nabla u \vert ^{ \gamma (x)}_{L^{s(x)}} \end{aligned}$$−A(x,|u|Lr(x))div(a(|∇u|p(x))|∇u|p(x)−2∇u)=f(x,u)|∇u|Lq(x)α(x)+g(x,u)|∇u|Ls(x)γ(x)on a bounded domain Ω in${\mathbb{R}}^{N}$RN($N >1$N>1) with$C^{2}$C2boundary, with a Dirichlet boundary condition is considered. Using the sub-supersolution method, the existence of at least one positive weak solution is proved. As an application, the existence of at least one solution of a generalized version of the logistic equation and a sublinear equation are shown.
Observational case series: six neurosurgical patients with septic shock demonstrating clinical improvement after a combination of standard care and blood purification
Authors: Burov A. I. , Abramov T. A. , Kostritca N. S. , Korotkov D. S. , Danilov G. V. , Strunina Y. V. , Savin I. A. 
Published: December 2021

Abstract
Background
For patients with primary brain injury, septic shock is especially dangerous due to the possibility of secondary cerebral damage. The key factor of sepsis-associated brain injury is inflammatory mediators, pathogen and damage-associated molecular patterns (PAMPs, DAMPs) release. Theoretically, blood purification may be beneficial for patients with primary brain injury due to its possibility for fast removal of inflammatory mediators.

Case presentation
We report on six post-neurosurgery septic shock patients treated with combined blood purification (CBP), which included CRRT with high adsorption capacity membrane in combination with CytoSorb adsorber. Clinical improvement in the course of CBP was registered in all patients. Three patients had a stable clinical improvement; the other three patients had only a transient improvement due to underlying neurological and cardiac deficits aggravation. We observed septic shock reversal in four patients. The key observations of the case series are a significant decrease in MOF severity (measured by SOFA score) and in catecholamine need (not statistically significant). By the end of CBP we observed a significant decrease in blood lactate, PCT and IL-6 levels. Two patients demonstrated level of consciousness increase in the setting of CBP therapy measured by GCS and FOUR score.

Conclusion
This case series demonstrates that CBP therapy may have a role for septic shock patients with primary brain injury.
Associations between facet tropism and vertebral rotation in patients with degenerative lumbar disease
Authors: Ma Yachao , Huang Peipei , Tu Zhipeng , Yao Zhou , Wang Zhe , Luo Zhuojing , Hu Xueyu 
Published: December 2021

Abstract
Background
Vertebral rotation and facet tropism are very common in various lumbar degenerative diseases. Facet tropism means the presence of asymmetric angles on both sides of the facet joints. Studies have shown that facet tropism contributes to lumbar degenerative disease, and also inevitably leads to the asymmetry of movement and the imbalance of force, which may be possible to rotate the vertebral body. The aim of this study was to explore the correlation between lumbar vertebral rotation and facet tropism in patients with lumbar degenerative diseases.

Methods
A total of 198 patients with lumbar degenerative diseases from 2018 to 2019 were enrolled. Five hundred and seventy vertebral rotation angles and 1140 facet angles were measured. The vertebral bodies are divided into non-rotation group (Group A) and rotation group (Group B) with the vertebral rotation angle of 3° as the boundary. The information including gender, age, BMI (body mass index), bone mineral density, history of smoking, drinking, hypertension, diabetes, diagnosis, segment distribution, and degree of facet degeneration were also counted. Using inter-class correlation coefficients (ICC) to test the reliability of measurement results. Univariate and multivariate logistic regression analysis were used to analyze the relationship between vertebral rotation and facet tropism.

Results
The consistency of the ICC within the groups of the observers is above 0.8, with good agreement. The results of univariate analysis showed that facet tropism was significantly different between group A and group B (OR (odds ratio)  = 3.30, 95% CI  =  2.03–5.35, P  < 0.0001). Other significant factors were included as adjustment variables into the multivariate regression model. Three models were analyzed separately (Model 1: non-adjusted. Model 2: adjust for age; facet degeneration; Model 3: adjust for age; disease distribution; segment distribution; facet degeneration). The results showed that after adjusting the confounders, the correlation between facet tropism and vertebral rotation did not change (Model 1: OR  = 3.30, 95% CI  = 2.03–5.35, P  < 0.0001; Model 2: adjusted OR  = 2.87, 95% CI  = 1.66–4.97, P  = 0.0002, Model 3: adjusted OR  = 2.84, 95% CI  = 1.56–5.17, P  = 0.0006).

Conclusion
Current research demonstrates that there is an association between vertebral rotation and facet tropism, suggesting that vertebral rotation may also have a certain degree of correlation with lumbar degenerative diseases.
Functional outcome of 103 fractures of the proximal fifth metatarsal bone
Authors: Pflüger Patrick , Zyskowski Michael , Müller Michael , Kirchhoff Chlodwig , Biberthaler Peter , Crönlein Moritz 
Published: December 2021

Abstract
Background
Metatarsal fractures are common skeletal injuries of the lower extremity in adults. The majority involves the proximal fifth metatarsal bone. In the current literature, there still exists controversy regarding treatment recommendations for the different fracture entities.

Methods
All patients suffering from single fractures to the proximal fifth metatarsal bone between 2003 and 2015 were enrolled in this retrospective analysis. Only patients with a minimum follow-up of 12 months were included. The fractures were classified according to Lawrence and Botte (L&B). Data were collected via patient registry, radiographs and a standardized questionnaire (Foot and Ankle Outcome Score = FOAS). For outcome analysis, the nonparametric Mann–Whitney U test was performed and Spearman’s rank correlation coefficient calculated.

Results
In total, the functional outcomes of 103 patients suffering from fractures to the proximal fifth metatarsal bone were analyzed. L&B type I fractures (n = 13) had a FAOS score of 91 ± 23, L&B type II (n = 67) presented a score of 91 ± 15 and L&B type III (n = 23) a score of 93 ± 11. Surgically treated patients with an L&B type II fracture had no statistically significant better functional outcome in comparison to conservative management (p = 0.89). Operatively treated L&B type III fractures tended to have a better functional score (p = 0.16). The follow-up time was 58 (min: 15; max: 164) months.

Conclusions
Overall, the functional outcome following fractures to the proximal fifth metatarsal bone is satisfactory. Conservatively treated L&B type II fractures showed an equivalent functional outcome compared to surgical management. Patients with an L&B type III fracture mainly were treated surgically, but difference in FAOS score did not reach level of significance.
Daratumumab and venetoclax in combination with chemotherapy provide sustained molecular remission in relapsed/refractory CD19, CD20, and CD22 negative acute B lymphoblastic leukemia with KMT2A-AFF1 transcript
Authors: Voruz Sophie , Blum Sabine , de Leval Laurence , Schoumans Jacqueline , Solly Françoise , Spertini Olivier 
Published: December 2021

AbstractRelapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) has a very poor prognosis with a median overall survival of four to nine months. Achieving a complete molecular response is most often required to obtain a sustained leukemia-free survival after allogeneic hematopoietic stem cell transplantation. Immunotherapies targeting CD19, CD20, or CD22 are very efficient in achieving this goal. However, in the absence of the expression of these immunotherapeutic targets by lymphoblasts, treatment options are extremely scarce. We report the successful treatment of a 26-year-old man who suffered R/R, CD19, CD20, and CD22 negative B-ALL targeting Bcl-2 and CD38 by combining venetoclax and daratumumab with chemotherapy.
The effect of two different types of forces on possible root resorption in relation to dentin phosphoprotein levels: a single-blind, split-mouth, randomized controlled trial
Authors: Ghaleb Sherifa , Tamish Nazla , ElKenany Walid , Guindi Myriam 
Published: December 2021

Abstract
Background
The purpose of this 2-arm-parallel split-mouth trial was to evaluate and compare the extent of possible root resorption using dentin phosphoprotein levels in gingival crevicular fluid between controlled continuous and intermittent orthodontic force groups.

Materials and methods
A sample of 16 maxillary first premolars from 8 patients requiring bilateral extractions of the upper first premolars as part of their orthodontic treatment were recruited. A buccally directed continuous force of 150 g, reactivated after 28 days, was applied to the upper first premolar on one side for 8 weeks. On the contralateral first premolar, a buccally directed intermittent force (21 days on, 7 days off) of the same magnitude was applied for the same period. Gingival crevicular fluid samples were collected at the beginning of the study, 1st, 3rd, 4th and 5th week, and at the end of the study to quantify and compare dentin phosphoprotein levels in both groups.

Results
Dentin phosphoprotein levels showed a higher concentration in the continuous force group than the intermittent force group in week 4 and 8 of sample collection; where the differences were statistically significant (95% CI 0.007–0.14; P < .04) and (95% CI 0.02–0.17; P < .04) respectively. No harm was observed.

Conclusions
Dentin phosphoprotein was found to be a useful early biomarker to detect and monitor root resorption, showing that the application of an intermittent orthodontic force caused less root resorption than a continuous force.

Trial registration

NCT04825665 ClinicalTrials.gov. Registered 1 April 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04825665.