bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual targeting of protein translation and nuclear protein export results in enhanced antimyeloma effects
Authors: Li Shirong , Fu Jing , Walker Christopher J. , Yang Jun , Bhutani Divaya , Chakraborty Rajshekhar , Mamillapalli Niha , Mapara Markus Y. , Landesman Yosef , Lentzsch Suzanne 
Published: February 2023

Abstract
Selinexor (KPT-330) is a small molecule inhibitor of XPO1, which mediates the transport of tumor suppressor proteins, oncogene messenger RNAs, and other proteins involved in governing cell growthfrom the cell nucleus to the cytoplasm. It is overexpressed in many cancer types. Because eukaryotic translation initiator factor 4E (eIF4E) plays a critical role in protein translation in cancer cells in multiple myeloma (MM), we evaluated the effectiveness of combined inhibition of protein translation and nuclear export in MM. Selinexor, an inhibitor of nuclear protein export, dose-dependently decreased eIF4E, IKZF1, and c-MYC protein levels. Using a doxycycline-inducible–pLKO-Tet-On vector, knockdown of eIF4E significantly enhanced the antiproliferative effects of selinexor, sensitized resistant MM cells to selinexor, and increased apoptosis in MM cells. Immunofluorescent analysis of MM cells showed that the combined treatment increased the localization of residual eIF4E to the nucleus compared with selinexor-only treatment. The overexpression of eIF4E at least partially rescued the effects of selinexor in MM cells by reducing G1 cell cycle arrest and increasing the selinexor-IC50 10-fold. Moreover, the combination of selinexor with pharmacologic inhibitors of protein translation showed synergistic anti-MM effects. These results suggest a synergistic anti-MM effect of selinexor combined with eIF4E inhibitors in vitro. Our work provides a better understanding of the potential mechanism of resistance to selinexor and a rationale for combining selinexor with eIF4E inhibitors for the treatment of MM.
Inhibition of miR-101-3p prevents human aortic valve interstitial cell calcification through regulation of CDH11/SOX9 expression
Authors: Chen Jianglei , Lin Yi , Sun Zhongjie 
Published: February 2023

Abstract
Background
Calcific aortic valve disease (CAVD) is the second leading cause of adult heart diseases. The purpose of this study is to investigate whether miR-101-3p plays a role in the human aortic valve interstitial cells (HAVICs) calcification and the underlying mechanisms.

Methods
Small RNA deep sequencing and qPCR analysis were used to determine changes in microRNA expression in calcified human aortic valves.

Results
The data showed that miR-101-3p levels were increased in the calcified human aortic valves. Using cultured primary HAVICs, we demonstrated that the miR-101-3p mimic promoted calcification and upregulated the osteogenesis pathway, while anti-miR-101-3p inhibited osteogenic differentiation and prevented calcification in HAVICs treated with the osteogenic conditioned medium. Mechanistically, miR-101-3p directly targeted cadherin-11 (CDH11) and Sry-related high-mobility-group box 9 (SOX9), key factors in the regulation of chondrogenesis and osteogenesis. Both CDH11 and SOX9 expressions were downregulated in the calcified human HAVICs. Inhibition of miR-101-3p restored expression of CDH11, SOX9 and ASPN and prevented osteogenesis in HAVICs under the calcific condition.

Conclusion
miR-101-3p plays an important role in HAVIC calcification through regulation of CDH11/SOX9 expression. The finding is important as it reveals that miR-1013p may be a potential therapeutic target for calcific aortic valve disease.
Numerical Visualization of Grease Flow in a Gearbox
Authors: Liu Hua , Dangl Florian , Lohner Thomas , Stahl Karsten 
Published: February 2023

AbstractLubricating greases are widely used in e.g. open gear drives and gearboxes with difficult sealing conditions. The efficiency and heat balance of grease-lubricated gearboxes depend strongly on the lubrication mechanisms channeling and circulating, for which the grease flow is causal. The computational fluid dynamics opens up the possibility to visualize and understand the grease flow in gearboxes in more detail. In this study, a single-stage gearbox lubricated with an NLGI 1-2 grease was modeled by the finite-volume method to numerically investigate the fluid flow. Results show that the rotating gears influence the grease sump only locally around the gears. For a low grease fill volume, the rotation of the gears is widely separated from the grease sump. For a high grease fill volume, a pronounced gear-grease interaction results in a circulating grease flow around the gears. The simulated grease distributions show good accordance with high-speed camera recordings.
Functional targeted therapy for glioma based on platelet membrane-coated nanogels
Authors: Li Qin , Shen Jinglan , Wu Lingling , Lei Siyun , Yang Yimin , Xu Weide , Hao Ke , Zhang Yi , Kong Fei , Yang Wei , Wang Yaling , Peng Lina , Li Kaiqiang , Wang Zhen 
Published: February 2023

AbstractGlioma treatment remains a challenge owing to unsatisfactory targeted chemotherapy, where the blood–brain barrier (BBB) hinders the efficient uptake of therapeutics into the brain. Vasculogenic mimicry (VM) formed by invasive glioma cells negatively affects the treatment of glioma. Herein, we developed a targeted biomimetic drug delivery system comprising a doxorubicin-loaded platelet membrane-coated nanogel (DOX@PNGs). The nanogels provide great redox/pH dual responsiveness, while the platelet membrane (PLTM) promotes stability and circulation time. In vitro cellular uptake and in vivo imaging experiments demonstrated that the DOX@PNGs delivery system could penetrate the BBB, target gliomas, and destruct VM. DOX@PNGs increased drug penetration and prolonged mouse survival time during the treatment of orthotopic gliomas. These results indicate this biomimetic drug delivery system to be promising for glioma treatment and may be clinically translated in the future.
Designing multi-epitope vaccine against important colorectal cancer (CRC) associated pathogens based on immunoinformatics approach
Authors: Motamedi Hamid , Ari Marzie Mahdizade , Shahlaei Mohsen , Moradi Sajad , Farhadikia Parisa , Alvandi Amirhoushang , Abiri Ramin 
Published: February 2023

Abstract
Background
It seems that several members of intestinal gut microbiota like Streptococcus bovis, Bacteroides fragilis, Helicobacter pylori, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, Peptostreptococcus anaerobius may be considered as the causative agents of Colorectal Cancer (CRC). The present study used bioinformatics and immunoinformatics approaches to design a potential epitope-based multi-epitope vaccine to prevent CRC with optimal population coverage.

Methods
In this study, ten amino acid sequences of CRC-related pathogens were retrieved from the NCBI database. Three ABCpred, BCPREDS and LBtope online servers were considered for B cells prediction and the IEDB server for T cells (CD4+ and CD8+) prediction. Then, validation, allergenicity, toxicity and physicochemical analysis of all sequences were performed using web servers. A total of three linkers, AAY, GPGPG, and KK were used to bind CTL, HTL and BCL epitopes, respectively. In addition, the final construct was subjected to disulfide engineering, molecular docking, immune simulation and codon adaptation to design an effective vaccine production strategy.

Results
A total of 19 sequences of different lengths for linear B-cell epitopes, 19 and 18 sequences were considered as epitopes of CD4+ T and CD8+ cells, respectively. The predicted epitopes were joined by appropriate linkers because they play an important role in producing an extended conformation and protein folding. The final multi-epitope construct and Toll-like receptor 4 (TLR4) were evaluated by molecular docking, which revealed stable and strong binding interactions. Immunity simulation of the vaccine showed significantly high levels of immunoglobulins, helper T cells, cytotoxic T cells and INF-γ.

Conclusion
Finally, the results showed that the designed multi-epitope vaccine could serve as an excellent prophylactic candidate against CRC-associated pathogens, but in vitro and animal studies are needed to justify our findings for its use as a possible preventive measure.
Draft genomes of three closely related low light-adapted Prochlorococcus
Authors: Berta-Thompson Jessie W. , Thomas Elaina , Cubillos-Ruiz Andrés , Hackl Thomas , Becker Jamie W. , Coe Allison , Biller Steven J. , Berube Paul M. , Chisholm Sallie W. 
Published: February 2023

Abstract
Objectives
The marine cyanobacterium Prochlorococcus is a critical part of warm ocean ecosystems and a model for studying microbial evolution and ecology. To expand the representation of this organism’s vast wild diversity in sequence collections, we performed a set of isolation efforts targeting low light-adapted Prochlorococcus. Three genomes resulting from this larger body of work are described here.

Data description
We present draft-quality Prochlorococcus genomes from enrichment cultures P1344, P1361, and P1363, sampled in the North Pacific. The genomes were built from Illumina paired reads assembled de novo. Supporting datasets of raw reads, assessments, and sequences from co-enriched heterotrophic marine bacteria are also provided. These three genomes represent members of the low light-adapted LLIV Prochlorococcus clade that are closely related, with 99.9% average nucleotide identity between pairs, yet vary in gene content. Expanding the powerful toolkit of Prochlorococcus genomes, these sequences provide an opportunity to study fine-scale variation and microevolutionary processes.
Endovascular repair of aortic pathologies involving the aortic arch using castor stent-graft combined with in-vitro fenestration technology
Authors: Luo Zeng-Rong , Zhang Jia-Xin , Huang Zhong-Yao , Chen Liang-Wan 
Published: February 2023

AbstractBackgroundAortic arch pathologies are concerning clinical conditions with poor prognoses. The use of thoracic endovascular aortic repair (TEVAR) has been investigated to treat aortic arch pathologies. Nonetheless, cerebral blood flow regulation during endovascular aortic arch repair therapy remains challenging. Castor, a unique single-branched stent graft, has been proven effective for retaining the left subclavian artery (LSA). This study aimed to determine whether endovascular therapy for pathologies involving the aortic arch using Castor in combination with the in-vitro fenestration technique is promising, effective, and safe.MethodsEligible patients were enrolled between June 2018 and December 2021. All patients underwent TEVAR with an evaluated proximal landing zone for “Castor” located in Ishimaru zones 0–1. Moreover, the supra-aortic branches (SABs) were reconstructed using the Castor in combination with the in-vitro fenestration technique.ResultsHerein, 57 patients with aortic arch lesions were treated with Castor in combination with the in-vitro fenestration technique. Innominate artery and the left carotid artery (LCA) were reconstructed in 5 patients, LCA and left subclavian artery (LSA) were reconstructed in 22 patients, and the total SABs were effectively reconstructed in 30 patients (including a hybrid arch repair case). Among them (excluding a hybrid arch repair case) were in-vitro fenestration methodologies for LCA in 32 of 34 cases (2 switched to in-situ fenestration) and LSA in 51 of 56 cases (3 switched to in-situ fenestration and 2 converted to spring coil caulking); furthermore, LCA and LSA in-vitro fenestration were simultaneously successfully performed in 27 of 34 cases. There were no surgical-related neurological complications, and early mortality was estimated at 5.26%. At a mean follow-up of 3.75 months, computed tomography (CTA) images confirmed that each branch stent remained patent. There were no signs of endoleaks, migrative manifestations, or the need for secondary endovascular intervention or conversion to open surgical procedures.ConclusionCastor, in combination with in-vitro fenestration, reflects a feasible, efficient procedure for re-developing SABs.
Unexplained visual loss after primary pars-plana-vitrectomy with silicone oil tamponade in fovea-sparing retinal detachment
Authors: Barth T. , Helbig H. , Maerker D. , Gamulescu M.-A. , Radeck V. 
Published: February 2023

Abstract
Background
To investigate the incidence and clinical characteristics of unexplained visual loss in patients with fovea-sparing rhegmatogenous retinal detachment (RRD) during or after silicone oil (SO) tamponade.

Methods
The medical charts of all patients with macula-on RRDs, who underwent pars-plana-vitrectomy (ppV) with SO tamponade were retrospectively assessed regarding unexplained visual loss (UVL) of ≥ 3 Snellen lines and alterations on optical coherence tomography (OCT) during or after SO tamponade. The clinical data analysed included visual acuity, surgical parameters, OCT images, duration of SO tamponade and the time point of visual decline. Cases with re-detachment or secondary causes of visual loss such as SO emulsification, epiretinal membranes or macular edema were excluded.

Results
Over a 15-year-period, 22 cases with macula-on RRD, which had primarily been treated with ppV and SO tamponade, met the inclusion criteria. In most eyes (n = 20; 91%), the RRD was caused by a giant retinal tear (GRT). In 11 of these 22 cases (50%), best-corrected visual acuity (BCVA) had dropped by at least 3 lines for no apparent reason. In these 11 cases, mean preoperative logMAR BCVA was 0.2 (SD 0.13; range 0-0.5), equal to Snellen’s VA of 0.63, and mean postoperative logMAR BCVA 1.0 (SD 0.24; range 0.5–1.3), equal to Snellen’s VA of 0.10. Visual decline occurred about 12 weeks postoperatively (SD 6.2; range 3–20 ) and comprised 8 lines (SD 2.3; range -11 to -4). SO was removed on average 139 (SD 50.0; range 88–271) days after the first ppV. In 9 cases visual decline occurred while the SO was in-situ. In 2 patients, BCVA decline was noted 2 weeks after SO removal. In all eyes, preoperative central foveal thickness (CFT) was 254 μm (SD 24.2), which decreased to 224 μm (SD 29.6) during SO tamponade and increased to 247 μm (SD 29.2) after SO removal, irrespective of the presence of UVL. The mean follow-up time was 20 months (SD 30.6) after SO removal.

Conclusion
UVL after SO tamponade for macula-on RRD is more frequent than expected. The incidence in our case series was 50%. The mechanism of this phenomenon is still unknown. In general, vitreoretinal surgeons should thoroughly question the need for SO tamponade, inform their patients of possible UVL and remove SO as early as possible.

Trial registration
The study was approved by the local ethics committee on 6th of May 2022 (Ethikkommission der Universität Regensburg, Votum 22-2925-104) and was conducted in accordance with the ethical standards of the Declaration of Helsinki.
Bioinformatic analysis of underlying mechanisms of Kawasaki disease via Weighted Gene Correlation Network Analysis (WGCNA) and the Least Absolute Shrinkage and Selection Operator method (LASSO) regression model
Authors: Xie Yaxue , Shi Hongshuo , Han Bo 
Published: February 2023

Abstract
Background
Kawasaki disease (KD) is a febrile systemic vasculitis involvingchildren younger than five years old. However, the specific biomarkers and precise mechanisms of this disease are not fully understood, which can delay the best treatment time, hence, this study aimed to detect the potential biomarkers and pathophysiological process of KD through bioinformatic analysis.

Methods
The Gene Expression Omnibus database (GEO) was the source of the RNA sequencing data from KD patients. Differential expressed genes (DEGs) were screened between KD patients and healthy controls (HCs) with the “limma” R package. Weighted gene correlation network analysis (WGCNA) was performed to discover the most corresponding module and hub genes of KD. The node genes were obtained by the combination of the least absolute shrinkage and selection operator (LASSO) regression model with the top 5 genes from five algorithms in CytoHubba, which were further validated with the receiver operating characteristic curve (ROC curve). CIBERSORTx was employed to discover the constitution of immune cells in KDs and HCs. Functional enrichment analysis was performed to understand the biological implications of the modular genes. Finally, competing endogenous RNAs (ceRNA) networks of node genes were predicted using online databases.

Results
A total of 267 DEGs were analyzed between 153 KD patients and 92 HCs in the training set, spanning two modules according to WGCNA. The turquoise module was identified as the hub module, which was mainly enriched in cell activation involved in immune response, myeloid leukocyte activation, myeloid leukocyte mediated immunity, secretion and leukocyte mediated immunity biological processes; included type II diabetes mellitus, nicotinate and nicotinamide metabolism, O-glycan biosynthesis, glycerolipid and glutathione metabolism pathways. The node genes included ADM, ALPL, HK3, MMP9 and S100A12, and there was good performance in the validation studies. Immune cell infiltration analysis revealed that gamma delta T cells, monocytes, M0 macrophage, activated dendritic cells, activated mast cells and neutrophils were elevated in KD patients. Regarding the ceRNA networks, three intact networks were constructed: NEAT1/NORAD/XIST-hsa-miR-524-5p-ADM, NEAT1/NORAD/XIST-hsa-miR-204-5p-ALPL, NEAT1/NORAD/XIST-hsa-miR-524-5p/hsa-miR-204-5p-MMP9.

Conclusion
To conclude, the five-gene signature and three ceRNA networks constructed in our study are of great value in the early diagnosis of KD and might help to elucidate our understanding of KD at the RNA regulatory level.
Undernutrition among the children below five years of age in Uganda: a spatial analysis approach
Authors: Maniragaba Vallence Ngabo , Atuhaire Leonard K. , Rutayisire Pierre Claver 
Published: February 2023

Abstract
Background
Undernutrition is a health condition caused by a lack of enough food intake, not having enough of the right combination of food nutrients, or the body’s failure to utilize the food eaten resulting in either, stunting, being underweight, or wasting. Globally, undernutrition affects more than 149 million under-five children, while in Uganda about 3 in every 10 children suffer from undernutrition. Undernutrition and its risk factors among under-five children in Uganda were unevenly distributed across the country and a study that focused on spatial distribution was prudent to examine the nature of the problem and salient factors associated with it. The current study addressed the issues of spatial heterogeneity of undernutrition and its determinants with the goal to identify hot spots and advise policymakers on the best actions to be taken to address the problem.

Methods
Data were obtained from the 2016 Uganda Demographic and Health Survey. Prevalence rates and percentages of risk factors were combined with the Uganda district shape file to allow spatial analysis. Moran’s I, Getis-Ord (GI*), and Geographically Weighted Regressions were respectively used to establish the local, global, and geographically weighted regressions across the country. Stata 15 and ArcGIS 10. 7 soft wares were used.

Results
The results indicate that undernutrition in Uganda shows varies spatially across regions. Evidence of hot spots exists in the Karamoja and Arua regions, cold spot areas exist around the central part of the country while the greatest part of Western Uganda, Northern, and Eastern were not significant.

Conclusion
The study reveals that a variation in the distribution of undernutrition throughout the country. Significant spatial patterns associated with undernutrition as identified through the hotspot and cold spot analysis do exist in Uganda. Programs targeting to reduce the undernutrition of under-five children in Uganda should consider the spatial distribution of undernutrition and its determinants whereby priority should be given to hotspot areas. The spatial intensity of undernutrition and its determinants indicate that focus should be tailored to meet the local needs as opposed to a holistic national approach.
Partial breast reconstruction of 30 cases with peri-mammary artery perforator flaps
Authors: Shen Meiying , Xu Yuhang , Wu Zongyuan , Wang Jiaming , Pan Huawen , Xu Bo 
Published: February 2023

Abstract
Background
Volume replacement is one of the vital techniques of oncoplastic surgery (OPS) when applying breast-conserving surgery. The clinical application of peri-mammary artery perforator flaps for this indication is uneven in China. Here, we describe the results of our clinical experience with peri-mammary artery flaps for partial breast reconstruction.

Methods
In this study, 30 patients underwent partial breast resection for quadrant breast cancer followed by partial breast reconstruction with peri-mammary artery perforator flaps, which included the thoracodorsal artery perforator flap (TDAP), anterior intercostal artery perforator flap (AICAP), lateral intercostal artery perforator flap (LICAP), and lateral thoracic artery perforator flap (LTAP). All the patients’ operation plans were discussed comprehensively and were performed by sticking to every step. The satisfaction outcome was assessed with the extracted version of the BREAST-Q version 2.0, Breast Conserving Therapy Module Preoperative and Postoperative Scales both preoperatively and postoperatively.

Results
According to the study outcomes, the mean flap size was 5.3*4.2*2.8 cm (3.0–7.0*3.0–5.0*1.0–3.5 cm). The mean surgical time was 142 min (100–250 min). No partial flap failure was detected, and no severe complications were observed. Most patients were satisfied with the outcomes regarding the dressing, sexual life, and breast shape postoperation. Furthermore, the sensation of the surgical area, scar satisfaction, and recovery state gradually improved. Overall, LICAP and AICAP had higher scores when different flaps were compared.

Conclusions
Based on this study, we found that peri-mammary artery flaps had significant value in breast-conserving surgery, especially in patients with small or medium-sized breasts. Perforators could be detected by vascular ultrasound before the operation. More than one perforator could be found most of the time. No severe complications occurred when performing a suitable plan, including discussing and recording the operation procedure; the focus of care, the choice for precise and proper perforators, and the mechanism for hiding the scars were all considered and recorded in a specific chart. Patients were satisfied with the reconstruction technique of peri-mammary artery perforator flaps after breast-conserving, and the satisfaction of AICAP and LICAP was higher. In general, this technique is suitable for partial breast reconstruction and has no negative impact on patient satisfaction.