bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable colony-stimulating factor 1 fusion protein treatment increases hematopoietic stem cell pool and enhances their mobilisation in mice
Authors: Kaur Simranpreet , Sehgal Anuj , Wu Andy C. , Millard Susan M. , Batoon Lena , Sandrock Cheyenne J. , Ferrari-Cestari Michelle , Levesque Jean-Pierre , Hume David A. , Raggatt Liza J. , Pettit Allison R. 
Published: January 2021

AbstractBackgroundPrior chemotherapy and/or underlying morbidity commonly leads to poor mobilisation of hematopoietic stem cells (HSC) for transplantation in cancer patients. Increasing the number of available HSC prior to mobilisation is a potential strategy to overcome this deficiency. Resident bone marrow (BM) macrophages are essential for maintenance of niches that support HSC and enable engraftment in transplant recipients. Here we examined potential of donor treatment with modified recombinant colony-stimulating factor 1 (CSF1) to influence the HSC niche and expand the HSC pool for autologous transplantation.MethodsWe administered an acute treatment regimen of CSF1 Fc fusion protein (CSF1-Fc, daily injection for 4 consecutive days) to naive C57Bl/6 mice. Treatment impacts on macrophage and HSC number, HSC function and overall hematopoiesis were assessed at both the predicted peak drug action and during post-treatment recovery. A serial treatment strategy using CSF1-Fc followed by granulocyte colony-stimulating factor (G-CSF) was used to interrogate HSC mobilisation impacts. Outcomes were assessed by in situ imaging and ex vivo standard and imaging flow cytometry with functional validation by colony formation and competitive transplantation assay.ResultsCSF1-Fc treatment caused a transient expansion of monocyte-macrophage cells within BM and spleen at the expense of BM B lymphopoiesis and hematopoietic stem and progenitor cell (HSPC) homeostasis. During the recovery phase after cessation of CSF1-Fc treatment, normalisation of hematopoiesis was accompanied by an increase in the total available HSPC pool. Multiple approaches confirmed that CD48−CD150+HSC do not express the CSF1 receptor, ruling out direct action of CSF1-Fc on these cells. In the spleen, increased HSC was associated with expression of the BM HSC niche macrophage marker CD169 in red pulp macrophages, suggesting elevated spleen engraftment with CD48−CD150+HSC was secondary to CSF1-Fc macrophage impacts. Competitive transplant assays demonstrated that pre-treatment of donors with CSF1-Fc increased the number and reconstitution potential of HSPC in blood following a HSC mobilising regimen of G-CSF treatment.ConclusionThese results indicate that CSF1-Fc conditioning could represent a therapeutic strategy to overcome poor HSC mobilisation and subsequently improve HSC transplantation outcomes.
Noncoding RNAs regulate alternative splicing in Cancer
Authors: Liu Yunze , Liu Xin , Lin Changwei , Jia Xianhong , Zhu Hongmei , Song Jun , Zhang Yi 
Published: January 2021

AbstractAS (alternative splicing) is a fundamental process by which a gene can generate multiple distinct mRNA transcripts to increase protein diversity. Defects in AS influence the occurrence and development of many diseases, including cancers, and are frequently found to participate in various aspects of cancer biology, such as promoting invasion, metastasis, apoptosis resistance and drug resistance. NcRNAs (noncoding RNAs) are an abundant class of RNAs that do not encode proteins. NcRNAs include miRNAs (microRNAs), lncRNAs (long noncoding RNAs), circRNAs (circular RNAs) and snRNAs (small nuclear RNAs) and have been proven to act as regulatory molecules that mediate cancer processes through AS. NcRNAs can directly or indirectly influence a plethora of molecular targets to regulate cis-acting elements, trans-acting factors, or pre-mRNA transcription at multiple levels, affecting the AS process and generating alternatively spliced isoforms. Consequently, ncRNA-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. In this review, we summarize the current mechanisms by which ncRNAs regulate AS in cancers and discuss their potential clinical applications as biomarkers and therapeutic targets.
Promotion of epithelial-mesenchymal transformation by hepatocellular carcinoma-educated macrophages through Wnt2b/β-catenin/c-Myc signaling and reprogramming glycolysis
Authors: Jiang Yu , Han Qiuju , Zhao Huajun , Zhang Jian 
Published: January 2021

Abstract
Background
Tumour-associated macrophages (TAMs) in the tumour microenvironment (TME) can promote the progression of hepatocellular carcinoma (HCC). Some tumours can be suppressed by targeting Wnt2b in tumour cells. However, the role of Wnt2b in HCC is still unknown. In particular, the role of Wnt2b-mediated signal activation in macrophage polarization in the HCC microenvironment, and the regulatory effect between Wnt and glycolysis in TAMs has not been described.

Methods
The expression of Wnt2b in TAMs was detected by qPCR and immunofluorescence. Wnt2b/β-catenin interference in HCC-TAMs was performed by lentivirus carrying targeted shRNA or TLR9 agonist. Markers related to macrophage polarization and the changes of key glycolytic enzymes expression were detected by flow cytometry and qPCR. ECAR was analysed by Seahorse analyser. MTT assay, wound healing assay, western blotting were used to evaluate the promoting effect of different HCC-TAMs on the proliferation, migration and EMT of HCC in vitro. Tumour cells and different HCC-TAMs were injected via subcutaneously into immunodeficient mice to assess the effects of CpG ODN, Wnt2b, or β-catenin on HCC-TAMs in tumour growth in vivo.

Results
Polarization-promoting factors derived from HCC cells upregulated the expression of Wnt2b in macrophages, which promoted the polarization of TAMs to M2-like macrophages by activating Wnt2b/β-catenin/c-Myc signalling. Furthermore, this process was associated with the activation of glycolysis in HCC-TAMs. These HCC-TAMs could promote the development of EMT, proliferation, and migration of HCC. In addition to silencing Wnt2b or β-catenin expression, TLR9 agonist CpG ODN downregulated the level of glycolysis and inhibited the M2 polarization of HCC-TAMs, reversing the tumour-promoting effects of TAMs in vitro and vivo.

Conclusions
As a potential target for HCC therapy, Wnt2b may play an important regulatory role for the functions of TAMs in the TME. Moreover, the TLR9 agonist CpG ODN might act as a Wnt2b signal inhibitor and can potentially be employed for HCC therapy by disturbing Wnt2b/β-catenin/c-Myc and inhibiting glycolysis in HCC-TAMs.
Selective exosome exclusion of miR-375 by glioma cells promotes glioma progression by activating the CTGF-EGFR pathway
Authors: Xu Xiangdong , Liu Yang , Li Yan , Chen Huajian , Zhang Yuxuan , Liu Jie , Deng Shaokang , Zheng Yaofeng , Sun Xinlin , Wang Jihui , Chen Taoliang , Huang Min , Ke Yiquan 
Published: January 2021

Abstract
Background
Exosomes are membrane-bound extracellular vesicles of 40–150 nm in size, that are produced by many cell types, and play an important role in the maintenance of cellular homeostasis. Exosome secretion allows for the selective removal of harmful substances from cells. However, it remains unclear whether this process also takes place in glioma cells.

Methods
Herein, the role of the tumour-suppressor miR-375 was explored in human glioma cells. Immunoblotting and qRT-PCR experiments demonstrated a functional link between miR-375 and its target, connectivetissuegrowthfactor (CTGF), which led to the identification of the underlying molecular pathways. The exosomes secreted by glioma cells were extracted by ultracentrifugation and examined by transmission electron microscopy. Exosomal expression of miR-375 was then analysed by qRT-PCR; while the exosome secretion inhibitor, GW4869, was used to examine the biological significance of miR-375 release. Moreover, the dynamics of miR-375 release by glioma cells was investigated using fluorescently labelled exosomes. Finally, exosomal miR-375 release was examined in an orthotopic xenograft model in nude mice.

Results
MiR-375 expression was downregulated in gliomas. MiR-375 suppressed glioma proliferation, migration, and invasion by inhibiting the CTGF-epidermalgrowthfactorreceptor (EGFR) signalling pathway. MiR-375-containing exosomes were also identified in human peripheral blood samples from glioma patients, and their level correlated with disease progression status. Exosomal miR-375 secretion impacted the CTGF-EGFR pathway activity. Once secreted, exosomal miR-375 was not taken back up by glioma cells.

Conclusions
Exosomal miR-375 secretion allowed for sustained activation of the CTGF-EGFR oncogenic pathway, promoting the proliferation and invasion of glioma cells. These findings enhance our understanding of exosome biology and may inspire development of new glioma therapies.
Survival among patients with severe high cervical spine injuries – a TraumaRegister DGU® database study
Authors:   the TraumaRegister DGU, Kamp O. , Jansen O. , Lefering R. , Aach M. , Waydhas C. , Dudda M. , Schildhauer T. A. , Hamsen U. 
Published: January 2021

Abstract
Background
Trauma is a significant cause of death and impairment. The Abbreviated Injury Scale (AIS) differentiates the severity of trauma and is the basis for different trauma scores and prediction models. While the majority of patients do not survive injuries which are coded with an AIS 6, there are several patients with a severe high cervical spinal cord injury that could be discharged from hospital despite the prognosis of trauma scores. We estimate that the trauma scores and prediction models miscalculate these injuries. For this reason, we evaluated these findings in a larger control group.

Methods
In a retrospective, multi-centre study, we used the data recorded in the TraumaRegister DGU® (TR-DGU) to select patients with a severe cervical spinal cord injury and an AIS of 3 to 6 between 2002 to 2015. We compared the estimated mortality rate according to the Revised Injury Severity Classification II (RISC II) score against the actual mortality rate for this group.

Results
Six hundred and twelve patients (0.6%) sustained a severe cervical spinal cord injury with an AIS of 6. The mean age was 57.8 ± 21.8 years and 441 (72.3%) were male. 580 (98.6%) suffered a blunt trauma, 301 patients were injured in a car accident and 29 through attempted suicide. Out of the 612 patients, 391 (63.9%) died from their injury and 170 during the first 24 h. The group had a predicted mortality rate of 81.4%, but we observed an actual mortality rate of 63.9%.

Conclusions
An AIS of 6 with a complete cord syndrome above C3 as documented in the TR-DGU is survivable if patients get to the hospital alive, at which point they show a survival rate of more than 35%. Compared to the mortality prognosis based on the RISC II score, they survived much more often than expected.
Physician-led prehospital management is associated with reduced mortality in severe blunt trauma patients: a retrospective analysis of the Japanese nationwide trauma registry
Authors: Endo Akira , Kojima Mitsuaki , Uchiyama Saya , Shiraishi Atsushi , Otomo Yasuhiro 
Published: January 2021

Abstract
Background
Although the results of previous studies suggested the effectiveness of physician-led prehospital trauma management, it has been uncertain because of the limited number of high-quality studies. Furthermore, the advantage of physician-led prehospital management might have been overestimated due to the shortened prehospital time by helicopter transportation in some studies. The present study aimed to evaluate the effect of physician-led prehospital management independent of prehospital time. Also, subgroup analysis was performed to explore the subpopulation that especially benefit from physician-led prehospital management.

Methods
This retrospective cohort study analyzed the data of Japan’s nationwide trauma registry. Severe blunt trauma patients, defined by Injury Severity Score (ISS) ≥16, who were transported directly to a hospital between April 2009 and March 2019 were evaluated. In-hospital mortality was compared between groups dichotomized by the occupation of primary prehospital healthcare provider (i.e., physician or paramedic), using 1:4 propensity score-matched analysis. The propensity score was calculated using potential confounders including patient demographics, mechanism of injury, vital signs at the scene of injury, ISS, and total time from injury to hospital arrival. Subpopulations that especially benefit from physician-led prehospital management were explored by assessing interaction effects between physician-led prehospital management and patient characteristics.

Results
A total of 30,551 patients (physician-led: 2976, paramedic-led: 27,575) were eligible for analysis, of whom 2690 propensity score-matched pairs (physician-led: 2690, paramedic-led: 10,760) were generated and compared. Physician-led group showed significantly decreased in-hospital mortality than paramedic-led group (in-hospital mortality: 387 [14.4%] and 1718 [16.0%]; odds ratio [95% confidence interval] = 0.88 [0.78–1.00], p = 0.044). Patients with age < 65 years, ISS ≥25, Abbreviated Injury Scale in pelvis and lower extremities ≥3, and total prehospital time < 60 min were likely to benefit from physician-led prehospital management.

Conclusions
Physician-led prehospital trauma management was significantly associated with reduced in-hospital mortality independent of prehospital time. The findings of exploratory subgroup analysis would be useful for the future research to establish efficient dispatch system of physician team.
Revisiting multiple erroneous genetic testing results and clinical misinterpretations in a patient with Li-Fraumeni syndrome: lessons for translational medicine
Authors: Sokolova Tatiana N. , Breder Valeriy V. , Shumskaya Irina S. , Suspitsin Evgeny N. , Aleksakhina Svetlana N. , Yanus Grigoriy A. , Tiurin Vladislav I. , Ivantsov Alexandr O. , Vona Barbara , Raskin Grigoriy A. , Gamajunov Sergey V. , Imyanitov Evgeny N. 
Published: January 2021

Abstract
Background
Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists.

Case presentation
We describe a patient with an extensive family history of cancer, who was diagnosed with bilateral breast cancer and two lung cancer lumps by the age of 40 years. She submitted a lung cancer specimen to a genetic profiling service, which reported the presence of the EGFR mutation (a combination of G719S and L833V substitutions) and the TP53 с.322_327del (p.G108_F109del) mutation in the tumor tissue. Possible therapeutic options were discussed at a medical conference, where one of the discussants raised a concern that the identified TP53 mutation may not necessarily be somatic, but reflect the germ-line status of the gene. Review of clinical records and follow-up dialog with the patient revealed, that she previously provided her blood for DNA analysis in two laboratories. The first laboratory utilized a custom NGS assay and did not detect the TP53 mutation, instead pointed to a potential pathogenic significance of the MSH6 c.2633 T > C (p.V878A) allele. The second laboratory revealed the TP53 с.322_327del (p.G108_F109del) allele but stated in the written report that it has an unknown pathogenic significance. To resolve the possible uncertainty regarding the role of the TP53 с.322_327del (p.G108_F109del) variant, we suggested that the patient invite her second cousin for genetic testing, as she was affected by neuroblastoma at the age of 3 years. This analysis revealed the presence of the same TP53 variant.

Conclusion
We provide point-by-point discussion, reviewing multiple laboratory mistakes and clinical misinterpretations occurred with this patient. This case report exemplifies the need to involve rigorous clinical expertise in the daily practice of medical laboratory facilities.
A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients
Authors: Macedo Etienne , Karl Bethany , Lee Euyhyun , Mehta Ravindra L. 
Published: January 2021

Abstract
Background
Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients.

Methods
A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded.

Results
Sixty-five patients were submitted to 249 sessions; the mean age was 58 ($$\pm$$
±
12), and 46 (70%) were male with a mean weight of 76 ($$\pm$$
±
18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS − 8.25 ml/kg/h (− 11.18 5.80) vs. 8.27 ml/kg/h (− 12.22 to 5.53) with albumin, p = 0.011].

Conclusion
In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients.
ClinicalTrials.gov Identifier: NCT04522635
Effect of sevoflurane on the inflammatory response during cardiopulmonary bypass in cardiac surgery: the study protocol for a randomized controlled trial
Authors: Cardoso Thiago Augusto Azevedo Maranhão , Kunst Gudrun , Neto Caetano Nigro , de Ribamar Costa Júnior José , Silva Carlos Gustavo Santos , Bastos Gisele Medeiros , Borges Jéssica Bassani , Hirata Mario Hiroyuki 
Published: January 2021

Abstract
Background
Recent experimental evidence shows that sevoflurane can reduce the inflammatory response during cardiac surgery with cardiopulmonary bypass. However, this observation so far has not been assessed in an adequately powered randomized controlled trial.

Methods
We plan to include one hundred patients undergoing elective coronary artery bypass graft with cardiopulmonary bypass who will be randomized to receive either volatile anesthetics during cardiopulmonary bypass or total intravenous anesthesia. The primary endpoint of the study is to assess the inflammatory response during cardiopulmonary bypass by measuring PMN-elastase serum levels. Secondary endpoints include serum levels of other pro-inflammatory markers (IL-1β, IL-6, IL-8, TNFα), anti-inflammatory cytokines (TGFβ and IL-10), and microRNA expression in peripheral blood to achieve possible epigenetic mechanisms in this process. In addition clinical endpoints such as presence of major complications in the postoperative period and length of hospital and intensive care unit stay will be assessed.

Discussion
The trial may determine whether adding volatile anesthetic during cardiopulmonary bypass will attenuate the inflammatory response.

Trial registration
ClinicalTrials.gov NCT02672345. Registered on February 2016 and updated on June 2020.
Effect of different rehabilitation training timelines to prevent shoulder dysfunction among postoperative breast cancer patients: study protocol for a randomized controlled trial
Authors: Shao Yu-Wei , Shu Qing , Xu Dan , Teng Hui , Wu Gao-Song , Hou Jin-Xuan , Tian Jun 
Published: January 2021

AbstractIntroductionDue to advancements in treatment, the survival of breast cancer (BC) patients has significantly improved. Improving the postoperative quality of life has become a widespread concern for patients and doctors. At present, the staged rehabilitation training program for postoperative BC patients has been recognized. However, there is not yet a consensus about the optimal time to initiate rehabilitation training. We designed this study to investigate the optimal intervention times for postoperative BC patients to begin different stages of rehabilitation.DesignThis is a randomized controlled trial. Female participants with BC who are scheduled to undergo mastectomy, including unilateral total breast or breast-conserving surgery plus axillary lymph node dissection, will be enrolled in this study. The intervention includes the following: 200 participants will be allocated using a 1:1:1:1 ratio to the A, B, C, and D groups, which have four different rehabilitation timelines for four phases of rehabilitation exercises. A therapist will evaluate the patient’s overall health and then adjust the training intensity before initiating training. The assessments include upper limb mobility, grip, limb circumference, postoperative drainage volume (PDV), and pain. The training will last for 12 weeks, and patients will undergo follow-up twice within 6 weeks after discharge. Outcomes include the following: Constant-Murley Score (CMS) is the primary parameter. European Organization Research and Treatment of Cancer Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23), SF-36, range of motion (ROM), strength, grip, circumference, PDV, and pain are the secondary parameters. All enrolled subjects will be assessed at 1 day, 3 days, 1 week, and 2, 3, 6, 9, 12, and 18 weeks after the surgery.DiscussionThis is a randomized controlled trial to evaluate the effect of different rehabilitation training timelines to prevent shoulder dysfunction among postoperative patients with BC. If the results are confirmed, this study will establish an optimal timeline for postoperative BC rehabilitation.Trial registrationClinicalTrials.govNCT03658265. Registered on September 2018.