bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-1231 decrease the risk of cancer-related mortality in patients combined with non-small cell lung cancer and diabetes mellitus
Authors: Li Jing , Xu Jialiang , Cao Zhijun , Du Shouzuo , Zhang Luyu 
Published: September 2020

Abstract
Background
Non-small cell lung cancer (NSCLC) is a deadly human malignancy, and previous studies support the contribution of microRNAs (miRNAs) to cancer assessment. It has been reported that miR-1231 can be used as a biomarker to assess prognosis in different cancers. However, the prognostic value of miR-1231 in NSCLC patients with comorbid diabetes mellitus (DM) remains unclear. The present study evaluated the risk factors for NSCLC with DM and developed a predictive model for it.

Methods
A real-world study was conducted, including data from 108 patients with NSCLC combined with DM from April 1, 2010, to June 1, 2015. MiR-1231 was recorded during hospital admission. Cox-proportional hazards model was applied for survival analysis of risk factors for cancer-related mortality and to create nomograms for prediction. The accuracy of the model was evaluated by C-index and calibration curves.

Results
The mortality rate in the high miR-1231 level (≥ 1.775) group was 57.4%. On the basis of univariate analysis, we put factors (P < 0.05) into multivariate regression models, and high miR-1231 levels (P < 0.001, HR = 0.57), surgery (P < 0.001, HR = 0.37) and KPS score > 80 (P = 0.01, HR = 0.47) had a better prognosis and were considered as independent protective factors. These independently relevant factors were used to create nomograms to predict long-term patient survival. Nomogram showed good accuracy in risk estimation with a guide-corrected C-index of 0.691.

Conclusion
MiR-1231 reduced the risk of cancer-related death in patients with combined NSCLC and DM. Nomogram based on multivariate analysis showed good accuracy in estimating the overall risk of death.
Beliefs, perceptions and practices of chiropractors and patients about mitigation strategies for benign adverse events after spinal manipulation therapy
Authors: Funabashi Martha , Pohlman Katherine A. , Goldsworthy Rachel , Lee Alex , Tibbles Anthony , Mior Silvano , Kawchuk Greg 
Published: September 2020

Abstract
Background
Approximately 50% of patients who receive spinal manipulative therapy (SMT) experience some kind of adverse event (AE), typically benign and transient in nature. Regardless of their severity, mitigating benign AEs is important to improve patient experience and quality of care. The aim of this study was to identify beliefs, perceptions and practices of chiropractors and patients regarding benign AEs post-SMT and potential strategies to mitigate them.

Methods
Clinicians and patients from two chiropractic teaching clinics were invited to respond to an 11-question survey exploring their beliefs, perceptions and practices regarding benign AEs post-SMT and strategies to mitigate them. Responses were analyzed using descriptive statistics.

Results
A total of 39 clinicians (67% response rate) and 203 patients (82.9% response rate) completed the survey. Most clinicians (97%) believed benign AEs occur, and 82% reported their own patients have experienced one. For patients, 55% reported experiencing benign AEs post-SMT, with the most common symptoms being pain/soreness, headache and stiffness. While most clinicians (61.5%) reported trying a mitigation strategy with their patients, only 21.2% of patients perceived their clinicians had tried any mitigation strategy. Clinicians perceived that patient education is most likely to mitigate benign AEs, followed by soft tissue therapy and/or icing after SMT. Patients perceived stretching was most likely to mitigate benign AEs, followed by education and/or massage.

Conclusions
This is the first study comparing beliefs, perceptions and practices from clinicians and patients regarding benign AEs post-SMT and strategies to mitigate them. This study provides an important step towards identifying the best strategies to improve patient safety and improve quality of care.
Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia
Authors: Gu Runxia , Liu Fang , Zou Dehui , Xu Yingxi , Lu Yang , Liu Bingcheng , Liu Wei , Chen Xiaojuan , Liu Kaiqi , Guo Ye , Gong Xiaoyuan , Lv Rui , Chen Xia , Zhou Chunlin , Zhong Mengjun , Wang Huijun , Wei Hui , Mi Yingchang , Qiu Lugui , Lv Lulu , Wang Min , Wang Ying , Zhu Xiaofan , Wang Jianxiang 
Published: September 2020

Abstract
Background
Recent evidence suggests that resistance to CD19 chimeric antigen receptor (CAR)-modified T cell therapy may be due to the presence of CD19 isoforms that lose binding to the single-chain variable fragment (scFv) in current use. As such, further investigation of CARs recognize different epitopes of CD19 antigen may be necessary.

Methods
We generated a new CD19 CAR T (HI19α-4-1BB-ζ CAR T, or CNCT19) that includes an scFv that interacts with an epitope of the human CD19 antigen that can be distinguished from that recognized by the current FMC63 clone. A pilot study was undertaken to assess the safety and feasibility of CNCT19-based therapy in both pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).

Results
Data from our study suggested that 90% of the 20 patients treated with infusions of CNCT19 cells reached complete remission or complete remission with incomplete count recovery (CR/CRi) within 28 days. The CR/CRi rate was 82% when we took into account the fully enrolled 22 patients in an intention-to-treat analysis. Of note, extramedullary leukemia disease of two relapsed patients disappeared completely after CNCT19 cell infusion. After a median follow-up of 10.09 months (range, 0.49–24.02 months), the median overall survival and relapse-free survival for the 20 patients treated with CNCT19 cells was 12.91 months (95% confidence interval [CI], 7.74–18.08 months) and 6.93 months (95% CI, 3.13–10.73 months), respectively. Differences with respect to immune profiles associated with a long-term response following CAR T cell therapy were also addressed. Our results revealed that a relatively low percentage of CD8+ naïve T cells was an independent factor associated with a shorter period of relapse-free survival (p = 0.012, 95% CI, 0.017–0.601).

Conclusions
The results presented in this study indicate that CNCT19 cells have potent anti-leukemic activities in patients with R/R B-ALL. Furthermore, our findings suggest that the percentage of CD8+ naïve T cells may be a useful biomarker to predict the long-term prognosis for patients undergoing CAR T cell therapy.

Trial registration
ClinicalTrials.gov: NCT02975687; registered 29 November, 2016. https://clinicaltrials.gov/ct2/keydates/NCT02975687
Severe haemophilia a in a preterm girl with turner syndrome - a case report from the prenatal period to early infancy (part I)
Authors: Berendt Agnieszka , Wójtowicz-Marzec Monika , Wysokińska Barbara , Kwaśniewska Anna 
Published: September 2020

Abstract
Background
Bleedings are more frequent in the population of preterm children than among those born at term, much less in older children. The reasons for such bleedings in preterms include plasma factor deficiencies, immaturity of small vessels in the germinal matrix region, prenatal hypoxia or sepsis. They affect the brain tissue, the gastrointestinal tract and the respiratory system, or are manifested by prolonged bleedings from injection sites. Haemophilia is a rare cause of haemorrhages in the neonatal period, and in the female population it is even seen as an extremely rare disorder. Its aetiology in girls is diverse: inheriting defective genes from their parents, skewed X inactivation or a single X chromosome.

Case presentation
The article presents a case of a preterm girl born in the 28th week of pregnancy, who was diagnosed with severe haemophilia A stemming from the absence of the X chromosome. The girl’s father is healthy, but her mother’s brother suffers from haemophilia.
On the second day of the child’s life, a prolonged bleeding from the injection site was observed. A coagulation profile revealed prolonged APTT which pointed to haemophilia A diagnosis. Moreover, a marked clinical dysmorphy, female sex and a negative family history on the father’s side led the treating team to extend the diagnostic procedures to encompass karyotype evaluation. The girl was diagnosed with Turner syndrome. No bleeding to the central nervous system was observed during her hospital stay.

Conclusions
Preterm children belong to the risk group of bleeding into the central nervous system or haemorrhages in the course of sepsis. Rare causes of such bleedings should also be borne in mind, including haemophilia.
The initial symptoms of haemophilia in preterm children occur in the first days of their lives, which is connected with a number of invasive procedures required in that period.
Genetic conditions may coexist with one another. Arriving at one diagnosis does not mean one should abandon further diagnostic procedures in cases where additional atypical symptoms are present which do not match the clinical image of a primary disease.
Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance
Authors: Martínez-Valladares María , Valderas-García Elora , Gandasegui Javier , Skuce Philip , Morrison Alison , Castilla Gómez de Agüero Verónica , Cambra-Pellejà Maria , Balaña-Fouce Rafael , Rojo-Vázquez Francisco A. 
Published: September 2020

Abstract
Background
Benzimidazole resistance is associated with isotype-1 β-tubulin gene F200Y, E198A and F167Y SNPs. In this study, the recently described polymorphism E198L was reported and analysed in Teladorsagia circumcincta.

Methods
The benzimidazole phenotypic resistance was measured by the faecal egg count reduction test (FECRT) and the egg hatch test (EHT) using a discriminating dose (DD) in 39 sheep flocks. Around 1000 larvae collected before and after treatment were used for DNA extraction. The resistant species identified in all flocks was T. circumcincta. The resistance alleles frequencies were measured for F200Y and E198A. A 371-bp fragment of the isotype-1 β-tubulin gene was analysed, including the three codons of interest, and a new pyrosequencing assay was designed for testing E198L.

Results
The percentage of resistant flocks was 35% by FECRT or 26% by EHT; however, F200Y and E198A SNPs were absent in T. circumcincta. The amplification of a 371-bp fragment confirmed the absence of F167Y and F200Y in 6 resistant flocks. Regarding codon 198, all samples after treatment carried a leucine (CTA). A pyrosequencing assay analysed the allele frequencies for the first two bases at codon 198 independently, G/C and A/T. The correlation between C and T frequencies was almost 1 (r = 0.929, P < 0.0001) and the mean value of both was calculated to measure the leucine frequency; this value ranged between 10.4–80.7% before treatment, and 82.3–92.8% after treatment. High and similar correlations were reported between the genotypic variables (C frequency, T frequency or mean of both frequencies) and phenotypic resistance (r > 0.720, P < 0.0001), although negatively associated with the FECRT and positively with the EHT. According to multivariate linear regression analysis, the T frequency was the most significant variable influencing the phenotypic resistance (FECRT or EHT; P < 0.0001). In the EHT, 67.1% of the phenotypic variability is associated with the T frequency but in the FECRT only 33.4%; therefore, the EHT using a DD seems to detect the genotypic resistance more accurately than the FECRT.

Conclusions
The E198L polymorphism can confer BZ resistance on its own in T. circumcincta.
Associations of maternal early-pregnancy blood glucose and insulin concentrations with DNA methylation in newborns
Authors: Geurtsen Madelon L. , Jaddoe Vincent W. V. , Gaillard Romy , Felix Janine F. 
Published: September 2020

AbstractBackgroundIntrauterine exposure to a disturbed maternal glucose metabolism is associated with adverse offspring outcomes. DNA methylation is a potential mechanism underlying these associations. We examined whether maternal early-pregnancy glucose and insulin concentrations are associated with newborn DNA methylation. In a population-based prospective cohort study among 935 pregnant women, maternal plasma concentrations of non-fasting glucose and insulin were measured at a median of 13.1 weeks of gestation (95% range 9.4–17.4). DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Ilumina). We analyzed associations of maternal early-pregnancy glucose and insulin concentrations with single-CpG DNA methylation using robust linear regression models. Differentially methylated regions were analyzed using the dmrff package in R. We stratified the analyses on normal weight versus overweight or obese women. We also performed a look-up of CpGs and differently methylated regions from previous studies to be associated with maternal gestational diabetes, hyperglycemia or hyperinsulinemia, or with type 2 diabetes in adults.ResultsMaternal early-pregnancy glucose and insulin concentrations were not associated with DNA methylation at single CpGs nor with differentially methylated regions in the total group. In analyses stratified on maternal BMI, maternal early-pregnancy glucose concentrations were associated with DNA methylation at one CpG (cg03617420,XKR6) among normal weight women and at another (cg12081946,IL17D) among overweight or obese women. No stratum-specific associations were found for maternal early-pregnancy insulin concentrations. The two CpGs were not associated with birth weight or childhood glycemic measures (pvalues > 0.1). Maternal early-pregnancy insulin concentrations were associated with one CpG known to be related to adult type 2 diabetes. Enrichment among nominally significant findings in our maternal early-pregnancy glucose concentrations was found for CpGs identified in a previous study on adult type 2 diabetes.ConclusionsMaternal early-pregnancy glucose concentrations, but not insulin concentrations, were associated with DNA methylation at one CpG each in the subgroups of normal weight and of overweight or obese women. No associations were present in the full group. The role of these CpGs in mechanisms underlying offspring health outcomes needs further study. Future studies should replicate our results in larger samples with early-pregnancy information on maternal fasting glucose metabolism.
hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β1/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats
Authors: Cui Linlu , Bao Hongchu , Liu Zhongfeng , Man Xuejing , Liu Hongyuan , Hou Yun , Luo Qianqian , Wang Siyuan , Fu Qiang , Zhang Hongqin 
Published: September 2020

AbstractObjectiveThe basic pathological changes of primary ovarian insufficiency (POI) include ovarian tissue fibrosis and follicular development disorders. The human umbilical cord mesenchymal stem cell (hUMSC) transplantation has been shown an effective method to improve the ovarian function in POI rat model; however, the exact mechanisms are still unclear. The purpose of this study is to investigate whether the recovery of ovarian function in POI rats is related to the inhibition of tissue fibrosis following hUMSC transplantation. Furthermore, the transforming growth factor-β1(TGF-β1) signaling pathway is explored to determine the mechanisms of ovarian function recovery through its inhibition of tissue fibrosis.MethodsThe primary ovarian insufficiency (POI) rat model was established by intraperitoneal injection of chemotherapy drug cisplatin (CDDP) for 7 days. The levels of serum sex hormones were measured using enzyme-linked immunosorbent assay (ELISA). The tissue fibrosis in the ovary was examined using Masson staining and Sirius red staining. The collagen fibers in the ovarian tissues were detected by Western blot analysis. To investigate the mechanisms of ovarian function recovery following hUMSC transplantation, ovarian stromal cells were isolated from the ovarian cortex of immature rats. The expression of Cytochrome P450 17A1 (Cyp17a1) and fibrosis marker of alpha smooth muscle actin (α-SMA) in ovarian stromal cells was examined using immunofluorescence analysis. Also, the protein levels of Cyp17a1 and α-SMA in ovarian stromal cells were examined by Western blot analysis. The expression of TGF-β1and Smad3 signals was measured by Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.ResultsThe results show that the function of the ovary in POI rats was significantly improved after hUMSC transplantation. The expression of fibrosis markers (α-SMA) and production of Collagen Type I (Collagen I) and Collagen Type III (Collagen III) in POI rats were significantly inhibited in POI rats following hUMSC transplantation. In the cultured ovarian stromal cells, the decrease of TGF-β1and p-Smad3 protein expression was observed in hUMSC-treated POI rats. The treatment with TGF-β1inhibitor of SB431542 further confirmed this signal pathway was involved in the process.ConclusionOur study demonstrated that the TGF-β1/Smad3 signaling pathway was involved in the inhibition of ovarian tissue fibrosis, which contributed to the restoration of ovarian function in POI rats following hUMSC transplantation.
Regeneration of a full-thickness defect of rotator cuff tendon with freshly thawed umbilical cord-derived mesenchymal stem cells in a rat model
Authors: Yea Ji-Hye , Park Jin-Kyung , Kim In Ja , Sym Gayoung , Bae Tae-Soo , Jo Chris Hyunchul 
Published: September 2020

Abstract
Background
It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model.

Methods
We evaluated morphology, viability, and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs, respectively. Two and 4 weeks later, macroscopic, histological, biomechanical, and cell trafficking were evaluated. T test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant.

Results
T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was more recovered at 2 and 4 weeks such as inflammation, defect size, neighboring tendon, swelling/redness, the connecting surrounding tissue and slidability. Histologically, the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization, and fiber coherence were improved by 33.33%, 42.75%, 1.86-fold, and 1.99-fold at 4 weeks, and GAG-rich area decreased by 88.13% and 94.70% at 2 and 4 weeks respectively. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both 2 and 4 weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Moreover, T-UC MSCs remained 8.77% at 4 weeks after injury, and there was no significant difference between C-UC MSCs and T-UC MSCs.

Conclusions
The morphology, viability, and proliferation of T-UC MSCs were comparable to those of C-UC MSCs. Treatment with T-UC MSCs could induce tendon regeneration of FTD at the macroscopic, histological, and biomechanical levels comparable to treatment with C-UC MSCs.
Multipotent adult progenitor cells grown under xenobiotic-free conditions support vascularization during wound healing
Authors: Vaes Bart , Van Houtven Ellen , Caluwé Ellen , Luttun Aernout 
Published: September 2020

AbstractBackgroundCell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. Here, the potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated.MethodsThe potential of XF-hMAPC cells to support blood vessel formation was first scored in an in vivo Matrigel assay in mice. Next, a dose-response study was performed with XF-hMAPC cells in which they were tested for their ability to support vascularization and (epi) dermal healing in a physiologically relevant splinted wound mouse model.ResultsXF-hMAPC cells supported blood vessel formation in Matrigel by promoting the formation of mature (smooth muscle cell-coated) vessels. Furthermore, XF-hMAPC cells dose-dependently improved wound vascularization associated with increasing wound closure and re-epithelialization, granulation tissue formation, and dermal collagen organization.ConclusionsHere, we demonstrated that the administration of clinical-grade XF-hMAPC cells in mice represents an effective approach for improving wound vascularization and healing that is readily applicable for translation in humans.
Bacillus velezensis 83 a bacterial strain from mango phyllosphere, useful for biological control and plant growth promotion
Authors: Balderas-Ruíz Karina A. , Bustos Patricia , Santamaria Rosa I. , González Víctor , Cristiano-Fajardo Sergio Andrés , Barrera-Ortíz Salvador , Mezo-Villalobos Miriam , Aranda-Ocampo Sergio , Guevara-García Ángel Arturo , Galindo Enrique , Serrano-Carreón Leobardo 
Published: September 2020

AbstractBacillus velezensis 83 was isolated from mango tree phyllosphere of orchards located in El Rosario, Sinaloa, México. The assessment of this strain as BCA (biological control agent), as well as PGPB (plant growth-promoting bacteria), were demonstrated through in vivo and in vitro assays. In vivo assays showed that B. velezensis 83 was able to control anthracnose (Kent mangoes) as efficiently as chemical treatment with Captan 50 PH™ or Cupravit hidro™. The inoculation of B. velezensis 83 to the roots of maize seedlings yielded an increase of 12% in height and 45% of root biomass, as compared with uninoculated seedlings. In vitro co-culture assays showed that B. velezensis 83 promoted Arabidopsis thaliana growth (root and shoot biomass) while, under the same experimental conditions, B. velezensis FZB42 (reference strain) had a suppressive effect on plant growth. In order to characterize the isolated strain, the complete genome sequence of B. velezensis 83 is reported. Its circular genome consists of 3,997,902 bp coding to 3949 predicted genes. The assembly and annotation of this genome revealed gene clusters related with plant-bacteria interaction and sporulation, as well as ten secondary metabolites biosynthetic gene clusters implicated in the biological control of phytopathogens. Despite the high genomic identity (> 98%) between B. velezensis 83 and B. velezensis FZB42, they are phenotypically different. Indeed, in vitro production of compounds such as surfactin and bacillomycin D (biocontrol activity) and γ-PGA (biofilm component) is significantly different between both strains.