bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship of prenatal antibiotic exposure and infant antibiotic administration with childhood allergies: a systematic review
Authors: Baron Ruth , Taye Meron , der Vaart Isolde Besseling-van , Ujčič-Voortman Joanne , Szajewska Hania , Seidell Jacob C. , Verhoeff Arnoud 
Published: June 2020

Abstract
Background
Early antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the relationship between early life antibiotic exposure and childhood asthma, eczema and hay fever.

Methods
Pubmed and Embase were searched for studies published between 01-01-2008 and 01-08-2018, examining the effects of (1) prenatal antibiotic exposure and (2) infant antibiotic administration (during the first 2 years of life) on childhood asthma, eczema and hay fever from 0 to 18 years of age. These publications were assessed using the Newcastle Ottawa Scale (NOS) and analysed narratively.

Results
(1) Prenatal antibiotics: Asthma (12 studies): The majority of studies (9/12) reported significant relationships (range OR 1.13 (1.02–1.24) to OR 3.19 (1.52–6.67)). Three studies reported inconsistent findings. Eczema (3 studies): An overall significant effect was reported in one study and in two other studies only when prenatal antibiotic exposure was prolonged. (2) Infant antibiotics: Asthma (27 studies): 17/27 studies reported overall significant findings (range HR 1.12 (1.08–1.16) to OR 3.21 (1.89–5.45)). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. 10/27 studies reported inconsistent findings depending on certain conditions and types of analyses. Of 19 studies addressing reverse causation or confounding by indication at least somewhat, 11 reported overall significant effects. Eczema (15 studies): 6/15 studies reported overall significant effects; 9 studies had either insignificant or inconsistent findings. Hay fever (9 studies): 6/9 reported significant effects, and the other three insignificant or inconsistent findings. General: Multiple and broad-spectrum antibiotics were more strongly associated with allergies. The majority of studies scored a 6 or 7 out of 9 based on the NOS, indicating they generally had a medium risk of bias. Although most studies showed significant findings between early antibiotic exposure and asthma, the actual effects are still unclear as intrapartum antibiotic administration, familial factors and confounding by maternal and child infections were often not addressed.

Conclusions
This review points to a moderate amount of evidence for a relationship between early life antibiotics (especially prenatal) and childhood asthma, some evidence for a relationship with hay fever and less convincing evidence for a relationship with eczema. More studies are still needed addressing intra-partum antibiotics, familial factors, and possible confounding by maternal and childhood infections. Children exposed to multiple, broad-spectrum antibiotics early in life appear to have a greater risk of allergies, especially asthma; these effects should be investigated further.
Clinical and Genetic Study on a Chinese Patient with Infantile Onset Epileptic Encephalopathy carrying a PPP3CA Null Variant: a case report
Authors: Yang Sai , Shen Xiang , Kang Qingyun , Kuang Xiaojun , Ning Zeshu , Liu Shulei , Liao Hongmei , Cao Zhenhua , Yang Liming 
Published: June 2020

Abstract
Background
PPP3CA gene encodes the catalytic subunit A of a calcium-dependent protein phosphatase called calcineurin. However, two distinct mechanisms in PPP3CA deficiency would cause two clinically different diseases. Gain-of-function mutations in the autoinhibitory domain at the C-terminus would cause ACCIID that stands for arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development. While loss-of-function mutations in PPP3CA would cause infantile or early childhood onset epileptic encephalopathy1, named as IECEE1. IECEE1 is a severe epileptic neurodevelopmental disorder and mainly characterized by psychomotor delay. Here, we report a Chinese patient who was clinically and genetically diagnosed as IECEE1. We also extensively analyzed electroencephalogram (EEG) features of the patient in this study.

Case presentation
A 2-year-old Chinese patient who had recurrent polymorphic seizures was clinically and genetically diagnosed as IECEE1. A frameshift variant c.1283insC (p.T429NfsX22) was identified in this case. Multiple types of abnormal features were observed in the EEG, comparing with the previous reports.

Conclusions
These findings could expand the spectrum of PPP3CA mutations and might also support the diagnosis and further study of IECEE1.
Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity
Authors: Bachman Thomas E. , Iyer Narayan P. , Newth Christopher J. L. , Ross Patrick A. , Khemani Robinder G. 
Published: June 2020

Abstract
Background
Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited.

Methods
This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50–80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels.

Results
Neonates were categorized by postmenstrual age: < 33 (n = 155), 33–36 (n = 192) and > 36 (n = 1031) weeks.
From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24–28) n = 2603; 34 (33–35) n = 2501; and 38 (37–39) n = 21,058. The chance of normoxemia (65, 95%-CI 64–67%) was similar across the SpO2 range of 88–95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21–29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18–33%), for infants 33–36 weeks at 97% SpO2 (24, 95%-CI 14–25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17–22%).

Conclusions
The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.
Comparison between minimally invasive deltoid-split and extended deltoid-split approach for proximal humeral fractures: a case-control study
Authors: Wang Ji-Qi , Lin Chui-cong , Zhao You-Ming , Jiang Bing-Jie , Huang Xiao-Jing 
Published: June 2020

Abstract
Background
With the rapid aging of the population, the incidence of proximal humeral fracture (PHF) has increased. However, the optimal method for open reduction and internal fixation (ORIF) remains controversial.

Methods
We performed a retrospective analysis of patients with PHF who underwent locking plate internal fixation at our institution from January 2016 to December 2018. Patients were divided into two groups based on the surgical approach used: an expanded deltoid-split approach group (ORIF group) and minimally invasive deltoid-split approach group (minimally invasive percutaneous plate osteosynthesis, [MIPPO] group). The groups were compared in terms of demographic and perioperative characteristics, and clinical outcomes.

Results
A total of 115 cases of PHF were included in our study, of which 64 cases were treated using the minimally invasive deltoid-split approach and 51 using the extended deltoid-split approach. Fluoroscopy was performed significantly less frequently in the ORIF group and the surgical duration was shorter. However, the postoperative visual analogue scale (VAS) pain score and duration of postoperative hospital stay were significantly higher compared to the MIPPO group. Moreover, secondary loss was significantly less extensive in the ORIF group compared to the MIPPO group, while there was no significant group difference in fracture healing time, Constant shoulder score, or complications at the last follow-up visit.

Conclusions
The clinical outcomes associated with both the minimally invasive and extended deltoid-split approaches were satisfactory. The data presented here suggest that the extended deltoid-split approach was superior to the minimally invasive deltoid-split approach in terms of operational time, fluoroscopy, and secondary loss of reduction, while the minimally invasive approach was superior in terms of postoperative pain and hospital stay. Accordingly, neither procedure can be considered definitively superior; the optimal surgical procedure for PHF can only be determined after full consideration of the situation and requirements of the individual patient.
Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma
Authors: Zhang Peng-Fei , Gao Chao , Huang Xiao-Yong , Lu Jia-Cheng , Guo Xiao-Jun , Shi Guo-Ming , Cai Jia-Bin , Ke Ai-Wu 
Published: June 2020

Abstract
Objective
Natural killer (NK) cells play a critical role in the innate antitumor immune response. Recently, NK cell dysfunction has been verified in various malignant tumors, including hepatocellular carcinoma (HCC). However, the molecular biological mechanisms of NK cell dysfunction in human HCC are still obscure.

Methods
The expression of circular ubiquitin-like with PHD and ring finger domain 1 RNA (circUHRF1) in HCC tissues, exosomes, and cell lines was detected by qRT-PCR. Exosomes were isolated from the culture medium of HCC cells and plasma of HCC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit and then characterized by transmission electronic microscopy, NanoSight and western blotting. The role of circUHRF1 in NK cell dysfunction was assessed by ELISA. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the molecular mechanisms of circUHRF1 in NK cells. In a retrospective study, the clinical characteristics and prognostic significance of circUHRF1 were determined in HCC tissues.

Results
Here, we report that the expression of circUHRF1 is higher in human HCC tissues than in matched adjacent nontumor tissues. Increased levels of circUHRF1 indicate poor clinical prognosis and NK cell dysfunction in patients with HCC. In HCC patient plasma, circUHRF1 is predominantly secreted by HCC cells in an exosomal manner, and circUHRF1 inhibits NK cell-derived IFN-γ and TNF-α secretion. A high level of plasma exosomal circUHRF1 is associated with a decreased NK cell proportion and decreased NK cell tumor infiltration. Moreover, circUHRF1 inhibits NK cell function by upregulating the expression of TIM-3 via degradation of miR-449c-5p. Finally, we show that circUHRF1 may drive resistance to anti-PD1 immunotherapy in HCC patients.

Conclusions
Exosomal circUHRF1 is predominantly secreted by HCC cells and contributes to immunosuppression by inducing NK cell dysfunction in HCC. CircUHRF1 may drive resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for patients with HCC.
Association of sleep duration with stroke, myocardial infarction, and tumors in a Chinese population with metabolic syndrome: a retrospective study
Authors: YE Yingnan , ZHANG Linxi , WANG Anping , Wang Yuxia , WANG Shiqing , NING Guang , MU Yiming 
Published: June 2020

AbstractBackgroundPrevious studies have suggested that abnormal sleep duration is associated with increased risk of metabolic syndrome (MetS). However, evidence on the association of sleep duration with stroke, myocardial infarction (MI) and tumors in populations with MetS is limited.MethodsA total of 8968 participants (2754 with MetS at baseline) were recruited in this retrospective study between March 2012 and December 2012. The baseline characteristics and information on sleep duration were collected by self-reported questionnaires. In addition, physical examination and blood test were also performed. The outcome events in this study were new onset of stroke, MI and tumors during subsequent follow-up. Multivariate logistic regressions were adopted to investigate the relationships between sleep duration and outcome events among different sleep duration groups (< 6 h, 6–7 h, 7–8 h [reference], 8–9 h, and > 9 h per day) in participants with MetS.ResultsThe mean self-reported total sleep duration was 7.8 ± 1.2 h. Compared with participants with MetS slept for 7–8 h per day, the adjusted odds ratios (ORs) for those slept for > 9 h in stroke, MI and tumors were 2.014 (95% confidence interval [CI]: 1.184–3.426,P = 0.010), 1.731 (95% CI: 0.896–3.344,P = 0.102) and 2.159 (95% CI: 0.991–4.704,P = 0.053), respectively, whereas the adjusted ORs for those slept for < 6 h in stroke, MI and tumors were 2.249 (95% CI: 0.973–5.195,P = 0.058), 1.213 (95% CI, 0.358–4.104,P = 0.756) and 1.743 (95% CI, 0.396–7.668,P = 0.462), respectively.ConclusionsLong sleep duration (> 9 h) significantly increased the risk of stroke but not MI and tumors in individuals with MetS compared with 7–8 h of sleep duration. Short sleep duration (< 6 h) was not associated with the increased risk of stroke, MI and tumors in individuals with MetS.
BRAFV600E mutation, BRAF-activated long non-coding RNA and miR-9 expression in papillary thyroid carcinoma, and their association with clinicopathological features
Authors: Shi Chenlei , Cao Jia , Shi Tiefeng , Liang Meihua , Ding Chao , Lv Yichen , Zhang Weifeng , Li Chuanle , Gao Wenchao , Wu Gang , Man Jianting 
Published: June 2020

Abstract
Background
The incidence of thyroid cancer is increasing worldwide. This study investigated the association of B-type RAF kinase (BRAF)V600E mutation status, the expression of BRAF-activated long non-coding RNA (BANCR) and microRNA miR-9, and the clinicopathological features of papillary thyroid carcinoma (PTC).

Methods
Clinicopathological data for PTC patients (n = 51) diagnosed and treated between 2018 and 2019 were collected. Carcinoma and adjacent normal tissue samples were analyzed for the presence of the BRAFV600E mutation and/or expression of BANCR and miR-9.

Results
Larger tumor, higher rate of bilateral tumors and multifocality, extracapsular invasion, and lateral lymph node metastasis (LNM) were observed in PTC patients with BRAF V600E mutation. Patients with higher BANCR expression had a higher rate of extracapsular invasion and lateral LNM in carcinoma tissue and a lower frequency of bilateral tumors and multifocality in normal adjacent tissue. Patients with higher miR-9 expression had a lower rate of central and lateral LNM in carcinoma tissue and higher rates of bilateral tumor location and multifocality in normal adjacent tissue. Patients with BRAFV600E mutation have a higher rate of BANCR overexpression and tended to have a lower rate of miR-9 overexpression (P = 0.057), and a negative association was observed between BANCR and miR-9 expression in carcinoma tissue.

Conclusions
BRAFV600E mutation and the BANCR and miR-9 expression were closely associated with the tumor size, bilateral tumor location, multifocality, extracapsular invasion, and lateral LNM. PTC patients with these clinicopathological characteristics, BRAFV600E mutation, and high BANCR expression and low miR-9 expression needed earlier surgical treatment and are recommended for total thyroidectomy in primary surgery for reducing the risk of recurrence. These findings provide new insight into the molecular basis for PTC and can inform strategies for the management of PTC.
27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction
Authors: Wang Ying , An Yu , Ma Weiwei , Yu Huiyan , Lu Yanhui , Zhang Xiaona , Wang Yushan , Liu Wen , Wang Tao , Xiao Rong 
Published: June 2020

Abstract
Background
Research on the brain-gut-microbiota axis has led to accumulating interest in gut microbiota dysbiosis and intestinal barrier dysfunction in Alzheimer’s disease (AD). Our previous studies have demonstrated neurotoxic effects of 27-hydroxycholesterol (27-OHC) in in vitro and in vivo models. Here, alterations in the gut microbiota and intestinal barrier functions were investigated as the possible causes of cognitive deficits induced by 27-OHC treatment.

Methods
Male APP/PS1 transgenic and C57BL/6J mice were treated for 3 weeks with 27-OHC (5.5 mg/kg/day, subcutaneous injection) and either a 27-OHC synthetase inhibitor (anastrozole, ANS) or saline. The Morris water maze and passive avoidance test were used to assess cognitive impairment. Injuries of the intestine were evaluated by histopathological examination. Intestinal barrier function was assessed by plasma diamine oxidase (DAO) activity and d-lactate. Systemic and intestinal inflammation were evaluated by IL-1β, TNF-α, IL-10, and IL-17 concentrations as determined by ELISA. The fecal microbiome and short-chain fatty acids (SCFAs) were analyzed using 16S rDNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Tight junction proteins were evaluated in the ileum and colon by qRT-PCR and Western blots. Tight junction ultrastructure was examined by transmission electron microscopy.

Results
Treatment with 27-OHC resulted in severe pathologies in the ileum and colon. There was impaired intestinal barrier integrity as indicated by dilated tight junctions and downregulation of tight junction proteins, including occludin, claudin 1, claudin 5, and ZO-1, and signs of inflammation (increased IL-1β, TNF-α, and IL-17). Fecal 16S rDNA sequencing and taxonomic analysis further revealed a decreased abundance of Roseburia and reduced fecal levels of several SCFAs in 27-OHC-treated mice. Meanwhile, co-treatment with ANS reduced intestinal inflammation and partially preserved intestinal barrier integrity in the presence of 27-OHC.

Conclusions
The current study demonstrates for the first time that 27-OHC treatment aggravates AD-associated pathophysiological alterations, specifically gut microbiota dysbiosis and intestinal barrier dysfunction, which suggests that the gut microbiome and intestinal barrier function warrant further investigation as potential targets to mitigate the neurotoxic impact of 27-OHC on cognitive function and the development of AD.
Bioproduction of succinic acid from xylose by engineered Yarrowia lipolytica without pH control
Authors: Prabhu Ashish A. , Ledesma-Amaro Rodrigo , Lin Carol Sze Ki , Coulon Frederic , Thakur Vijay Kumar , Kumar Vinod 
Published: June 2020

Abstract
Background
Xylose is the most prevalent sugar available in hemicellulose fraction of lignocellulosic biomass (LCB) and of great interest for the green economy. Unfortunately, most of the cell factories cannot inherently metabolize xylose as sole carbon source. Yarrowia lipolytica is a non-conventional yeast that produces industrially important metabolites. The yeast is able to metabolize a large variety of substrates including both hydrophilic and hydrophobic carbon sources. However, Y. lipolytica lacks effective metabolic pathway for xylose uptake and only scarce information is available on utilization of xylose. For the economica feasibility of LCB-based biorefineries, effective utilization of both pentose and hexose sugars is obligatory.

Results
In the present study, succinic acid (SA) production from xylose by Y. lipolytica was examined. To this end, Y. lipolytica PSA02004 strain was engineered by overexpressing pentose pathway cassette comprising xylose reductase (XR), xylitol dehydrogenase (XDH) and xylulose kinase (XK) gene. The recombinant strain exhibited a robust growth on xylose as sole carbon source and produced substantial amount of SA. The inhibition of cell growth and SA formation was observed above 60 g/L xylose concentration. The batch cultivation of the recombinant strain in a bioreactor resulted in a maximum biomass concentration of 7.3 g/L and SA titer of 11.2 g/L with the yield of 0.19 g/g. Similar results in terms of cell growth and SA production were obtained with xylose-rich hydrolysate derived from sugarcane bagasse. The fed-batch fermentation yielded biomass concentration of 11.8 g/L (OD600: 56.1) and SA titer of 22.3 g/L with a gradual decrease in pH below 4.0. Acetic acid was obtained as a main by-product in all the fermentations.

Conclusion
The recombinant strain displayed potential for bioconversion of xylose to SA. Further, this study provided a new insight on conversion of lignocellulosic biomass into value-added products. To the best of our knowledge, this is the first study on SA production by Y. lipolytica using xylose as a sole carbon source.
Colonic mucosa-associated lymphoid tissue in a renal transplant recipient: a case report
Authors: Martin Kylie , Taylor Andrew , Tam Constantine , Hill Prue , Machet David , Goodman David 
Published: June 2020

Abstract
Background
Extra-gastric (particularly colonic) lymphoma of mucosa-associated lymphoid tissue in the immunosuppressed solid organ transplant recipient is rare. We report a case of low-volume mucosa-associated lymphoid tissue lymphoma with colonic and bone marrow involvement in a renal transplant recipient that has been managed conservatively.

Case presentation
A 62-year-old Caucasian man, 14 years after kidney transplantation, was diagnosed as having extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue with bone marrow and colonic involvement, after a colonoscopy identified mucosa-associated lymphoid tissue lymphoma in a sessile sigmoid polyp following surveillance fecal occult blood testing that returned a positive result. A gastric biopsy showed no evidence of Helicobacter pylori, but Helicobacter pylori immunoglobulin G was positive. He received Helicobacter pylori eradication treatment and is being managed expectantly. Immunosuppression was unchanged with prednisolone, mycophenolate mofetil, and cyclosporine A. Renal allograft function has remained stable.

Conclusions
This case highlights the unexpected occurrence of colonic mucosa-associated lymphoid tissue lymphoma in a kidney transplant recipient. The case emphasizes the importance of histopathological diagnosis of colonic lesions in this patient cohort because the unusual diagnosis of low-volume mucosa-associated lymphoid tissue lymphoma can be managed expectantly as it does not appear to be clinically aggressive in the immunosuppressed solid organ transplant.