bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mid-Term Outcomes of an Alternative Remodelling Technique for Aortic Root Replacement Without Coronary Ostial Mobilisation or Reimplantation
Authors: Acharya Metesh , Dominici Carmelo , Biancari Fausto , Raheel Furqan , Ahmed Aamer , Hadjinikolaou Leonidas , Mariscalco Giovanni 
Published: June 2022

Abstract
Background: We compare the early and late outcomes of a modified aortic root remodelling (ARR) technique for aortic root replacement without mobilisation or reimplantation of the coronary ostia, with those of the modified Bentall procedure.Methods: A retrospective observational study was performed comprising 181 consecutive patients who underwent aortic root replacement with a Bentall procedure (104 patients) or ARR (77 patients) between January 2013 and December 2019. Primary endpoints included hospital mortality and late survival. Secondary endpoints included incidence of post-operative complications and freedom from late re-operation. Results: ARR procedures were performed with shorter cross-clamp times and comparable cardiopulmonary bypass times to Bentall procedures. The incidence of early post-complications was comparable between groups. 30-day mortality was numerically lower with ARR than Bentall procedure. Over 7-year follow-up, 4 patients (3.8%) required repeat aortic surgery after Bentall procedure, and none after ARR. Long-term mortality after ARR and after Bentall procedures was 17.1% and 22.7%, respectively. The cumulative incidence of reintervention on the aortic root/valve was 3.2% after a Bentall procedure and 0% after ARR. When adjusted for other independent risk factors, late mortality was not influenced by the procedure performed, although competing risk adjusted for age showed that Bentall procedure was associated with an increased risk of aortic root/aortic valve re-operation.Conclusions: The modified ARR technique is associated with reduced myocardial ischaemia time, lower post-operative mortality and aortic re-intervention rates compared to a Bentall procedure. It may be considered a safe and feasible procedure for aortic root/ascending aortic replacement offering good long-term outcomes.
LKB1 is the gatekeeper of carotid body chemo-sensing and the hypoxic ventilatory response: deficiency precipitates Cheyne Stokes breathing
Authors: MacMillan Sandy , Holmes Andrew , Dallas Mark , Mahmoud Amira , Shipston Michael , Peers Chris , Hardie David , Kumar Prem , Evans A. 
Published: June 2022

Abstract
The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply to the body and is primarily mediated by the carotid bodies. Here we reveal that carotid body afferent discharge during hypoxia and hypercapnia is determined by the expression of Liver Kinase B1 (LKB1), the principal kinase that mediates AMPK activation during metabolic stresses. Conversely, conditional deletion in catecholaminergic cells of AMPK, the principal downstream target of LKB1, had no effect on carotid body responses to hypoxia or hypercapnia. By contrast, the HVR was attenuated by LKB1 and AMPK deletion. However, in LKB1 knockouts hypoxia evoked hypoventilation, apnoea and Cheyne Stokes like breathing, while only hypoventilation and apnoea were observed after AMPK deletion. We therefore identify LKB1 as a novel and essential regulator of carotid body chemo-sensing and uncover a divergence in dependency on LKB1 and AMPK between the carotid body on one hand and the HVR on the other.
An analysis on the machinability aspects of the turning process using WEDM for profile generation
Authors: Roy Biplab Kumar , Tiwari Saransh , MANDAL AMITAVA 
Published: June 2022

Abstract
Wire Electrical Discharge Turning (WEDT) is a unique adaption of the Wire Electrical Discharge Machining (WEDM) process and enables one to generate precise 3-D axis-symmetric profiles on electrically conductive materials irrespective of their hardness. In the present study, profile geometries like spherical, cylindrical, and taper are generated on the same workpiece to create a combined-shape structure. The effect of parametric settings on Volumetric Error (VE), Roundness (Ront), Average Surface Roughness (Ra), and Volumetric Material Removal Rate (VMRR) is investigated for the above-said geometries based on Response Surface Methodology (RSM). Experimental results show that the volumetric or geometric error is maximum for spherical and minimum for cylindrical turned surfaces. The roughness of the cylindrical part is better as compared to the spherical and tapered surfaces. A minimum roundness value of 28.19 µm for the spherical, 11.80 µm for the cylindrical, and 26.25 µm for the taper-turned surfaces has been observed. The VMRR of the cylindrical part was found to be higher than that of spherical and tapered parts. FESEM has been utilized to study the surface integrity of the geometries machined by WEDT, and a recast layer was observed in all three cases.
Partial nephrectomy versus radical nephrectomy for T1bN0M0 clear cell renal cell carcinomas: A population-based propensity score-matched analysis
Authors: Li Chengwen , Liu Chang , Ma Chunlei , Tian Ding 
Published: June 2022

Abstract
Purpose: Clear cell renal cell carcinoma (cc-RCC) comprises 70% of RCC and the majority of cancer-related deaths. The oncological comparison between partial nephrectomy (PN) and radical nephrectomy (RN) is undefined and previous studies have not indicated any significant benefit from PN compared with RN, for T1b renal tumors in terms of overall survival (OS). We retrieved T1bN0M0 cc-RCC patients and performed propensity score matching (PSM) to compare the oncological OS between PN and RN.Method: All cc-RCC cases were divided into two groups according to different surgical approaches, namely, PN and RN. Log-rank tests were used to assess the differences in OS, and subgroup analysis was performed in terms of age and tumor size. PSM was performed between the PN and RN groups.Results:11,966 T1bN0M0 cc-RCC patients were collected. After PSM, the log-rank test indicated that PN patients had better prognoses than those with RN. Age subgroup analysis indicated that PN was better than RN in all age subgroups. Cox analysis revealed that younger, larger tumor size, Black, and RN were associated with worse survival.Conclusion: PN had significantly better oncological prognoses than RN for T1bN0M0 cc-RCC patients, and age, race, tumor size, and surgical approach were effective prognostic factors.
Protective mechanism of gold nanoparticles on human neural stem cells injured by β-amyloid protein through miR-21-5p/SOCS6 pathway
Authors: Wang Guoqing , Shen Xiangpeng , Song Xiangkong , Wang Ningfen , Wo Xuewen , Gao Yonglei 
Published: June 2022

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive memory loss in dementia. Gold nanoparticles (AuNPs) were reported beneficial for human neural stem cells (hNSCs) treated with Amyloid-beta (Aβ), but the neuroprotective mechanisms still are unknown. Cell Counting Kit-8 (CCK-8) was performed to detect hNSCs viability. The content of interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α) was analyzed by enzyme-linked immunosorbent (ELISA) assay. Immunocytochemistry was carried out to determinate Tuj-1 and glial fibrillary acidic protein (GFAP). The reactive oxygen species (ROS) and JC-1 assay kits were performed to detect ROS generation and mitochondrial membrane potential. miRNA array was used to systematically detect the differential miRNAs. Dual-luciferase reporter assay was applied to verify the targeting relationship between miR-21-5p and the suppressor of cytokine signalling 6(SOCS6). Quantitative PCR (qPCR) and Western blot assessments were also used to detect related gene expression intracellularly or in the supernatant. The pro-inflammation IL-6 and TNF-α were significantly decreased in the AuNPs co-treatment group. AuNPs could ameliorate neural stem cell differentiation inhibition due to Aβ accumulation. AuNPs co-treatment repressed the high expression of total tau (T-tau), phosphorylated tau (P-tau), and Aβ protein caused by the Aβ treatment. The apoptosis rate of hNSCs induced by Aβ was inhibited by AuNPs co-treatment and the expression of proteins associated with apoptosis was also reduced in AuNPs co-treatment group. Aβ-induced decreased mitochondrial membrane potential and mitochondria in the hNSCs were damaged, while AuNPs co-treatment showed a protective effect on mitochondrial membrane potential. Co-treatment with AuNPs significantly increased dynamin-related protein 1 (DRP1), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM) mRNA levels. AuNPs may improve mitochondrial function impairment due to Aβ by elevating mitochondrial membrane potential, upregulating regulators of mitochondrial biogenesis, and inhibiting ROS production. hNSCs transfected with miR-21-5p inhibitor reversed AuNPs mediated cytoprotection induced by Aβ. miR-21-5p was involved in AuNPs protecting against Aβ-induced cell toxicity by reduced mitochondrial function. Overexpression of miR-21-5p contributes to enhancing the effect of cytoprotection of AuNPs. MiR-21-5p direct targeting SOCS6 and overexpression SOCS6 exerted opposite effects on hNSCs compared with miR-21-5p mimic. AuNPs can protect hNSCs from Aβ injury and decrease mitochondrial damage by regulating the miR-21-5p/SOCS6 pathway.
Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study
Authors: Huang Lingtong , Pang Lisha , Sheng Peng , Wang Yanqiu , Yang Fan , Yu Huili , Zhang Ning , cai Hongliu , Tang Lingling , Fang Xueling 
Published: June 2022

Abstract
Purpose: This study aims to assess the clinical features of virome in the early onset of severe pneumonia in ICU patients.Methods: A total of 97 patients’ clinical data was collected retrospectively from intensive care units of five teaching hospitals in China from June 2018 to July 2021 followed by metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) at the onset of severe pneumonia.Results: Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition, viral reactivation resulted in an overall increase of 2.052 folds of 28-day all-cause mortality (95% CI: 1.004-4.194). Conclusion: This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients in the ICU at the onset of severe pneumonia. Viral reactivation is common and associated with an increased risk of mortality.
Intravaginal lactic acid gel versus oral metronidazole for treating women with recurrent bacterial vaginosis: the VITA randomised controlled trial
Authors: ROSS Jonathan D. C. , BRITTAIN Clare , Watkins Jocelyn Anstey , KAI Joe , DAVID Miruna , OZOLINS Mara , JACKSON Louise , ABDALI Zainab , Hepburn Trish , GRIFFITHS Frances , Montgomery Alan , DANIELS Jane , MANLEY Alice , DEAN Gillian , ARMSTRONG-BUISSERET Lindsay K. 
Published: June 2022

Abstract
Background: Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis.Methods: We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400mg twice daily oral metronidazole tablets or 5ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects.Results: 518 participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). Conclusions: Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects.Trial registration: ISRCTN14161293, prospectively registered on 18th September 2017. https://doi.org/10.1186/ISRCTN14161293.
The risk factors of neuropathic pain in neuromyelitis optica spectrum disorder: a retrospective case-cohort study
Authors: Li Xiaojun , Xu Haoyou , Zheng Zequan , Ouyang Huiying , Chen Guixian , Lou Zhenzhen , Chen Haoxuan , Zhang Jiahui , Zhan Yibo , Mao Hui , Zhang Changlin , Zhao Min , Zhao Yuanqi 
Published: June 2022

Abstract
BackgroundNeuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain.ObjectiveTo investigate the risk factors of neuropathic pain in a NMOSD cohort. Materials and MethodsOur study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria. (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI) and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”. Results119 patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions and extended thoracic lesions. Multivariate regression analysis showed that extended thoracic lesions (OR 23.24 [1.97-274.59], P=0.013) and gender (OR 13.97 [1.3-150.59], P=0.03) were independently associated with neuropathic pain among NMOSD patients.ConclusionExtended thoracic lesions and gender were independent risk factors of neuropathic pain among patients with NMOSD.
Retrospective study of more than 5 million emergency hospital admissions: epidemiology and outcomes for people with dementia
Authors: Reeves David , Holland Fiona , Morbey Hazel , Hann Mark , Ahmed Faraz , Davies Linda , Keady John , Leroi Iracema , Reilly Siobhan T 
Published: June 2022

Abstract
BackgroundPeople with dementia (PwD) as emergency acute hospital admissions may be at higher risk of inappropriate care and poorer outcomes including longer hospitalisations and higher risk of emergency re-admission or death. Since 2009, numerous national and local initiatives in England have sought to improve hospital care for PwD. We compared outcomes of emergency admissions for patients aged 65+ with and without dementia across three points in time.MethodsWe analysed emergency admissions (EAs) from the Hospital Episodes Statistics datasets for England 2010/11, 2012/13 and 2016/17. Dementia upon admission was based on a diagnosis in the patient’s hospital records within the last five years. Outcomes were length of hospital stays (LoS), long stays (>=15 days), emergency re-admissions (ERAs) and deaths within 30 days of discharge. Covariates included patient demographics, pre-existing health and reasons for admission. Hospital indices of dementia care relating to staff training, hospital governance and patient-focus were derived from National Audit of Dementia survey returns. Hierarchical multivariate regression analysis was used - separately for males and females – to evaluate patient group differences on each outcome adjusted for covariates and to examine associations with the dementia care indices.ResultsWe included 178 acute hospitals with a total of 2,569,007 EAs for male patients and 3,011,099 for female patients, of which 356,992 (13.9%) were male PwD and 561,349 (18.6%) female PwD. Covariate-adjusted differences in LoS changed little over time and in 2016/17 were 17% (95%CI 15%-18%) and 12% (10%-14%) longer for male and female PwD respectively. Adjusted excess risk of an ERA for PwD reduced over time to 17% (15%-18%) for males and 17% (16%-19%) for females. Adjusted mortality for PwD was around 30% higher throughout. No associations were found between outcomes and hospital indices of dementia care.ConclusionsOver the six-year period, covariate-adjusted hospital LoS, ERA and mortality rates for PwD showed little beneficial change relative to similar patients without dementia, despite many national and local efforts to improve hospital care for this patient group. Group differences after adjustment were mostly small and may reflect factors beyond hospital control. Greater emphasis is needed on avoiding unnecessary hospitalisations for PwD.
Microbial diversity and metabolic inference of diclofenac removal in heterotrophic denitrifying conditions
Authors: Pirete Luciana de Melo , Camargo Franciele Pereira , Grosseli Guilherme Martins , Sakamoto Isabel K. , Fadini Pedro S. , Silva Edson Luiz , Varesche Maria Bernadete Amâncio 
Published: June 2022

Abstract
Diclofenac (DCF) is an anti-inflammatory and organochlorine micropollutant whose degradation is poorly known, mainly in anoxic systems with organic cosubstrate. Using the Response Surface Methodology (RSM) and Rotational Central Composite Design (RCCD), this study evaluated the removal of DCF under denitrifying conditions, with ethanol as cosubstrate, in batch reactors. It considered the individual and multiple effects of the variables: nitrate (130–230 mg NO3− L− 1), DCF (60–100 µg DCF L− 1) and ethanol (130–230 mg EtOH L− 1). The highest drug removal efficiency (17.5%) and total nitrate removal were obtained at 176.6 ± 4.3 mg NO3− L− 1, 76.8 ± 3.7 µg DCF L− 1, and 180.0 ± 2.5 mg EtOH L− 1. Under such conditions, the addition of ethanol and nitrate was significant for the additional removal of diclofenac (p < 0.05). The prevalence of Rhodanobacter, Haliangium and Terrimonas in the inoculum biomass (activated sludge systems) was identified through the 16S rRNA gene sequencing. The potential of these genera to remove nitrate and degrade diclofenac was inferred. The main enzymes potentially involved in this process were α-methylacyl-CoA racemase, long-chain fatty acid-CoA ligase, catalases and pseudoperoxidases.
IL-15 receptor alpha reduces the toxicity of IL-15 during CAR-T immunotherapy
Authors: ZHANG YING , ZHUANG QINGHUI , WANG FANG , ZHANG CAN , XU CHANG , TONG SHUAI , AN ZHIJING , YU ZHEN , GU AIQIN , HU YI , ZHONG XIAOSONG 
Published: June 2022

Abstract
Background:Chimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy against both B cell malignancies and some types of solid tumors. Interleukin (IL) -15 is an important immune stimulator that may offer ideal long-term persistent CAR-T cells. However, higher base line or peak serum IL-15 levels also relate to severe toxicity, such as cytokine release syndrome (CRS), graft-versus-host disease (GVHD) and neurotoxicity.Methods:We successfully constructed CD19 specific armored CAR-T cells overexpressing IL-I5 and IL-15 receptor alpha (IL-15Ra). In vitro cell differentiation and viability were monitored by flow cytometry, and an in vivo xenograft mouse models was used to evaluate the anti-tumor efficiency and toxicity of CAR-T cells. Results:CAR-T cells overexpressing just IL-15 demonstrated enhanced viability, retarded exhaustion in vitro and superior tumor inhibitory effects in vivo. However, these tumor-cured mice had lower survival rate, because of, to some extent, toxicity. Nevertheless, CAR-IL-15 T cells transduced with IL-15Ra had reduced CD132 expression and released less cytokines (IFNγ, IL-2 and IL-15) in vitro, and improved mouse survival compared to CAR-IL-15 T cells.Conclusion:These results indicated that the importance of IL-15 in enhancing T cells persistence and IL-15Ra in reducing the adverse events of IL-15, with superior tumor retardation during CAR-T therapy, which paves the way for the rapid exploitation of IL-15 in adoptive cell therapy.