bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canine Mesenchymal Stromal Cell-Mediated Bone Regeneration is Enhanced in the Presence of Sub-Therapeutic Concentrations of BMP-2 in a Murine Calvarial Defect Model
Authors: Dobson Lauren K. , Zeitouni Suzanne , McNeill Eoin P. , Bearden Robert N. , Gregory Carl A. , Saunders W. Brian 
Published: November 2021

Novel bone regeneration strategies often show promise in rodent models yet are unable to successfully translate to clinical therapy. Sheep, goats, and dogs are used as translational models in preparation for human clinical trials. While human MSCs (hMSCs) undergo osteogenesis in response to well-defined protocols, canine MSCs (cMSCs) are more incompletely characterized. Prior work suggests that cMSCs require additional agonists such as IGF-1, NELL-1, or BMP-2 to undergo robust osteogenic differentiation in vitro. When compared directly to hMSCs, cMSCs perform poorly in vivo. Thus, from both mechanistic and clinical perspectives, cMSC and hMSC-mediated bone regeneration may differ. The objectives of this study were twofold. The first was to determine if previous in vitro findings regarding cMSC osteogenesis were substantiated in vivo using an established murine calvarial defect model. The second was to assess in vitro ALP activity and endogenous BMP-2 gene expression in both canine and human MSCs. Calvarial defects (4 mm) were treated with cMSCs, sub-therapeutic BMP-2, or the combination of cMSCs and sub-therapeutic BMP-2. At 28 days, while there was increased healing in defects treated with cMSCs, defects treated with cMSCs and BMP-2 exhibited the greatest degree of bone healing as determined by quantitative μCT and histology. Using species-specific qPCR, cMSCs were not detected in relevant numbers 10 days after implantation, suggesting that bone healing was mediated by anabolic cMSC or ECM-driven cues and not via engraftment of cMSCs. In support of this finding, defects treated with cMSC + BMP-2 exhibited robust deposition of Collagens I, III, and VI using immunofluorescence. Importantly, cMSCs exhibited minimal ALP activity unless cultured in the presence of BMP-2 and did not express endogenous canine BMP-2 under any condition. In contrast, human MSCs exhibited robust ALP activity in all conditions and expressed human BMP-2 when cultured in control and osteoinduction media. This is the first in vivo study in support of previous in vitro findings regarding cMSC osteogenesis, namely that cMSCs require additional agonists to initiate robust osteogenesis. These findings are highly relevant to translational cell-based bone healing studies and represent an important finding for the field of canine MSC-mediated bone regeneration.
Molecular Characterization Based on Whole-Genome Sequencing of Streptococcus pneumoniae in Children Living in Southwest China During 2017-2019
Authors: Yan Ziyi , Cui Yali , Huang Xiaocui , Lei Shikun , Zhou Wei , Tong Wen , Chen Wen , Shen Meijing , Wu Kaifeng , Jiang Yongmei 
Published: November 2021

BackgroundStreptococcus pneumoniae is an important pathogen causing high morbidity and high mortality in children and undergoes frequent recombination for capsule switching to neutralize the 13-valent pneumococcal conjugate vaccine (PCV13). This study aimed to investigate the prevalence, and molecular characteristics including serotypes and antibiotic susceptibility of S. pneumoniae isolated from children living in Southwest China from 2017 to 2019 to facilitate the selection of effective vaccine formulations and appropriate antibiotic treatment regimens.MethodsThis study was conducted at West China Second University Hospital (Chengdu, Sichuan Province, China), Zunyi Medical University Third Affiliated Hospital/First People’s Hospital of Zunyi (Zunyi, Guizhou Province, China) and Chengdu Jinjiang District Maternal and Child Healthcare Hospital (Chengdu, Sichuan Province, China). Demographic and clinical characteristics of children infected with S. pneumoniae were collected and analysed. Next-generation sequencing and sequence analysis were used to determine the serotypes, sequence types, antibiotic resistance and potential protein vaccine target genes of the pneumococcal isolates. The coverage rate provided by PCV13 was estimated by calculating the percentage of the specific serotypes that were specifically the PCV13-included serotypes. Antimicrobial susceptibility was determined by the microdilution broth method.ResultsThe most prevalent pneumococcal serotypes were 19F (25.8%), 19A (14.1%), 6B (12.5%), 6A (9.4%) and 14 (7.8%). The predominant STs were ST271 (23.3%), ST320 (15.5%) and ST90 (8.6%), dominated by the clonal complex Taiwan19F-14 (39.1%). The coverage rate of PCV13 was 77.3% in all the isolates, with relatively higher values in invasive isolates (86.4%). Over the decade, the rates of resistance to penicillin, amoxicillin and cefotaxime were 5.6%, 5.3% and 5.1%, respectively, with significantly higher values in invasive isolates (22.4%, 14.9% and 11.9%). Almost all the isolates were resistant to erythromycin (99.1%) and clindamycin (95.9%). All isolates carried virulence-related genes, including ply, psaA, piaA, piuA, phtE, nanA, pepO, danJ, pvaA, clpP, pcsB, stkP, potD, and strH. The carriage of virulence and resistance genes varied among serotypes and clades, with serotype 19F/ST271 showing higher resistance to antibiotics and being more likely to carry pilus genes and other virulence genes.ConclusionThese data provide valuable information for the understanding of pneumococcal pathogenesis, antimicrobial resistance and the development of protein-based vaccines against pneumococcal infection.
Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4+ T-Cell Responses
Authors: Marklund Emelie , Leach Susannah , Nyström Kristina , Lundgren Anna , Liljeqvist Jan-Åke , Nilsson Staffan , Yilmaz Aylin , Andersson Lars-Magnus , Bemark Mats , Gisslén Magnus 
Published: November 2021

BackgroundThe risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.Method314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.FindingsSeroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from &lt;30% in the N-assay to &gt;90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.ConclusionsHCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy
Authors: Alonso-Fernández Alberto , Ribot Quetglas Caterina , Herranz Mochales Andrea , Álvarez Ruiz De Larrinaga Ainhoa , Sánchez Barón Andrés , Rodríguez Rodríguez Paula , Gil Gómez Ana Victoria , Pía Martínez Carla , Cubero Marín José Pablo , Barceló Nicolau Maria , Cerdà Moncadas María , Codina Marcet Mercedes , De La Peña Bravo Mónica , Barceló Bennasar Antònia , Iglesias Coma Amanda , Morell-Garcia Daniel , Peña Zarza José Antonio , Giménez Carrero María Paloma , Durán Cantolla Joaquín , Marín Trigo José María , Piñas Cebrian María Concepción , Soriano Joan B. , García-Río Francisco 
Published: November 2021

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy.Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea–hypopnea index (AHI) of ≥ 5 h−1. Plasma cytokines levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were determined by multiple immunoassays.Results: We included 11 patients with OSA and 22 women with AHI &lt; 5 h−1, who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1β, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1β (r = 0.36), IL-6 (r = 0.52), IL-8 (r = 0.43), between obstructive apnea index and TNF-α (r = 0.46) and between AHI and IL-1β (r = 0.43). We also found that CT90% was related to IL-8 (r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = −0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age (r = −0.48).Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age.
Effect of Hepatitis B Virus Infection on Sperm Quality and Outcomes of Assisted Reproductive Techniques in Infertile Males
Authors: Wang Zichun , Liu Wanpeng , Zhang Mingming , Wang Minglei , Wu Huaying , Lu Meisong 
Published: November 2021

Background: Hepatitis B virus (HBV) infection is one of the health problems and has adverse effects on public health. However, the consequences of male HBV carriers for assisted reproductive techniques (ART) remain unclear.Objective: To examine whether men with HBV would impact sperm quality and the intrauterine insemination (IUI)/ in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) outcomes.Methods: We retrospectively analyzed data from 681 infertile couples for IUI/IVF/ICSI fresh cycle outcomes. Case group was 176 infertile couples with male HBV infection undergoing embryo transfer in our center (99 for IVF and 77 for ICSI) and 51 infertile couples for IUI. Negative control was 454 non-infected infertility couples, matched for female age, BMI and infertility duration (102 for IUI and 198 for IVF and 154 for ICSI).Results: Sperm viability among infertile men with HBV infection was significantly lower than control group (74.1 ± 13.7 vs. 77.0 ± 12.8, P &lt; 0.01). Sperm motility was significantly decreased in HBV positive men in comparison to the control group (32.5 ± 14.6 vs. 35.5 ± 12.9, P &lt; 0.05). In IVF/ICSI cycles, two groups had similar results in two pronuclear (2PN) fertilization rate, implantation rate, clinical pregnant rate and abortion rate (P &gt; 0.05). There was also no difference in the clinical pregnant rate and abortion rate in IUI cycles (P &gt; 0.05).Conclusion: Men with HBV infection will affect their sperm quality, but not affect the outcomes of ART.
Analysis of the Status and Trends of Chinese Clinical Practice Guideline Development Between 2010 and 2020: A Systematic Review
Authors: Zhang Rong , Yan Si-yu , Wang Yun-yun , Huang Qiao , Ren Xiang-ying , Tan Ran , Deng Yu-qing , Su Lin-xia , Wang Yong-bo , Zhao Zheng-rong , Jin Ying-hui 
Published: November 2021

Objective: This study aimed to systematically review the status and trends of Chinese clinical practice guidelines (CPGs) during the time period 2010–2020 and explore their methodological characteristics. Then, based on the strengths and weaknesses in development, offer several recommendations for the quality improvement which will serve as a reference for the users and developers of CPG.Introduction: With the development of evidence-based medicine (EBM), the CPGs play an increasingly important role in healthcare decision-making both in China and worldwide.Inclusion criteria: The CPGs that have been used to help the health professionals in the healthcare decision-making were included.Methodology: The China National Knowledge Infrastructure (CNKI) and WanFang databases were searched from 2010 to 2020 for the studies describing the general and methodological characteristics of Chinese CPGs. Comparisons of the methodological characteristics between the groups were conducted using the chi-square test or Fisher's exact test. The M-K test was adopted to identify the monotonically increasing or decreasing trends of methodological characteristics over the timespan.Results: A total of 2,654 CPGs fulfilled the inclusion criteria. The quantity and quality of the guidelines developed in China have improved over the time span. From 2010 to 2020,the guidelines had differing characteristics and covered a wide range of subjects. In total, 2,318(87.34%) guidelines focused on Western Medicine. Eight (0.30%) had been developed for patient versions of guidelines, 10(0.38%) were tentative guidelines, and 16(0.60%) were rapid advice guidelines. Medical specialty societies (including their branches) (71.1%) were the main guideline makers. The most addressed diseases were neoplasms (14.43%). The target population is mainly adults (84.97%). The methodological quality of consensus-based (CB)-CPGs was obviously lower than evidence-based (EB)-CPGs. Except for the item, “recommendations were based on evidence of systematic reviews,” there were statistical differences in all other methodological items between the EB-CPGS and CB-CPGS (P &lt; 0.01). Higher methodological quality has been observed in EB-CPGs. All the data relating to the methodological characteristics indicated that higher methodological quality was present in the guidelines using GRADE (P &lt; 0.01).Conclusion: The quantity and quality of the guidelines developed in China have improved between 2010 and 2020. CB-CPGs have also paid attention to the methodology quality, but obviously, this is lower than that in the EB-CPGs.
Does Prior Stroke Predict Long-Term Recurrent Stroke After Percutaneous Coronary Intervention? Five-Year Results From a Large Cohort Study
Authors: Xu Jing-jing , Jia Si-da , Zhu Pei , Jiang Lin , Jiang Ping , Song Ying , Zhao Xue-yan , Li Jian-xin , Chen Jue , Yang Yue-jin , Gao Run-lin , Qiao Shu-bin , Xu Bo , Yuan Jin-qing 
Published: November 2021

Background: We found a positive correlation between the prior stroke history and recurrent stroke in patients who underwent percutaneous coronary intervention (PCI) in our previous study, which indicated the close interaction of stroke and cardiovascular diseases. However, it is unclear whether prior stroke is still associated with worse prognosis at a longer follow-up period.Methods: A total of 10,724 coronary heart disease (CHD) patients who received PCI from January to December 2013 were prospectively enrolled and were subsequently divided into the prior stroke (n = 1,150) and non-prior stroke (n = 9,574) groups according to their history. Baseline characteristics and 5-year outcomes were recorded.Results: Patients with prior stroke had more clinical risk factors, as well as more extensive coronary artery lesions. Although in-hospital outcomes were similar between patients from the two groups, the 5-year follow-up result revealed that patients with prior stroke experienced higher incidence of stroke, major adverse cardiac and cerebrovascular events (MACCEs), all-cause death, and cardiac death (7.0 vs. 3.0%, p &lt; 0.001; 25.9 vs. 20.3%, p &lt; 0.001; 5.3 vs. 3.5%, p = 0.002; 3.1 vs. 2.1%, p = 0.032, respectively). After the propensity score matching, the 5-year stroke rate was still higher in the prior stroke group (6.8 vs. 3.4%, p = 0.001). The multivariable regression analysis also identified the prior stroke as a risk predictor of the 5-year stroke (HR = 2.011, 95% CI: 1.322–3.059, p = 0.001).Conclusions: Coronary heart disease patients with prior stroke who received PCI had a higher incidence of 5-year long-term adverse cardiovascular and cerebrovascular events, especially recurrent stroke. Prior stroke was a strong risk predictor of future stroke events.
Frequency-Specific Effects of Galvanic Vestibular Stimulation on Response-Time Performance in Parkinson's Disease
Authors: Lee Soojin , Smith Paul F. , Lee Won Hee , McKeown Martin J. 
Published: November 2021

Background: Galvanic vestibular stimulation (GVS) is being increasingly explored as a non-invasive brain stimulation technique to treat symptoms in Parkinson's disease (PD). To date, behavioral GVS effects in PD have been explored with only two stimulus types, direct current and random noise (RN). The interaction between GVS effects and anti-parkinsonian medication is unknown. In the present study, we designed multisine (ms) stimuli and investigated the effects of ms and RN GVS on motor response time. In comparison to the RN stimulus, the ms stimuli contained sinusoidal components only at a set of desired frequencies and the phases were optimized to improve participants' comfort. We hypothesized GVS motor effects were a function of stimulation frequency, and specifically, that band-limited ms-GVS would result in better motor performance than conventionally used broadband RN-GVS.Materials and Methods: Eighteen PD patients (PDMOFF/PDMON: off-/on-levodopa medication) and 20 healthy controls (HC) performed a simple reaction time task while receiving sub-threshold GVS. Each participant underwent nine stimulation conditions: off-stimulation, RN (4–200 Hz), ms-θ (4–8 Hz), ms-α (8–13 Hz), ms-β (13–30 Hz), ms-γ (30–50 Hz), ms-h1 (50–100 Hz), ms-h2 (100–150 Hz), and ms-h3 (150–200 Hz).Results: The ms-γ resulted in shorter response time (RPT) in both PDMOFF and HC groups compared with the RN. In addition, the RPT of the PDMOFF group decreased during the ms-β while the RPT of the HC group decreased during the ms-α, ms-h1, ms-h2, and ms-h3. There was considerable inter-subject variability in the optimum stimulus type, although the frequency range tended to fall within 8–100 Hz. Levodopa medication significantly reduced the baseline RPT of the PD patients. In contrast to the off-medication state, GVS did not significantly change RPT of the PD patients in the on-medication state.Conclusions: Using band-limited ms-GVS, we demonstrated that the GVS frequency for the best RPT varied considerably across participants and was &gt;30 Hz for half of the PDMOFF patients. Moreover, dopaminergic medication was found to influence GVS effects in PD patients. Our results indicate the common “one-size-fits-all” RN approach is suboptimal for PD, and therefore personalized stimuli aiming to address this variability is warranted to improve GVS effects.
GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity
Authors: Wang Yu , Han Jing , Zhu Jing , Zhang Mizhen , Ju Minda , Du Yueshan , Tian Zhanzhuang 
Published: November 2021

Graphical AbstractSurgery induced HPA axis hyperactivity, while EA intervention inhibited the activation of hypothalamic GluN2A/ERK/CREB signaling pathway, thereby reducing the synthesis and secretion of CRH, alleviating the hyperactivity of the HPA axis after surgery.
Re-Irradiation With Stereotactic Body Radiotherapy for In-Field Recurrence of Pancreatic Cancer After Prior Stereotactic Body Radiotherapy: Analysis of 24 Consecutive Cases
Authors: Shen Yuxin , Zhu Xiaofei , Cao Fei , Xie Hongliang , Ju Xiaoping , Cao Yangsen , Qing Shuiwang , Jia Zhen , Gu Lei , Fang Fang , Zhang Huojun 
Published: November 2021

Purpose/ObjectivesLocally recurrent pancreatic cancer is a therapeutic challenge, and aggressive approaches are needed to improve its clinical outcomes. Stereotactic body radiotherapy (SBRT) is a promising treatment for pancreatic cancer with an excellent local control and acceptable toxicity. However, the safety and efficacy of SBRT for in-field recurrence after initial SBRT remain unknown. The aim of the study was to investigate the feasibility of re-irradiation with SBRT for locally recurrent pancreatic cancer after prior definitive SBRT.Material/MethodsTwenty-four consecutive patients with pancreatic cancer received two courses of SBRT in our center between January 2014 and December 2016. The median prescription dose of the initial and second courses of SBRT was 35.5 Gy/5–7f and 32 Gy/5–8f, respectively. Clinical outcomes including overall survival (OS), disease control, and toxicity were evaluated after treatment.ResultsThe median interval between two courses of SBRT was 13 months (range: 6–29 months). From the first SBRT, the median OS of 18 patients with limited diseases was 26 months (95% CI: 19.1–32.95 months). The median OS of 12 patients without metastasis was 14 months (95% CI: 10.6–17.4 months) from re-irradiation of SBRT. The overall response rate and disease control rate were 50% and 13%, and 100% and 86.9% after each SBRT, respectively. Carbohydrate antigen 19-9 (CA19-9) levels declined dramatically after re-irradiation within 1 month (p = 0.002) and 3 months (p = 0.028). Twelve (75%) out of 16 patients had pain relief after re-irradiation. None of the patients experienced gastrointestinal toxicity.ConclusionsRe-irradiation with SBRT can provide favorable outcomes and effective analgesia with mild toxicity after prior SBRT for in-field recurrent pancreatic cancer, which might be feasible for locally relapsed pancreatic cancer.