bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term trajectories of BMI predict carotid stiffness and plaque volume in type 2 diabetes older adults: a cohort study
Authors: Botvin Moshe Chen , Haratz Salo , Ravona-Springer Ramit , Heymann Anthony , Hung-Mo Lin , Schnaider Beeri Michal , Tanne David 
Published: September 2020

Abstract
Background
High body mass index (BMI) is a risk factor for type 2 diabetes and cardiovascular disease. However, its relationships with indices of carotid stiffness and plaque volume are unclear. We investigated associations of long-term measurements of BMI with indices of carotid stiffness and atherosclerosis among non-demented diabetes patients from the Israel Diabetes and Cognitive Decline (IDCD) study.

Methods
Carotid ultrasound indices [carotid intima media thickness (cIMT), distensibility, elastography and plaque volume] were assessed in N = 471 participants. Mean BMI across all MHS diabetes registry measurements and trajectories of BMI were calculated. BMI was categorized into three trajectory groups representing: a relatively stable normal weight (n = 185, 44%), overweight trajectory (n = 188, 44.8%) and a trajectory of obesity (n = 47, 11.2%). Linear and logistic regressions estimated associations of carotid indices with mean BMI and BMI trajectories.

Results
Compared to the normal weight trajectory, an obesity trajectory was associated with carotid distensibility (β = − 3.078, p = 0.037), cIMT (β = 0.095, p = 0.004), and carotid elastography (β = 0.181, p = 0.004) but not with plaque volume (β = 0.066, p = 0.858). Compared with the normal weight trajectory, an obesity trajectory was associated with increased odds for impaired carotid distensibility (OR = 2.790, p = 0.033), impaired cIMT (OR = 5.277, p = 0.001) and large carotid plaque volume (OR = 8.456, p = 0.013) but not with carotid elastography (OR = 1.956, p = 0.140). Mean BMI was linearly associated with Distensibility (β = − 0.275, p = 0.005) and cIMT (β = 0.005, p = 0.026).

Conclusions
Long-term measurements of adiposity are associated with indices of carotid stiffness and plaque volume among older type 2 diabetes adults.
Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea
Authors: Liang Junheng , Wang Huimin , Bian Xiaoying , Zhang Youming , Zhao Guoping , Ding Xiaoming 
Published: September 2020

Abstract
Background
Epothilone B is a natural product that stabilizes microtubules, similar to paclitaxel (Taxol); therefore, epothilone B and several derivatives have shown obvious antitumour activities. Some of these products are in clinical trials, and one (ixabepilone, BMS) is already on the market, having been approved by the FDA in 2007. The terminal step in epothilone B biosynthesis is catalysed by the cytochrome P450 enzyme EpoK (CYP167A1), which catalyses the epoxidation of the C12–C13 double bond (in epothilone C and D) to form epothilone A and B, respectively. Although redox partners from different sources support the catalytic activity of EpoK in vitro, the conversion rates are low, and these redox partners are not applied to produce epothilone B in heterologous hosts.

Results
Schlegelella brevitalea DSM 7029 contains electron transport partners that efficiently support the catalytic activity of EpoK. We screened and identified one ferredoxin, Fdx_0135, by overexpressing putative ferredoxin genes in vivo and identified two ferredoxin reductases, FdR_0130 and FdR_7100, by whole-cell biotransformation of epothilone C to effectively support the catalytic activity of EpoK. In addition, we obtained strain H7029-3, with a high epothilone B yield and found that the proportion of epothilone A + B produced by this strain was 90.93%. Moreover, the whole-cell bioconversion strain 7029-10 was obtained; this strain exhibited an epothilone C conversion rate of 100% in 12 h. Further RT-qPCR experiments were performed to analyse the overexpression levels of the target genes. Gene knock-out experiments showed that the selected ferredoxin (Fdx_0135) and its reductases (FdR_0130 and FdR_7100) might participate in critical physiological processes in DSM 7029.

Conclusion
Gene overexpression and whole-cell biotransformation were effective methods for identifying the electron transport partners of the P450 enzyme EpoK. In addition, we obtained an epothilone B high-yield strain and developed a robust whole-cell biotransformation system. This strain and system hold promise for the industrial production of epothilone B and its derivatives.
Prognostic nutritional index and the prognosis of diffuse large b-cell lymphoma: a meta-analysis
Authors: Luan Chunyan , Wang Fei , Wei Ning , Chen Baoan 
Published: September 2020

Abstract
Background
Some studies have investigated the prognostic value exhibited by the Prognostic Nutritional Index (PNI) in patients suffering diffuse large B-cell lymphoma (DLBCL), but varying results were obtained. In order to determine the specific prognostic value more accurately, a meta-analysis was conducted in this study.

Methods
Literatures were searched from the China National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, the Cochrane Library, and Web of Science. Pooled hazard ratio (HR) and the 95% confidence interval (CI) were calculated to assess the association between PNI and the overall survival (OS) and the progression-free survival (PFS) of patients with DLBCL.

Results
Based on seven studies with a total number of 1311 patients, our meta-analysis revealed that low PNI may meant poor OS (HR = 2.14, 95% CI 1.66–2.75, p < 0.001) and poor PFS (HR = 1.75, 95% CI 1.36–2.25, p = 0.438). Subgroup analysis showed that, in Asians, low PNI was correlated to poor OS (pooled HR = 2.06 95% CI 1.59–2.66) and poor PFS (pooled HR = 1.66, 95% CI 1.28–2.15). Similar results were obtained from one European study, which is the only study performed outside of Asia from our literature search.

Conclusion
For patients with DLBCL, low PNI may be interpreted as adverse prognosis. More data from European patients are required in this study to avoid analysis bias.
Research progress on long non-coding RNAs and their roles as potential biomarkers for diagnosis and prognosis in pancreatic cancer
Authors: Wang Yizhi , Zhou Li , Lu Jun , Jiang Bolun , Liu Chengxi , Guo Junchao , Xiao Gary Guishan 
Published: September 2020

AbstractPancreatic cancer is one of the main causes of tumor-related deaths worldwide because of its low morbidity but extremely high mortality, and is therefore colloquially known as the “king of cancer.” Sudden onset and lack of early diagnostic biomarkers directly contribute to the extremely high mortality rate of pancreatic cancer patients, and also make it indistinguishable from benign pancreatic diseases and precancerous pancreatic lesions. Additionally, the lack of effective prognostic biomarkers makes it difficult for clinicians to formulate precise follow-up strategies based on the postoperative characteristics of the patients, which results in missed early diagnosis of recurrent pancreatic cancer. Long non-coding RNAs (lncRNAs) can influence cell proliferation, invasion/migration, apoptosis, and even chemoresistance via regulation of various signaling pathways, leading to pro- or anti-cancer outcomes. Given the versatile effects of lncRNAs on tumor progression, using a single lncRNA or combination of several lncRNAs may be an effective method for tumor diagnosis and prognostic predictions. This review will give a comprehensive overview of the most recent research related to lncRNAs in pancreatic cancer progression, as targeted therapies, and as biomarkers for the diagnosis and prognosis of pancreatic cancer.
The effects of pressure- versus volume-controlled ventilation on ventilator work of breathing
Authors: Monjezi Mojdeh , Jamaati Hamidreza 
Published: September 2020

Abstract
Background
Measurement of work of breathing (WOB) during mechanical ventilation is essential to assess the status and progress of intensive care patients. Increasing ventilator WOB is known as a risk factor for ventilator-induced lung injury (VILI). In addition, the minimization of WOB is crucial to facilitate the weaning process. Several studies have assessed the effects of varying inspiratory flow waveforms on the patient’s WOB during assisted ventilation, but there are few studies on the different effect of inspiratory flow waveforms on ventilator WOB during controlled ventilation.

Methods
In this paper, we analyze the ventilator WOB, termed mechanical work (MW) for three common inspiratory flow waveforms both in normal subjects and COPD patients. We use Rohrer’s equation for the resistance of the endotracheal tube (ETT) and lung airways. The resistance of pulmonary and chest wall tissue are also considered. Then, the resistive MW required to overcome each component of the respiratory resistance is computed for square and sinusoidal waveforms in volume-controlled ventilation (VCV), and decelerating waveform of flow in pressure-controlled ventilation (PCV).

Results
The results indicate that under the constant I:E ratio, a square flow profile best minimizes the MW both in normal subjects and COPD patients. Furthermore, the large I:E ratio may be used to lower MW. The comparison of results shows that ETT and lung airways have the main contribution to resistive MW in normals and COPDs, respectively.

Conclusion
These findings support that for lowering the MW especially in patients with obstructive lung diseases, flow with square waveforms in VCV, are more favorable than decelerating waveform of flow in PCV. Our analysis suggests the square profile is the best choice from the viewpoint of less MW.
Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model
Authors: Kim Jung Min , Kim Da Hye , Park Hyo Jeong , Ma Hyun Woo , Park I Seul , Son Mijeong , Ro So Youn , Hong Seokmann , Han Hyo Kyung , Lim Soo Jeong , Kim Seung Won , Cheon Jae Hee 
Published: September 2020

Abstract
Background
Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration.

Results
All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17).

Conclusion
We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.
Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review
Authors: Guiotto M. , Raffoul W. , Hart A. M. , Riehle M. O. , di Summa P. G. 
Published: September 2020

AbstractBackgroundFoetal bovine serum (FBS), is the most commonly used culture medium additive for in vitro cultures, despite its undefined composition, its potential immunogenicity and possible prion/zoonotic transmission. For these reasons, significant efforts have been targeted at finding a substitute, such as serum free-media or human platelet-lysates (hPL). Our aim is to critically appraise the state-of-art for hPL in the published literature, comparing its impact with FBS.Materials and methodsIn June 2019 a systematic search of the entire Web of Science, Medline and PubMed database was performed with the following search terms: (mesenchymal stem cells) AND (fetal bovine serum OR fetal bovine calf) AND (human platelet lysate). Excluded from this search were review articles that were published before 2005, manuscripts in which mesenchymal stem cells (MSCs) were not from human sources, and when the FBS controls were missing.ResultsBased on our search algorithm, 56 papers were selected. A review of these papers indicated that hMSCs cultured with hPL showed a spindle-shaped elongated morphology, had higher proliferation indexes, similar cluster of differentiation (CD) markers and no significant variation in differentiation lineage (osteocyte, adipocyte, and chondrocyte) compared to those cultured with FBS. Main sources of primary hMSCs were either fat tissue or bone marrow; in a few studies cells isolated from alternative sources showed no relevant difference in their response.ConclusionDespite the difference in medium choice and a lack of standardization of hPL manufacturing, the majority of publications support that hPL was at least as effective as FBS in promoting adhesion, survival and proliferation of hMSCs. We conclude that hPL should be considered a viable alternative to FBS in hMSCs culture—especially with a view for their clinical use.
Correlation of the two most frequent HLA haplotypes in the Italian population to the differential regional incidence of Covid-19
Authors: Pisanti Simona , Deelen Joris , Gallina Anna Maria , Caputo Mariella , Citro Marianna , Abate Mario , Sacchi Nicoletta , Vecchione Carmine , Martinelli Rosanna 
Published: September 2020

Abstract
Background
Understanding how HLA polymorphisms may affect both susceptibility, course and severity of Covid-19 infection could help both at the clinical level to identify individuals at higher risk from the disease and at the epidemiological one to explain the differences in the epidemic trend among countries or even within a specific country. Covid-19 disease in Italy showed a peculiar geographical distribution from the northern most affected regions to the southern ones only slightly touched.

Methods
In this study we analysed the regional frequencies for the most common Italian haplotypes from the Italian Bone Marrow Donor Registry (HLA-A, -B, -C and -DRB1 at four-digit level). Then we performed Pearson correlation analyses among regional haplotypes estimated frequency in the population and Covid-19 incidence and mortality.

Results
In this study we found that the two most frequent HLA haplotypes in the Italian population, HLA-A*:01:01g-B*08:01 g-C*07:01g-DRB1*03:01g and HLA-A*02.01g-B*18.01g-C*07.01g-DRB1*11.04g, had a regional distribution overlapping that of Covid-19 and showed respectively a positive (suggestive of susceptibility) and negative (suggestive of protection) significant correlation with both Covid-19 incidence and mortality.

Conclusions
Based on these results, in order to define such HLA haplotypes as a factor effectively associated to the disease susceptibility, the creation of national networks that can collect patients’ samples from all regions for HLA typing should be highly encouraged.
Astrocyte remodeling in the beneficial effects of long-term voluntary exercise in Alzheimer’s disease
Authors: Belaya Irina , Ivanova Mariia , Sorvari Annika , Ilicic Marina , Loppi Sanna , Koivisto Hennariikka , Varricchio Alessandra , Tikkanen Heikki , Walker Frederick R. , Atalay Mustafa , Malm Tarja , Grubman Alexandra , Tanila Heikki , Kanninen Katja M. 
Published: September 2020

AbstractBackgroundIncreased physical exercise improves cognitive function and reduces pathology associated with Alzheimer’s disease (AD). However, the mechanisms underlying the beneficial effects of exercise in AD on the level of specific brain cell types remain poorly investigated. The involvement of astrocytes in AD pathology is widely described, but their exact role in exercise-mediated neuroprotection warrant further investigation. Here, we investigated the effect of long-term voluntary physical exercise on the modulation of the astrocyte state.MethodsMale 5xFAD mice and their wild-type littermates had free access to a running wheel from 1.5 to 7 months of age. A battery of behavioral tests was used to assess the effects of voluntary exercise on cognition and learning. Neuronal loss, impairment in neurogenesis, beta-amyloid (Aβ) deposition, and inflammation were evaluated using a variety of histological and biochemical measurements. Sophisticated morphological analyses were performed to delineate the specific involvement of astrocytes in exercise-induced neuroprotection in the 5xFAD mice.ResultsLong-term voluntary physical exercise reversed cognitive impairment in 7-month-old 5xFAD mice without affecting neurogenesis, neuronal loss, Aβ plaque deposition, or microglia activation. Exercise increased glial fibrillary acid protein (GFAP) immunoreactivity and the number of GFAP-positive astrocytes in 5xFAD hippocampi. GFAP-positive astrocytes in hippocampi of the exercised 5xFAD mice displayed increases in the numbers of primary branches and in the soma area. In general, astrocytes distant from Aβ plaques were smaller in size and possessed simplified processes in comparison to plaque-associated GFAP-positive astrocytes. Morphological alterations of GFAP-positive astrocytes occurred concomitantly with increased astrocytic brain-derived neurotrophic factor (BDNF) and restoration of postsynaptic protein PSD-95.ConclusionsVoluntary physical exercise modulates the reactive astrocyte state, which could be linked via astrocytic BDNF and PSD-95 to improved cognition in 5xFAD hippocampi. The molecular pathways involved in this modulation could potentially be targeted for benefit against AD.
Health plan adaptations to a mailed outreach program for colorectal cancer screening among Medicaid and Medicare enrollees: the BeneFIT study
Authors: Coronado Gloria D. , Schneider Jennifer L. , Green Beverly B. , Coury Jennifer K. , Schwartz Malaika R. , Kulkarni-Sharma Yogini , Baldwin Laura Mae 
Published: September 2020

Abstract
Background
Promoting uptake of evidence-based innovations in healthcare systems requires attention to how innovations are adapted to enhance their fit with a given setting. Little is known about real-world variation in how programs are delivered over time and across multiple populations and contexts, and what motivates adaptations.

Methods
As part of the BeneFIT study of mailed fecal immunochemical tests (FIT) to increase colorectal cancer screening, we interviewed 9 leaders from two participating Medicaid/Medicare health insurance plans to examine adaptations to their health plan-initiated mailed FIT outreach programs in the second year of implementation. We applied an adaptation and modification model developed by Stirman and colleagues to document content and context modifications made to the two programs.

Results
Both health plans made substantial changes to their programs in the second year; adaptations differed substantially across health plans. In Health Plan Oregon, adaptations generally targeted health centers and member populations, most content adaptations involved tailoring program components, and the program was expanded to four additional health centers. In contrast, Health Plan Washington’s second-year content adaptations were primarily at the level of members, and generally involved adding program components. Moreover, Health Plan Washington undertook large-scale context adaptations to the setting where the program was led (local vs. national), the personnel who administered the program (vendor and staffing), and the population selected for outreach (limiting outreach to dual-eligible members).

Conclusions
Both programs implemented a variety of adaptations that reflected the values and incentives of the broader health plan contexts. Financial incentives for screening allowed Health Plan Oregon to expand but led Health Plan Washington to offer more targeted outreach to a subset of eligible enrollees. The breadth of changes made by each health system reflects the necessity of evaluating programs in context and adjusting to specific challenges as they are identified. Further research is needed to understand the effects of these types of adaptations on program efficiency and enrollee and health system outcomes.
Three-dimensional alignment changes of the shoulder girdle between the supine and standing positions
Authors: Matsumura Noboru , Yamada Yoshitake , Oki Satoshi , Yoshida Yuki , Yokoyama Yoichi , Yamada Minoru , Nagura Takeo , Jinzaki Masahiro 
Published: September 2020

Abstract
Background
Although humans spend most of their day in a standing or sitting position, it is difficult to accurately evaluate the alignment of the shoulder girdle during daily activity, and its alignment changes between positions. The purpose of this study was to evaluate the 3-dimensional alignment of the shoulder girdle in the supine and standing positions by computed tomography (CT) and to assess the alignment changes of the shoulder girdle between these two positions.

Methods
CT scans of both shoulders of 100 healthy volunteers were prospectively taken in both supine and standing positions on the same day. The local 3-dimensional coordinate systems of the thorax, clavicle, and scapula were defined from the specific bony landmarks, and 3-dimensional angular rotations and positions of the clavicle and scapula were calculated. Differences in rotations and positions of the clavicle and scapula were evaluated between the supine and standing positions.

Results
Compared with the supine position, the clavicle showed significantly less elevation and greater retraction, and the scapula showed significantly less upward rotation, anterior tilting, and internal rotation in the standing position. Compared with the supine position, the clavicle center was located more inferiorly, posteriorly, and laterally, and the scapula center was located more inferiorly, posteriorly, and medially in the standing position.

Conclusions
The present study showed that angular rotations and positions of the clavicle and scapula change significantly with position due to the effect of gravity.
Effect of using the WeChat platform on the perioperative health education of parents of children who underwent transthoracic device closure of VSDs
Authors: Zhang Qi-Liang , Xu Ning , Huang Shu-Ting , Chen Qiang , Cao Hua 
Published: September 2020

Abstract
Objective
To explore the effects of using the WeChat platform on the perioperative health education of parents of children who underwent transthoracic device closure of ventricular septal defects (VSDs).

Methods
Participants were divided into a WeChat group and a leaflet group. Responses to relevant questionnaires and clinical data were recorded and analyzed.

Results
Before the operation, the scores of the Caretaker Knowledge Questionnaire in the WeChat group were significantly higher than those in the leaflet group. The scores of PSQ-18 in the WeChat group were significantly higher than those in the leaflet group. All the children in the WeChat group were followed up 1 month after discharge, while four children in the leaflet group were lost to follow-up. The rate of attrition in the leaflet group was significantly higher than that in the WeChat group. For the postoperative complications, there was no significant difference between the two groups.

Conclusion
Perioperative health education for parents of children who undergo transthoracic device closure of VSDs through the WeChat platform can effectively enhance parents’ knowledge of care, improve parent satisfaction, which is an effective method to ensure convenient operation and reduce loss to follow-up.