bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and predictive factors of complementary medicine use during the first wave of the COVID-19 pandemic of 2020 in the Netherlands
Authors: Mulder Louise T. C. , Busch Martine , Kristoffersen Agnete E. , Hök Nordberg Johanna , van der Werf Esther T. 
Published: February 2022

Abstract
Introduction
Major life changing events such as the COVID-19 pandemic may have major impact on one’s health and general well-being. This study aimed to determine the prevalence and predictive factors, including gender specific differences, of Complementary Medicine (CM) use (including CM consultations, self-care management and self-help techniques) during the first wave of the COVID-19 pandemic in 2020 in the Netherlands.

Methods
CM use was studied among a random representative sample (n = 1004) of the adult Dutch population using an online survey conducted from 22–27 May 2020. The survey included a modified version of I-CAM-Q and additional questions on demographic characteristics, reasons for CM use, perceived effectiveness and side effects.

Results
68.0% of the participants reported to have used CM (CM consultations (13.3%), self-management strategies (59.4%), self-help techniques (30.0%)). Most frequently reported reason of CM use was to improve general well-being (61.6%), prevention and/or treatment of COVID-19 was only reported by 10%. Perceived effectiveness of CM was high and number of experienced side effects low. Being a women, worried to get infected with COVID-19, higher education and living in northern/ middle region of the Netherlands were predictive factors to use CM.

Conclusions
In the Netherlands, specific groups (e.g. women/ highly educated) use CM, mainly to improve general wellbeing, and seem to benefit of it during the first months of the pandemic. The high perceived effectiveness and low reporting of side effects should encourage medical professionals and policy makers for more openness towards considering CM as being part of an integrative approach to public health in times life changing events occur.
Reimbursement decisions for medical services in Austria: an analysis of influencing factors for the hospital individual services catalogue between 2008 and 2020
Authors: Goetz Gregor , Panteli Dimitra , Busse Reinhard , Wild Claudia 
Published: February 2022

Abstract
Objectives
To (1) describe the (evidence-based) reimbursement process of hospital individual services, (2) evaluate the accordance between evidence-based recommendations and reimbursement decision of individual services and (3) elaborate potential aspects that play a role in the decision-making process in Austria.

Method
The reimbursement process is described based on selected relevant sources such as official documents. Evidence-based recommendations and subsequent reimbursement decisions for the annual maintenance of the hospital individual service catalogue in Austria between 2008 and 2020 were analysed using a mixed methods approach, encompassing descriptive statistics and a focus group with Austrian decision makers.

Results
118 evidence-based recommendations were analysed. There were 93 (78.8%) negative and 25 (21.2%) positive evidence-based recommendations. In total, 107 out of 118 evidence-based recommendations (90.1%) did not lead to a deviating reimbursement decision. We identified six aspects that may have played a role in the decision-making process for the annual maintenance of the hospital individual service catalogue, with clinical evidence being the most notable. Further aspects included quality assurance/organisational aspects (i.e., structural quality assurance), costs (if comparable to already existing medical services, not: cost-effectiveness), procedural aspects (e.g., if certain criteria for adoption have not been met formally through the proposals), “other countries” (i.e., taking into account how other countries decided) and situational aspects (such as the COVID-19 pandemic).

Conclusions
There is good accordance between evidence-based recommendations and reimbursement decisions regarding hospital individual services in Austria. Beyond clinical evidence, organisational aspects seem to be considered often with regard to quality assurance but costs do not appear to play a major role. The Austrian system has mechanisms in place that can restrict widespread adoption of novel hospital individual services with uncertain clinical benefits. Future studies could investigate how well these mechanisms work and how they compare to other health systems in Europe.
Source matters: a survey of cost variation for fecal immunochemical tests in primary care
Authors: Coury Jennifer , Ramsey Katrina , Gunn Rose , Judkins Jon , Davis Melinda 
Published: February 2022

Abstract
Background
Colorectal cancer (CRC) screening can improve health outcomes, but screening rates remain low across the US. Mailed fecal immunochemical tests (FIT) are an effective way to increase CRC screening rates, but is still underutilized. In particular, cost of FIT has not been explored in relation to practice characteristics, FIT selection, and screening outreach approaches.

Methods
We administered a cross-sectional survey drawing from prior validated measures to 252 primary care practices to assess characteristics and context that could affect the implementation of direct mail fecal testing programs, including the cost, source of test, and types of FIT used. We analyzed the range of costs for the tests, and identified practice and test procurement factors. We examined the distributions of practice characteristics for FIT use and costs answers using the non-parametric Wilcoxon rank-sum test. We used Pearson’s chi-squared test of association and interpreted a low p-value (e.g. < 0.05) as evidence of association between a given practice characteristic and knowing the cost of FIT or fecal occult blood test (FOBT).

Results
Among the 84 viable practice survey responses, more than 10 different types of FIT/FOBTs were in use; 76% of practices used one of the five most common FIT types. Only 40 practices (48%) provided information on FIT costs. Thirteen (32%) of these practices received the tests for free while 27 (68%) paid for their tests; median reported cost of a FIT was $3.04, with a range from $0.83 to $6.41 per test. Costs were not statistically significantly different by FIT type. However, practices who received FITs from manufacturer’s vendors were more likely to know the cost (p = 0.0002) and, if known, report a higher cost (p = 0.0002).

Conclusions
Our findings indicate that most practices without lab or health system supplied FITs are spending more to procure tests. Cost of FIT may impact the willingness of practices to distribute FITs through population outreach strategies, such as mailed FIT. Differences in the ability to obtain FIT tests in a cost-effective manner could have consequences for implementation of outreach programs that address colorectal cancer screening disparities in primary care practices.
Development of an efficient and precise adenine base editor (ABE) with expanded target range in allotetraploid cotton (Gossypium hirsutum)
Authors: Wang Guanying , Xu Zhongping , Wang Fuqiu , Huang Yuefan , Xin Yanfeng , Liang Sijia , Li Bo , Si Huan , Sun Lin , Wang Qiongqiong , Ding Xiao , Zhu Xiangqian , Chen Luo , Yu Lu , Lindsey Keith , Zhang Xianlong , Jin Shuangxia 
Published: February 2022

Abstract
Background
Base editors (BEs) display diverse applications in a variety of plant species such as Arabidopsis, rice, wheat, maize, soybean, and cotton, where they have been used to mediate precise base pair conversions without the collateral generation of undesirable double-stranded breaks (DSB). Studies of single-nucleotide polymorphisms (SNPs) underpinning plant traits are still challenging, particularly in polyploidy species where such SNPs are present in multiple copies, and simultaneous modification of all alleles would be required for functional analysis. Allotetraploid cotton has a number of homoeologous gene pairs located in the A and D sub-genomes with considerable SNPs, and it is desirable to develop adenine base editors (ABEs) for efficient and precise A-to-G single-base editing without DSB in such complex genome.

Results
We established various ABE vectors based on different engineered adenosine deaminase (TadA) proteins fused to Cas9 variants (dCas9, nCas9), enabling efficient A to G editing up to 64% efficiency on-target sites of the allotetraploid cotton genome. Comprehensive analysis showed that GhABE7.10n exhibited the highest editing efficiency, with the main editing sites specifically located at the position A5 (counting the PAM as positions 21–23). Furthermore, DNA and RNA off-target analysis of cotton plants edited with GhABE7.10n and GhABE7.10d by whole genome and whole-transcriptome sequencing revealed no DNA off-target mutations, while very low-level RNA off-target mutations were detected. A new base editor, namely GhABE7.10dCpf1 (7.10TadA + dCpf1), that recognizes a T-rich PAM, was developed for the first time. Targeted A-to-G substitutions generated a single amino acid change in the cotton phosphatidyl ethanolamine-binding protein (GhPEBP), leading to a compact cotton plant architecture, an ideotype for mechanized harvesting of modern cotton production.

Conclusions
Our data illustrate the robustness of adenine base editing in plant species with complex genomes, which provides efficient and precise toolkit for cotton functional genomics and precise molecular breeding.
Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease
Authors: You Mei , Liu Yushuang , Wang Bowen , Li Li , Zhang Hexuan , He Hongbo , Zhou Qing , Cao Tingbing , Wang Lijuan , Zhao Zhigang , Zhu Zhiming , Gao Peng , Yan Zhencheng 
Published: February 2022

Abstract
Background
Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated.

Methods
33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM + PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT).

Results
The circulating levels of asprosin in DM + PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD. Logistic regression analysis revealed that asprosin is an independent risk factor for PAD and receiver-operator characteristic (ROC) curve determined a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD. Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in patients with PAD and activation of TGF-β signaling pathway appeared in the aortic tissue of db/db mice. Asprosin directly induces EndMT in HUVECs in a TGF-β-dependent manner as TGF-β signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT.

Conclusions
Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-β signaling pathway.
Trial registration This trial was registered at clinicaltrials.gov as NCT05068895
Identification of UAP1L1 as a critical factor for prostate cancer and underlying molecular mechanism in tumorigenicity
Authors: Wu Xing-cheng , Yu Yu-zhong , Zuo Yu-zhi , Song Xian-Lu , Zhou Zhi-en , Xiao Yu , Luo Dao-sheng , Yan Wei-gang , Zhao Shan-Chao 
Published: February 2022

Abstract
Background
Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment.

Methods
In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown.

Results
The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed.

Conclusions
In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.
In vivo detection of dysregulated choline metabolism in paclitaxel-resistant ovarian cancers with proton magnetic resonance spectroscopy
Authors: Lu Jing , Li Ying , Li Yong Ai , Wang Li , Zeng An Rong , Ma Xiao Liang , Qiang Jin Wei 
Published: February 2022

Abstract
Background
Chemoresistance gradually develops during treatment of epithelial ovarian cancer (EOC). Metabolic alterations, especially in vivo easily detectable metabolites in paclitaxel (PTX)-resistant EOC remain unclear.

Methods
Xenograft models of the PTX-sensitive and PTX-resistant EOCs were built. Using a combination of in vivo proton-magnetic resonance spectroscopy (1H-MRS), metabolomics and proteomics, we investigated the in vivo metabolites and dysregulated metabolic pathways in the PTX-resistant EOC. Furthermore, we analyzed the RNA expression to validate the key enzymes in the dysregulated metabolic pathway.

Results
On in vivo 1H-MRS, the ratio of (glycerophosphocholine + phosphocholine) to (creatine + phosphocreatine) ((GPC + PC) to (Cr + PCr))(i.e. Cho/Cr) in the PTX-resistant tumors (1.64 [0.69, 4.18]) was significantly higher than that in the PTX-sensitive tumors (0.33 [0.10, 1.13]) (P = 0.04). Forty-five ex vivo metabolites were identified to be significantly different between the PTX-sensitive and PTX-resistant tumors, with the majority involved of lipids and lipid-like molecules. Spearman’s correlation coefficient analysis indicated in vivo and ex vivo metabolic characteristics were highly consistent, exhibiting the highest positive correlation between in vivo GPC + PC and ex vivo GPC (r = 0.885, P < 0.001). These metabolic data suggested that abnormal choline concentrations were the results from the dysregulated glycerophospholipid metabolism, especially choline metabolism. The proteomics data indicated that the expressions of key enzymes glycerophosphocholine phosphodiesterase 1 (GPCPD1) and glycerophosphodiester phosphodiesterase 1 (GDE1) were significantly lower in the PTX-resistant tumors compared to the PTX-sensitive tumors (both P < 0.01). Decreased expressions of GPCPD1 and GDE1 in choline metabolism led to an increased GPC levels in the PTX-resistant EOCs, which was observed as an elevated total choline (tCho) on in vivo 1H-MRS.

Conclusions
These findings suggested that dysregulated choline metabolism was associated with PTX-resistance in EOCs and the elevated tCho on in vivo 1H-MRS could be as an indicator for the PTX-resistance in EOCs.
CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro
Authors: Noda Seiji , Hosoya Tadashi , Komiya Yoji , Tagawa Yasuhiro , Endo Kentaro , Komori Keiichiro , Koga Hideyuki , Takahara Yasuhiro , Sugimoto Kazutaka , Sekiya Ichiro , Saito Tetsuya , Mizoguchi Fumitaka , Yasuda Shinsuke 
Published: February 2022

Abstract
Objective
Synovial fibroblasts (SFs) in rheumatoid arthritis (RA) and osteoarthritis (OA) play biphasic roles in joint destruction and regeneration of bone/cartilage as mesenchymal stem cells (MSCs). Although MSCs contribute to joint homeostasis, such function is impaired in arthritic joints. We have identified functionally distinct three SF subsets characterized by the expression of CD34 and THY1 as follows: CD34+THY1+, CD34−THY1−, and CD34−THY1+. The objective of this study was to clarify the differentiation potentials as MSCs in each SF subset since both molecules would be associated with the MSC function.

Methods
SF subsets were isolated from synovial tissues of 70 patients (RA: 18, OA: 52). Expressions of surface markers associated with MSCs (THY1, CD34, CD73, CD271, CD54, CD44, and CD29) were evaluated in fleshly isolated SF subsets by flow cytometry. The differentiation potentials of osteogenesis, chondrogenesis, and adipogenesis were evaluated with histological staining and a quantitative polymerase chain reaction of differentiation marker genes. Small interfering RNA was examined to deplete THY1 in SFs.

Results
The expression levels of THY1+, CD73+, and CD271+ were highest and those of CD54+ and CD29+ were lowest in CD34+THY1+ among three subsets. Comparing three subsets, the calcified area, alkaline phosphatase (ALP)-stained area, and cartilage matrix subset were the largest in the CD34+THY1+ subset. Consistently, the expressions of differentiation markers of the osteoblasts (RUNX2, ALPL, and OCN) or chondrocytes (ACAN) were the highest in the CD34+THY1+ subset, indicating that the CD34+THY1+ subset possessed the highest osteogenic and chondrogenic potential among three subsets, while the differentiation potentials to adipocytes were comparable among the subsets regarding lipid droplet formations and the expression of LPL and PPARγ. The knockdown of THY1 in bulk SFs resulted in impaired osteoblast differentiation indicating some functional aspects in this stem-cell marker.

Conclusion
The CD34+THY1+ SF subset has high osteogenic and chondrogenic potentials. The preferential enhancement of MSC functions in the CD34+THY1+ subset may provide a new treatment strategy for regenerating damaged bone/cartilage in arthritic joints.
Selection and validation of reference gene for RT-qPCR studies in co-culture system of mouse cementoblasts and periodontal ligament cells
Authors: Yong Jiawen , Groeger Sabine , Ruiz-Heiland Gisela , Ruf Sabine 
Published: February 2022

AbstractObjectiveRT-qPCR is a reliable method for gene expression analysis, but the accuracy of the quantitative data depends on the appropriate selection of reference genes. A Co-culture system consisting of periodontal ligament cells (SV-PDL) and cementoblasts (OCCM-30) to investigate the crosstalk between these two cell lines under orthodontic condition is essential for experimental orthodontic setups in-vitro. Therefore, we aimed to identify a set of reliable reference genes suitable for RT-qPCR studies for prospective co-culture systems of OCCM-30 and SV-PDL cells.ResultsThe results demonstrated thatPPIB,GUSBandRPLP0turned out to be the three most stable reference genes for OCCM-30 in the co-culture system, whilePPIB,POLR2AandRPLP0have the three highest rankings for SV-PDL cells in the co-culture system. The most stable gene combination werePPIBandPOLR2Ain the co-culture system. In conclusion,PPIBis overall the most stably expressed reference gene for OCCM-30 or SV-PDL cell line in the system. The combination ofPPIBandPOLR2Aas reference genes are indicated to be the potential and mandatory to obtain accurate quantification results for normalizing RT-qPCR data in genes of interest expression in these two cell lines co-culture systems.
Hyperbaric oxygen treatment for long coronavirus disease-19: a case report
Authors: Bhaiyat Aisha M. , Sasson Efrat , Wang Zemer , Khairy Sherif , Ginzarly Mouzayan , Qureshi Umair , Fikree Moin , Efrati Shai 
Published: February 2022

Abstract
Background
The coronavirus disease 2019 pandemic has resulted in a growing population of individuals who experience a wide range of persistent symptoms referred to as “long COVID.” Symptoms include neurocognitive impairment and fatigue. Two potential mechanisms could be responsible for these long-term unremitting symptoms: hypercoagulability, which increases the risk of blood vessel occlusion, and an uncontrolled continuous inflammatory response. Currently, no known treatment is available for long COVID. One of the options to reverse hypoxia, reduce neuroinflammation, and induce neuroplasticity is hyperbaric oxygen therapy. In this article, we present the first case report of a previously healthy athletic individual who suffered from long COVID syndrome treated successfully with hyperbaric oxygen therapy.

Case presentation
A previously healthy 55-year-old Caucasian man presented 3 months after severe coronavirus disease 2019 infection with long COVID syndrome. His symptoms included a decline in memory, multitasking abilities, energy, breathing, and physical fitness. After evaluation that included brain perfusion magnetic resonance imaging, diffusion tensor imaging, computerized cognitive tests, and cardiopulmonary test, he was treated with hyperbaric oxygen therapy. Each session included exposure to 90 minutes of 100% oxygen at 2 atmosphere absolute pressure with 5-minute air breaks every 20 minutes for 60 sessions, 5 days per week. Evaluation after completing the treatment showed significant improvements in brain perfusion and microstructure by magnetic resonance imaging and significant improvement in memory with the most dominant effect being on nonverbal memory, executive functions, attention, information procession speed, cognitive flexibility, and multitasking. The improved cognitive functions correlated with the increased cerebral blood flow in brain regions as measured by perfusion magnetic resonance imaging. With regard to physical capacity, there was a 34% increase in the maximum rate of oxygen consumed during exercise and a 44% improvement in forced vital capacity. The improved physical measurements correlated with the regain of his pre-COVID physical capacity.

Conclusions
We report the first case of successfully treated long COVID symptoms with hyperbaric oxygen therapy with improvements in cognition and cardiopulmonary function. The beneficial effects of hyperbaric oxygen shed additional light on the pathophysiology of long COVID. As this is a single case report, further prospective randomized control studies are needed.