bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rubus idaeus extract improves symptoms in knee osteoarthritis patients: results from a phase II double-blind randomized controlled trial
Authors: Henrotin Yves , Cozannet Romain Le , Fança-Berthon Pascale , Truillet Romain , Cohen-Solhal Martine , DunnGalvin Gillian , Grouin Jean-Marie , Doolan Andrea 
Published: July 2022

Abstract
Background
Osteoarthritis (OA) is the most frequent cause of disability in elderly people. In daily practice, the main objective of the physician is to reduce patient symptoms using treatments without adverse effects. However, the most prescribed treatment to manage OA symptoms remains nonsteroidal anti-inflammatory drugs which are associated with severe adverse effects. Therefore, we need a safe alternative to managing OA. One candidate is Rubus idaeus leaf extracts known to inhibit inflammatory responses.

Objective
This study aimed to evaluate the effects of a 12-weeks intervention with an ethanolic extract from Rubus idaeus leaf on symptoms of knee osteoarthritis.

Method
The study was a randomized, double-blind, placebo-controlled, monocentric trial of 198 participants with femorotibial osteoarthritis. Participants were randomized equally to receive one daily during 3 months either 1 capsule of Rubus idaeus leaf extract 400 mg, 1 capsule of Rubus idaeus leaf extract 200 mg, or 1 capsule of placebo. The participants were assessed at baseline and after one and three months of treatment. The primary endpoint was an absolute change of the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. The secondary endpoints were WOMAC global score, stiffness and function sub-scales, knee pain VAS score at walking, the Short Form (SF)-36, the Short Physical Performance Battery (SPPB), the 20-m walk test, and the International Physical Activity Questionnaire (IPAQ) and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responders rate. Statistical analyses were conducted on the intent-to-treat (ITT) population.

Results
In the Intention-to-treat population, WOMAC pain was not significantly modified by Rubus idaeus leaf extract compared to placebo. In contrast, Rubus idaeus leaf extract 400 mg after 12 weeks of treatment significantly reduced pain measured by the VAS. The mean pain decrease induced by Rubus ideaus leaf extract was over -7 mm which is clinically relevant and reached a clinically statistical difference compared to placebo with the highest dose. Rubus Ideaus was not significantly more efficient than the placebo on WOMAC global score, stiffness, and physical function subscores, IPAQ, SF-36, walking distance in treadmill test, SPPB, and evaluation of associated treatments needed to manage OA.

Conclusion
Rubus idaeus leaf extract was well tolerated and effective to relieve pain in a patient with knee osteoarthritis.

Trial registration
NCT03703024 (11/10/2018).
Association between history of abortion and current use of contraceptives among Mongolian Women
Authors: Phiri Yohane V. A. , Nyam Gunchmaa , Wardani Yuniar , Phiri Doreen , Chuang Kun-Yang , Chao Hsing Jasmine , Nkoka Owen 
Published: July 2022

Abstract
Background
Understanding the factors associated with the adoption of contraceptive methods among women of childbearing age is imperative to improving maternal health outcomes. This study aimed at exploring the association between history of abortion and contraceptive use among Mongolian women.

Materials and methods
We analyzed cross-sectional data of 8373 women aged 15–49 years from the 2018 Mongolian Social Indicator Sample Survey (MSISS). Binary logistic regression models were used to assess the association between abortion history and current contraceptive use while accounting for both individual- and community- level factors.

Results
A total of 4347 (51.92%) and 2525 (30.16%) reported current use of various contraceptive methods and a history of abortion in their lifetime, respectively. Women with a history of abortion were less likely to report current use of contraceptives (adjusted odds ratio (AOR) = 0.72, 95% confidence interval (CI) [0.58–0.89]). Specifically, women with a history of abortion were less likely to report use of IUD (AOR = 0.79, 95% CI [0.71–0.90)]) and injectables (AOR = 0.59, 95% CI [0.41–0.84]). History of abortion was associated with increased likelihood of using abstinence (OR = 1.82, 95% CI [1.31–2.53]) as a contraceptive method.

Conclusion
Our results demonstrated a significant association between history of abortion and contraceptive use. Public health interventions aiming to improve maternal health outcomes through contraceptive use should target women with a history of abortion to improve their uptake.
Oridonin attenuates low shear stress-induced endothelial cell dysfunction and oxidative stress by activating the nuclear factor erythroid 2-related factor 2 pathway
Authors: Chen Zhipeng , Liu Heqian , Zhao Xiaoqi , Mamateli Subinur , Liu Cheng , Wang Lei , Yu Jing , Liu Yutong , Cai Jing , Qiao Tong 
Published: July 2022

Abstract
Background
Atherosclerosis (AS) is the primary cause of cardiovascular disease and the incidence is extremely common; however, there are currently few drugs that can effectively treat AS. Although oridonin has been widely used to treat inflammation and cancer for numerous years, to the best of our knowledge, its protective effect against AS has not been reported. Therefore, the present study aimed to investigate whether oridonin attenuated AS.

Methods
By using text mining, chemometric and chemogenomic methods, oridonin was predicted to be a beneficial agent for the treatment of AS. A parallel flow chamber was used to establish a low shear stress (LSS)-induced endothelial cell (EC) dysfunction model. Briefly, ECs were exposed to 3 dyn/cm2 LSS for 30 min and subsequently treated with oridonin or transfected with a small interfering RNA (siRNA) targeting nuclear factor erythroid 2-related factor 2 (NRF2). Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide (GSSG) in EA.hy926 cells were analyzed to determine the level of oxidative stress. The nitric oxide (NO) levels and mRNA expression levels of endothelial NO synthase (eNOS), endothelin-1 (ET-1) and prostaglandin synthase (PGIS) in EA.hy926 cells were analyzed to determine EC dysfunction. Furthermore, the mRNA and protein expression levels of NRF2 were analyzed using reverse transcription-quantitative PCR and western blot. In addition, zebrafish were fed with a high-cholesterol diet to establish a zebrafish AS model, which was used to observe lipid accumulation and inflammation under a fluorescence microscope.

Results
We found LSS led to oxidative stress and EC dysfunction; this was primarily indicated through the significantly decreased SOD and GSH content, the significantly increased MDA, GSSG and ROS content, the upregulated mRNA expression levels of ET-1, and the downregulated NO levels and mRNA expression levels of eNOS and PGIS in ECs. Notably, oridonin could improve LSS-induced oxidative stress and EC dysfunction, and the effects of oridonin were reversed by the transfection with NRF2 siRNA. Oridonin also attenuated lipid accumulation and neutrophil recruitment at the LSS regions in the zebrafish AS model.

Conclusions
In conclusion, the results of the present study suggested that oridonin may ameliorate LSS-induced EC dysfunction and oxidative stress by activating NRF2, thereby attenuating AS.
Determinants of drug expenditure in the Swiss healthcare market in 2006
Authors: Eggli Yves , Decollogny Anne , Piaget-Rossel Romain , Taffé Patrick 
Published: July 2022

Abstract
Background
Several measures are in force in Switzerland to control the cost of drugs, but are not effective enough. There are many determinants influencing these expenditures, related to treatments, markets, physicians, patients and regions, but their impact on costs is not clear.

Methods
We applied a Bayesian multilevel model with five levels to adjust for patients, drugs’ market, and physicians ‘characteristics, treatment type, and district (i.e. Swiss canton). We used data of the Swiss drugs’ market in 2006, offering real choices for doctors and patients (multiple products for similar active substances), with a neutral position of pharmacists (no financial incentives).

Results
Variance partitioning of yearly drugs’ cost per insured showed that market level (delivered substance) contributed to 76% of the variance, treatment level (delivered product) to 20%, whereas patients’ and physicians’ levels accounted for only 2% each, without significant differences between Swiss cantons. After adjusting for covariables at each level, the model explained about 51% of the variation at the market and 20% at the treatment levels. We found that older but substitutable drugs, generics, larger size of the market and physician’s specialty were associated with lower expenditure, whereas drugs requiring a physician’s prescription, the number of prescribers per patient, patient’ age, male gender, and comorbidities increased expenditure. Our results show that for a specific medication the yearly cost of recently released drugs was 36 CHF higher than for similar and substitutable drugs introduced 15 years earlier, corresponding to one third of the average annual treatment cost observed in our dataset. Competition did not seem to be effective to reduce expenditure on the drug market.

Conclusion
The main finding of this study is that recentness of drugs was associated with an increase in drug expenditure in 2006, even after adjustment for all non-controllable determinants. Further research is recommended to confirm those results with updated data.
First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia
Authors: Jin Xin , Zhang Meng , Sun Rui , Lyu Hairong , Xiao Xia , Zhang Xiaomei , Li Fan , Xie Danni , Xiong Xia , Wang Jiaxi , Lu Wenyi , Zhang Hongkai , Zhao Mingfeng 
Published: July 2022

AbstractRelapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis. In this study, we evaluated chimeric antigen receptor (CAR) T cell therapy targeting CLL-1 in adults with R/R AML patients. Patients received conditioning chemotherapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days and an infusion of a dose of 1–2 × 106 CAR-T cells/kg. The incidence of dose-limiting toxicity was the primary endpoint. Ten patients were treated, and all developed cytokine release syndrome (CRS); 4 cases were low-grade, while the remaining 6 were considered high-grade CRS. No patient developed CAR-T cell-related encephalopathy syndrome (CRES). Severe pancytopenia occurred in all patients. Two patients died of severe infection due to chronic agranulocytosis. The complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 70% (n = 7/10). The median follow-up time was 173 days (15–488), and 6 patients were alive at the end of the last follow-up. CAR-T cells showed peak expansion within 2 weeks. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML.
Time course of lung ultrasound findings in patients with COVID-19 pneumonia and cardiac dysfunction
Authors: Leote Joao , Judas Tiago , Broa Ana Luísa , Lopes Miguel , Abecasis Francisca , Pintassilgo Inês , Gonçalves Afonso , Gonzalez Filipe 
Published: July 2022

Abstract
Background
Lung ultrasound (LUS) is a valuable tool to predict and monitor the COVID-19 pneumonia course. However, the influence of cardiac dysfunction (CD) on LUS findings remains to be studied. Our objective was to determine the effect of CD on LUS in hospitalized patients with COVID-19 pneumonia.

Material and methods
Fifty-one patients with COVID-19 pneumonia participated in the study. Focused echocardiography (FoCUS) was carried out on day 1 to separate patients into two groups depending on whether they had FoCUS signs of CD (CD+ vs CD−). LUS scores, based on the thickness of the pleural line, the B-line characteristics, and the presence or not of consolidations, were obtained three times along the patient’s admission (D1, D5, D10) and compared between CD+ and CD− patients. A correlation analysis was carried out between LUS scores and the ratio of the arterial partial pressure of oxygen to the fraction of the inspired oxygen (P/F ratio).

Results
Twenty-two patients were CD+ and 29 patients were CD−. Among the CD+ patients, 19 were admitted to the intensive care unit (ICU), seven received invasive mechanical ventilation (IMV), and one did not survive. Among the CD− patients, 11 were admitted to the ICU, one received IMV and seven did not survive. CD+ patients showed a significantly lower P/F ratio than CD− patients. However, LUS scores showed no between-group differences, except for fewer subpleural consolidations in the upper quadrants of CD+ than on CD− patients.

Conclusion
In patients with COVID-19, CD contributed to a worse clinical course, but it did not induce significant changes in LUS. Our findings suggest that pathophysiological factors other than those reflected by LUS may be responsible for the differences in clinical condition between CD+ and CD− patients.
Fixed point results for generalized rational type $$\alpha$$ -admissible contractive mappings in the setting of partially ordered b-metric spaces
Authors: Haji Kedir Husen , Tola Kidane Koyas , Mamud Mustefa Abduletif 
Published: July 2022

Abstract
Objectives
In this paper we introduce fixed point theorems for generalized rational type $$\alpha$$
α
-admissible contractive mappings in partially ordered b-metric spaces and prove the existence and uniqueness of fixed points for self-mappings satisfying the established theorems. Finally, we provide examples in support of our main findings in the setting of partially ordered b-metric spaces.

Result
New fixed point results have been obtained for generalized rational type $$\alpha$$
α
-admissible contractive mappings in the setting of partially ordered b-metric space and we applied one of our results to determine a solution to an integral equation.
Level-wise aligned dual networks for text–video retrieval
Authors: Lin Qiubin , Cao Wenming , He Zhiquan 
Published: July 2022

AbstractThe vast amount of videos on the Internet makes efficient and accurate text–video retrieval tasks increasingly important. The current methods leverage a high-dimensional space to align video and text for these tasks. However, a high-dimensional space cannot fully use different levels of information in videos and text. In this paper, we put forward a method called level-wise aligned dual networks (LADNs) for text–video retrieval. LADN uses four common latent spaces to improve the performance of text–video retrieval and utilizes the semantic concept space to increase the interpretability of the model. Specifically, LADN first extracts different levels of information, including global, local, temporal, and spatial–temporal information, from videos and text. Then, they are mapped into four different latent spaces and one semantic space. Finally, LADN aligns different levels of information in various spaces. Extensive experiments conducted on three widely used datasets, including MSR-VTT, VATEX, and TRECVID AVS 2016-2018, demonstrate that our proposed approach is superior to several state-of-the-art text–video retrieval approaches.
Characterization and mitigation option of greenhouse gas emissions from lactating Holstein dairy cows in East China
Authors: Jia Peng , Tu Yan , Liu Zhihao , Lai Qi , Li Fadi , Dong Lifeng , Diao Qiyu 
Published: July 2022

Abstract
Background
This study investigated greenhouse gas (GHG) emission characteristics of lactating Holstein dairy cows in East China and provided a basis for formulating GHG emission reduction measures. GreenFeed system was used to measure the amount of methane (CH4) and carbon dioxide (CO2) emitted by the cows through respiration. Data from a commercial cow farm were used to observe the effects of parity, body weight, milk yield, and milk component yield on CH4 and CO2 emissions.

Results
Mean herd responses throughout the study were as follows: 111 cows completed all experimental processes, while 42 cows were rejected because they were sick or had not visited the GreenFeed system 20 times. On average, lactating days of cows was 138 ± 19.04 d, metabolic weight was 136.5 ± 9.5 kg, parity was 2.8 ± 1.0, dry matter intake (DMI) was 23.1 ± 2.6 kg/d, and milk yield was 38.1 ± 6.9 kg/d. The GreenFeed system revealed that CH4 production (expressed in CO2 equivalent, CO2-eq) was found to be 8304 g/d, $$ {\mathrm{CH}}_{4\left({\mathrm{CO}}_2-\mathrm{eq}\right)} $$

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4
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/DMI was 359 g/kg, $$ {\mathrm{CH}}_{4\left({\mathrm{CO}}_2-\mathrm{eq}\right)} $$

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/energy-corrected milk (ECM) was 229.5 g/kg, total CO2 production (CH4 production plus CO2 production) was 19,201 g/d, total CO2/DMI was 831 g/kg, and total CO2/ECM was 531 g/kg. The parity and metabolic weight of cows had no significant effect on total CO2 emissions (P > 0.05). Cows with high milk yield, milk fat yield, milk protein yield, and total milk solids yield produced more total CO2 (P < 0.05), but their total CO2 production per kg of ECM was low (P < 0.05). The total CO2/ECM of the medium and high milk yield groups was 17% and 27% lower than that of the low milk yield group, respectively.

Conclusions
The parity and body condition had no effect on total CO2 emissions, while the total CO2/ECM was negatively correlated with milk yield, milk fat yield, milk protein yield, and total milk solids yield in lactating Holstein dairy cows. Measurement of total CO2 emissions of dairy cows in the Chinese production system will help establish regional or national GHG inventories and develop mitigation approaches to dairy production regimes.
Establishment of a male fertility prediction model with sperm RNA markers in pigs as a translational animal model
Authors: Pang Won-Ki , Amjad Shehreen , Ryu Do-Yeal , Adegoke Elikanah Olusayo , Rahman Md Saidur , Park Yoo-Jin , Pang Myung-Geol 
Published: July 2022

Abstract
Background
Male infertility is an important issue that causes low production in the animal industry. To solve the male fertility crisis in the animal industry, the prediction of sperm quality is the most important step. Sperm RNA is the potential marker for male fertility prediction. We hypothesized that the expression of functional genes related to fertilization will be the best target for male fertility prediction markers. To investigate optimum male fertility prediction marker, we compared target genes expression level and a wide range of field data acquired from artificial insemination of boar semen.

Results
Among the genes related to acrosomal vesicle exocytosis and sperm–oocyte fusion, equatorin (EQTN), zona pellucida sperm-binding protein 4 (ZP4), and sperm acrosome membrane-associated protein 3 exhibited high accuracy (70%, 90%, and 70%, respectively) as markers to evaluate male fertility. Combinations of EQTN-ZP4, ZP4-protein unc-13 homolog B, and ZP4-regulating synaptic membrane exocytosis protein 1 (RIMS1) showed the highest prediction value, and all these markers are involved in the acrosome reaction.

Conclusion
The EQTN-ZP4 model was efficient in clustering the high-fertility group and may be useful for selection of animal that has superior fertility in the livestock industry. Compared to the EQTN-ZP4 model, the ZP4-RIMS1 model was more efficient in clustering the low-fertility group and may be useful in the diagnosis of male infertility in humans and other animals. The appointed translational animal model and established biomarker combination can be widely used in various scientific fields such as biomedical science.
13C tracer analysis suggests extensive recycling of endogenous CO2 in vivo
Authors: Duan Likun , Cooper Daniel E. , Scheidemantle Grace , Locasale Jason W. , Kirsch David G. , Liu Xiaojing 
Published: July 2022

Abstract
Background
13C tracer analysis is increasingly used to monitor cellular metabolism in vivo and in intact cells, but data interpretation is still the key element to unveil the complexity of metabolic activities. The distinct 13C labeling patterns (e.g., M + 1 species in vivo but not in vitro) of metabolites from [U-13C]-glucose or [U-13C]-glutamine tracing in vivo and in vitro have been previously reported by multiple groups. However, the reason for the difference in the M + 1 species between in vivo and in vitro experiments remains poorly understood.

Methods
We have performed [U-13C]-glucose and [U-13C]-glutamine tracing in sarcoma-bearing mice (in vivo) and in cancer cell lines (in vitro). 13C enrichment of metabolites in cultured cells and tissues was determined by LC coupled with high-resolution mass spectrometry (LC-HRMS). All p-values are obtained from the Student’s t-test two-tailed using GraphPad Prism 8 unless otherwise noted.

Results
We observed distinct enrichment patterns of tricarboxylic acid cycle intermediates in vivo and in vitro. As expected, citrate M + 2 or M + 4 was the dominant mass isotopologue in vitro. However, citrate M + 1 was unexpectedly the dominant isotopologue in mice receiving [U-13C]-glucose or [U-13C]-glutamine infusion, but not in cultured cells. Our results are consistent with a model where the difference in M + 1 species is due to the different sources of CO2 in vivo and in vitro, which was largely overlooked in the past. In addition, a time course study shows the generation of high abundance citrate M + 1 in plasma of mice as early as few minutes after [U-13C]-glucose infusion.

Conclusions
Altogether, our results show that recycling of endogenous CO2 is substantial in vivo. The production and recycling of 13CO2 from the decarboxylation of [U-13C]-glucose or [U-13C]-glutamine is negligible in vitro partially due to dilution by the exogenous HCO3−/CO2 source, but in vivo incorporation of endogenous 13CO2 into M + 1 metabolites is substantial and should be considered. These findings provide a new paradigm to understand carbon atom transformations in vivo and should be taken into account when developing mathematical models to better reflect carbon flux.