bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis
Authors: Mo Yulan , Leung Leanne L. , Mak Celia S. L. , Wang Xueyu , Chan Wai-Sun , Hui Lynn M. N. , Tang Hermit W. M. , Siu Michelle K. Y. , Sharma Rakesh , Xu Dakang , Tsui Stephen K. W. , Ngan Hextan Y. S. , Yung Mingo M. H. , Chan Karen K. L. , Chan David W. 
Published: January 2023

AbstractBackgroundMetastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood.MethodsPCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations.ResultsHsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers.ConclusionsThis study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases.
Inadequate response to antiplatelet therapy in patients with peripheral artery disease: a prospective cohort study
Authors: Kremers B. M. M. , Daemen J. H. C. , ten Cate H. , Spronk H. M. H. , Mees B. M. E. , ten Cate-Hoek A. J. 
Published: January 2023

Abstract
Background
Patients with peripheral artery disease (PAD) are treated with preventive strategies to improve the cardiovascular risk. The incidence of cardiovascular events and mortality however remains high in PAD populations. We therefore aimed to better characterize PAD patients suffering from cardiovascular events and mortality in order to tailor preventive treatment.

Methods
Between 2018 and 2020, 246 PAD outpatients (17 newly diagnosed, 229 with known PAD) were prospectively enrolled in this observational cohort study. Patient data and blood samples were collected after inclusion, and the primary composite endpoint (myocardial infarction, elective coronary revascularization, ischemic stroke, acute limb ischemia, mortality) was evaluated after one year. Secondary outcomes included platelet reactivity, measured using the VerifyNow assay, and medication adherence, assessed using the Morisky Medication Adherence Scale-8 (MMAS-8). Logistic regression models were used to identify associations between characteristics and the occurrence of events.

Results
The cohort comprised 207 patients with claudication and 39 with chronic limb threatening ischemia. Twenty-six (10.6%) patients suffered from an event during follow-up. Prior myocardial infarction (OR 3.3 [1.4–7.7]), prior ischemic stroke (OR 4.5 [1.8–10.9]), higher levels of creatinine (OR 5.2 [2.2–12.6]), lower levels of high-density lipoprotein (OR 4.2 [1.5–10.6]) and lower haemoglobin levels (OR 3.1 [1.3–7.1]) were associated with events. Patients with events had more often high on-treatment platelet reactivity (HTPR) on aspirin (OR 5.9 [1.4–25.1]) or clopidogrel (OR 4.3 [1–19.3]). High adherence to medication was associated with the occurrence of events (OR 4.1 [1–18]).

Conclusions
Patients suffering from cardiovascular events and mortality were characterized by prior cardiovascular events as compared to patients who did not experience any events. Antiplatelet therapy was not optimally protective despite high medication adherence, and HTPR was independently associated with the occurrence of events. More research is needed on alternative treatment strategies such as dual antiplatelet therapy or combinations with anticoagulant drugs.

Trial registration
The Medical Ethics Committee (METC) of the MUMC+ approved the study (NL63235.068.17) and the study was registered in the Netherlands Trial Register (NTR7250).
Acute toxicities and cumulative dose to the brain of repeated sessions of stereotactic radiotherapy (SRT) for brain metastases: a retrospective study of 184 patients
Authors: Kuntz L. , Le Fèvre C. , Jarnet D. , Keller A. , Meyer P. , Thiery A. , Cebula H. , Noel G. , Antoni D. 
Published: January 2023

Abstract
Background
Stereotactic radiation therapy (SRT) is a focal treatment for brain metastases (BMs); thus, 20 to 40% of patients will require salvage treatment after an initial SRT session, either because of local or distant failure. SRT is not exempt from acute toxicity, and the acute toxicities of repeated SRT are not well known. The objective of this study was to analyze the acute toxicities of repeated courses of SRT and to determine whether repeated SRT could lead to cumulative brain doses equivalent to those of whole-brain radiotherapy (WBRT).

Material and methods
Between 2010 and 2020, data from 184 patients treated for 915 BMs via two to six SRT sessions for local or distant BM recurrence without previous or intercurrent WBRT were retrospectively reviewed. Patients were seen via consultations during SRT, and the delivered dose, the use of corticosteroid therapy and neurological symptoms were recorded and rated according to the CTCAEv4. The dosimetric characteristics of 79% of BMs were collected, and summation plans of 76.6% of BMs were created.

Results
36% of patients developed acute toxicity during at least one session. No grade three or four toxicity was registered, and grade one or two cephalalgy was the most frequently reported symptom. There was no significant difference in the occurrence of acute toxicity between consecutive SRT sessions. In the multivariate analysis, acute toxicity was associated with the use of corticosteroid therapy before irradiation (OR = 2.6; p = 0.01), BMV grade (high vs. low grade OR = 5.17; p = 0.02), and number of SRT sessions (3 SRT vs. 2 SRT: OR = 2.64; p = 0.01). The median volume equivalent to the WBRT dose (VWBRT) was 47.9 ml. In the multivariate analysis, the VWBRT was significantly associated with the total GTV (p < 0.001) and number of BMs (p < 0.001). Even for patients treated for more than ten cumulated BMs, the median BED to the brain was very low compared to the dose delivered during WBRT.

Conclusion
Repeated SRT for local or distant recurrent BM is well tolerated, without grade three or four toxicity, and does not cause more acute neurological toxicity with repeated SRT sessions. Moreover, even for patients treated for more than ten BMs, the VWBRT is low.
The three steps method for uniportal video-assisted thoracoscopic right upper lobectomy
Authors: Liu Caiyang , Ran Ran , Luo Lei , Li Xiaoliang , Liu Gaohua , Shao Hong , Li Ji 
Published: January 2023

Abstract
Background
The uniportal video-assisted thoracoscopic right upper lobectomy (UVATRUL), as a common procedure for thoracic surgeons, is difficult to manipulate and has some inherent challenges. To solve both of problems, we summarized a series of techniques as the three steps method and investigated its feasibility on the patients of right upper lung cancer.

Methods
Forty-eight patients with right upper lobe lung cancer who underwent the three steps method UVATRUL in our hospital from January 2020 to May 2022 were selected as the three steps method group. Forty-seven patients who underwent the traditional UVATRUL were selected as the traditional method group. The intraoperative condition and postoperative condition of the two groups were retrospectively analysed. Multiple linear regression analysis was carried out to analyze the relationship between positive results and surgical method.

Results
All patients had successfully completed their surgeries. There was no significant difference between the two groups in respect of intraoperative blood loss, rate of conversion, day one thoracic drainage volume, chest tube indwelling time, incidence of postoperative complications, number of lymph node, and postoperative hospital stay (P > 0.05). Operative time of the three steps method group was significantly shorter than the traditional method group (P < 0.001), and number of reloads used was also significantly less than the traditional method group (P = 0.014). Multiple linear regression analysis showed that operative time (β = − 0.470, P < 0.001), and number of reloads (β = − 0.254, P = 0.007) correlated with surgical method.

Conclusion
Compared with the traditional UVATRUL, the three steps method trims the surgery procedures, shortens the operative time, and reduces the use of reloads which makes it an effective procedure for UVATRUL.
Predicting nitrogen use efficiency, nitrogen loss and dry matter intake of individual dairy cows in late lactation by including mid-infrared spectra of milk samples
Authors: Shi Rui , Lou Wenqi , Ducro Bart , van der Linden Aart , Mulder Han A. , Oosting Simon J. , Li Shengli , Wang Yachun 
Published: January 2023

Abstract
Background
Nitrate leaching to groundwater and surface water and ammonia volatilization from dairy farms have negative impacts on the environment. Meanwhile, the increasing demand for dairy products will result in more pollution if N losses are not controlled. Therefore, a more efficient, and environmentally friendly production system is needed, in which nitrogen use efficiency (NUE) of dairy cows plays a key role. To genetically improve NUE, extensively recorded and cost-effective proxies are essential, which can be obtained by including mid-infrared (MIR) spectra of milk in prediction models for NUE. This study aimed to develop and validate the best prediction model of NUE, nitrogen loss (NL) and dry matter intake (DMI) for individual dairy cows in China.

Results
A total of 86 lactating Chinese Holstein cows were used in this study. After data editing, 704 records were obtained for calibration and validation. Six prediction models with three different machine learning algorithms and three kinds of pre-processed MIR spectra were developed for each trait. Results showed that the coefficient of determination (R2) of the best model in within-herd validation was 0.66 for NUE, 0.58 for NL and 0.63 for DMI. For external validation, reasonable prediction results were only observed for NUE, with R2 ranging from 0.58 to 0.63, while the R2 of the other two traits was below 0.50. The infrared waves from 973.54 to 988.46 cm−1 and daily milk yield were the most important variables for prediction.

Conclusion
The results showed that individual NUE can be predicted with a moderate accuracy in both within-herd and external validations. The model of NUE could be used for the datasets that are similar to the calibration dataset. The prediction models for NL and 3-day moving average of DMI (DMI_a) generated lower accuracies in within-herd validation. Results also indicated that information of MIR spectra variables increased the predictive ability of models. Additionally, pre-processed MIR spectra do not result in higher accuracy than original MIR spectra in the external validation. These models will be applied to large-scale data to further investigate the genetic architecture of N efficiency and further reduce the adverse impacts on the environment after more data is collected.
Prevalence and associated factors of binge eating disorder among Bahraini youth and young adults: a cross-sectional study in a self-selected convenience sample
Authors: Abdulla Zahraa A. Rasool Abbas , Almahmood Hend Omar , Alghasra Razan Raed , Alherz Zahra Abdulameer Sadeq , Alsharifa Husain A. Ghaffar , Qamber Seham Jamal , Alomar Nadia Aaref , Almajed Fatema Ebrahim , Almahroos Taher Reyadh , Alnajjas Zainab Ali , Alsayyad Adel Salman 
Published: January 2023

Abstract
Background
Binge eating disorder (BED) is defined as recurrent ingestion of an unusually large amount of food in a discrete period of time. BED has the highest prevalence of all eating disorders. Studies have shown a strong relationship between BED and both physical and psychological factors such as obesity, depression and anxiety. This research aimed to report the prevalence and associated factors of BED among Bahrainis (aged 15–30 years).

Methods
A total of 959 participants (aged 15–30 years) completed self-administered online questionnaires. BED was measured using the binge eating disorder Screener-7. The Patient Health Questionnaire-9 and General Anxiety Disorder-7 were used to measure depression and anxiety, respectively.

Results
Out of all participants, 21.2% had binge eating symptoms. A higher BMI, a restricted diet, depression and anxiety were associated with more frequent binge eating symptoms. Out of all associated factors, depression had the strongest association with binge eating, (rp = 0.371, p < 0.0001). However, sociodemographic variables including age and other medical conditions were not significantly associated with BED symptoms.

Conclusion
In conclusion, the prevalence of BED symptoms was significantly high among the study participants. The results point out the crucial role of awareness of the interaction between obesity, depression and anxiety as potential risk factors for binge eating tendencies. Further research should examine their relationship with BED.
Visualizing water seepage dynamics in grotto relics via atom-based representative model
Authors: Wang Junxia 
Published: January 2023

Abstract
Water seepage in grotto relics, i.e., Yungang Grottoes, Dazu Rock Carvings, is a key issue to accurately describe the deterioration and weathering process of grotto rock mass. Considering rainfall infiltration, Finite element simulation was performed for studying the water flow through macro-channel of fractured rock in the 4th cave of Yungang Grottoes, where a group of joints with directions of S62°E and N5°W are widely developed. A 3D atom-based representative model was derived from X-ray diffraction (XRD) patterns and the related semi-quantitative calculation of grotto rock powders, for visualizing the associated seepage characteristics through micro-channel by means of molecular dynamics simulation, for the first time. By analyzing various properties, ranging from the configuration and energetic behaviors to the dynamic characteristics, the calculated water flux and mass flow rate were equal to 270 ns−1 and 8.10 × 10–12 g s
−1, respectively. A dynamic process of water transport from the entrance region to the exit region was examined and it is consistent with the relative concentration profiles at the corresponding stage. The tagged O atoms experienced a zigzag movement instead of linear motion as expected, roughly exhibited the same target direction. The seepage characteristics in grotto relics experienced a complex evolution process and three types can be summarized: water infiltrates through micro-channels with a low flow rate; it flows through fracture with a relatively high flow rate; it turned into a kind of analogous pipe flow in inter-connected fracture network, resulting in water seepage hazard. Current simulation studies provide helpful insights for understanding the water flow-infiltration behavior of fractured rock in grotto relics.
Higher incidence of pegfilgrastim-induced bone pain in younger patients receiving myelosuppressive chemotherapy: a real-world experience
Authors: Tsuboi Shinya , Hayama Tatsuya , Miura Katsuhiro , Uchiike Akihiro , Tsutsumi Daisuke , Yamauchi Takashi , Hatta Yoshihiro , Ootsuka Susumu 
Published: January 2023

Abstract
Background
Pegfilgrastim is widely used for the prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy for various types of cancer. However, pegfilgrastim-induced bone pain (PIBP) is a relevant adverse event occurring during cancer treatment. Thus, we aimed to determine the risk factors for PIBP in real-world clinical practice.

Main body
We retrospectively collected the clinical records of patients who received pegfilgrastim to support myelosuppressive chemotherapy with at least a 10% risk of FN between 2015 and 2018 at our center. Patients received pegfilgrastim 3.6 mg between days 2 and 7 after chemotherapy administration (day 1) for primary or secondary prophylaxis against FN. All adverse events were recorded according to the Common Terminology Criteria for Adverse Events. Patients who experienced intermittent bone pain in the back, femur, or other anatomic sites after the pegfilgrastim administration were considered to have PIBP. To evaluate the relationship between PIBP incidence and patient characteristics, we performed univariate and multivariate logistic regression analyses to calculate the odds ratios (ORs) of possible risk factors for PIBP. We analyzed the data of 305 patients (median age: 63 years), who underwent 1220 chemotherapy cycles with pegfilgrastim per cycle. Univariate analysis revealed that female sex (vs. male sex), younger age (< 55 years vs. ≥ 55 years), and solid cancers (vs. hematologic cancers) had significantly higher ORs (p < 0.05). However, only younger age (< 55 years) was an independent risk factor for PIBP on multivariate analysis (OR 3.62, 95% confidence interval 1.51–8.69, p = 0.004).

Conclusions
Younger age (< 55 years) was significantly associated with a higher risk of PIBP among patients receiving chemotherapy with a ≥ 10% risk of FN. Therefore, oncologists should meticulously formulate management plan for PIBP in younger patients after administering pegfilgrastim.
BLOod Test Trend for cancEr Detection (BLOTTED): protocol for an observational and prediction model development study using English primary care electronic health record data
Authors: Virdee Pradeep S. , Bankhead Clare , Koshiaris Constantinos , Drakesmith Cynthia Wright , Oke Jason , Withrow Diana , Swain Subhashisa , Collins Kiana , Chammas Lara , Tamm Andres , Zhu Tingting , Morris Eva , Holt Tim , Birks Jacqueline , Perera Rafael , Hobbs F. D. Richard , Nicholson Brian D. 
Published: January 2023

Abstract
Background
Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer.

Methods
Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots.

Discussion
These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.
Biomarkers as ecological indices in monitoring the status of market fish
Authors: Nagarani N. , Krishnaveni G. , Dharshini V. Dhivya , Manohari K. Gowri , Jeyapandi Monisha Archana , Mariappan Pandiselvi Vinothini , Sangeetha R. 
Published: January 2023

Abstract
Background
Environmental contamination has become a major concern over the past few decades, drawing the attention of numerous researchers from both developed and developing nations. The aquatic system serves as the primary sink for the disposal of garbage, which has a negative impact on the aquatic environment and biota. The reality is that heavy metals cannot be totally removed from the ecosystem because they can bioaccumulate and grow in strength as they move up the food chain. Particularly heavy metals can build up in the tissues of aquatic animals, and as a result, tissue concentrations of heavy metals may be harmful to both human and animal health. Our study aimed to elucidate the possible use of biomarkers in monitoring and assessing the heavy metals contaminants among fresh water fish.

Results
From the present study, we conclude that glutathione peroxidase can be used as the bioindicator for nickel and iron contamination. Ultimately, these studies focus on measuring levels of pollution that may induce irreversible ecological changes to aquatic ecosystems. Till now the level of toxicity was moderate, and it was progressing toward the danger. Efforts can be made to control the activities that release pollutants unnaturally into the environment from both public and government so that the clean and clear environment can be maintained.

Conclusions
The work concludes that a multiparameter analysis is needed to assess and monitor the ecological status of the aquatic environment.