bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL7 playing a dominant role in recruiting early OCPs to facilitate osteolysis at metastatic site of colorectal cancer
Authors: Yang He , Jian Li , Jin Qian , Xia Kang , Cai-ru Wang , Jun Sheng , Chen Huang , Wei Wang , Ben-jing Song , Shi-hong Li , Shi-wei Long , Juan Wu , Wei Zheng 
Published: June 2022

Abstract
Background
Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear.

Methods
Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1.

Results
OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7.

Conclusion
Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target.
Tumor-associated macrophages promote epithelial–mesenchymal transition and the cancer stem cell properties in triple-negative breast cancer through CCL2/AKT/β-catenin signaling
Authors: Chen Xiangzhou , Yang Mingqiang , Yin Jiang , Li Pan , Zeng Shanshan , Zheng Guopei , He Zhimin , Liu Hao , Wang Qian , Zhang Fan , Chen Danyang 
Published: June 2022

Abstract
Background
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis and limited treatment. As a major component of the tumor microenvironment, tumor-associated macrophages (TAMs) play an important role in facilitating the aggressive behavior of TNBC. This study aimed to explore the novel mechanism of TAMs in the regulation of epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties in TNBC.

Methods
Expression of the M2-like macrophage marker CD163 was evaluated by immunohistochemistry in human breast cancer tissues. The phenotype of M2 macrophages polarized from Tohoku-Hospital-Pediatrics-1 (THP1) cells was verified by flow cytometry. Transwell assays, wound healing assays, western blotting, flow cytometry, ELISA, quantitative polymerase chain reaction (qPCR), luciferase reporter gene assays, and immunofluorescence assays were conducted to investigate the mechanism by which TAMs regulate EMT and CSC properties in BT549 and HCC1937 cells.

Results
Clinically, we observed a high infiltration of M2-like tumor-associated macrophages in TNBC tissues and confirmed that TAMs were associated with unfavorable prognosis in TNBC patients. Moreover, we found that conditioned medium from M2 macrophages (M2-CM) markedly promoted EMT and CSC properties in BT549 and HCC1937 cells. Mechanistically, we demonstrated that chemokine (C–C motif) ligand 2 (CCL2) secretion by TAMs activated Akt signaling, which in turn increased the expression and nuclear localization of β-catenin. Furthermore, β-catenin knockdown reversed TAM-induced EMT and CSC properties.

Conclusions
This study provides a novel mechanism by which TAMs promote EMT and enhance CSC properties in TNBC via activation of CCL2/AKT/β-catenin signaling, which may offer new strategies for the diagnosis and treatment of TNBC.
Identification of characteristic metabolic panels for different stages of prostate cancer by 1H NMR-based metabolomics analysis
Authors: Zhang Xi , Xia Binbin , Zheng Hong , Ning Jie , Zhu Yinjie , Shao Xiaoguang , Liu Binrui , Dong Baijun , Gao Hongchang 
Published: June 2022

AbstractBackgroundProstate cancer (PCa) is the second most prevalent cancer in males worldwide, yet detecting PCa and its metastases remains a major challenging task in clinical research setups. The present study aimed to characterize the metabolic changes underlying the PCa progression and investigate the efficacy of related metabolic panels for an accurate PCa assessment.MethodsIn the present study, 75 PCa subjects, 62 PCa patients with bone metastasis (PCaB), and 50 benign prostatic hyperplasia (BPH) patients were enrolled, and we performed a cross-sectional metabolomics analysis of serum samples collected from these subjects using a1H nuclear magnetic resonance (NMR)-based metabolomics approach.ResultsMultivariate analysis revealed that BPH, PCa, and PCaB groups showed distinct metabolic divisions, while univariate statistics integrated with variable importance in the projection (VIP) scores identified a differential metabolite series, which included energy, amino acid, and ketone body metabolism. Herein, we identified a series of characteristic serum metabolic changes, including decreased trends of 3-HB and acetone as well as elevated trends of alanine in PCa patients compared with BPH subjects, while increased levels of 3-HB and acetone as well as decreased levels of alanine in PCaB patients compared with PCa. Additionally, our results also revealed the metabolic panels of discriminant metabolites coupled with the clinical parameters (age and body mass index) for discrimination between PCa and BPH, PCaB and BPH, PCaB and PCa achieved the AUC values of 0.828, 0.917, and 0.872, respectively.ConclusionsOverall, our study gave successful discrimination of BPH, PCa and PCaB, and we characterized the potential metabolic alterations involved in the PCa progression and its metastases, including 3-HB, acetone and alanine. The defined biomarker panels could be employed to aid in the diagnosis and classification of PCa in clinical practice.
Targeting choroid plexus epithelium as a novel therapeutic strategy for hydrocephalus
Authors: Yang Yijian , He Jian , Wang Yuchang , Wang Chuansen , Tan Changwu , Liao Junbo , Tong Lei , Xiao Gelei 
Published: June 2022

AbstractThe choroid plexus is a tissue located in the lateral ventricles of the brain and is composed mainly of choroid plexus epithelium cells. The main function is currently thought to be the secretion of cerebrospinal fluid and the regulation of its pH, and more functions are gradually being demonstrated. Assistance in the removal of metabolic waste and participation in the apoptotic pathway are also the functions of choroid plexus. Besides, it helps to repair the brain by regulating the secretion of neuropeptides and the delivery of drugs. It is involved in the immune response to assist in the clearance of infections in the central nervous system. It is now believed that the choroid plexus is in an inflammatory state after damage to the brain. This state, along with changes in the cilia, is thought to be an abnormal physiological state of the choroid plexus, which in turn leads to abnormal conditions in cerebrospinal fluid and triggers hydrocephalus. This review describes the pathophysiological mechanism of hydrocephalus following choroid plexus epithelium cell abnormalities based on the normal physiological functions of choroid plexus epithelium cells, and analyzes the attempts and future developments of using choroid plexus epithelium cells as a therapeutic target for hydrocephalus.
Wearable airbag technology and machine learned models to mitigate falls after stroke
Authors: Botonis Olivia K. , Harari Yaar , Embry Kyle R. , Mummidisetty Chaithanya K. , Riopelle David , Giffhorn Matt , Albert Mark V. , Heike Vallery , Jayaraman Arun 
Published: June 2022

Abstract
Background
Falls are a common complication experienced after a stroke and can cause serious detriments to physical health and social mobility, necessitating a dire need for intervention. Among recent advancements, wearable airbag technology has been designed to detect and mitigate fall impact. However, these devices have not been designed nor validated for the stroke population and thus, may inadequately detect falls in individuals with stroke-related motor impairments. To address this gap, we investigated whether population-specific training data and modeling parameters are required to pre-detect falls in a chronic stroke population.

Methods
We collected data from a wearable airbag’s inertial measurement units (IMUs) from individuals with (n = 20 stroke) and without (n = 15 control) history of stroke while performing a series of falls (842 falls total) and non-falls (961 non-falls total) in a laboratory setting. A leave-one-subject-out crossvalidation was used to compare the performance of two identical machine learned models (adaptive boosting classifier) trained on cohort-dependent data (control or stroke) to pre-detect falls in the stroke cohort.

Results
The average performance of the model trained on stroke data (recall = 0.905, precision = 0.900) had statistically significantly better recall (P = 0.0035) than the model trained on control data (recall = 0.800, precision = 0.944), while precision was not statistically significantly different. Stratifying models trained on specific fall types revealed differences in pre-detecting anterior–posterior (AP) falls (stroke-trained model’s F1-score was 35% higher, P = 0.019). Using activities of daily living as non-falls training data (compared to near-falls) significantly increased the AUC (Area under the receiver operating characteristic) for classifying AP falls for both models (P < 0.04). Preliminary analysis suggests that users with more severe stroke impairments benefit further from a stroke-trained model. The optimal lead time (time interval pre-impact to detect falls) differed between control- and stroke-trained models.

Conclusions
These results demonstrate the importance of population sensitivity, non-falls data, and optimal lead time for machine learned pre-impact fall detection specific to stroke. Existing fall mitigation technologies should be challenged to include data of neurologically impaired individuals in model development to adequately detect falls in other high fall risk populations.
Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05076565; Unique Identifier: NCT05076565. Retrospectively registered on 13 October 2021
“No Regrets” Purchasing in a pandemic: making the most of advance purchase agreements
Authors: Thornton Ian , Wilson Paul , Gandhi Gian 
Published: June 2022

Abstract“No regrets” buying – using Advance Purchase Agreements (APAs) – has characterized the response to recent pandemics such as Avian flu, Zika Virus, and now COVID-19. APAs are used to reduce demand uncertainty for product developers and manufacturers; to hedge against R&D and manufacturing risks; and to secure availability of products in the face of spiking demand. Evidence on the use of APAs to buy vaccines, medicines, diagnostics, and personal protective equipment during recent pandemics illustrates how these contracts can achieve their intended objectives for buyers. But, transferring risk from suppliers to buyers - as APAs do - can have consequences, including overbuying and overpaying. Furthermore, the widespread use of APAs by high-income countries has contributed to the striking inequities that have characterized the Swine flu and COVID-19 responses, delaying access to vaccines and other supplies for low- and middle-income countries (L&MICs).We identify seven ways to address some of the risks and disadvantages of APAs, including adoption of a global framework governing how countries enter into APAs and share any resulting supplies; voluntary pooling through joint or coordinated APAs; a concessional-capital-backed facility to allow international buyers and L&MICs to place options on products as an alternative to full purchase commitments; greater collection and sharing of market information to help buyers place smarter APAs; support for a resale market; building in mechanisms for donation from the outset; and transitioning away from APAs as markets mature. While a binding global framework could in theory prevent the competitive buying and hoarding that have characterized country/state responses to pandemics, it will be very challenging to put in place. The other solutions, while less sweeping, can nonetheless mitigate both the inequities associated with the current uncoordinated use of APAs and also some of the risks to individual buyers.Analysis of recent experiences can provide useful lessons on APAs for the next pandemic. It will be important to keep in mind, however, that these contractual instruments work by transferring risk to the buyer, and that buyers must therefore accept the consequences. In the spirit of “no regrets” purchasing, having bought what hindsight suggests was too much is generally preferable to having bought not enough.
Mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder: case report and literature review
Authors: Ren Xu , Jiang Hong , Sun Kan , Qin Xufu , Qu Yongping , Xia Tian , Chen Yan 
Published: June 2022

Abstract
Background
Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) of the gallbladder are rare malignancies. Here we presented two cases and reviewed the related literature.

Case presentation
Our two patients were postoperatively diagnosed with gallbladder MiNENs, which pathologically consisted of a large cell neuroendocrine carcinoma and papillary adenocarcinoma. After cholecystectomy, one patient had a survival time of 30 months, while the other remained alive through 12 months of follow-up. In the literature, a total of 72 cases of gallbladder MiNENs were identified, and with our two patients included, we calculated a male-to-female ratio of 0.22 and a mean age of 64.5 years for the 74 reported cases. About one-half of these patients were found to have gallstones and presented with abdominal pain or discomfort in a relatively early stage. The preoperative diagnosis of these 74 cases mainly relied on abdominal ultrasound, contrast-enhanced computed tomography (CT) scanning, and magnetic resonance imaging or positron emission tomography/CT. However, the final diagnosis was established based upon the pathological evidence and expression of synaptophysin (Syn) and/or chromogranin A identified by immunohistochemical staining or neurosecretory granules detected by electron microscopy. Fifty-eight patients (78.4%) underwent various operations including simple cholecystectomy (n = 14), en bloc cholecystectomy (n = 9), standard or non-standard radical cholecystectomy (n = 25), or extended radical cholecystectomy (n = 6). The mean size of the resected gallbladder masses was 50.8 ± 36.1 mm (n = 63) with regional lymph node metastasis in 37 patients (52.1%), liver invasion or staging greater than T3 in 33 patients (45.8%), and hepatic metastasis in 26 patients (35.1%). The postoperative median survival time was 36 ± 11.42 months (95% confidence interval, 13.62 to 58.38 months). The log-rank analysis did not find that postoperative adjuvant chemotherapy contributed to a longer survival time relative to that among the patients who did not receive chemotherapy (numbers of patients, 15 versus 43; survival times, 36 months versus 30 months, p > 0.05).

Conclusions
Our two cases and the cases in the literature suggest that MiNENs of the gallbladder predominantly occur in women; are associated with early lymph node metastasis, local hepatic invasion, and hepatic metastasis; and can be managed by various surgeries as well as chemotherapy combined with somatostatin analogs.
Green pharmacy at the tips of your toes: medicinal plants used by Setos and Russians of Pechorsky District, Pskov Oblast (NW Russia)
Authors: Belichenko Olga , Kolosova Valeria , Kalle Raivo , Sõukand Renata 
Published: June 2022

AbstractBackgroundWhile the hybridization of ecological knowledge has attracted substantial attention from researchers, the coexistence of local and allopathic medicinal traditions in literate societies widely exposed to centralized schooling and medical services has not yet been investigated. To this end, we studied the current and remembered local ethnomedical practices of Setos and neighboring Russians at the border with Estonia.MethodsDuring 2018–2019, we carried out 62 semi-structured interviews in the Pechorsky District of Pskov Oblast, NW Russia. For cross-border comparison, we utilized the data from 71 interviews carried out at the same time among Setos in Estonia. The Jaccard Similarity Index and qualitative comparison were used to analyze the data.ResultsThe study participants mentioned 819 uses of 112 taxa belonging to 54 families. More than two-thirds of the uses (565) were quoted by 36 Russian interviewees, while the remaining third (254) were quoted by 26 Seto interviewees, with the top 3 in both groups beingViburnum opulus,Rubus idaeus, andPlantago major. The Seto intraethnic similarity index was lower (0.43) than the interethnic similarity in Estonia (0.52) and comparable to the interethnic similarity in Russia (0.43). Setos in Russia and local Russians rely more on wild plants (86% and 80% of medicinal plants, respectively), while Setos in Estonia and Estonians show less preference to them (63% and 61%, respectively). Nevertheless, Setos tend to source wild plants available in their gardens (33% of plants for Setos in Estonia and 38% in Russia), while Russians prefer to source them in the wild (38%).ConclusionsThe preference of both groups in Russia for wild plants over cultivated and purchased plants was inspired by the overall plant literacy, access to nature, and one-to-many knowledge transfer favoring wild plants. Setos in Russia reported a narrower and more homogenous set of plants transferred vertically. However, due to atomization and the erosion of horizontal connections, there are singular plant uses among Setos that overlap with the local Russian set of medicinal plants and differ qualitatively from that of Setos in Estonia.
Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury
Authors: Li Haiyan , Yang Dong-Hua , Zhang Yanmei , Zheng Fuchun , Gao Fenfei , Sun Jiajia , Shi Ganggang 
Published: June 2022

Abstract
Background
NLRP3 inflammasome activation and pyroptosis play a significant role in myocardial ischemia reperfusion injury (MI/RI). Geniposide was reported to show potential therapeutic use for MI/RI with its anti-inflammatory and anti-oxidative properties. However, research on the specific mechanism of geniposide has not been reported.

Methods
The MIRI model of animal was created in male C57BL/6J mice and the hypoxia reoxygenation (H/R) model was established for the in vitro experiments. Neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown of TXNIP or NLRP3 were used. Geniposide was administered to mice before vascular ligation. HE staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, echocardiography, oxidative stress and myocardial enzyme detection were used to evaluate the cardioprotective effect of geniposide. Meanwhile, pharmacological approaches of agonist and inhibitor were used to observe potential pathway for geniposide cardioprotective in vitro and in vivo. Moreover, ELISA kits were adopted to detect the levels of inflammatory factors, such as IL-1β and IL-18. The gene and protein expression of NLRP3 and pyroptosis-related factors in heart tissue were performed by RT-PCR, western blotting and immunofluorescence in vivo and in vitro, respectively.

Results
Our results indicate that geniposide can reduce the area of myocardial infarction, improve heart function, and inhibit the inflammatory response in mice after MI/RI. In addition, RT-PCR and western blotting shown geniposide promoting AMPK phosphorylation to activate myocardium energy metabolism and reducing the levels of genes and proteins expression of NLRP3, ASC, N-GSDMD and cleaved caspase-1, IL-1β, IL-18. Meanwhile, geniposide improved NRVMs energy metabolism, which decreased ROS levels and the protein expression of TXNIP and thus suppressed the expression of NLRP3. AMPK antagonist or agonist and siRNA downregulation of TXNIP or NLRP3 were also verify the effect of geniposide against H/R injury. Further research found that geniposide promoted the translocation of TXNIP and reduce the binding of TXNIP and NLRP3.

Conclusions
In our study, geniposide can significantly inhibit NLRP3 inflammasome activation via the AMPK signaling pathway and inhibit pyroptosis of cardiomyocytes in myocardial tissues.
Reappraising the clinical usability of consolidation-to-tumor ratio on CT in clinical stage IA lung cancer
Authors: Yoon Dong Woog , Kim Chu Hyun , Hwang Soohyun , Choi Yoon-La , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Kim Jhingook , Shim Young Mog , Shin Sumin , Lee Ho Yun 
Published: June 2022

Abstract
Objectives
Ground-glass opacity (GGO) on computed tomography is associated with prognosis in early-stage non-small cell lung cancer (NSCLC) patients. However, the stratification of the prognostic value of GGO is controversial. We aimed to evaluate clinicopathologic characteristics of early-stage NSCLC based on the consolidation-to-tumor ratio (CTR), conduct multi-pronged analysis, and stratify prognosis accordingly.

Methods
We retrospectively investigated 944 patients with clinical stage IA NSCLC, who underwent curative-intent lung resection between August 2018 and January 2020. The CTR was measured and used to categorize patients into six groups (1, 0%; 2, 0–25%; 3, 25–50%; 4, 50–75%; 5, 75–100%; and 6, 100%).

Results
Pathologic nodal upstaging was found in 1.8% (group 4), 9.0% (group 5), and 17.4% (group 6), respectively. The proportion of patients with a high grade of tumor-infiltrating lymphocytes tended to decrease as the CTR increased. In a subtype analysis of patients with adenocarcinoma, all of the patients with predominant micro-papillary patterns were in the CTR > 50% groups, and most of the patients with predominant solid patterns were in group 6 (47/50, 94%). The multivariate analysis demonstrated that CTR 75–100% (hazard ratio [HR], 3.85; 95% confidence interval [CI], 1.58–9.36) and CTR 100% (HR, 5.58; 95% CI, 2.45–12.72) were independent prognostic factors for DFS, regardless of tumor size.

Conclusion
We demonstrated that the CTR could provide various noninvasive clinicopathological information. A CTR of more than 75% is the factor associated with a poor prognosis and should be considered when making therapeutic plans for patients with early-stage NSCLC.