Thermal stratification controls taste and odour compounds by regulating the phytoplankton community in a large subtropical water source reservoir (Xin'anjiang Reservoir).

2-Methylisoborneol (2-MIB) and geosmin are compounds released by algae that significantly degrade reservoir water quality, posing a threat to both the safety of drinking water and the quality of aquatic products sourced from these environments. However, few studies have explored how enhanced thermal stratification affects the occurrence and regulation of odorants in large drinking water reservoirs. Through systematic monitoring and investigation of Xin'anjiang Reservoir, we found that enhanced thermal stratification promotes filamentous cyanobacteria, particularly Leptolyngbya sp., as the primary contributor to 2-MIB production within the 1-10 m layer of the water column. The highest 2-MIB concentration, 92.5 ng/L, was recorded in the riverine region, which was 2.54 and 14.52 times higher than that in the transitional and central parts of the reservoir, respectively. Temperature indirectly impacted algal growth and odorant production by modulating TN/TP ratios. Geosmin concentration responded rapidly to relatively low TN/TP ratios (< 25). Our findings suggest that phosphorus control in estuaries should be enhanced during thermal stratification period. In summary, our study provides valuable insights to inform pragmatic water intake strategies and the distribution and release of odorants caused by thermal stratification. This is particularly relevant in the context of future global warming and extremely high temperatures during the warm season.

Oral compound probiotic supplements can improve the quality of life for patients with lung cancer during chemotherapy: A randomized placebo-controlled study.

BACKGROUND: Chemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy. METHODS: This randomized, double-blind, placebo-controlled trial enrolled chemotherapy-naive patients with lung cancer who were scheduled to receive platinum-based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP-1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy. RESULTS: A total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP-1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP-1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001). CONCLUSIONS: Compound probiotic supplements can improve the quality of life and relieve chemotherapy-related gastrointestinal side effects for lung cancer patients receiving platinum-based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269).

Status and influential factors of spiritual well-being in cancer patients with drug clinical trials: a cross-sectional study.

PURPOSE: The purpose of this study was to investigate the spiritual well-being status of cancer patients in drug clinical trials and its influencing factors, and to provide theoretical support for the spiritual health intervention of clinical trial cancer patients. METHODS: This cross-section study was conducted among 244 cancer patients in clinical trials. The Memorial Symptom Assessment Scale Short Form (MSAS-SF), Connor-Davidson Resilience Scale 10 (CD-RISC 10), and Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-SP-12) were used to measure symptom burden, psychological resilience, and spiritual well-being. The Multiple Linear Regression Model was used to determine the influencing factors of patients' spiritual health. RESULTS: The overall spiritual health level of cancer patients with clinical trials was high (36.87 ± 11.0), and the spiritual health level was positively correlated with psychological resilience (r = 0.872, P < 0.001). Religious belief, nationality, treatment regimen, and resilience were independent risk factors for the spiritual health of cancer patients in clinical trials. Patients with religious beliefs (ß = 0.097, P = 0.012), ethnic minorities (ß = 0.087, P = 0.023), and high resilience scores (ß = 0.874, P < 0.001) had higher levels of spiritual health. Patients who received single antineoplastic therapy (ß = - 0.079, P = 0.028) had lower levels of spiritual health. CONCLUSION: Our study found that the spiritual health of cancer patients in clinical trials was at a high level, superior to cancer patients receiving conventional anti-tumor therapy. Religious belief, nationality, treatment regimen, and psychological resilience were the influential factors of spiritual health.

Challenges with using popular entertainment to address mental health: a content analysis of Netflix series 13 Reasons Why controversy in mainstream news coverage.

Background: Mental health conditions and psychiatric disorders are among the leading causes of illness, disability, and death among young people around the globe. In the United States, teen suicide has increased by about 30% in the last decade. Raising awareness of warning signs and promoting access to mental health resources can help reduce suicide rates for at-risk youth. However, death by suicide remains a taboo topic for public discourse and societal intervention. An unconventional approach to address taboo topics in society is the use of popular media. Method: We conducted a quantitative content analysis of mainstream news reporting on the controversial Netflix series 13 Reasons Why Season 1. Using a combination of top-down and bottom-up search strategies, our final sample consisted of 97 articles published between March 31 and May 31, 2017, from 16 media outlets in 3,150 sentences. We systematically examined the news framing in these articles in terms of content and valence, the salience of health/social issue related frames, and their compliance with the WHO guidelines. Results: Nearly a third of the content directly addressed issues of our interest: 61.6% was about suicide and 38.4% was about depression, bullying, sexual assault, and other related health/social issues; it was more negative (42.8%) than positive (17.4%). The criticism focused on the risk of suicide contagion, glamorizing teen suicide, and the portrayal of parents and educators as indifferent and incompetent. The praise was about the show raising awareness of real and difficult issues young people struggle with in their everyday life and serving as a conversation starter to spur meaningful discussions. Our evaluation of WHO guideline compliance for reporting on suicide yielded mixed results. Although we found recommended practices across all major categories, they were minimal and could be improved. Conclusion: Despite their well intentions and best efforts, the 13 Reasons Why production team missed several critical opportunities to be better prepared and more effective in creating social impact entertainment and fostering difficult dialogs. There is an urgent need to train news reporters about established health communication guidelines and promote best practices in media reporting on sensitive topics such as suicide.

Research progress of dihydromyricetin in the treatment of diabetes mellitus.

Diabetic Mellitus (DM), a chronic metabolic disorder disease characterized by hyperglycemia, is mainly caused by the absolute or relative deficiency of insulin secretion or decreased insulin sensitivity in target tissue cells. Dihydromyricetin (DMY) is a flavonoid compound of dihydroflavonol that widely exists in Ampelopsis grossedentata. This review aims to summarize the research progress of DMY in the treatment of DM. A detailed summary of related signaling induced by DMY are discussed. Increasing evidence implicates that DMY display hypoglycemic effects in DM via improving glucose and lipid metabolism, attenuating inflammatory responses, and reducing oxidative stress, with the signal transduction pathways underlying the regulation of AMPK or mTOR/autophagy, and relevant downstream cascades, including PGC-1α/SIRT3, MEK/ERK, and PI3K/Akt signal pathways. Hence, the mechanisms underlying the therapeutic implications of DMY in DM are still obscure. In this review, following with a brief introduction of the absorption, metabolism, distribution, and excretion characteristics of DMY, we summarized the current pharmacological developments of DMY as well as possible molecular mechanisms in the treatment of DM, aiming to push the understanding about the protective role of DMY as well as its preclinical assessment of novel application.

AMPK activation coupling SENP1-Sirt3 axis protects against acute kidney injury.

Acute kidney injury (AKI) is a critical clinical condition that causes kidney fibrosis, and it currently lacks specific treatment options. In this research, we investigate the role of the SENP1-Sirt3 signaling pathway and its correlation with mitochondrial dysfunction in proximal tubular epithelial cells (PTECs) using folic acid (FA) and ischemia-reperfusion-induced (IRI) AKI models. Our findings reveal that Sirt3 SUMOylation site mutation (Sirt3 KR) or pharmacological stimulation (metformin) protected mice against AKI and subsequent kidney inflammation and fibrosis by decreasing the acetylation level of mitochondrial SOD2, reducing mitochondrial reactive oxygen species (mtROS), and subsequently restoring mitochondrial ATP level, reversing mitochondrial morphology and alleviating cell apoptosis. In addition, AKI in mice was similarly alleviated by reducing mtROS levels using N-acetyl-L-cysteine (NAC) or MitoQ. Metabolomics analysis further demonstrated an increase in antioxidants and metabolic shifts in Sirt3 KR mice during AKI, compared with Sirt3 wild-type (WT) mice. Activation of the AMPK pathway using metformin promoted the SENP1-Sirt3 axis and protected PTECs from apoptosis. Hence, the augmented deSUMOylation of Sirt3 in mitochondria, activated through the metabolism-related AMPK pathway, protects against AKI and subsequently mitigated renal inflammation and fibrosis through Sirt3-SOD2-mtROS, which represents a potential therapeutic target for AKI.

A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling.

N6-methyladenosine (m6A) of mRNAs modulated by the METTL3-METTL14-WTAP-RBM15 methyltransferase complex and m6A demethylases such as FTO play important roles in regulating mRNA stability, splicing, and translation. Here, we demonstrate that FTO-IT1 long noncoding RNA (lncRNA) was upregulated and positively correlated with poor survival of patients with wild-type p53-expressing prostate cancer (PCa). m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., FAS, TP53INP1, and SESN2) and induced PCa cell cycle arrest and apoptosis. We further showed that FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs. Therapeutic depletion of FTO-IT1 restored mRNA m6A level and expression of p53 target genes and inhibited PCa growth in mice. Our study identifies FTO-IT1 lncRNA as a bona fide suppressor of the m6A methyltransferase complex and p53 tumor suppression signaling and nominates FTO-IT1 as a potential therapeutic target of cancer.

RSPO2 and RANKL signal through LGR4 to regulate osteoclastic premetastatic niche formation and bone metastasis.

Therapeutics targeting osteoclasts are commonly used treatments for bone metastasis; however, whether and how osteoclasts regulate premetastatic niche and bone tropism are largely unknown. In this study, we report that osteoclast precursors (OPs) can function as a premetastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interaction with their receptor LGR4, promoted osteoclastic premetastatic niche formation and enhanced BCa bone metastasis. This was achieved by RSPO2/RANKL-LGR4 signal modulating the WNT inhibitor DKK1 through Gαq and ß-catenin signaling. DKK1 directly facilitated OP recruitment through suppression of its receptor LDL receptor-related protein 5 (LRP5) but not LRP6, upregulating Rnasek expression via inhibition of canonical WNT signaling. In clinical samples, RSPO2, LGR4, and DKK1 expression showed a positive correlation with BCa bone metastasis. Furthermore, soluble LGR4 extracellular domain (ECD) protein, acting as a decoy receptor for RSPO2 and RANKL, significantly alleviated bone metastasis and osteolytic lesions in a mouse bone metastasis model. These findings provide unique insights into the functional role of OPs as key components of the premetastatic niche for BCa bone metastasis and identify RSPO2/RANKL-LGR4 signaling as a promising target for inhibiting BCa bone metastasis.

Compassionate goals, prosocial emotions, and prosocial behaviours during the COVID-19 pandemic.

During the COVID-19 pandemic, it is important for people to engage in prosocial behaviours to support one another. The aim of this research is to answer a key question: in a social crisis, what motivates Americans to help others? Guided by research on appraisal theories and ecosystem theory, we examined the role of compassionate goals and prosocial emotions in promoting prosocial behaviours towards either out-group or in-group members. Study 1 (N = 943) was conducted in February 2020, before the widespread transmission of COVID-19 began in the United States. Results show that people with high compassionate goals are more likely to experience sympathy, which in turn makes them more willing to help people suffering from COVID-19 in China. Study 2 (N = 1,009) was conducted with a nationally representative sample after COVID-19 became more prevalent in the United States. Although people with high compassionate goals still experience more sympathy and solidarity, sympathy does not predict donation intention. Instead, solidarity mediates the relationship between compassionate goals and donation intention. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.

Passive social media use and psychological well-being during the COVID-19 pandemic: The role of social comparison and emotion regulation.

Social media browsing is commonly seen as a trigger of unhealthy social comparison (i.e., upward contrast), which negatively affects well-being. One underlying assumption is the predominance of positive self-presentation on social media, which may have shifted during the COVID-19 pandemic when negative disclosures have become more prevalent. In this study, we conceptualize social comparison as a multi-dimensional construct based on different comparing targets and processes, and explore how individual (i.e., cognitive reappraisal) and contextual (i.e., quarantine status) factors may influence the relationships among passive social media use, social comparison and stress during the COVID-19 pandemic. Drawing on a survey with 1131 Wuhan residents in China, we found that passive social media use was positively related to both upward contrast and downward identification, which in turn predicted a higher level of stress. Cognitive reappraisal was negatively associated with unhealthy social comparison (i.e., upward contrast and downward identification) but was positively related to healthy social comparison such as upward identification. Quarantined people tended to report more upward contrast, especially when they engaged in more frequent social media browsing. This study contributes to the larger debate about the impact of social media on mental health and offers practical implications.

SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis.

Human hexokinase 2 is an essential regulator of glycolysis that couples metabolic and proliferative activities in cancer cells. The binding of hexokinase 2 to the outer membrane of mitochondria is critical for its oncogenic activity. However, the regulation of hexokinase 2 binding to mitochondria remains unclear. Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K492. SUMO-specific protease SENP1 mediates the de-SUMOylation of hexokinase 2. SUMO-defective hexokinase 2 preferably binds to mitochondria and enhances both glucose consumption and lactate production and decreases mitochondrial respiration in parallel. This metabolic reprogramming supports prostate cancer cell proliferation and protects cells from chemotherapy-induced cell apoptosis. Moreover, we demonstrate an inverse relationship between SENP1-hexokinase 2 axis and chemotherapy response in prostate cancer samples. Our data provide evidence for a previously uncovered posttranslational modification of hexokinase 2 in cancer cells, suggesting a potentially actionable strategy for preventing chemotherapy resistance in prostate cancer.

HOXD13 suppresses prostate cancer metastasis and BMP4-induced epithelial-mesenchymal transition by inhibiting SMAD1.

The HOX genes are a group of highly conserved Homeobox-containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor-suppressive activity of HOXD13 in prostate cancer. HOXD13 depletion contributes to more aggressiveness of prostate cancer cells in vitro and in vivo. These effects were corroborated in a metastatic mice model, where we observed more bone metastatic lesions formed by prostate cancer cells with HOXD13 ablation. Mechanistically, HOXD13 prevents BMP4-induced epithelial-mesenchymal transition (EMT) by inhibiting mothers against decapentaplegic homolog 1 (SMAD1) transcription. Both bioinformation and our tissue microarray cohort data show that HOXD13 expression inversely correlated in advanced prostate cancer patient specimens. Our findings establish HOXD13 as a negative regulator of prostate cancer progression and metastasis by preventing BMP4/SMAD1 signaling, and potentially suggest new strategies for targeting metastatic prostate cancer.

Assessing the thrombosis risk of peripherally inserted central catheters in cancer patients using Caprini risk assessment model: a prospective cohort study.

PURPOSE: There was no optimal risk assessment tool to stratify the risk of peripherally inserted central catheter-related venous thromboembolism (PICC-RVT) in cancer patients. We currently use the Caprini risk assessment model for thrombotic risk assessment, but no evidence exists on the effectiveness of Caprini in such patients. This study was to assess the validity of the Caprini in Chinese cancer patients with PICCs. METHODS: We conducted a prospective study of 468 participants. Following calculating the Caprini score, color Doppler ultrasonography was performed every 7 days for 3 weeks to confirm PICC-RVT. RESULTS: There was a correlation between PICC-RVT and the Caprini score. Compared with scores of 5, the risk was 2.089-fold greater (95% CI 1.165-3.743, P = 0.012) in patients with a score of 6 and 7, and 7.156-fold greater (95% CI 3.157-16.217, P < 0.001) in patients with scores ≥8. The area under the receiver-operating characteristic curve was 0.636 (95% CI 0.590-0.680; P < 0.001). 6 was the best cutoff point for Caprini, with a sensitivity of 0.76 and a specificity of 0.44. CONCLUSIONS: The Caprini can be used for high-risk screening of the PICC-RVT in cancer patients, and classification of the highest risk level using a score of 6 can be more clinically significant compared to 5 as recommended. The results provide evidence for the practitioner's early use of the Caprini to assess the thrombotic risk in patients with PICCs and take timely prevention measures. But pharmacological prevention should be considered seriously for its low specificity.

Fast and Frugal: Information Processing Related to The Coronavirus Pandemic.

This research focuses on three factors that influence how individuals cognitively process information related to the coronavirus outbreak. Guided by dual-process theories of information processing, we establish how the two different information processing modes (system 1: heuristic processing; system 2: systematic processing) are influenced by individuals' responsibility attribution, discrete negative emotions, and risk perception. In an experiment, participants were exposed to a news article that either blames China (n = 445) or does not blame China (n = 498) for the pandemic. Results reveal that exposure to the responsibility attribution frame led individuals to engage in more heuristic processing, but it did not influence systematic processing. Discrete negative emotions and risk perception mediated the relationship between responsibility attribution and information processing. The indirect relationships suggest a more intricate process underlying heuristic processing and systematic processing. In particular, information processing styles seem to be determined by social judgment surrounding the coronavirus pandemic.

Anxiety and depression among Tibetan inpatients with cancer: a multicenter investigation.

BACKGROUND: The Tibetan population is minority in southwest China, and data on the psychological states of Tibetan cancer inpatients are not available. The study participants included Tibetan and Han cancer inpatients, and their depression and anxiety were investigated and analyzed to understand the psychological states of Tibetan cancer patients. The aim of the present study was to understand the incidence of depression and anxiety among Tibetan cancer inpatients, and the factors affecting their depression and anxiety. METHODS: We used questionnaires to investigate the anxiety and depression of Tibetan and Han cancer inpatients. The questionnaires included the Zung Self-Rating Anxiety Scale, Zung Self-Rating Depression Scale, and a general information questionnaire. RESULTS: The results showed that there were 61 cases (53%) of depression and 43 (37.4%) of anxiety among Tibetan cancer inpatients, and 27 cases (23.5%) and 16 (13.9%) among Han cancer patients. The major factors affecting depression among Tibetan cancer patients were permanent address and type and stage of cancer; the major factors affecting anxiety among Tibetan cancer patients were education level and type and stage of cancer. CONCLUSIONS: The incidence of depression and anxiety among Tibetan cancer inpatients was significantly greater than that of Han cancer inpatients. The major factors affecting the incidence of depression and anxiety were permanent address, education level, and type and stage of cancer. We suggest that further research should be directed at mental health problems among Tibetan cancer patients in order to determine the best possible psychological interventions.

Regulation of body length and bone mass by Gpr126/Adgrg6.

Adhesion G protein-coupled receptor G6 (Adgrg6; also named GPR126) single-nucleotide polymorphisms are associated with human height in multiple populations. However, whether and how GPR126 regulates body height is unknown. In this study, we found that mouse body length was specifically decreased in Osx-Cre;Gpr126fl/fl mice. Deletion of Gpr126 in osteoblasts resulted in a remarkable delay in osteoblast differentiation and mineralization during embryonic bone formation. Postnatal bone formation, bone mass, and bone strength were also significantly affected in Gpr126 osteoblast deletion mice because of defects in osteoblast proliferation, differentiation, and ossification. Furthermore, type IV collagen functioned as an activating ligand of Gpr126 to regulate osteoblast differentiation and function by stimulating cAMP signaling. Moreover,the cAMP activator PTH(1-34), could partially restore the inhibition of osteoblast differentiation and the body length phenotype induced by Gpr126 deletion.Together, our results demonstrated that COLIV-Gpr126 regulated body length and bone mass through cAMP-CREB signaling pathway.

Calcium Homeostasis: A Potential Vicious Cycle of Bone Metastasis in Breast Cancers.

Cancers have been considered as one of the most severe health problems in the world. Efforts to elucidate the cancer progression reveal the importance of bone metastasis for tumor malignancy, one of the leading causes for high mortality rate. Multiple cancers develop bone metastasis, from which breast cancers exhibit the highest rate and have been well-recognized. Numerous cells and environmental factors have been believed to synergistically facilitate bone metastasis in breast cancers, from which breast cancer cells, osteoclasts, osteoblasts, and their produced cytokines have been well-recognized to form a vicious cycle that aggravates tumor malignancy. Except the cytokines or chemokines, calcium ions are another element largely released from bones during bone metastasis that leads to hypercalcemia, however, have not been well-characterized yet in modulation of bone metastasis. Calcium ions act as a type of unique second messenger that exhibits omnipotent functions in numerous cells, including tumor cells, osteoclasts, and osteoblasts. Calcium ions cannot be produced in the cells and are dynamically fluxed among extracellular calcium pools, intracellular calcium storages and cytosolic calcium signals, namely calcium homeostasis, raising a possibility that calcium ions released from bone during bone metastasis would further enhance bone metastasis and aggravate tumor progression via the vicious cycle due to abnormal calcium homeostasis in breast cancer cells, osteoclasts and osteoblasts. TRPs, VGCCs, SOCE, and P2Xs are four major calcium channels/routes mediating extracellular calcium entry and affect calcium homeostasis. Here we will summarize the overall functions of these four calcium channels in breast cancer cells, osteoclasts and osteoblasts, providing evidence of calcium homeostasis as a vicious cycle in modulation of bone metastasis in breast cancers.

An Accelerated Physarum Solver for Network Optimization.

As a novel computational paradigm, Physarum solver has received increasing attention from the researchers in tackling a plethora of network optimization problems. However, the convergence of Physarum solver is grounded by solving a system of linear equations iteratively, which often leads to low computational performance. Two factors have been highlighted along the process: 1) high time complexity in solving the system of linear equations and 2) extensive iterations required for convergence. Thus, Physarum solver has been largely restricted by its unsatisfactory computational performance. In this paper, we aim to address these two issues by developing two enhancement strategies: 1) pruning inactive nodes and 2) terminating Physarum solver in advance. First, extensive nodes and edges become and stay inactive after a few iterations in identifying the shortest path. Removing these inactive nodes and edges significantly decreases the graph size, thereby reducing computational complexity. Second, we define a transition phase for edges. All of the paths experiencing such a transition phase are dynamically aggregated to form a set of near-optimal paths among which the optimal path is included. Depth-first search is then leveraged to identify the optimal path from the near-optimal paths set. Earlier termination of Physarum solver saves considerable iterations while guaranteeing the optimality of the found solution. Empirically, 20 randomly generated sparse and complete graphs with network sizes ranging from 50 to 2000 as well as two real-world traffic networks are used to compare the performance of accelerated Physarum solver to the other two state-of-the-art algorithms.

Machine learning approaches for risk assessment of peripherally inserted Central catheter-related vein thrombosis in hospitalized patients with cancer.

OBJECTIVE: The aim of this study was to conduct an effective assessment of peripherally inserted central venous catheter (PICC)-related thrombosis based on machine learning (ML) techniques considering genotype. DESIGN: We conducted a prospective cohort study of 348 cancer patients with PICCs who were admitted to the Department of Oncology of West China Hospital, over a 1-year period, between February 1, 2016, and February 31, 2017. We obtained the clinical attributes, onset, duration, and outcome of thrombosis from electronic health records. We assigned all patients to either the training or testing set, and used four models for comparison with the currently used criteria. RESULTS: ML methods showed good efficiency in PICC-related thrombosis risk assessment (with areas under the curve of 0.7733, 0.7869, 0.7833, and 0.7717 respectively) and outperform the currently used criteria (Seeley), which did not identify any positive case. CONCLUSIONS: Our research confirmed that ML approaches are powerful tools to identify cancer patients with a high risk of PICC-related thrombosis, which outperform the currently used criteria (Seeley). Moreover, our research also offers some indications on the predictors and risk factors of PICC-related thrombosis. From our research, more-precise assessments can be performed in cancer patients with PICCs to help decide the prophylaxis and effectively lower the incidence of PICC-related thrombosis.

LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/ß-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/ß-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.