Measuring Spiritual Well-being using a numerical rating scale: Additional evidence of the validity of the Well-being Numerical Rating Scales (WB-NRSs).

The Well-being Numerical Rating Scales (WB-NRSs) can be used to assess rapidly and accurately different types of well-being. However, the spiritual well-being scale showed slightly weaker psychometric properties. This study aimed to further investigate its suitability in measuring spiritual well-being. Participants (N = 270, age: M = 32.98; SD = 15.64; 67% females) were administered a questionnaire including spiritual well-being, gratitude, compassionate love, and personality traits measures. A network analysis (based on correlations) was used to display graphically the pattern of relationships among the measured constructs (i.e. the nomological net). Results provided evidence that the scale measures spiritual well-being as defined in the literature, that is, a component distinct from faith and compassionate love, but connected to meaning in life, quality of relationships, personality traits, and gratitude. These findings confirm the WB-NRSs is a psychometrically sound and easy-to-use tool with clear benefits for both research and clinical assessment.

Should I Stay or Should I Go? Seasonal Fluctuations of Wood Mouse Populations in Fields Surrounded by Woodlands.

The wood mouse Apodemus sylvaticus is common in woodlands and open areas of the Western Palearctic. Despite extensive research, little is known about its population ecology in fields in the Mediterranean area, where the climate involves great seasonal changes in environmental features. Here, we investigated wood mice seasonal fluctuations in the number of captures and population structure by sampling long-fallow fields and woodlands, i.e., oak forest and conifer plantation, in a heterogeneous landscape of central Italy. Mice were live-trapped every two months for three years (23.814 trap-days). The number of captures, mice body weight, and proportion of adult, residents and breeding individuals were analyzed. Mice dynamics changed across seasons and habitats. In fields, we recorded more captures, more reproductive individuals, and fewer non-adults and resident individuals in the warmer months compared to the colder months; mice were heavier in warmer months. During the cold season, the captures and adult proportion in fields were lower than in resource-rich woodlands. Breeding and non-resident mice were more abundant in fields than in woodlands in warmer months. Overall, the seasonal demographic variations we recorded provide evidence that fields can represent a suboptimal habitat in Mediterranean heterogeneous landscapes, acting nonetheless as a source of food resources, cover, and mates for mice in spring-summer.

Needs evaluation questionnaire for liver disease: a novel assessment of unmet needs in patients with chronic liver disease.

Patients with chronic liver disease face debilitating complications in their daily living and constantly report several types of unmet needs, but there is a paucity of validated questionnaires to assess these needs. In this study, we present the development of the Needs Evaluation Questionnaire for Liver Diseases (NEQ-LD) for the assessment of unmet needs in patients with chronic liver disease. Two hundred eighty-six outpatients with chronic liver diseases from a single tertiary referral center completed the NEQ-LD and related validity measures. Item response theory analyses were performed and demonstrated the strong psychometric properties of the questionnaire. Differential item functioning analyses showed that the scale functions equally across groups differing for age, sex, and presence of cirrhosis, suggesting the large applicability of the NEQ-LD for the assessment of unmet needs and between-group comparisons. Criterion validity measures provided evidence that unmet needs were positively associated with measures of depression and anxiety and negatively associated with measures of subjective well-being and physical and mental health. Unmet needs were expressed by a high percentage of patients, especially in the areas of information and dialogue with clinicians. One third of the sample reported material needs. Most of the items describing unmet needs were reported more frequently by patients with cirrhosis. Conclusion: We developed a reliable, valid, and largely employable instrument that can promote patient-centered care and facilitate support services in Hepatology.

Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study.

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

Rapid and sound assessment of well-being within a multi-dimensional approach: The Well-being Numerical Rating Scales (WB-NRSs).

The assessment of well-being remains an important topic for many disciplines including medical, psychological, social, educational, and economic fields. The present study assesses the reliability and validity of a five-item instrument for evaluating physical, psychological, spiritual, relational, and general well-being. This measure uniquely utilizes a segmented numeric version of the visual analog scale in which a respondent selects a whole number that best reflects the intensity of the investigated characteristic. In study one, 939 clinical (i.e., diagnosed with cancer and liver disease with cirrhosis) and non-clinical (i.e., undergraduate students and their family and acquaintances) participants between the ages of 18 to 87 years (M = 47.20 years, SD = 19.62, 54% males) were recruited. Results showed items have strong discriminant ability and the spread of threshold parameters attests to the appropriateness of the response categories. Moreover, convergent and discriminant validity were found with other self-report measures (e.g., depression, anxiety, optimism, well-being) and the measure showed responsiveness to two separate interventions for clinical populations. In study two, 287 Canadian (ages ranged from 18 to 30 years; M = 20.78, SD = 3.32; 23% males) and 342 Italian undergraduate psychology students (age ranged from 18 to 29 years, M = 21.21 years, SD = 1.73, 38% males) were recruited to complete self-report questionnaires. IRT-based differential item functioning analyses provided evidence that the item properties were similar for the Italian and English versions of the scale. Additionally, the validity results obtained in study one were replicated and similar relationships between criterion variables were found when comparing the Italian- and the English-speaking samples. Overall, the current study provides evidence that the Italian and English versions of the WB-NRSs offer added value in research focused on well-being and in assessing well-being changes prompted by intervention programs.

Measuring self-control across gender, age, language, and clinical status: A validation study of the Italian version of the Brief Self- Control Scale (BSCS).

The present study aims to develop and validate an Italian version of the Brief Self-Control Scale (BSCS). A large sample of Italian-speaking participants (N = 1139) completed the BSCS and measures of personality and individual dispositions. A clinical sample (N = 217) was administered the Italian version and an English-speaking sample (N = 274) completed the original version to test measurement invariance. Using confirmatory factor analysis, the best fit was observed for a shortened two-factor model (i.e., impulse control and self-discipline). Metric invariance across languages and partial strong invariance across genders, ages, and clinical status were demonstrated. Internal consistency and test-retest reliability for the total scale were adequate, and validity was established based on its correlations with related constructs and confirming that males and young individuals are more likely to have lower self-control. Results support the use of the shortened BSCS version to assess self-control in Italian-speaking individuals.

Sociodemographic, clinical, and psychological characteristics identify groups of Italian cancer patients with high rates of unmet needs.

PURPOSE: Although an optimal goal remains the routine assessment of unmet needs of all patients with cancer, particular attention should be paid to those groups of patients with characteristics known to be more frequently associated with unmet needs in general or with specific areas of need. This report aims to describe the sociodemographic, clinical, and psychological characteristics associated with higher unmet needs in Italian cancer patients. METHODS: A total of 835 cancer patients from different care settings (ward, day hospital, follow-up ambulatory, rehabilitation unit, and palliative care) filled out the Needs Evaluation Questionnaire (NEQ), the Psychological Distress Inventory, and the Sense of Coherence Scale. Association of NEQ scores with the clinical and demographic variables were tested using analysis of variance. RESULTS: Higher NEQ total score was associated with lower educational level, inpatient care setting, radiotherapy treatment, psychological distress, and lower resilience trait sense of coherence. Different predictors were identified for different areas of unmet needs. Care setting, psychological distress, and resilience trait were the strongest indicators of unmet needs in every area: information/communication, assistance/care, material needs, relational needs, and psychoemotional support. CONCLUSIONS: Clinicians should consider that inpatients with a high distress and a low resilience trait sense of coherence represent a group of cancer patients to be investigated with particular attention regarding unmet needs.

Live music intervention for cancer inpatients: The Music Givers format.

ABSTRACTObjective:The present study intended to evaluate the impact of a standardized format-called the "Music Givers," based on a single session of music intervention followed by a buffet-on the psychological burden and well-being of hospitalized cancer patients. METHOD: The Distress Thermometer (DT), the Hospital Anxiety and Depression Scale (HADS), and self-reported visual analogue scales (score range = 1-10) to assess pain, fatigue, and five areas of well-being (i.e., physical, psychological, relational, spiritual, and overall well-being) were administered to 242 cancer patients upon admission to and at discharge from the hospital. Among them, 103 were hospitalized during which time a live concert took place (intervention group), whereas 139 patients were hospitalized when it did not (control group). RESULTS: Compared to the control group, patients in the intervention group demonstrated less distress at discharge according to the DT (adjusted estimate of difference = -0.8, p = 0.001), lower HADS-Anxiety (-1.7, p < 0.001) and HADS-Depression scores (-1.3, p = 0.001), and higher scores on all the well-being scales, with the exception of spiritual well-being. In addition, no between-group differences were found in terms of pain and fatigue scores at discharge. SIGNIFICANCE OF RESULTS: The one-session format of the Music Givers intervention is an effective, standardized, easy-to-replicate, and low-cost intervention that reduces psychological burden and improves the well-being of hospitalized cancer patients. Listening to live music and the opportunity to establish better relationships between patients and staff could explain these results.

Unmet needs of Italian cancer patients in different stages of the disease and care process.

PURPOSE: Assessing patients' unmet supportive care needs is essential in order to prioritize areas of cancer care that require improvement. The aim of the present cross-sectional study was to compare the unmet needs of cancer patients in different stages of the disease and care process (diagnosis, treatments following diagnosis, follow-up and/or rehabilitation, relapse/recurrence, progression of the disease, and palliative care). METHODS: The research focused on patients from 7 oncology units of the same geographic region (Tuscany, a region of central Italy) in the same period of time regardless of primary tumor site. A total of 752 patients filled in the Needs Evaluation Questionnaire and the Psychological Distress Inventory. RESULTS: We observed high rates of cancer patients who expressed unmet needs, especially in the areas of information and relational and material needs. The multiple regression models showed a direct correlation between psychological distress and extent of unmet needs. Individual unmet needs had significantly different entities at diverse phases. CONCLUSIONS: The present study confirmed the dynamic nature of needs of cancer patients, highlighting some critical aspects in different stages of the care process on which to concentrate attention and resources and suggesting the usefulness of periodic and repeated assessments of principal needs.

Assessing unmet needs in patients with cancer: An investigation of differential item functioning of the Needs Evaluation Questionnaire across gender, age and phase of the disease.

OBJECTIVE: The main aim of this study was to provide evidence of the broad employability of the NEQ with patients of different gender and age with cancer in different phases of the disease and care process, using an Item Response Theory (IRT) approach and investigating Differential Item Functioning (DIF). METHODS: The NEQ was completed by 762 patients visiting, consecutively, outpatient clinics or admitted to oncology wards. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. The properties of the questionnaire were analyzed by applying IRT to test how well each item of the scale concurs in measuring unmet needs, how reliable the whole scale is, and whether the scale was metrically invariant across gender, age, and phase of the disease. RESULTS: Results showed that the NEQ performed well in measuring unmet needs and measurement equivalence of the scale across gender, age, and phase of the disease was verified. CONCLUSIONS: The current study supports the utility and broad employability of the NEQ, thus providing empirical evidence that it is psychometrically sound and metrically equivalent across different groups of cancer patients. As such, the scale could be an effective tool when planning psychosocial interventions to improve the care process and patients' quality of life.

Actual and preferred place of death of home-dwelling patients in four European countries: making sense of quality indicators.

BACKGROUND: Dying at home and dying at the preferred place of death are advocated to be desirable outcomes of palliative care. More insight is needed in their usefulness as quality indicators. Our objective is to describe whether "the percentage of patients dying at home" and "the percentage of patients who died in their place of preference" are feasible and informative quality indicators. METHODS AND FINDINGS: A mortality follow-back study was conducted, based on data recorded by representative GP networks regarding home-dwelling patients who died non-suddenly in Belgium (n = 1036), The Netherlands (n = 512), Italy (n = 1639) or Spain (n = 565). "The percentage of patients dying at home" ranged between 35.3% (Belgium) and 50.6% (The Netherlands) in the four countries, while "the percentage of patients dying at their preferred place of death" ranged between 67.8% (Italy) and 86.0% (Spain). Both indicators were strongly associated with palliative care provision by the GP (odds ratios of 1.55-13.23 and 2.30-6.63, respectively). The quality indicator concerning the preferred place of death offers a broader view than the indicator concerning home deaths, as it takes into account all preferences met in all locations. However, GPs did not know the preferences for place of death in 39.6% (The Netherlands) to 70.3% (Italy), whereas the actual place of death was known in almost all cases. CONCLUSION: GPs know their patients' actual place of death, making the percentage of home deaths a feasible indicator for collection by GPs. However, patients' preferred place of death was often unknown to the GP. We therefore recommend using information from relatives as long as information from GPs on the preferred place of death is lacking. Timely communication about the place where patients want to be cared for at the end of life remains a challenge for GPs.

Use and perceived benefits of complementary therapies by cancer patients receiving conventional treatment in Italy.

CONTEXT: In Italy, data regarding the use of complementary therapies (CTs) among patients with cancer are sparse and discordant. OBJECTIVES: The present study aimed to investigate the demographic and psychological characteristics of Italian cancer patients who use CTs and the perceived benefit of users. METHODS: Eight hundred three patients from six Italian oncology departments were interviewed about CT use and completed two questionnaires to explore psychological distress and the resilience trait called sense of coherence (SOC). Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. RESULTS: At the time of measurement, 37.9% of patients were using one or more types of CTs. The most commonly used CTs were diets and dietary supplements (27.5%), herbs (10.8%), homeopathy (6.4%), and mind-body therapies (5.5%). The Italian context is characterized by a high percentage of patients who informed their physicians about CT use (66.3%) and who experienced benefits (89.6%); 75.2% of the patients had used CTs in the past. Multivariate analysis revealed that young, female patients, who previously used complementary and alternative medicine in the past, appear more likely to use at least one type of CT in the present. Predictors of the use of CTs varied according to the type of CT. Among psychological factors, SOC was positively associated with both past and present CT use. CONCLUSION: Overall prevalence of CTs among Italian cancer patients is high and is in accordance with the European average. In addition to clinical and sociodemographic factors, the resilience trait SOC also was associated with CT use.

The accuracy of the Life Orientation Test-Revised (LOT-R) in measuring dispositional optimism: evidence from item response theory analyses.

The accuracy of the Life Orientation Test-Revised (LOT-R) in measuring dispositional optimism was investigated applying item response theory (IRT). The study was conducted on a sample of 484 university students (62% males, M age = 22.79 years, SD = 5.63). After testing the 1-factor structure of the scale, IRT was applied to evaluate the functioning of the LOT-R along the pessimism-optimism continuum. Item parameter estimates and the test information function showed that each item and the global scale satisfactorily measured the latent trait. Referring to the IRT estimated trait levels, the validity of the LOT-R was studied examining the relationships between dispositional optimism and psychological well-being, sense of mastery, and sense of coherence. Overall findings based on IRT analyses provide evidence of the accuracy of the LOT-R and suggest possible modifications of the scale to improve the assessment of dispositional optimism.

Temperament and character traits associated with health-related quality of life in cancer patients.

BACKGROUND: There is an increase in the attention to factors influencing the quality of life of cancer patients. The aim of the present study was to evaluate temperament and character traits related to health-related quality of life (HRQoL) in patients with cancer. METHODS: Two hundred and three inpatients from three Italian oncology departments filled in the Temperament Character Inventory (TCI-140) based on Cloninger's personality model, the SF-36 questionnaire assessing HRQoL, and the Hospital Anxiety and Depression Scale (HADS). Eighty percent of patients were undergoing chemotherapy. RESULTS: Lower levels of harm avoidance and higher levels of self-directedness were significantly correlated with a better HRQoL. Regression analysis controlling for psychopathology (anxiety and depression symptoms) showed that the influence of temperament and character traits on quality of life seemed to add little to the influence of psychopathology. CONCLUSIONS: The present study demonstrates the existence of some relations between HRQoL and temperament and character traits assessed using the TCI-140 questionnaire. However, among the psychological factors, psychopathology seems to retain more influence on HRQoL of cancer patients.

Is the spiritual life of cancer patients a resource to be taken into account by professional caregivers from the time of diagnosis?

BACKGROUND AND AIM: Spiritual life can be defined as the search for personal contact with the transcendent. Careful assessment of spiritual life can help to value its importance to cancer patients from the moment of their diagnosis. METHODS: This is a cross-sectional study. Two hundred fifty-seven patients undergoing cancer treatment filled in the validated Italian version of the Systems of Belief Inventory (SBI-15R). Patients were also asked to attribute themselves to one of the following, mutually exclusive categories: believer and churchgoer, believer but no churchgoer, and non-believer. RESULTS: Five patients did not report their religious stance and were therefore excluded from the analysis. Of the remaining 252 patients, 49% declared to be believers and churchgoers, 43% believers but not churchgoers, and 8% non-believers. Of the 20 cancer patients who declared not to have a religious faith, 7 patients agreed with the statement that they felt certain that God exists in some form, and 4 had experienced peace of mind through prayer and meditation. Almost all of the patients who declared to have a religious faith and to be churchgoers explicitly affirmed to have been helped by prayer and meditation in coping with their illness. Among believer churchgoers, only 30% declared to seek out the religious or spiritual community when they needed help. CONCLUSIONS: A large proportion of cancer patients find themselves involved with the search for a personal contact with the transcendent, also beyond any specific religious affiliation. These spiritual issues may be important even when they are not expressed as participation in religious rituals or adherence to specific religious beliefs. On the other hand, participation in religious rituals often implies the need for a personal spiritual life, both through those rituals and beyond them, as through personal prayer and meditation. These results ask for more attention on the part of professionals towards spiritual resources among cancer patients. It might be appropriate to look systematically for these resources from the moment of the diagnosis, through the sensitive administration of an easy and valid assessment tool like the SBI-15R.

Nuclear localization of TRK-A in liver cells.

The liver represents a site of expression of neurotrophins and their receptors. We have characterized the expression and intracellular localization of the nerve growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both normal and fibrotic liver tissue, Trk-A immunostaining was present in different cell types, including parenchymal cells and cells of the inflammatory infiltrate. In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant nuclear localization, both in the presence and absence of injury. In cultured HSC, Trk-A was found to be functional, because exposure of the cells to recombinant NGF resulted in stimulation of cell migration and activation of intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in cultured HSC, Trk-A staining was found constitutively in the nucleus. In these cells, Trk-A could be stained only by antibodies directed against the intracellular domain but not by those recognizing the extracellular portion of Trk-A suggesting that the intracellular portion of the receptor is the major determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated hepatocytes did not show any nuclear localization of the intracellular portion of Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in conditions of serum deprivation, but could be induced by exposure to NGF or to a mixture of soluble mediators. We conclude that nuclear localization of the intracellular domain of Trk-A is observed constitutively in liver cells such as HSC, while in other cell types it could be induced in response to soluble factors.

Thrombopoietin stimulates migration and activates multiple signaling pathways in hepatoblastoma cells.

Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-kappaB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.

Differential requirement of members of the MAPK family for CCL2 expression by hepatic stellate cells.

Hepatic stellate cells (HSC) coordinate the liver wound-healing response through secretion of several cytokines and chemokines, including CCL2 (formerly known as monocyte chemoattractant protein-1). In this study, we evaluated the role of different proteins of the MAPK family (ERK, p38(MAPK), and JNK) in the regulation of CCL2 expression by HSC, as an index of their proinflammatory activity. Several mediators activated all three MAPK, including TNF, IL-1, and PDGF. To assess the relative role of the different MAPKs, specific pharmacological inhibitors were used; namely, SB203580 (p38(MAPK)), SP600125 (JNK), and PD98059 (MEK/ERK). The efficacy and specificity of the different inhibitors in our cellular system were verified analyzing the enzymatic activity of the different MAPKs using in vitro kinase assays and/or testing the inhibition of phosphorylation of downstream substrates. SB203580 and SP600125 dose-dependently inhibited CCL2 secretion and gene expression induced by IL-1 or TNF. In contrast, inhibition of ERK did not affect the upregulation of CCL2 induced by the two cytokines. Finally, activin A was also found to stimulate CCL2 expression and to activate ERK, JNK, p38, and their downstream targets. Unlike in cells exposed to proinflammatory cytokines, all three MAPKs were required to induce CCL2 secretion in response to activin. We conclude that members of the MAPK family differentially regulate cytokine-induced chemokine expression in human HSC.

The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C.

BACKGROUND AND AIMS: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied. METHODS: Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype. RESULTS: In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8(+) T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor kappaB, resulting in induction of proinflammatory genes. CONCLUSIONS: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.