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Abstract After endoscopic resection of T1 colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM), additional surgery is required. However, the actual frequency of LNM based on conventional risk factors is less than 16%. There is a need for biomarkers to identify T1 CRC carrying a high risk of metastasis to avoid unnecessary radical surgery. Based on the comparison of serum miRNA between stage I/II and stage III from a large-scale in silico dataset, we conducted a validation analysis of the selected miRNAs using plasma samples from LNM-positive and LNM-negative T1 CRC patients who underwent endoscopic treatment followed by radical surgery at our hospital. In the validation cohort, the three-miRNA classifiers (miR-195-5p, miR-221-3p, and miR-193b-3p) effectively identified LNM-positive T1 CRC patients who received upfront surgery with an area under the curve (AUC) value of 0.74. Moreover, in T1 CRC patients after endoscopic resection, miR-195-5p and miR-221-3p were able to predict LNM with an AUC of 0.74. Plasma miRNA signatures may serve as effective predictors for LNM in T1 CRC both before upfront surgery and after endoscopic resection.

Abstract Background The detection of tumor localization is difficult in robotic surgery because surgeons have no sense of touch and rely on visual information. This study aimed to evaluate the efficacy of preoperative CT-guided dye marking of lung nodules prior to robotic surgery. Methods Patients undergoing CT-guided dye marking prior to robotic surgery at our hospital between September 2019 and April 2024 were retrospectively analyzed. Results Thirty lung nodules from 29 patients were analyzed. The dye marking procedure was successfully completed. Indigo carmine and indocyanine green were used for 20 and 10 pulmonary nodules, respectively. Slight pneumothorax was the most common complication and occurred in 6 patients (20.7%), none of whom required chest tube placement. Dye marking was visualized in 29/30 (96.7%) nodules and one nodule had poor intraoperative visualization due to severe adhesions. One patient underwent open thoracotomy because of difficulty ventilating one lung. Fourteen patients underwent wide wedge resection and 16 patients underwent segmentectomy for the target nodules. All target nodules were successfully resected with negative margins. Conclusions CT-guided dye marking of small pulmonary nodules prior to robotic surgery appears feasible and safe. This procedure can facilitate the performance of robotic sublobar resection.

Abstract Background Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. Methods MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen‐inducible MP‐specific VDR‐deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross‐sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3–4). In addition, a vitamin D‐deficient diet was provided to wild‐type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. Results Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1‐mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR‐deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil‐Red O+ area). In consistency with in‐vitro findings, VdrMPcKO mice and mice fed a vitamin D‐deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. Conclusions Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Abstract Endobronchial tuberculosis (EBTB) presents significant clinical challenges, particularly when complete bronchial obstruction occurs. In this case, a young woman with right main bronchus occlusion due to tuberculosis (TB) was treated using a novel approach. Instead of using a traditional rigid bronchoscope, a flexible approach was adopted. Under precise fluoroscopic guidance, a 21‐gauge transbronchial aspiration needle was used to puncture the obstruction, allowing passage of the guidewire and subsequent balloon dilation. The use of virtual bronchoscopy, developed using computed tomography scans, ensures safe navigation around critical vascular structures. Postoperatively, the patient showed significant symptomatic improvement without complications. This innovative approach not only demonstrates the efficacy and safety of using biopsy needles and virtual bronchoscopy for managing complete bronchial obstructions in EBTB but also opens the door for future innovative solutions in such complex cases.

Abstract Background Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol. Methods Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery. Discussion Since previous findings showed a high percentage of grade 3–4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC. Trial Registration Japan Registry of Clinical Trials jRCTs031210660.

Abstract Background Small cell carcinoma of the uterine cervix (SCCC) is a rare and highly malignant human papillomavirus (HPV)‐associated cancer in which human genes related to the integration site can serve as a target for precision medicine. The aim of our study was to establish a workflow for precision medicine of HPV‐associated cancer using patient‐derived organoid. Methods Organoid was established from the biopsy of a patient diagnosed with HPV18‐positive SCCC. Therapeutic targets were identified by whole exome sequencing (WES) and RNA‐seq analysis. Drug sensitivity testing was performed using organoids and organoid‐derived mouse xenograft model. Results WES revealed that both the original tumor and organoid had 19 somatic variants in common, including the KRAS p.G12D pathogenic variant. Meanwhile, RNA‐seq revealed that HPV18 was integrated into chromosome 8 at 8q24.21 with increased expression of the proto‐oncogene MYC. Drug sensitivity testing revealed that a KRAS pathway inhibitor exerted strong anti‐cancer effects on the SCCC organoid compared to a MYC inhibitor, which were also confirmed in the xenograft model. Conclusion In this study, we confirmed two strategies for identifying therapeutic targets of HPV‐derived SCCC, WES for identifying pathogenic variants and RNA sequencing for identifying HPV integration sites. Organoid culture is an effective tool for unveiling the oncogenic process of rare tumors and can be a breakthrough for the development of precision medicine for patients with HPV‐positive SCCC.

Abstract Background Vitamin D is an essential nutrient in musculoskeletal function; however, its relationship to sarcopenia remains ambiguous, and the mechanisms and targets of vitamin D activity have not been elucidated. This study aimed to clarify the role of vitamin D in mature skeletal muscle and its relationship with sarcopenia. Methods This epidemiological study included 1653 community residents who participated in both the fifth and seventh waves of the National Institute for Longevity Sciences, Longitudinal Study of Aging and had complete background data. Participants were classified into two groups: vitamin D‐deficient (serum 25‐hydroxyvitamin D

Abstract Postoperative recurrence of colorectal cancer (CRC) eventually leads to therapeutic failure; therefore, treatment strategies based on accurate prediction of recurrence are urgently required. To identify biomarkers that can predict treatment outcomes, we compared the mutational profiles of surgically resected specimens from patients with recurrent cancer with those from patients with non‐recurrent cancer. Target sequencing, whole‐exome sequencing (WES), or whole‐genome sequencing (WGS) was performed on 89 and 58 tumors from recurrent and non‐recurrent cases, respectively. WGS revealed the driver mutations that were not detected with target sequencing or WES, including the structural variations affecting ZFP36L2. Loss of function of ZFP36L2 was frequently observed in primary tumors from recurrent cases. Furthermore, the recurrence‐free survival of patients with loss of function of ZFP36L2 was significantly shorter relative to patients with no loss of ZFP36L2 function. In summary, the study demonstrated that detailed genomic analysis could help improve precision medicine for CRC.

Abstract Regulatory T cells (Tregs) suppress the host immune response and maintain immune homeostasis. Tregs also promote cancer progression and are involved in resistance to immune checkpoint inhibitor treatments. Recent studies identified selective CCR8 expression on tumor-infiltrating Tregs; CCR8+ Tregs have been indicated as a possible new target of cancer immunotherapy. Here, we investigated the features of CCR8+ Tregs in lung cancer patients. CCR8+ Tregs were highly activated and infiltration of CCR8+ Tregs in tumors was associated with poor prognosis in lung cancer patients. We also investigated their immune suppressive function, especially the influence on cytotoxic T lymphocyte cell function. The Cancer Genome Atlas analysis revealed that CD8 T cell activities were suppressed in high CCR8-expressing tumors. Additionally, depletion of CCR8+ cells enhanced CD8 T cell function in an ex vivo culture of lung tumor-infiltrating cells. Moreover, CCR8+ Tregs, but not CCR8− Tregs, induced from human PBMCs markedly suppressed CD8 T cell cytotoxicity. Finally, we demonstrated the therapeutic effect of targeting CCR8 in a murine model of lung cancer. These findings reveal the significance of CCR8+ Tregs for immunosuppression in lung cancer, especially via cytotoxic T lymphocyte cell suppression, and suggest the potential value of CCR8-targeted therapy for cancer treatment.

Abstract Background Linalool, an acyclic monoterpene alcohol, is extensively used in the flavor and fragrance industries and exists as two enantiomers, (S)- and (R)-linalool, which have different odors and biological properties. Linalool extraction from natural plant tissues suffers from low product yield. Although linalool can also be chemically synthesized, its enantioselective production is difficult. Microbial production of terpenes has recently emerged as a novel, environmental-friendly alternative. Stereoselective production can also be achieved using this approach via enzymatic reactions. We previously succeeded in producing enantiopure (S)-linalool using a metabolically engineered Pantoea ananatis, a member of the Enterobacteriaceae family of bacteria, via the heterologous mevalonate pathway with the highest linalool titer ever reported from engineered microbes. Results Here, we genetically modified a previously developed P. ananatis strain expressing the (S)-linalool synthase (AaLINS) from Actinidia arguta to further improve (S)-linalool production. AaLINS was mostly expressed as an insoluble form in P. ananatis; its soluble expression level was increased by N-terminal fusion of a halophilic β-lactamase from Chromohalobacter sp. 560 with hexahistidine. Furthermore, in combination with elevation of the precursor supply via the mevalonate pathway, the (S)-linalool titer was increased approximately 1.4-fold (4.7 ± 0.3 g/L) in comparison with the original strain (3.4 ± 0.2 g/L) in test-tube cultivation with an aqueous-organic biphasic fermentation system using isopropyl myristate as the organic solvent for in situ extraction of cytotoxic and semi-volatile (S)-linalool. The most productive strain, IP04S/pBLAAaLINS-ispA*, produced 10.9 g/L of (S)-linalool in “dual-phase” fed-batch fermentation, which was divided into a growth-phase and a subsequent production-phase. Thus far, this is the highest reported titer in the production of not only linalool but also all monoterpenes using microbes. Conclusions This study demonstrates the potential of our metabolically engineered P. ananatis strain as a platform for economically feasible (S)-linalool production and provides insights into the stereoselective production of terpenes with high efficiency. This system is an environmentally friendly and economically valuable (S)-linalool production alternative. Mass production of enantiopure (S)-linalool can also lead to accurate assessment of its biological properties by providing an enantiopure substrate for study.

Severe cases of COVID-19 continue to put pressure on medical operations by prolonging hospitalization, occupying intensive care beds, and forcing medical personnel to undergo harsh labor. The eradication of SARS-CoV-2 through vaccine development has yet to be achieved, mainly due to the appearance of multiple mutant-incorporating strains. The present study explored the utility of human intravenous immunoglobulin (IVIG) preparations in suppressing the aggravation of any COVID-19 infection using a SARS-CoV-2 pseudovirus assay. Our study revealed the existence of IgG antibodies in human IVIG preparations, which recognized the spike protein of SARS-CoV-2. Remarkably, the pretreatment of ACE2/TMPRSS2-expressing host cells (HEK293T cells) with IVIG preparations (10 mg/mL) inhibited approximately 40% entry of SARS-CoV-2 pseudovirus even at extremely low concentrations of IgG (0.16–1.25 mg/mL). In contrast, the antibody-dependent enhancement of viral entry was confirmed when SARS-CoV-2 pseudovirus was treated with some products at an IgG concentration of 10 mg/mL. Our data suggest that IVIG may contribute to therapy for COVID-19, including for cases caused by SARS-CoV-2 variants, since IVIG binds not only to the spike proteins of the virus, but also to human ACE2/TMPRSS2. An even better preventive effect can be expected with blood collected after the start of the COVID-19 pandemic.

Abstract Background Although cases of multiple primary malignant neoplasms are increasing, reports of more than three or four primary metachronous malignant neoplasms are extremely rare. Moreover, very few publications have provided a genetic mutational analysis or have evaluated risk factors associated with such neoplasms. We present an extremely rare case of nine primary malignant lesions in a man who was successfully treated. We also report on microsatellite stability status, analyze risk factors, and discuss the relevant literature. Case presentation Between 67 and 73 years of age, a male patient developed nine primary metachronous malignant lesions: Three were located in the esophagus, two in the stomach, two in the colorectum, one in the prostate gland, and one in the external ear canal. The patient’s clinical history included hypertension, atrial fibrillation, an acoustic schwannoma, and heavy smoking. The lesions were diagnosed during regular screening over a six-year period. He was successfully treated with surgery (both open surgical and endoscopic resection of lesions) and adjuvant chemotherapy. Immunohistochemistry and mutational analysis showed that the lesions were microsatellite stable, and the KRAS, BRAF, p53, and nuclear β-catenin status was not uniform among the lesions. Conclusions Given that the presence of more than three or four neoplasms is extremely rare, the present case of nine primary malignancies with no associated microsatellite instability and no apparent predisposing hereditary conditions, is extraordinary. Our case study shows that it is possible for up to nine sporadic neoplasms to occur, and efficient disease management requires diligent screening and early detection.

Abstract Background The usefulness of residual tumor resection after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment remains unclear. We describe two patients who underwent residual tumor resection after responding to EGFR-TKIs for advanced non-small cell lung cancer (NSCLC) harboring EGFR gene mutations, along with a review of the literature. Case presentation The patient in Case 1 was a 72-year-old female non-smoker who was initially diagnosed with T2aN2M0, stage IIIA adenocarcinoma harboring an EGFR exon 21 L858R mutation. After 8 months of gefitinib therapy, a marked radiologic response was noted, and right upper lobectomy with systemic lymph node dissection was performed. The patient developed brain metastasis despite continuous gefitinib therapy. The patient in Case 2 was a 68-year-old female non-smoker who was initially diagnosed with T3N2M0, stage IIIA adenocarcinoma and an extensive pulmonary thromboembolism. After 3 months of therapy with afatinib and anticoagulants, a marked radiologic response and symptom relief were achieved. We then performed right bilobectomy with systemic lymph node dissection. She developed bone metastasis despite postoperative afatinib therapy. Conclusion The timing and validity of salvage surgery for residual lesions remain unclear when TKIs are offered as first-line therapy to patients with advanced NSCLC. In our two cases, surgery was performed without any complications. Surgical resection of the residual tumor might contribute to good local control. The accumulation of more clinical data is needed to further investigate the role of surgery in patients with advanced NSCLC harboring EGFR gene mutations.

Legume plants can establish symbiosis with soil bacteria called rhizobia to obtain nitrogen as a nutrient directly from atmospheric N2 via symbiotic nitrogen fixation. Legumes and rhizobia form nodules, symbiotic organs in which fixed-nitrogen and photosynthetic products are exchanged between rhizobia and plant cells. The photosynthetic products supplied to rhizobia are thought to be dicarboxylates but little is known about the movement of dicarboxylates in the nodules. In terms of dicarboxylate transporters, an aluminum-activated malate transporter (ALMT) family is a strong candidate responsible for the membrane transport of carboxylates in nodules. Among the seven ALMT genes in the Lotus japonicus genome, only one, LjALMT4, shows a high expression in the nodules. LjALMT4 showed transport activity in a Xenopus oocyte system, with LjALMT4 mediating the efflux of dicarboxylates including malate, succinate, and fumarate, but not tricarboxylates such as citrate. LjALMT4 also mediated the influx of several inorganic anions. Organ-specific gene expression analysis showed LjALMT4 mRNA mainly in the parenchyma cells of nodule vascular bundles. These results suggest that LjALMT4 may not be involved in the direct supply of dicarboxylates to rhizobia in infected cells but is responsible for supplying malate as well as several anions necessary for symbiotic nitrogen fixation, via nodule vasculatures.

The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.

Neurofibromatosis type 1 (NF1), also called von Recklinghausen’s disease, is a multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor located on the long arm of chromosome 17 (17q11.2). Loss of the gene function, due to a point mutation, leads to an increase in cell proliferation and the development of several tumors. We report a 60-year-old female patient manifesting hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT) of the pleura, multiple gastrointestinal stromal tumors (GISTs), and moyamoya disease associated with NF1. The SFT and GISTs were removed by staged operations. Then, hypercalcemia was successfully controlled after resection of the parathyroid adenoma. Based on a literature review, these combinations have never been reported, and the relevant literature is briefly discussed.

Intrapericardial paraganglioma remains a surgical challenge because of its hypervascular nature and firm adhesion to adjacent mediastinal structures. Here, we describe a 63-year-old female with a giant nonfunctioning intrapericardial paraganglioma tightly adhered to the left atrium. Marginal but complete resection of the tumor was achieved via right posterolateral thoracotomy. At the time of dissection between the tumor and the left atrial wall, we encountered massive hemorrhage leading to cardiac arrest. We were able to repair the wall laceration with minimal time under an optimal operative field, which avoids air embolism. She was discharged without complications and is currently in good health with no recurrence or metastasis for 15 months. Based on our experience, cardiopulmonary bypass should be considered, if surgeons are able to secure suitable sites for arterial and venous cannulations while right posterolateral thoracotomy is employed.

Environmental stresses lower the efficiency of photosynthesis and sometimes cause irreversible damage to plant functions. When spinach thylakoids and Photosystem II membranes were illuminated with excessive visible light (100-1,000 µmol photons m(-1) s(-1)) for 10 min at either 20°C or 30°C, the optimum quantum yield of Photosystem II decreased as the light intensity and temperature increased. Reactive oxygen species and endogenous cationic radicals produced through a photochemical reaction at and/or near the reaction center have been implicated in the damage to the D1 protein. Here we present evidence that lipid peroxidation induced by the illumination is involved in the damage to the D1 protein and the subunits of the light-harvesting complex of Photosystem II. This is reasoned from the results that considerable lipid peroxidation occurred in the thylakoids in the light, and that lipoxygenase externally added in the dark induced inhibition of Photosystem II activity in the thylakoids, production of singlet oxygen, which was monitored by electron paramagnetic resonance spin trapping, and damage to the D1 protein, in parallel with lipid peroxidation. Modification of the subunits of the light-harvesting complex of Photosystem II by malondialdehyde as well as oxidation of the subunits was also observed. We suggest that mainly singlet oxygen formed through lipid peroxidation under light stress participates in damaging the Photosystem II subunits.

The swimbladder volume is regulated by O(2) transfer between the luminal space and the blood In the swimbladder, lactic acid generation by anaerobic glycolysis in the gas gland epithelial cells and its recycling through the rete mirabile bundles of countercurrent capillaries are essential for local blood acidification and oxygen liberation from hemoglobin by the "Root effect." While O(2) generation is critical for fish flotation, the molecular mechanism of the secretion and recycling of lactic acid in this critical process is not clear. To clarify molecules that are involved in the blood acidification and visualize the route of lactic acid movement, we analyzed the expression of 17 members of the H(+)/monocarboxylate transporter (MCT) family in the fugu genome and found that only MCT1b and MCT4b are highly expressed in the fugu swimbladder. Electrophysiological analyses demonstrated that MCT1b is a high-affinity lactate transporter whereas MCT4b is a low-affinity/high-conductance lactate transporter. Immunohistochemistry demonstrated that (i) MCT4b expresses in gas gland cells together with the glycolytic enzyme GAPDH at high level and mediate lactic acid secretion by gas gland cells, and (ii) MCT1b expresses in arterial, but not venous, capillary endothelial cells in rete mirabile and mediates recycling of lactic acid in the rete mirabile by solute-specific transcellular transport. These results clarified the mechanism of the blood acidification in the swimbladder by spatially organized two lactic acid transporters MCT4b and MCT1b.

Background Clinical nursing competence includes ethics, cooperation with other professionals, and management, in addition to nursing abilities and responding per situation. Therefore, it may vary depending on one's experience and the work environment. However, there is a lack of studies exploring the competence for different experience levels. Therefore, this study aimed to clarify the association between clinical nursing competence and the work environment by experience groups. Methods Anonymous self-administered questionnaire surveys were conducted on 717 nurses in regional core hospitals from December 2017 to March 2018. Clinical nursing competence was measured using the Clinical Nursing Competence Self-Assessment Scale (CNCSS). Association of CNCSS with experience and work environment was examined. Results Responses from 231 nurses with 1-10 years of experience were analyzed. Compared with those in the 2-year experience group, those in the 3-5- and 6-10-year experience groups assessed their "planned development of nursing care" and "assessment of care" competencies to be higher. Additionally, compared with those in the 2-year experience group, those in the 6-10-year experience group assessed their "clinical judgment" and "care coordination" competencies to be higher. Nurses with 1 year of experience showed significant positive correlations between clinical nursing competence and "good interpersonal relationship," "clarity about the organization's vision," and "ease of taking time off"; and those with 6-10 years of experience showed significant positive correlations between clinical nursing competence and "support from superiors and senior coworkers" and "established and easily accessible support system for taking time off for childcare and caregiving.". Results Responses from 231 nurses with 1-10 years of experience were analyzed. Compared with those in the 2-year experience group, those in the 3-5- and 6-10-year experience groups assessed their "planned development of nursing care" and "assessment of care" competencies to be higher. Additionally, compared with those in the 2-year experience group, those in the 6-10-year experience group assessed their "clinical judgment" and "care coordination" competencies to be higher. Nurses with 1 year of experience showed significant positive correlations between clinical nursing competence and "good interpersonal relationship," "clarity about the organization's vision," and "ease of taking time off"; and those with 6-10 years of experience showed significant positive correlations between clinical nursing competence and "support from superiors and senior coworkers" and "established and easily accessible support system for taking time off for childcare and caregiving.". [ABSTRACT FROM AUTHOR]