Unmixing biological fluorescence image data with sparse and low-rank Poisson regression.

MOTIVATION: Multispectral biological fluorescence microscopy has enabled the identification of multiple targets in complex samples. The accuracy in the unmixing result degrades (i) as the number of fluorophores used in any experiment increases and (ii) as the signal-to-noise ratio in the recorded images decreases. Further, the availability of prior knowledge regarding the expected spatial distributions of fluorophores in images of labeled cells provides an opportunity to improve the accuracy of fluorophore identification and abundance. RESULTS: We propose a regularized sparse and low-rank Poisson regression unmixing approach (SL-PRU) to deconvolve spectral images labeled with highly overlapping fluorophores which are recorded in low signal-to-noise regimes. First, SL-PRU implements multipenalty terms when pursuing sparseness and spatial correlation of the resulting abundances in small neighborhoods simultaneously. Second, SL-PRU makes use of Poisson regression for unmixing instead of least squares regression to better estimate photon abundance. Third, we propose a method to tune the SL-PRU parameters involved in the unmixing procedure in the absence of knowledge of the ground truth abundance information in a recorded image. By validating on simulated and real-world images, we show that our proposed method leads to improved accuracy in unmixing fluorophores with highly overlapping spectra. AVAILABILITY AND IMPLEMENTATION: The source code used for this article was written in MATLAB and is available with the test data at https://github.com/WANGRUOGU/SL-PRU.

Unmixing Biological Fluorescence Image Data with Sparse and Low-Rank Poisson Regression.

Multispectral biological fluorescence microscopy has enabled the identification of multiple targets in complex samples. The accuracy in the unmixing result degrades (1) as the number of fluorophores used in any experiment increases and (2) as the signal-to-noise ratio in the recorded images decreases. Further, the availability of prior knowledge regarding the expected spatial distributions of fluorophores in images of labeled cells provides an opportunity to improve the accuracy of fluorophore identification and abundance. We propose a regularized sparse and low-rank Poisson unmixing approach (SL-PRU) to deconvolve spectral images labeled with highly overlapping fluorophores which are recorded in low signal-to-noise regimes. Firstly, SL-PRU implements multi-penalty terms when pursuing sparseness and spatial correlation of the resulting abundances in small neighborhoods simultaneously. Secondly, SL-PRU makes use of Poisson regression for unmixing instead of least squares regression to better estimate photon abundance. Thirdly, we propose a method to tune the SL-PRU parameters involved in the unmixing procedure in the absence of knowledge of the ground truth abundance information in a recorded image. By validating on simulated and real-world images, we show that our proposed method leads to improved accuracy in unmixing fluorophores with highly overlapping spectra.

Applying social cognitive career theory to the study abroad choice process.

Studying abroad during college is an educational choice that has significant implications for students' career, academic, and personal development. This study adapted the social cognitive models of career choice (Lent et al., 1994) and self-management (Lent & Brown, 2013) to examine predictors of study abroad interest and choice intentions. The psychometric properties of new and revised domain-specific measures of self-efficacy, outcome expectations, supports, and barriers were first assessed with an initial sample of 325 college students. The measures yielded an 8-factor structure and adequate reliability and validity estimates. The factor structure was cross-validated in an independent sample of students (N = 277). Support was also found for a higher order model of study abroad self-efficacy, with a single second order factor and three first order factors corresponding to cultural adjustment, decision-making, and administrative task self-efficacy. A structural path model offered good fit to the data and support for most of the paths predicting study abroad interests and intentions. We discuss directions for future research extending social cognitive career models to engagement in the study abroad experience and related academic/career behaviors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Metachronous small bowel adenocarcinoma after rectal adenocarcinoma: A case report.

RATIONALE: Small bowel adenocarcinoma (SBA), an uncommon gastrointestinal malignant tumor, is difficult to diagnose at an early stage because of its non-specific disease presentation. Metachronous SBA is a special type of SBA that is rarely reported. We herein report a case of metachronous primary SBA following resection of rectal adenocarcinoma. PATIENT CONCERNS: A 65-year-old man presented to our hospital after having experienced recurrent bowel obstruction for 6 months. He had undergone a Dixon operation 30 months previously followed by adjuvant chemotherapy with capecitabine plus oxaliplatin. DIAGNOSIS: Abdominal computed tomography showed thickened bowel walls in the right lower abdomen, and the patient was initially misdiagnosed with intestinal adhesion. After the operation, he was diagnosed with primary SBA (T3N0M0, stage IIA). INTERVENTIONS: Treatment with a transnasal ileus tube was ineffective. Therefore, we performed small intestinal segmental resection and side-to-side anastomosis through open surgery. OUTCOMES: The patient completed all postoperative adjuvant chemotherapy, and posttreatment surveillance revealed no further abnormalities. LESSONS: This case suggests that patients with colorectal adenocarcinoma may have an increased risk of metachronous SBA. Corresponding symptoms in high-risk patients should raise clinicians' suspicion for SBA, and further detailed examinations are imperative. Early screening for SBA may help to improve the patients' prognosis.

Facilitating client collaboration and insight through interpretations and probes for insight in psychodynamic psychotherapy: A case study of one client with three successive therapists.

We investigated therapist interpretations (Ints) and probes for insight (PIs) in relation to changes in client collaboration and insight for 1 male client paired with 3 successive doctoral student therapists in psychodynamic psychotherapy for 192 sessions over 5 years. Judges coded client collaboration and insight in the antecedent and subsequent 3 min for all Ints and PIs in each of 6 middle sessions for each treatment. Qualitative analyses showed that PIs were more helpful than Ints for this defended client. More gains in collaboration were found when antecedent client collaboration was high, antecedent client insight was low, and therapists gave PIs instead of Ints, but no differences were found among therapists. More gains in insight were found when antecedent insight in a given session was higher than in other sessions with the same therapist, with Therapist 3 facilitating more insight than Therapist 1; no differences were found between Ints and PIs. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma.

As documented, the expression, biological roles, and prognostic significance of FKBP10 in stomach adenocarcinoma (STAD) have not been investigated till now. This drives us to detect the biological roles and clinical significance of FKBP10 in STAD. The expression level of FKBP10 was measured based on the data obtained from the TCGA, ONCOMINE, and GEPIA databases, and STAD cell lines. Through in vitro experiments, cell behaviors were investigated to evaluate the effects of FKBP10 on STAD. Moreover, the PI3K-AKT signaling pathway was measured. Relying on the data of TCGA, ONCOMINE, and GEPIA databases, and cancer cell lines, FKBP10 was up-regulated in STAD when compared with normals. The patients with low expression of FKBP10 had higher survival rate than those with high FKBP10 expression. After knockdown of FKBP10 in AGS cells, cell vitality, colony formation ability, and the migratory and invasive potential were inhibited. Western blotting analysis exhibited that knockdown of FKBP10 significantly reduced the expression level of p-AKT, and p-PI3K, but it did not influence the total expression level of AKT, and PI3K. FKBP10 might serve as a crucial player in gastric cancer, and targeting FKBP10 might provide clinical utility in gastric cancer in future.

Viewing the Career Indecision Profile within a theoretical context: Application of the social cognitive career self-management model.

The Career Indecision Profile (CIP; Brown et al., 2012) is an empirically derived measure tapping common sources of career indecision: interpersonal conflict, neuroticism/negative affect, lack of readiness, and choice/commitment anxiety. We adapted the social cognitive model of career self-management (Lent & Brown, 2013) to provide a theoretical structure for these sources of indecision, focusing on how they interrelate and jointly predict career decision progress. Supplementing the CIP's focus on negative decisional influences, the social cognitive model included positive sources of career decidedness, in particular, self-efficacy, mastery experiences, and positive emotions related to decision-making. Three hundred sixty-five college students completed the short form of the CIP (Xu & Tracey, 2017), along with measures of career decision self-efficacy, prior experiences with career decision-making, social barriers, trait conscientiousness and neuroticism, and career decidedness. Factor analytic findings indicated that the CIP's interpersonal conflict, negative affect, and lack of readiness items loaded together with conceptually similar social cognitive, barrier, and personality scales, with lack of readiness items divided between self-efficacy and conscientiousness factors. A path analysis, couching the CIP factors in terms of the career self-management model, provided good fit to the data and accounted for substantial portions of the variance in decisional discomfort (choice/commitment anxiety) and levels of career decidedness. We consider implications of the findings for the study of career decision-making and for practical ways to promote it. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PABPC1L depletion inhibits proliferation and migration via blockage of AKT pathway in human colorectal cancer cells.

Numerous studies have demonstrated that PABPC1 participates in the process of carcinogenesis and its function is inconsistent in different types of cancers. PABPC1-like (PABPC1L) is an important paralog of PABPC1 and few studies are available on the roles of PABPC1L in colorectal cancer (CRC) development. Hence, we explored the biological function and prognostic impact of PABPC1L in CRC. The mRNA expression of PABPC1L in CRC was determined based on the data obtained from The Cancer Genome Atlas (TCGA) database. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to determine the PABPC1L mRNA expression level in CRC HT-29 and LS-174T cell lines. Kaplan-Meier method and Cox proportional-hazards model were utilized to conduct the survival and prognosis analyses. HT-29 cells with silenced PABPC1L were constructed to explore the effect of PABPC1L on cell proliferation, invasion and migration capacities using cell counting kit-8 (CCK-8), clone formation, wound-healing and Transwell assays, respectively. To uncover the potential mechanisms of how PABPC1L influences CRC proliferation and migration, we analyzed the expression of AKT, p-AKT, PI3K, and p-PI3K in HT-29 cells using western blotting. Our results revealed that PABPC1L was overexpressed in CRC tissues compared with normal tissues based on the data obtained from TCGA database. Similarly, the mRNA expression of PABPC1L was higher in HT-29 and LS-174T cells than that in CCD-18Co cells. The expression of PABPC1L in CRC was found to be significantly related to age, pathologic stage, pathologic-node, pathologic-metastasis, and death. In univariate and multivariate analyses, pathologic-tumor and pathologic-metastasis were identified as independent prognostic factors for CRC. After PABPC1L depletion, cell proliferation rate, colony numbers, and the invasive and migratory capacity of HT-29 cells were all reduced. Western blot analysis showed that reduction of PABPC1L significantly inhibited p-AKT, and p-PI3K expression level in HT-29 cells. Collectively, our results suggested that PABPC1L is a potential novel candidate oncogene in CRC, and targeting PABPC1L may provide clinical utility in CRC.

A novel spherical magnetic compression device for colorectal anastomosis in a Swine model.

BACKGROUND: We designed a novel, spherical magnetic compression colorectal anastomosis device and established a swine model to assess the feasibility and safety, as well as advantages, of the device. METHODS AND MATERIALS: Fifteen animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with 3 in each group. In each group, a magnetic compression device was used in 2 animals (experimental animals), and a stapled device was used in 1 animal (control animal). Feeding status, bowel movements, the discharge time of the magnetic anastomosis device, burst pressure, and magnetic field strength were recorded. Gross anatomical and histological examinations were performed. RESULTS: The average device discharge time was 7.5 days. The burst pressure increased over time for both the experimental and control animals. Both the gross anatomical and histological examinations suggested that the inflammatory reaction was milder. Healing occurred more quickly, and the incidence of complications was lower for the experimental animals than for the control animals. CONCLUSIONS: The potential benefits of the spherical magnetic compression colorectal anastomosis device, relative to the stapled device, were in terms of effectiveness and complication incidence, which encourages us to further study its application in gastrointestinal anastomosis.

Cell surface nucleolin interacts with CXCR4 receptor via the 212 c-terminal portion.

Previously, we reported that CXCR4 receptor interacted with cell surface nucleolin, and the synergy of CXCR4 and nucleolin plays an essential role in malignant transformation. Here, we continued to conduct a structure-function analysis of nucleolin to identify which portion can efficaciously bind to CXCR4. In the present study, the expression of CXCR4 and nucleolin in 100 cases of papillary thyroid cancer (PTC) samples was investigated through immunohistochemistry (IHC). Subsequently, using nucleolin mutants and pull-down assay, we investigated precise interactions between CXCR4 and nucleolin in HEK-293 cells. A previous study demonstrated CXCR4 and nucleolin co-expressed in cell lines, and the present study further identified that CXCR4 and nucleolin co-expressed in PTC tissues, instead of normal tissues. The nucleolin mutant analysis revealed that nucleolin can efficaciously bind CXCR4 to activate CXCR4 signaling by 212 C-terminal domain. Conversely, N-terminal, RBD and GAR mutants of nucleolin showed no sign of activation of CXCR4 signaling, and differences were statistically insignificant (p > 0.05). In conclusion, these results suggested nucleolin is essential to activate CXCR4 signaling via 212 C-terminal domain, which is required for cell growth, migration, and invasiveness. Furthermore, nucleolin may interact with more G protein-coupled receptors, at least chemokine receptor. Our study will lay a new foundation for cancer therapy by antagonizing nucleolin and CXCR4.

Role of wild type p53 and double suicide genes in interventional therapy of liver cancer in rabbits.

PURPOSE: To investigate the feasibility of interventional lipiodol embolism and multigene therapy in combination with focal chemotherapy in the treatment of VX2 liver cancer in rabbits. METHODS: Forty five rabbits with cancer larger than 2cm in diameter were randomly divided into five groups (n=9 per group). In Group 1, animals were treated with 0.9% sodium chloride. In Group 2, animals received lipiodol embolism. In Group 3, animals received lipiodol embolism and p53 gene therapy. In Group 4, animals received lipiodol embolism and TK/CD gene therapy. In Group 5, animals received lipiodol embolism and p53 and TK/CD gene therapy. Ultrasonography and CT were performed before and at ten days after interventional therapy. RESULTS: The VX2 model of liver cancer was successfully established in rabbits and interventional therapy smoothly performed. At ten days after interventional therapy, significant difference in the tumor volume was noted among five groups (p<0.05) and different treatments could inhibit the cancer growth. The inhibition of cancer growth was the most evident in the Group 5. Factorial analysis revealed gene therapy with p53 or TK/CD and lipiodol embolism independently exert significantly inhibitory effect on cancer growth. In addition, the suppression on tumor growth rate was the most obvious in the Group 5. CONCLUSIONS: Combination of gene therapy with lipiodol embolism can effectively inhibit the cancer growth and prolong the survival time. These findings demonstrate the effectiveness of multigene therapy in combination with lipiodol embolism in the treatment of liver cancer.

Role of wild type p53 and double suicide genes in interventional therapy of liver cancer in rabbits / Papel do p53 selvagem e do duplo genes suicidas na terapia intervencionista do câncer de fígado em coelhos

PURPOSE: To investigate the feasibility of interventional lipiodol embolism and multigene therapy in combination with focal chemotherapy in the treatment of VX2 liver cancer in rabbits. METHODS: Forty five rabbits with cancer larger than 2cm in diameter were randomly divided into five groups (n=9 per group). In Group 1, animals were treated with 0.9% sodium chloride. In Group 2, animals received lipiodol embolism. In Group 3, animals received lipiodol embolism and p53 gene therapy. In Group 4, animals received lipiodol embolism and TK/CD gene therapy. In Group 5, animals received lipiodol embolism and p53 and TK/CD gene therapy. Ultrasonography and CT were performed before and at ten days after interventional therapy. RESULTS: The VX2 model of liver cancer was successfully established in rabbits and interventional therapy smoothly performed. At ten days after interventional therapy, significant difference in the tumor volume was noted among five groups (p<0.05) and different treatments could inhibit the cancer growth. The inhibition of cancer growth was the most evident in the Group 5. Factorial analysis revealed gene therapy with p53 or TK/CD and lipiodol embolism independently exert significantly inhibitory effect on cancer growth. In addition, the suppression on tumor growth rate was the most obvious in the Group 5. CONCLUSIONS: Combination of gene therapy with lipiodol embolism can effectively inhibit the cancer growth and prolong the survival time. These findings demonstrate the effectiveness of multigene therapy in combination with lipiodol embolism in the treatment of liver cancer.

OBJETIVO: Investigar a possibilidade de terapia multigênica e intervenção por embolização com lipiodol em combinação com quimioterapia focal no tratamento de câncer de fígado VX2 em coelhos. MÉTODOS: Quarenta e cinco coelhos com câncer maior do que 2cm de diâmetro foram distribuídos, aleatoriamente, em cinco grupos (n=9 por grupo). Grupo 1: animais foram tratados com cloreto de sódio 0,9% e no grupo 2 os animais receberam embolização com lipidol. Grupo 3: animais receberam embolização com lipiodol e terapia do gene p53 e grupo 4 animais receberam embolização com lipiodol e terapia do gene TK/CD. Grupo 5: animais receberam embolização com lipiodol e terapia do gene p53 e do gene TK/CD. Ultrassonografia e tomografia computadorizada foram realizadas antes e dez dias após a intervenção terapêutica. RESULTADOS: O modelo VX2 de câncer de fígado foi estabelecido com sucesso em coelhos e a terapia intervencionista foi bem executada. Dez dias após a intervenção terapêutica, uma diferença significativa no volume do tumor foi observada entre os cinco grupos (p<0,05) e diferentes tratamentos poderiam inibir o crescimento do câncer. A inibição do crescimento do cancer foi mais evidente no grupo 5. Análise fatorial revelou que a terapia com gene p53 ou TK/CD e embolia por lipiodol independentemente exerce um efeito inibidor significativo sobre o crescimento do câncer. Além disso, a supressão da taxa de crescimento do tumor foi mais evidente no Grupo 5. CONCLUSÕES: A combinação de terapia gênica com embolização com lipiodol pode inibir efetivamente o crescimento do câncer e prolongar o tempo de sobrevida. Estes resultados demonstram a eficácia da terapia multigênica em combinação com embolização com lipidol no tratamento de câncer hepático.