bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrin(ogen) Mechanistically Contributes to Atopic Dermatitis Pathogenesis and Allergic Sensitization
Authors: Filuta Alyssa , Amezcua Peter K , Ruff Brandy , He Hua , Martin Lisa J , Palumbo Joseph S. , Khurana Hershey Gurjit K , Sherenian Michael G
Published: November 2021

Adults with atopic dermatitis (AD) have an increased risk for thromboembolic events. While coagulation is critical for almost all healing responses, dysregulated clotting and fibrin(ogen) deposition lead to inflammation that exacerbates tissue damage and impairs tissue repair. While plasma fibrin(ogen) has been associated with established asthma, fibrin(ogen)'s mechanistic role in AD pathogenesis and allergic sensitization has not been investigated. Here we show that fibrinogen plays a critical role in a murine model atopic dermatitis pathogenesis by markedly attenuating disease severity, barrier dysfunction, and allergic sensitization.

To determine if fibrinogen impacts AD pathogenesis, we used mice with complete fibrinogen deficiency (Fib -/-), partial deficiency (Fib +/-), and wildtype controls (Fib WT) in our established model of AD. This model uses repeated cutaneous allergen sensitization with heat-killed Aspergillus fumigatus (Asp) extract. Notably, Fib +/- mice produce approximately half as much fibrinogen as Fib WT mice. After each patch and at sacrifice each mouse underwent an objective disease severity assessment as well as transepidermal water loss (TEWL) measurements to assess skin barrier function. Our results show that complete and partial fibrinogen deficiency abrogated AD development. We found that Fib -/-and Fib +/- mice had markedly attenuated TEWL (P-value <0.0001) and disease severity (P-value <0.0001) compared with controls (Figure 1). In addition, we found that the TEWL and disease severity in Fib -/- and Fib +/- were comparable to unchallenged controls. There was also no difference in either outcome between Fib -/- and Fib +/- mice within the experimental group. Lastly, none of the Fib -/- and Fib +/- mice developed spontaneous bleeding.

Next, to elucidate the impact of fibrinogen on allergic sensitization we measured plasma allergen specific immunoglobulin E (sIgE) to Asp in all mice in our AD model at sacrifice. We found that Fib -/- and Fib +/- mice had significantly lower Asp sIgE compared with controls (p-value <0.0001 and 0.0002, respectively; Figure 2). In addition, we found that the amount of sIgE to Asp produced was comparable between Fib -/- and Fib +/- mice as well as with unchallenged controls.

Thus, our findings suggest that fibrin(ogen) plays a critical mechanistic role in driving AD development and allergic sensitization. While fibrinogen's role in established allergic disease has been shown, these novel findings suggest a critical role for fibrinogen in allergic disease pathogenesis which may allow for additional therapeutic targets to treat atopic dermatitis and other allergic diseases.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Persistent Control of SIV Infection in Rhesus Macaques By Expressing a Highly Potent SIV Decoy Receptor after In Vivo HSC Transduction
Authors: Li Chang , Wang Hongjie , Gil Sucheol , Nelson Veronica , Kiem Hans-Peter , Lieber Andre
Published: November 2021

Despite the success achieved by antiretroviral HIV-1 therapies, long-term and repeated drug administration is associated with toxicity, virus evasion and high cost. We aim to develop a gene therapy approach for persistent control against HIV-1 infection by delivering the transgene expressing a decoy receptor (eCD4-Ig) to hematopoietic stem cells (HSCs) by in vivo transduction. In this approach, HSCs are mobilized from the bone marrow into the peripheral blood stream and transduced with intravenously injected virus vectors. We use an integrating, helper-dependent adenovirus (HDAd5/35++) vector system that targets human CD46, a receptor that is abundantly expressed on primitive HSCs. Transgene integration is achieved by a hyperactive Sleeping Beauty transposase and transgene marking in peripheral blood cells can be increased by in vivo selection. The efficacy and safety of our in vivo HSC transduction/selection strategy has been previously demonstrated for the treatment of b-hemoglobinopathies, hemophilia A, and cancer in murine disease models. In non-human primates, we showed efficient transgene (g-globin) expression in peripheral red blood cells using this strategy. eCD4-Ig functions like a neutralizing antibody and shows broad neutralization spectrum against HIV-1, HIV-2 and SIV isolates. We have designed and produced an HDAd5/35++ vector expressing rhesus eCD4-Ig (rh-eCD4-Ig) from a constitutive and highly active EF1a promoter. In CD46-transgenic mice, over 50µg/mL eCD4-Ig in serum was measured after in vivo transduction and selection, with no obvious adverse events observed. Neutralization assay with serum samples showed that the produced eCD4-Ig effectively inhibited HIV-1 and SIV infection. We then performed studies in a rhesus macaque. After in vivo HSC transduction/selection of a rhesus macaque, eCD4-Ig serum levels were stable at 20-30 mg/ml. In vitro SIVmac239 neutralization assays using week 13 serum and recombinant eCD4-Ig protein determined that the IC50 of eCD4-Ig in rhesus serum is 1.0 mg/ml. This implies that the serum eCD4-Ig concentration at the time of SIVmac239 challenge was ~25-fold higher than the IC50. High-level eCD4-Ig expression had no clinical or hematological side effects. The first SIVmac239 challenge (20pg) was given on June 22 nd. Increasing rechallenge doses are currently injected monthly. So far, the viral load measured by quantitative RT-PCR is below detection limit. The animal is without symptoms and has normal lymphocyte/subset counts. Our study demonstrates an in vivo HSC transduction approach for potential long-term control of HIV-1 infection.

Disclosures

Kiem: VOR Biopharma: Consultancy; Ensoma Inc.: Consultancy, Current holder of individual stocks in a privately-held company; Homology Medicines: Consultancy. Lieber: Ensoma: Research Funding.
Anti-Myeloma Effects of Panobinostat in Combination with Duvelisib
Authors: Chen Haiming , Li Mingjie , Goldwater Marissa , Behare Stacy , Cao Jasmin , Wallingford Cara , Hekmati Ava , Levin Rocky , Souther Eric , Xu Ning , Berenson James R.
Published: November 2021

Introduction: Panobinostat (Secura Bio) is a non-selective histone deacetylase inhibitor (HDACi) that has shown anti-tumor activity in preclinical studies in both solid and hematological malignancies. Duvelisib (Secura Bio) is an FDA-approved oral drug and a potent small molecule inhibitor of the delta (δ) and gamma (γ) isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. There is no data regarding in combination of an HDACi with duvelisib for multiple myeloma (MM) treatment. We evaluated the anti-myeloma effects of the panobinostat in combination with duvelisib.

Methods: The human MM cell lines U266, RPMI 8226 and MM1s were obtained from ATCC. Primary MM tumor cells were isolated from MM patients' bone marrow (BM) aspirates and mononuclear cells (MCs) were isolated. The cells were seeded at 10 5 cells/well in 96-well plates and incubated for 24 h in the presence of vehicle, panobinostat or duvelisib alone, or the two drugs together for 48 h. Cell viability was quantified using the MTS cell proliferation assay. For the apoptosis assay, U266, RPMI 8226, MM1s, or primary MM tumor cells were cultured at 1 x 10 6 cells per well for 48 hours at 37°C in 5% CO2 with or without the addition of panobinostat or duvelisib. Next, the cells were washed twice with PBS, re-suspended in binding buffer, and stained with FITC-conjugated annexin V and fluorescent dye propidium iodide (PrI) following annexin V assay standard protocol (BioVision, USA). For each drug treatment, 1 x 10 5 gated events were recorded.

Results and Discussion: The MTS cell proliferation assay showed that panobinostat alone inhibited cell proliferation of the MM cell lines U266 and MM1s but not RPMI8226. Panobinostat alone induced concentration-dependent inhibition of BMMCs. Panobinostat (20nM) in combination with duvelisib markedly increased inhibition of primary MM cell proliferation. Panobinostat alone induced MM cell apoptosis in all three MM cell lines. Panobinostat in combination with duvelisib enhanced MM cell apoptosis in MM1s but not U266 and RPMI 8226 cells. We further examined apoptosis of primary MM cell treated with panobinostat alone and in combination with duvelisib. The results showed panobinostat alone induced primary MM cell apoptosis and in combination with duvelisib markedly increased the induction of apoptosis. This study illustrates that the combination of panobinostat and duvelisib shows potent anti-MM effects in vitro and we are currently evaluating the anti-MM effects of this combination in vivo using our human MM xenograft models.

*The study was partially funded by Secura Bio, Inc

Disclosures

No relevant conflicts of interest to declare.
Development and Validation of a Novel Prognostic Nomogram Model and a Web-Based Survival Rate Calculator for Diffuse Large B-Cell Lymphoma in the Rituximab Era
Authors: Zhong Qiaofeng , Chen Haizhu , Qin Yan , He Xiaohui , Yang Sheng , Zhou Shengyu , Liu Peng , Shi Yuankai , Jing Hongmei
Published: November 2021

Objective This study aimed to develop a novel prognostic nomogram and a web-based survival rate calculator to improve discriminative and predictive accuracy for diffuse large B cell lymphoma (DLBCL) in rituximab era.

Methods We retrospectively collected data about 906 DLBCL patients who received R-CHOP or R-CHOP-like chemotherapy from January 2005 to December 2018 in National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences. COX proportional hazard regression analysis was performed to assess the independent prognostic significance of clinical and histopathological variables on overall survival, which were used to develop the nomogram. We performed internal and external validation of the nomogram, and compared it's discriminative and predictive accuracy with the traditional IPI, R-IPI, and NCCN-IPI.

ResultsThe patients were divided into the training (n = 636) and validation (n = 270) cohorts at a ratio of 7:3. We identified six independent predictors for survival including age, ECOG, number of extranodal sites, bulky, and β2-MG, which were used to construct the nomogram and the web-based survival rate calculator. The C-index of the nomogram was 0.767 (95% CI, 0.735-0.799) in the training cohort and 0.732 (95% CI, 0.678-0.786) in the validation cohort. The AUC values of the nomogram for predicting the 1-, 5-, and 10-year OS rates for DLBCL were 0.794, 0.799, 0.805 in the training cohort and 0.828, 0.773, 0.771 in the validation cohort. All calibration curves revealed optimal consistency between predicted and actual survival both in the training and validation cohort. The nomogram divided DLBCL patients into three risk groups, the score of low risk, moderate risk, and high risk were 0-45，46-228，and higher than 228, respectively. The risk stratification model generated based on the nomogram showed a favorable level of predictive accuracy compared with the IPI, R-IPI, and NCCN-IPI in both cohorts according to the K-M survival curves. The AUC values of the nomogram model compared with the IPI, R-IPI, and NCCN-IPI for predicting the 10-year OS rates for DLBCL patients were 0.756 vs 0.748, 0.732, 0.713 in the training cohort and 0.742 vs 0.712, 0.713, 0.757 in the validation cohort.

ConclusionsIn conclusion, we have established and validated a novel prognostic nomogram model and a web-based survival rate calculator, which revealed more discriminative and predictive accuracy than IPI, R-IPI, and NCCN-IPI in the rituximab era.

Disclosures

No relevant conflicts of interest to declare.
ICG/LY@HES-PCL Nanomedicine Improving the Efficacy of CAR-T Therapy in Lymphoma
Authors: Tang Yuxiang , Mei Heng , Chen ZhaoZhao , Yao Weiqi , Li Chenggong , Xiong Wei , Hu Yu
Published: November 2021

Background :

The presence of tumor immunosuppressive microenvironment, abnormal vascular microenvironment, and the presence of a cross-linked matrix barrier may hinder the recruitment, proliferation, and activation of CAR-T to lymphoma tissue infiltration, which limit the efficacy of CAR-T in the treatment of lymphoma. The enhanced infiltration effect of ICG photothermal effect on CAR-T and the effect of LY on improving tumor immunosuppressive microenvironment have been confirmed. In this work, we have constructed LY/ICG@HES-PCL nanomedicine to improve the accumulation, proliferation and activation of CAR-T in lymphoma tissue, further improving the therapy efficacy of CAR-T in lymphoma.

Methods:

The effect of LY/ICG@HES-PCL on the proliferation and activation of CAR-T was studied by Transwell experiment. LY/ICG@HES-PCL was studied in vivo to investigate its improving the efficacy of CAR-T therapy in lymphoma. Biefly, 1×10 7 Raji human lymphoma cells were subcutaneously injected into both sides of each mouse. After ≈20 days, when the tumor volume reached ≈100 mm 3, mice were randomly assigned to 5 groups (n=6) and were treated by PBS, ICG@HES-PCL, ICG@HES-PCL+NIR, LY/ICG@HES-PCL, LY/ICG@HES-PCL+NIR, respectively. (4.0 mg/kg as ICG, 4.0 mg/kg as ICG). NIR groups were irradiated with an 808 nm laser at the power density of 0.3 W cm −2 for 10 mins. Two hours later, 1 × 10 7 CAR-T cells were intravenously injected into the mice. The tumor sizes were recorded by a digital caliper every 3 days. LY/ICG@HES-PCL in vivo was monitored using an in vivo bioluminescence imaging system. Lymphoma microenvironment was analyzed by immunofluorescence and FCM.

Results:

LY/ICG@HES-PCL increased CAR-T quantity by 3.7 times, IL-2 and IFN-λ release by 2.5 and 2.1 times in vitro, increased CAR-T accumulation in tumor tissue by 4.45 times within 3 days in vivo, achieving CAR-T activation, proliferation, and tumor accumulation enhancement. LY/ICG@HES-PCL improved CAR T efficacy in lymphoma by 3.4 times and CAR T longevity within 15 days by 1.6 times.

Discussion:

LY/ICG@HES-PCL co-delivered the photosensitifier ICG and TGF-β inhibitor LY to the lymphoma tissue. The photothermal effect of ICG decreased the density of lymphoma matrix and activated CD4+ T cells, CD8+ T cells and NK cells in tumor tissue. LY was used to inhibit PD-1 and CLTA-4 of CAR-T, so as to promotes CAR-T proliferation, improve CAR-T activity and longevity in vivo, and ultimately improve the anti-lymphoma efficacy of CAR-T cells.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing
Authors: Chen Dongju , Shao Minghui , Meng Pei , Wang Chunli , Li Qi , Cai Yuhang , Song Chengcheng , Wang Xi , Shi Taiping
Published: November 2021

Background

The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair.

Results

In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan™ assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples.

Conclusions

This new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.
Spinoculation and retronectin highly enhance the gene transduction efficiency of Mucin-1-specific chimeric antigen receptor (CAR) in human primary T cells
Authors: Rajabzadeh Alireza , Hamidieh Amir Ali , Rahbarizadeh Fatemeh
Published: November 2021

Background

Producing an appropriate number of engineered cells is considered as one of the influential factors in the successful treatments with chimeric antigen receptor (CAR) T cells. To this aim, the transduction rate of the viral vectors can play a significant role. In addition, improving transduction rates can affect the success rate of this treatment due to hard-transduced T lymphocytes.

Results

In this study, activated T cells were transduced using different transduction methods such as spinoculation, retronectin, polybrene, spinoculation + retronectin, and spinoculation + polybrene after selecting the most efficient transfection method to produce recombinant viral particles containing MUC1 CAR. PEI and lipofectamine with the amount of 73.72 and 72.53%, respectively, showed the highest transfection rates with respect to calcium phosphate (14.13%) for producing lentiviral particles. However, the cytotoxicity of transfection methods was not significantly different. Based on the results, spinoculation + retronectin leads to the highest transduction rates of T cells (63.19 ± 4.45%) relative to spinoculation + polybrene (34.6 ± 4.44%), polybrene (10.23 ± 0.79%), retronectin (10.37 ± 1.85%), and spinoculation (21.11 ± 1.55%). Further, the polybrene (40.02%) and spinoculation + polybrene (48.83% ± 4.83) increased cytotoxicity significantly compared to other groups.

Conclusion

Improving transduction conditions such as using spinoculation with retronectin can ameliorate the production of CAR-T cells by increasing the rate of transduction, as well as the success rate of treatment.
Rapidly evolving genetic features for desert adaptations in Stipagrostis pennata
Authors: Ding Xixu , Zhang Tingting , Ma Lei
Published: November 2021

Background

Stipagrostis pennatais distributed in the mobile and semi-mobile sand dunes which can adapt well to extreme environments such as drought and high temperature. It is a pioneer plant species with potential for stabilizing sand dunes and ecological restoration. It can settle on moving sand dunes earlier than other desert plants. It can effectively improve the stability of sand dunes and help more plants settle down and increase plant diversity. However, despite its important ecological value, the genetic resources available for this species are limited.

Results

We used single-molecule real-time sequencing technology to obtain the complete full-length transcriptome ofStipagrostis pennata, including 90,204 unigenes with an average length of 2624 bp. In addition, the 5436 transcription factors identified in these unigenes are rich in stress resistance genes, such as MYB-related, C3H, bHLH, GRAS and HSF,etc., which may play a role in adapting to desert drought and strong wind stress. Intron retention events are abundant alternative splicing events. Stipagrostis pennatahas experienced stronger positive selection, accelerating the fixation of advantageous variants. Thirty-eight genes, such as CPP/TSO1-like gene, have evolved rapidly and may play a role in material transportation, flowering and seed formation.

Conclusions

The present study captures the complete full-length transcriptome ofStipagrostis pennataand reveals its rapid evolution. The desert adaptation inStipagrostis pennatais reflected in the regulation of gene expression and the adaptability of gene function. Our findings provide a wealth of knowledge for the evolutionary adaptability of desert grass species.
Is myocardial bridge more frequently detected on radial access coronary angiography?
Authors: Şenöz Oktay , Yapan Emren Zeynep
Published: November 2021

Background

Although the incidence of myocardial bridge (MB) has been defined in different femoral access conventional coronary angiography (FACCA) studies, the frequency of MB on radial access coronary angiography (RACA) is unknown. The aim of this study was to determine the difference in the incidence of MB between patients undergoing RACA and FACCA.

Method

A total of 2500 consecutive patients who underwent RACA and a total of 1455 consecutive patients who underwent FACCA were retrospectively investigated to detect the presence of MB. The incidences of the groups were calculated separately and compared. The clinical and angiographic features of the patients with MB were analyzed.

Results

MB was detected at an incidence of 10.2%, in 255/2500 patients who underwent RACA, and 1.8% in 27/1455 patients who underwent FACCA (p < 0.001). In both RACA and FACCA patients, the most involved coronary artery was the left anterior descending artery (LAD) (86.9% and 93.1%) and the mid-segment (84.9% and 88.9%) was the most affected section. Co-involvement of multiple coronary arteries by MB was 7.8% in patients who underwent RACA and 7.4% in patients who underwent FACCA. Coronary artery disease (CAD) was determined in 111 (35.7%) of the coronary arteries with MB, of which 81.9% were proximal to the MB. No significant CAD was detected in any of the vessels of 69.8% (178/255) of the patients who underwent RACA for different clinical indications.

Conclusion

These data demonstrated that the incidence of myocardial bridge able to be detected on RACA was much higher than FACCA.
Effects of vibrotactile-enhanced music-based intervention on sensorimotor control capacity in the hand of an aging brain: a pilot feasibility randomized crossover trial
Authors: Hsu Hsiu-Yun , Lin Che-Wei , Lin Yu-Ching , Wu Po-Ting , Kato Hirokazu , Su Fong-Chin , Kuo Li-Chieh
Published: November 2021

Background

Music-based interventions (MBI), using music as a therapeutic medium, has been utilized as a promising strategy for motor relearning and shaping. However, currently, MBI with active performance training is restricted to being extensively applied for patients with various levels of defects in fine motor skills and cognitive functions. Therefore, the integration of vibrotactile stimulation with MBI has been adopted as a motor training strategy intended to enhance motor learning through use of vibration stimuli. The current study was designed to investigate differences in the sensorimotor performance of older adults’ hands under baseline, a single session of active MBI, and vibrotactile-enriched MBI conditions.

Methods

Thirty healthy older adults were recruited and randomized to receive either the single session of 30-min of vibrotactile-enriched MBI or 30-min of active MBI at the beginning of the experiment. After a one-week washout period, they switched their treatment programs and then were assessed to study the training effects of both approaches through measuring precision pinch performance, hand function, and sensory status.

Results

The results of the Pinch-Holding-Up Activity test revealed a statistically significant difference in the FRpeak parameter (F = 14.37, p < 0.001, η2p = 0.507) under the vibrotactile-enriched MBI condition compared to the baseline and active MBI conditions. In addition, significant beneficial effects were found on the results of the barognosis (F = 19.126, p < 0.001, η2p = 0. 577) and roughness differentiation subtests (F = 15.036, p < 0.001, η2p = 0.518) in the Manual Tactile Test for the participants in the vibrotactile-enriched MBI group. In addition, the participants under both the active MBI and vibrotactile-enriched MBI conditions exhibited better performance in the three subtests of the Purdue Pegboard Test as compared to under the baseline condition (p < 0.016).

Conclusions

The findings indicated that vibrotactile-enriched MBI potentially improves the precision pinch performance of hands in healthy older adults. In addition, the add-on effect of vibrotactile stimulation to the MBI condition provides beneficial effects on the sensory functions of the upper extremities.

Trial registration

NCT04802564.

Date of registration: 15/03/2021.

The first posted date: 17/03/2021.
Integrating medication risk management interventions into regular automated dose dispensing service of older home care clients – a systems approach
Authors: Tahvanainen Heidi , Kuitunen Sini , Holmström Anna-Riia , Airaksinen Marja
Published: November 2021

Background

Automated dose dispensing (ADD) services have been implemented in many health care systems internationally. However, the ADD service itself is a logistic process that requires integration with medication risk management interventions to ensure safe and appropriate medication use. National policies and regulations guiding ADD in Finland have recommended medication reconciliation, review, and follow-up for suitable risk management interventions. This implementation study aimed to develop a medication management process integrating these recommended risk management interventions into a regular ADD service for older home care clients.

Methods

This study applied an action research method and was carried out in a home care setting, part of primary care in the City of Lahti, Finland. The systems-approach to risk management was applied as a theoretical framework.

Results

The outcome of the systems-based development process was a comprehensive medication management procedure. The medication risk management interventions of medication reconciliation, review and follow-up were integrated into the medication management process while implementing the ADD service. The tasks and responsibilities of each health care professional involved in the care team became more explicitly defined, and available resources were utilized more effectively. In particular, the hospital pharmacists became members of the care team where collaboration between physicians, pharmacists, and nurses shifted from parallel working towards close collaboration. More efforts are needed to integrate community pharmacists into the care team.

Conclusion

The transition to the ADD service allows implementation of the effective medication risk management interventions within regular home care practice. These systemic defenses should be considered when national ADD guidelines are implemented locally. The same applies to situations in which public home care organizations responsible for services e.g., municipalities, purchase ADD services from private service providers.
Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
Authors: Zhang Peng , Xu Jian , Zhang Hua , Liu Xiao-Yu
Published: November 2021

Background

Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown.

Methods

Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1.

Results

Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1.

Conclusions

Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.
A descriptive, retrospective case series of patients with factitious disorder imposed on self
Authors: Bérar Antoine , Bouzillé Guillaume , Jego Patrick , Allain Jean-Sébastien
Published: November 2021

Background

Despite cases of factitious disorder imposed on self being documented in the literature for decades, it appears to remain an under-identified and under-diagnosed problem. The present study aimed to explore factitious disorder imposed on self in a series of French patients.

Methods

Patients 18 years old and over with factitious disorder imposed on self were retrospectively included by two independent reviewers according to DSM-5 criteria in Rennes University Hospital for the period 1995 to 2019. Patients were identified from a clinical data warehouse.

Results

49 patients with factitious disorder imposed on self were included. Among them, 36 (73.5%) were female. The average age at diagnosis was 38.4 years. The 16 patients with a health-related profession were all female. Direct evidence of falsification was found in 20.4% of cases. Falsification was mainly diagnosed on the basis of indirect arguments: history of factitious disorder diagnosed in another hospital (12.2%), extensive use of healthcare services (22.4%), investigations that were normal or inconclusive (69.4%), inconsistent or incomplete anamnesis and/or patient refusal to allow access to outside information sources (20.4%), atypical presentation (59.2%), evocative patient behaviour or comments (32.7%), and/or treatment failure (28.6%). Dermatology and neurology were the most frequently involved specialities (24.5%). Nine patients were hospitalized in intensive care. Some of them received invasive treatments, such as intubations, because of problems that were only reported or feigned. The diagnosis of factitious disorder imposed on self was discussed with the patient in 28 cases (57.1%). None of them admitted to making up the disorder intentionally. Two suicide attempts occurred within 3 months after the discussion of the diagnosis. No deaths were recorded. 44.9% of the patients returned to the same hospital at least once in relation to factitious disorder imposed on self.

Conclusions

The present study reinforces data in favour of a predominance of females among patients with factitious disorder imposed on self. This diagnosis is difficult and is based on a range of arguments. While induced cases can be of low severity, cases that are only feigned can lead to extreme medical interventions, such as intubation.
Provision of physical activity advice for patients with chronic diseases in Shenzhen, China
Authors: Hu Rui , Hui Stanley Sai-chuen , Lee Eric Kam-pui , Stoutenberg Mark , Wong Samuel Yeung-shan , Yang Yi-jian
Published: November 2021

Background

Physical activity (PA) may best be promoted to patients during clinical consultations. Few studies investigated the practice of PA advice given by physicians, especially in China. This study aimed to investigate the prevalence and contents of PA advice given by physicians in China and its association with patients’ characteristics.

Methods

Face-to-face questionnaire asking the prevalence and contents of PA advice given by physicians was administered to adult patients in three major hospitals in Shenzhen, China. Attitude of compliance, stature, PA level, and socio-demographic information were also collected. Data was analyzed via descriptive statistics and binary logistic regression.

Results

Of the 454 eligible patients (Age: 47.0 ± 14.4 years), only 19.2% (n = 87) reported receiving PA advice, whereas 21.8%, 23.0%, 32.2%, and 55.2% of patients received advices on PA frequency, duration, intensity, and type, respectively. Male patients were more likely to receive PA advice from physicians [odds ratio (OR): 1.81; 95% confidence interval (CI): 1.08–3.05], whereas patients who were unemployed (OR: 0.16; 95% CI: 0.04–0.67), and who already achieved adequate amount of PA (OR: 0.29; 95% CI: 0.12–0.71) were less likely to receive PA advice.

Conclusions

Prevalence of physicians providing physical activity advice to patients is low, there is a pressing need to take intervention measures to educate healthcare providers.
Effect of educational program based on theory of planned behavior on osteoporosis preventive behaviors: a randomized clinical trial
Authors: Pakyar Nasim , Poortaghi Sarieh , Pashaeypoor Shahzad , Sharifi Farshad
Published: November 2021

Background

The prevalence of chronic diseases is increasing worldwide. Implementing educational programs is an important step in prevention of chronic diseases in the community setting. This study was conducted to assess the effect of educational program based on the Theory of Planned Behavior (TPB) on the osteoporosis preventive behaviors in middle-aged individuals.

Methods

A randomized clinical trial was conducted on 64 middle-aged individuals presenting to primary care centers. A researcher-made questionnaire developed according to “a guide for compiling and analyzing the questionnaire based on TPB” was used for data collection. Random block sampling was applied to assign participants to control and intervention groups after ensuring the validity and reliability. An educational program on osteoporosis prevention was conducted in six educational sessions based on the TPB constructs for the intervention group in primary care centers. Control group received routine education about lifestyle changes including osteoporosis by primary care centers. Eight weeks after the intervention, the questionnaires were completed again and the data were analyzed using the SPSS V16 software.

Results

Independent t-test found no significant difference in the mean score of knowledge, osteoporosis preventive behavior, attitude, subjective norms, perceived behavioral control and behavioral intention between intervention and control groups before intervention (p > 0.05). After the intervention, however, a significant difference was found in the mean score of knowledge, attitude, subjective norms, perceived behavioral control and behavioral intention between the cases in intervention and control groups (P < 0.05). In addition, based on repeated measurement ANOVA, the intervention had a significant effect on knowledge, preventive behaviors, attitude, subjective norms, perceived behavioral control, and behavioral intention (P < 0.05).

Conclusions

The results of the present study showed that implementation of an educational intervention based on the Theory of Planned Behavior significantly increased the knowledge along with all constructs of TPB in osteoporosis preventive behaviors.

Trial registration

This study was registered in the Iranian Registry of Clinical Trials IRCT2017081735647N2 (11/10/2017).
Paradoxical spinopelvic motion: does global balance influence spinopelvic motion in total hip arthroplasty?
Authors: Lin Yu-Hsien , Lin Yu-Tsung , Chen Kun-Hui , Pan Chien-Chou , Shih Cheng-Min , Lee Cheng-Hung
Published: November 2021

Background

Recent research has proposed a classification of spinopelvic stiffness according to pelvic spatial orientation for risk stratification in patients who undergo total hip arthroplasty (THA). However, the influence of global alignment was not investigated, and this study evaluated the effect of global balance (sagittal vertical axis [SVA]) on spinopelvic motion.

Methods

We conducted a retrospective review of consecutive primary THA patients. We measured SVA, spinopelvic parameters (pelvic tilt [PT], pelvic incidence, and sacral slope), thoracic kyphosis (TK), lumbar lordosis (LL), proximal femur angle (PFA), and cup version using functional radiographs of patients in the standing and upright sitting positions. Linear regression was performed to identify parameters related to global trunk alignment change (∆SVA). Spinopelvic stiffness was defined as PT position change < 10°, and a subset of patients with PT change < 0° was categorized into a paradoxical spinopelvic motion group.

Results

One hundred twenty-four patients were analyzed (mean age: 65 years, 61% female). In univariate regression analysis, ∆TK, ∆LL, and ∆PFA were correlated to ∆SVA. In multivariate regression analysis, ΔLL (p < 0.001) and ΔPFA (p < 0.001) were found to be correlated to ΔSVA (ΔSVA = − 11.97 + 0.05ΔTK – 0.23ΔLL – 0.17ΔPFA; adjusted R2 = 0.558). Spinopelvic stiffness was observed in 40 patients (32%), including five (4%) with paradoxical motion (∆PT = − 3° ± 1°, p < 0.001) with characteristics of balanced standing global trunk alignment (standing SVA = − 1.0 ± 5.1 cm), similar stiffness of the lumbosacral spine (∆LL = − 7° ± 5°), higher hip motion (∆PFA = − 78° ± 6°, p = 0.017), and higher anterior trunk shift (∆SVA = 6.2 ± 2.0 cm, p = 0.003) from standing to sitting as compared to the stiffness group. Two of these five patients experienced dislocation events after THA.

Conclusions

The lumbosacral and hip motions were the major contributors to global alignment postural change. Paradoxical motion is a rare but dangerous clinical condition in THA that might be related to a disproportionally large trunk shift in the stiff lumbosacral spine causing excessive hip motion. In paradoxical motion, diminishing functional acetabular clearance during position change might pose the prosthesis at higher risk of impingement and instability than spinopelvic stiffness.
Guided endodontics: accuracy of access cavity preparation and discrimination of angular and linear deviation on canal accessing ability—an ex vivo study
Authors: Su Yinghui , Chen Chenghui , Lin Chiahua , Lee Huina , Chen Kerkong , Lin Yenkun , Chuang Fuhsiung
Published: November 2021

Background

Guided endodontics technique has been introduced for years, but the accuracy in different types of teeth has yet to be assessed. The aim of this study is to evaluate the accuracy of three dimensional (3D)-printed endodontic guides for access cavity preparation in different types of teeth, and to evaluate the predictive ability of angular and linear deviation on canal accessibility ex vivo.

Method

Eighty-four extracted human teeth were mounted into six jaw models and categorised into three groups: anterior teeth (AT), premolar (P), and molar (M). Preoperative cone beam computed tomography (CBCT) and surface scans were taken and matched using implant planning software. Virtual access cavity planning was performed, and templates were produced using a 3D printer. After access cavities were performed, the canal accessibility was recorded. Postoperative CBCT scans were superimposed in software. Coronal and apical linear deviations and angular deviations were measured and evaluated with nonparametric statistics. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of angular and linear deviation for canal accessibility in SPSS v20.

Results

A total of 117 guided access cavities were created and 23 of them were record as canal inaccessibility, but all canals were accessible after canal negotiation. The average linear deviation for all groups was 0.13 ± 0.21 mm at coronal position, 0.46 ± 0.4 mm at apical position, and 2.8 ± 2.6° in angular deviation. At the coronal position, the linear deviations of the AT and P groups were significantly lower than M group deviation (P < 0.05), but no statistically significant difference between AT group and P group. The same results were found in linear deviation at the apical position and in angular deviation. The area under the ROC curve was 0.975 in angular deviation, 0.562 in linear deviation at the coronal position, and 0.786 at the apical position. Statistical significance was noted in linear deviation at the apical position and in angular deviation (P < 0.001).

Conclusions

In conclusion, this study demonstrated that the accuracy of access cavity preparation with 3D-printed endodontic guides was acceptable. The linear and angular deviations in the M group were significantly higher than those in the other groups, which might be caused by the interference of the opposite teeth. Angular deviation best discriminated the canal access ability of guided access cavity preparation.

Graphical Abstract
Patient-reported outcome measures for masticatory function in adults: a systematic review
Authors: Fan Yanpin , Shu Xin , Leung Katherine Chiu Man , Lo Edward Chin Man
Published: November 2021

Objective

The aim of this systematic review was to critically evaluate the Patient-Reported Outcome Measures (PROMs) for masticatory function in adults.

Methods

Five electronic databases (Medline, Embase, Web of Science Core Collection, CINAHL Plus and APA PsycINFO) were searched up to March 2021. Studies reporting development or validation of PROMs for masticatory function on adults were identified. Methodological quality of the included studies was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Psychometric properties of the PROM in each included study were rated against the criteria for good measurement properties based on the COSMIN guideline.

Results

Twenty-three studies investigating 19 PROMs were included. Methodological qualities of these studies were diverse. Four types of PROMs were identified: questions using food items to assess masticatory function (13 PROMs), questions on chewing problems (3 PROMs), questions using both food items and chewing problems (2 PROMs) and a global question (1 PROM). Only a few of these PROMs, namely chewing function questionnaire-Chinese, Croatian or Albanian, food intake questionnaire-Japanese, new food intake questionnaire-Japanese, screening for masticatory disorders in older adults and perceived difficulty of chewing-Tanzania demonstrated high or moderate level of evidence in several psychometric properties.

Conclusions

Currently, there is no PROM for masticatory function in adults with high-level evidence for all psychometric properties. There are variations in the psychometric properties among the different reported PROMs.

Trial Registration PROSPERO (CRD42020171591).
Genetic/genomic testing: defining the parameters for ethical, legal and social implications (ELSI)
Authors: Ascencio-Carbajal Tania , Saruwatari-Zavala Garbiñe , Navarro-Garcia Fernando , Frixione Eugenio
Published: November 2021

Background

Genetic/genomic testing (GGT) are useful tools for improving health and preventing diseases. Still, since GGT deals with sensitive personal information that could significantly impact a patient’s life or that of their family, it becomes imperative to consider Ethical, Legal and Social Implications (ELSI). Thus, ELSI studies aim to identify and address concerns raised by genomic research that could affect individuals, their family, and society. However, there are quantitative and qualitative discrepancies in the literature to describe the elements that provide content to the ELSI studies and such problems may result in patient misinformation and harmful choices.

Methods

We analyzed the major international documents published by international organizations to specify the parameters that define ELSI and the recognized criteria for GGT, which may prove useful for researchers, health professionals and policymakers. First, we defined the parameters of the ethical, legal and social fields in GGT to avoid ambiguities when using the acronym ELSI. Then, we selected nine documents from 44 relevant publications by international organizations related to genomic medicine.

Results

We identified 29 ELSI sub-criteria concerning to GGT, which were organized and grouped within 10 minimum criteria: two from the ethical field, four from the legal field and four from the social field. An additional analysis of the number of appearances of these 29 sub-criteria in the analyzed documents allowed us to order them and to determine 7 priority criteria for starting to evaluate and propose national regulations for GGT.

Conclusions

We propose that the ELSI criteria identified herein could serve as a starting point to formulate national regulation on personalized genomic medicine, ensuring consistency with international bioethical requirements.
A genetic researcher’s devil’s dilemma: Warn relatives about their genetic risk or respect confidentiality agreements with research participants?
Authors: van den Heuvel Lieke M. , Maeckelberghe Els L. M. , Ploem M. Corrette , Christiaans Imke
Published: November 2021

Background

With advances in sequencing technologies, increasing numbers of people are being informed about a genetic disease identified in their family. In current practice, probands (the first person in a family in whom a genetic predisposition is identified) are asked to inform at-risk relatives about the diagnosis. However, previous research has shown that relatives are sometimes not informed due to barriers such as family conflicts. Research on family communication in genetic diseases aims to explore the difficulties encountered in informing relatives and to identify ways to support probands in this.

Main body

Research on family communication may also reveal that participants did not inform their relatives about the risk of a serious genetic condition, even when preventive and treatment options are available. Researchers may then face a dilemma: Do they need to warn at-risk relatives about the finding? Or do they keep silent due to prior confidentiality agreements with study participants?

Conclusions

We believe that the absolute confidence promised to research participants outweighs the interests of their relatives, even though it can be claimed that relatives at risk of a genetic disease do, in principle, have a right to know information collected about their health. Not respecting confidentiality agreements could cause distrust between researchers and research participants and possibly harm the relationship between probands and relatives. Relatives' health interests can still be taken into account without jeopardizing participant trust, by considering alternative scenarios, including sharing general study findings on the barriers participants experience with their healthcare professionals and by offering participants psychosocial support for family communication.