Viral reprogramming of host transcription initiation.

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes 'de novo' transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, Zta and Rta and are influenced by directional proximity to existing canonical cell promoters, a configuration that fosters transcription through existing promoters and transcriptional interference. These studies reveal a new way that viruses interact with the host transcriptome to inhibit host gene expression and they shed light on primal features driving eukaryotic promoter function.

The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent.

Prior evidence indicates that the erythroid cellular response to glucocorticoids (GC) has developmental specificity, namely, that developmentally more advanced cells that are undergoing or have undergone fetal to adult globin switching are more responsive to GC-induced expansion. To investigate the molecular underpinnings of this, we focused on the major developmental globin regulator BCL11A. We compared: a) levels of expression and nuclear content of BCL11A in adult erythroid cells upon GC stimulation; b) response to GC of CD34+ cells from patients with BCL11A microdeletions and reduced BCL11A expression, and; c) response to GC of two cellular models (HUDEP-2 and adult CD34+ cells) before and after reduction of BCL11A expression by shRNA. We observed that: a) GC-expanded erythroid cells from a large cohort of blood donors displayed amplified expression and nuclear accumulation of BCL11A; b) CD34+ cells from BCL11A microdeletion patients generated fewer erythroid cells when cultured with GC compared to their parents, while the erythroid expansion of the patients was similar to that of their parents in cultures without GC, and; c) adult CD34+ cells and HUDEP-2 cells with shRNA-depleted expression of BCL11A exhibit reduced expansion in response to GC. In addition, RNA-seq profiling of shRNA-BCL11A CD34+ cells cultured with and without GC was similar (very few differentially expressed genes), while GC-specific responses (differential expression of GILZ and of numerous additional genes) were observed only in controls cells with unperturbed BCL11A expression. These data indicate that BCL11A is an important participant of certain aspects of the stress pathway sustained by GC.

The Heavy Atom Structure, "cis effect" on Methyl Internal Rotation, and 14N Nuclear Quadrupole Coupling of 1-Cyanopropene from Quantum Chemical and Microwave Spectroscopic Analysis.

The microwave spectrum of 1-cyanopropene (crotonitrile) was remeasured using two pulsed molecular jet Fourier transform microwave spectrometers operating from 2.0 to 40.0 GHz. The molecule exists in two isomer forms, E and Z, with respect to the orientation between the methyl and the cyano groups. The spectrum of the Z isomer is more intense. Due to internal rotation of the methyl group, doublets containing A and E torsional species were found for all rotational transitions. Hyperfine splittings arising from the 14N nuclear quadrupole coupling were resolved. The heavy atom structure of the Z isomer was determined by observation of 13C and 15N isotopologue spectra in natural abundances. The experimental results were supported by quantum chemistry. The complex spectral patterns were analyzed and fitted globally, and the barriers to methyl internal rotation are determined to be 478.325(28) cm-1 and 674.632(76) cm-1 for the Z and E isomers, respectively. The non-bonded intramolecular electrostatic attraction between the methyl group and the 1-cyano substituent overcomes steric hindrance, leading to higher stability of the Z isomer. The consequence is a slight opening of 3.2° of the C(1)-C(2)-C(3) angle and a radical decrease of the methyl torsional barrier in the Z isomer due to steric repulsion.

Assessment of Two Restraint Potentials for Coarse-Grained Chemical-Cross-Link-Assisted Modeling of Protein Structures.

The influence of distance restraints from chemical cross-link mass spectroscopy (XL-MS) on the quality of protein structures modeled with the coarse-grained UNRES force field was assessed by using a protocol based on multiplexed replica exchange molecular dynamics, in which both simulated and experimental cross-link restraints were employed, for 23 small proteins. Six cross-links with upper distance boundaries from 4 Å to 12 Å (azido benzoic acid succinimide (ABAS), triazidotriazine (TATA), succinimidyldiazirine (SDA), disuccinimidyl adipate (DSA), disuccinimidyl glutarate (DSG), and disuccinimidyl suberate (BS3)) and two types of restraining potentials ((i) simple flat-bottom Lorentz-like potentials dependent on side chain distance (all cross-links) and (ii) distance- and orientation-dependent potentials determined based on molecular dynamics simulations of model systems (DSA, DSG, BS3, and SDA)) were considered. The Lorentz-like potentials with properly set parameters were found to produce a greater number of higher-quality models compared to unrestrained simulations than the MD-based potentials, because the latter can force too long distances between side chains. Therefore, the flat-bottom Lorentz-like potentials are recommended to represent cross-link restraints. It was also found that significant improvement of model quality upon the introduction of cross-link restraints is obtained when the sum of differences of indices of cross-linked residues exceeds 150.

Translation and validation of the Vietnamese Epilepsy Self-Management Scale (V-ESMS).

OBJECTIVES: This study aimed to translate and validate the Vietnamese version of the Epilepsy Self-Management Scale (V-ESMS). METHODS: The translation and cross-cultural adaptation of the original version of the ESMS into Vietnamese followed the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures guideline with "forward-backward" translation and culturally adapted. The participants were recruited consecutively at neurology clinics at Nguyen Tri Phuong Hospital and University Medical Center, Ho Chi Minh City, from January 2022 to July 2022 and required to complete the V-ESMS. The validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Cronbach's alpha and intraclass correlation coefficient (ICC) were used to evaluate internal and temporal reliability, respectively. RESULTS: A total of 200 participants were recruited for analysis. The V-ESMS included 36 items and five domains. The factor loading ranged between 0.313 and 0.927; most items loaded in their hypothesized factors proved in the original scale. Using the CFA, theCMIN/DF, comparative fit index, and root mean square error of approximation were 2.883, 0.80, and 0.097, respectively. The Cronbach's alpha in each domain was 0.79-0.907; the scale was 0.936. The ICC from 0.94 to 0.98 showed excellent test-retest reliability. CONCLUSION: The 36-item V-ESMS with five domains presented good validity and reliability. This instrument could be used to assess self-management in people with epilepsy in Vietnam.

Profound importance of the conventional O-H⋯O hydrogen bond versus a considerable blue shift of the Csp2-H bond in complexes of substituted carbonyls and carboxyls.

Using quantum chemical approaches, we investigated the conventional O-H⋯O and nonconventional Csp2-H⋯O hydrogen bonds between carboxylic acids and aldehydes in 21 stable complexes. The strength of complexes is determined by the conventional O-H⋯O bond together with the nonconventional Csp2-H⋯O hydrogen bond, in which the former one is 4-5 times as strong as the latter one. Proportional linear correlations of the interaction energy with both individual energies of the O-H⋯O and Csp2-H⋯O hydrogen bonds are proposed. Different impacts of electron-donating and electron-withdrawing groups in substituted formaldehyde and formic acid on characteristics of conventional and nonconventional hydrogen bonds, as well as the strength of both hydrogen bond types and complexes, are also evaluated. Following complexation, it is noteworthy that the largest blue shift of the Csp2-H stretching frequency in the Csp2-H⋯O bond up to 105.3 cm-1 in CH3CHO⋯FCOOH is due to a decisive role of the O-H⋯O hydrogen bond, which has been rarely reported in the literature. The obtained results show that the conventional O-H⋯O hydrogen bond plays a pivotal role in the significant blue shift of the Csp2-H stretching frequency in the nonconventional Csp2-H⋯O hydrogen bond. Remarkably, the considerable blue shift of the Csp2-H stretching frequency is found to be one H of C-H in formic acid substituted by the electron-withdrawing group and one H in formaldehyde substituted by the electron-donating group. In addition, the change in the Csp2-H stretching frequency following complexation is proportional to both changes of electron density in σ*(Csp2-H) and σ*(O-H) orbitals, in which a dominant role of σ*(O-H) versus σ*(Csp2-H) is observed.

Anion photoelectron spectroscopy and chemical bonding of ThS2- and ThSO.

Anion photoelectron spectra of ThSO- and ThS2- were recorded using the third (355 nm) harmonic of an Nd-YAG laser; these provided the measured vertical detachment energies of each anion. The experiments are supported by extensive coupled cluster calculations on ThSO, ThSO-, ThS2, and ThS2-, as well as the oxygen congeners ThO2 and ThO2-. The ab initio calculations, which included complete basis set extrapolations, spin-orbit effects using four-component coupled cluster, and higher-order correlation contributions through CCSDT(Q), yielded an adiabatic electron affinity for ThO2 that was within 0.02 eV of the previously determined experimental value. The singly occupied molecular orbital (SOMO) in all three anions corresponds primarily to the 7s orbital on Th. Successive substitution of S for each O in ThO2 leads to larger electron affinities and smaller bond angles in the neutral molecules, but larger angles in the anions. As demonstrated by Franck-Condon simulations of the spectra using the CCSD(T) spectroscopic constants, substitution of O by S significantly complicates the resulting detachment spectra due to the lower vibrational frequencies in the sulfur species. Overall the calculated vertical detachment energies are in very good agreement with the experiment. In addition to the adiabatic electron affinities of each species, atomization energies and heats of formation have also been determined via the FPD approach with expected uncertainties of 1-2 kcal/mol.

ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans. METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories. RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021). CONCLUSION: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.

Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. METHODS: Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis (DCA). RESULTS: Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), and EAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. CONCLUSIONS: The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.

Wearing masks as a protective measure for children against traffic-related air pollution: A comparison of perceptions between school children and their caregivers in Ho Chi Minh City, Vietnam.

BACKGROUND: Traffic-related air pollution (TRAP) problems are unlikely to be solved in the short term, making it imperative to educate children on protective measures to mitigate the negative impact on their health. Children and their caregivers may hold differing views on wearing a face mask as a safeguard against air pollution. While many studies have focused on predicting children's health-protective behaviours against air pollution, few have explored the differences in perceptions between children and their caregivers. OBJECTIVES: To examine this, we conducted a study that compared the health beliefs of two generations and evaluated the factors that influence the use of masks by children to reduce air pollution exposure. METHODS: The study was conducted in 24 secondary schools and involved 8420 children aged 13-14 and their caregivers. We used a Health Belief Model (HBM)-based instrument containing 17-item self-administered health beliefs questionnaires to gather data. The results were analysed using hierarchical logistic regression to determine the probability of children frequently wearing masks to protect against TRAP. RESULTS: Our study showed both children and caregivers recognised that several factors could influence mask-wearing among children: discomfort or difficulty breathing while wearing a mask and forgetting to bring a mask when going outside; perceived threats of the poor quality of air and children's respiratory health problems; and cues to mask use (i.e., seeing most of their friends wearing facemasks and ease of finding masks in local stores). However, only children were significantly concerned with public perception of their appearance while wearing a mask. Females were more likely to wear masks, and caregivers with higher levels of education were more likely to encourage their children to wear masks. Children who commuted to schools by walking, biking, or motorbiking were also more accepting of mask-wearing than those who travelled by car or bus. CONCLUSIONS: Children and their caregivers hold different perceptions of wearing masks to protect against air pollution. Children are more susceptible to social judgements regarding their appearance when wearing a mask.

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and prostate cancer grading accuracy.

PURPOSE: To assess the most efficient biopsy method to improve International Society of Urological Pathology (ISUP) grade group accuracy with final pathology of the radical prostatectomy (RP) specimen in the era of magnetic resonance imaging (MRI)-driven pathway. METHODS: A total of 753 patients diagnosed by transrectal MRI-targeted and systematic biopsies (namely "standard method"), treated by RP, between 2016 and 2021 were evaluated. Biopsy methods included MRI-targeted biopsy, side-specific systematic biopsies relative to index MRI lesion and combination of both. Number of MRI-targeted biopsy cores and positive cores needed per index MRI lesion were assessed. Multivariable analysis was performed to analyze predictive factors of upgrading using MRI targeted and ipsilateral systematic biopsies method. RESULTS: Overall, ISUP grade group accuracy varied among biopsy methods with upgrading rate of 35%, 49%, 27%, and 24% for MRI targeted, systematic, MRI targeted and ipsilateral systematic biopsies and standard methods, respectively (p < 0.001). A minimum of two positive MRI-targeted biopsies cores per index MRI lesion were required when testing MRI targeted and ipsilateral systematic biopsies method to reach equivalent accuracy compared to standard method. Omitting contralateral systematic biopsies spared an average of 5.9 cores per patient. At multivariable analysis, only the number of positive MRI-targeted biopsy cores per index MRI lesion was predictive of upgrading. CONCLUSION: MRI targeted and ipsilateral systematic biopsies allowed an accurate definition of ISUP grade group and appears to be an interesting alternative when compared with standard method, reducing total number of biopsy cores needed.

Research on texture images and radiomics in urology: a review of urological MR imaging applications.

PURPOSE OF REVIEW: Tumor volume and heterogenicity are associated with diagnosis and prognosis of urological cancers, and assessed by conventional imaging. Quantitative imaging, Radiomics, using advanced mathematical analysis may contain information imperceptible to the human eye, and may identify imaging-based biomarkers, a new field of research for individualized medicine. This review summarizes the recent literature on radiomics in kidney and prostate cancers and the future perspectives. RECENT FINDINGS: Radiomics studies have been developed and showed promising results in diagnosis, in characterization, prognosis, treatment planning and recurrence prediction in kidney tumors and prostate cancer, but its use in guiding clinical decision-making remains limited at present due to several limitations including lack of external validations in most studies, lack of prospective studies and technical standardization. SUMMARY: Future challenges, besides developing prospective and validated studies, include automated segmentation using artificial intelligence deep learning networks and hybrid radiomics integrating clinical data, combining imaging modalities and genomic features. It is anticipated that these improvements may allow identify these noninvasive, imaging-based biomarkers, to enhance precise diagnosis, improve decision-making and guide tailored treatment.

Efficacy and accuracy of artificial intelligence to overlay multimodal images from different optical instruments in patients with retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) represents a group of progressive, genetically heterogenous blinding diseases. Recently, relationships between measures of retinal function and structure are needed to help identify outcome measures or biomarkers for clinical trials. The ability to align retinal multimodal images, taken on different platforms, will allow better understanding of this relationship. We investigate the efficacy of artificial intelligence (AI) in overlaying different multimodal retinal images in RP patients. METHODS: We overlayed infrared images from microperimetry on near-infra-red images from scanning laser ophthalmoscope and spectral domain optical coherence tomography in RP patients using manual alignment and AI. The AI adopted a two-step framework and was trained on a separate dataset. Manual alignment was performed using in-house software that allowed labelling of six key points located at vessel bifurcations. Manual overlay was considered successful if the distance between same key points on the overlayed images was ≤1/2°. RESULTS: Fifty-seven eyes of 32 patients were included in the analysis. AI was significantly more accurate and successful in aligning images compared to manual alignment as confirmed by linear mixed-effects modelling (p < 0.001). A receiver operating characteristic analysis, used to compute the area under the curve of the AI (0.991) and manual (0.835) Dice coefficients in relation to their respective 'truth' values, found AI significantly more accurate in the overlay (p < 0.001). CONCLUSION: AI was significantly more accurate than manual alignment in overlaying multimodal retinal imaging in RP patients and showed the potential to use AI algorithms for future multimodal clinical and research applications.

Collective Cognition on Global Density in Dynamic Swarm.

Swarm density plays a key role in the performance of a robot swarm, which can be averagely measured by swarm size and the area of a workspace. In some scenarios, the swarm workspace may not be fully or partially observable, or the swarm size may decrease over time due to out-of-battery or faulty individuals during operation. This can result in the average swarm density over the whole workspace being unable to be measured or changed in real-time. The swarm performance may not be optimal due to unknown swarm density. If the swarm density is too low, inter-robot communication will rarely be established, and robot swarm cooperation will not be effective. Meanwhile, a densely-packed swarm compels robots to permanently solve collision avoidance issues rather than performing the main task. To address this issue, in this work, the distributed algorithm for collective cognition on the average global density is proposed. The main idea of the proposed algorithm is to help the swarm make a collective decision on whether the current global density is larger, smaller or approximately equal to the desired density. During the estimation process, the swarm size adjustment is acceptable for the proposed method in order to reach the desired swarm density.

Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Improving ligand-ranking of AutoDock Vina by changing the empirical parameters.

AutoDock Vina (Vina) achieved a very high docking-success rate, p^ , but give a rather low correlation coefficient, R , for binding affinity with respect to experiments. This low correlation can be an obstacle for ranking of ligand-binding affinity, which is the main objective of docking simulations. In this context, we evaluated the dependence of Vina R coefficient upon its empirical parameters. R is affected more by changing the gauss2 and rotation than other terms. The docking-success rate p^ is sensitive to the alterations of the gauss1, gauss2, repulsion, and hydrogen bond parameters. Based on our benchmarks, the parameter set1 has been suggested to be the most optimal. The testing study over 800 complexes indicated that the modified Vina provided higher correlation with experiment Rset1=0.556±0.025 compared with RDefault=0.493±0.028 obtained by the original Vina and RVina1.2=0.503±0.029 by Vina version 1.2. Besides, the modified Vina can be also applied more widely, giving R≥0.500 for 32/48 targets, compared with the default package, giving R≥0.500 for 31/48 targets. In addition, validation calculations for 1036 complexes obtained from version 2019 of PDBbind refined structures showed that the set1 of parameters gave higher correlation coefficient ( Rset1=0.617±0.017 ) than the default package ( RDefault=0.543±0.020 ) and Vina version 1.2 ( RVina1.2=0.540±0.020 ). The version of Vina with set1 of parameters can be downloaded at https://github.com/sontungngo/mvina. The outcomes would enhance the ranking of ligand-binding affinity using Autodock Vina.

BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.

BACKGROUND: Malignant mesothelioma (MM) is an aggressive mesothelial cell cancer type linked mainly to asbestos inhalation. MM characterizes by rapid progression and resistance to standard therapeutic modalities such as surgery, chemotherapy, and radiotherapy. Our previous studies have suggested that tumor cell-derived connective tissue growth factor (CTGF) regulates the proliferation of MM cells as well as the tumor growth in mouse xenograft models. METHODS: In this study, we knock downed the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and CTGF in MM cells and investigated the relationship between both and their impact on the cell cycle and cell proliferation. RESULTS: The knockdown of CTGF or BAMBI reduced MM cell proliferation. In contrast to CTGF knockdown which decreased BAMBI, knockdown of BAMBI increased CTGF levels. Knockdown of either BAMBI or CTGF reduced expression of the cell cycle regulators; cyclin D3, cyclin-dependent kinase (CDK)2, and CDK4. Further, in silico analysis revealed that higher BAMBI expression was associated with shorter overall survival rates among MM patients. CONCLUSIONS: Our findings suggest that BAMBI is regulated by CTGF promoting mesothelioma growth by driving cell cycle progression. Therefore, the crosstalk between BAMBI and CTGF may be an effective therapeutic target for MM treatment.

Pro-angiogenic Potential of Mesenchymal Stromal Cells Regulated by Matrix Stiffness and Anisotropy Mimicking Right Ventricles.

Capillary rarefaction is a hallmark of right ventricle (RV) failure. Mesenchymal stromal cell (MSC)-based therapy offers a potential treatment due to its pro-angiogenic function. However, the impact of RV tissue mechanics on MSC behavior is unclear, especially when referring to RV end-diastolic stiffness and mechanical anisotropy. In this study, we assessed MSC behavior on electrospun scaffolds with varied stiffness (normal vs failing RV) and anisotropy (isotropic vs anisotropic). In individual MSCs, we observed the highest vascular endothelial growth factor (VEGF) production and total tube length in the failing, isotropic group (2.00 ± 0.37, 1.53 ± 0.24), which was greater than the normal, isotropic group (0.70 ± 0.15, 0.55 ± 0.07; p < 0.05). The presence of anisotropy led to trends of increased VEGF production on normal groups (0.75 ± 0.09 vs 1.20 ± 0.17), but this effect was absent on failing groups. Our findings reveal synergistic effects of RV-like stiffness and anisotropy on MSC pro-angiogenic function and may guide MSC-based therapies for heart failure.

Hospital-based prostate cancer screening in vietnamese men with lower urinary tract symptoms: a classification and regression tree model.

BACKGROUND: Prostate cancer (PCa) is a common disease in men over 65 years of age, and should be detected early, while reducing unnecessary biopsies. This study aims to construct a classification and regression tree (CART) model (i.e., risk stratification algorithm) using multivariable approach to select Vietnamese men with lower urinary tract symptoms (LUTS) for PCa biopsy. METHODS: We conducted a case-control study on 260 men aged ≥ 50 years who visited MEDIC Medical Center, Vietnam in 2017-2018 with self-reported LUTS. The case group included patients with a positive biopsy and the control group included patients with a negative biopsy diagnosis of PCa. Bayesian Model Averaging (BMA) was used for selecting the most parsimonious prediction model. Then the CART with 5-fold cross-validation was constructed for selecting men who can benefit from PCa biopsy in steps by steps and intuitive way. RESULTS: BMA suggested five potential prediction models, in which the most parsimonious model including PSA, I-PSS, and age. CART advised the following cut-off points in the marked screening sequence: 18 < PSA < 33.5 ng/mL, I-PSS ≥ 19, and age ≥ 71. Patients with PSA ≥ 33.5 ng/mL have a PCa risk was 91.2%; patients with PSA < 18 ng/mL and I-PSS < 19 have a PCa risk was 7.1%. Patient with 18 ≤ PSA < 33.5ng/mL and I-PSS < 19 have a PCa risk is 70% if age ≥ 71; and is 16% if age < 71. In overall, CART reached high predictive value with AUC = 0.915. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CART at the 20% diagnosis probability threshold were 91.5%, 86.2%, 86.9%, 91.2%, and 88.9% respectively; at 80% diagnosis probability threshold were 79.2%, 92.3%, 91.2%, 81.6%, and 85.8% respectively. CONCLUSION: CART combining PSA, I-PSS, and age has practical use in hospital-based PCa screening in Vietnamese men with lower urinary tract symptoms.