Up-regulation of extracellular-matrix and inflammation related genes in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy with late-presentation, site-specific heterogeneity, and high-propensity for recurrence/metastasis that has shown rise in mortality. Lately, research emphasize on dynamic interactions between tumor-cells and extracellular-matrix components within tumor-microenvironment that promote tissue integrity loss and carcinogenesis. Therefore, OSCC clinical-management is still challenging. DESIGN: Present study validated clinical utility of a 13 gene-panel in two chief sub-sites of OSCC: Buccal mucosa squamous cell carcinoma (BMSCC) (N = 50) and Tongue squamous cell carcinoma (TSCC) (N = 52) using qRT-PCR. Principal component analysis and binary logistic regression analysis were applied to acquire definite multi gene models. Protein expression analysis was employed using the Human Protein Atlas, UALCAN and TIMER 2.0 databases to explore potential correlation between immune cells and gene-panels. RESULTS: Significant up-regulation of CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, PLAU, SERPINE1 and SPP1 except OASL was observed in OSCC tissue in comparison of absolute normal controls. Although, this gene-panel could potentially discriminate OSCC tissues from absolute normal controls as solitarily diagnostic and/or predictive biomarkers, models generated also showed substantial discriminating efficacy. Eight-genes were found to be significantly associated with poor-prognosis on clinico-pathological association. Protein-expression confirmed overexpression of gene-panel and added advantage of being secretory-protein. Importantly, up-regulated genes in our study showed significant relation with immune-cells infiltration suggesting their contribution in immune-escape. CONCLUSION: Thus, we propose that the 13 gene-panel could pave the way to effective and personalized clinical-management of OSCC in terms of diagnostic and prognostic measures and thereby as therapeutic targets.

Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies.

Chimeric antigen receptor T cells have dramatically improved the treatment of hematologic malignancies. T cell antigen receptor (TCR)-based cell therapies are yet to achieve comparable outcomes. Importantly, chimeric antigen receptors not only target selected antigens but also reprogram T cell functions through the co-stimulatory pathways that they engage upon antigen recognition. We show here that a fusion receptor comprising the CD80 ectodomain and the 4-1BB cytoplasmic domain, termed 80BB, acts as both a ligand and a receptor to engage the CD28 and 4-1BB pathways, thereby increasing the antitumor potency of human leukocyte antigen-independent TCR (HIT) receptor- or TCR-engineered T cells and tumor-infiltrating lymphocytes. Furthermore, 80BB serves as a switch receptor that provides agonistic 4-1BB co-stimulation upon its ligation by the inhibitory CTLA4 molecule. By combining multiple co-stimulatory features in a single antigen-agnostic synthetic receptor, 80BB is a promising tool to sustain CD3-dependent T cell responses in a wide range of targeted immunotherapies.

Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function.

Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. Persisting SUV39H1-edited CAR T cells demonstrate improved expansion and tumor rejection upon multiple rechallenges. Transcriptional and genome accessibility profiling of repeatedly challenged CAR T cells shows improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells. SUV39H1 editing also reduces expression of inhibitory receptors and limits exhaustion in CAR T cells that have undergone multiple rechallenges. Our findings thus demonstrate the potential of epigenetic programming of CAR T cells to balance their function and persistence for improved adoptive cell therapies. SIGNIFICANCE: T cells engineered with CD28-based CARs possess robust effector function and antigen sensitivity but are hampered by limited persistence, which may result in tumor relapse. We report an epigenetic strategy involving disruption of the SUV39H1-mediated histone-silencing program that promotes the functional persistence of CD28-based CAR T cells. See related article by López-Cobo et al., p. 120. This article is featured in Selected Articles from This Issue, p. 5.

Association of FTO gene variant rs9939609 with polycystic ovary syndrome from Gujarat, India.

BACKGROUND: Polycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India. METHOD: We enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA). RESULTS: The present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group. CONCLUSION: This is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients.

An Updated Mutation Spectrum of the γ-Secretase Complex: Novel NCSTN Gene Mutation in an Indian Family with Hidradenitis Suppurativa and Acne Conglobata.

Background: Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin disorder whose pathophysiology is poorly understood. Genetic studies have shown that HS is predisposed by mutations in the γ-secretase gene, but only a proportion of familial and partial sporadic cases have been shown to possess such mutations. HS has high genetic heterogeneity and is thought to be triggered by a combination of genetics and environmental factors. Aims: The study aimed to investigate the genetic causes of HS in a large cohort of patients and to update the mutation spectrum of γ-secretase complex genes. Methods: We conducted mutational screening of 95 sporadic HS cases and one large family with both HS and acne conglobata (AC) to identify mutations in the coding and splice junction region of γ-secretase complex genes (nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN), and aph-1 homolog B, gamma-secretase subunit (APH1B)). Results: Our study identified a nucleotide substitution of 1876C>T in the NCSTN gene, which caused a stop codon (p.Arg626X) in the affected members of a large family with HS and AC. No pathogenic variants were detected in 95 sporadic cases of HS, indicating there is possible genetic heterogeneity. Conclusion: We report a new family with a nonsense mutation in the NCSTN gene that supports the role of the γ-secretase complex genes in HS with AC. The updated γ-secretase mutation spectrum for HS now includes 78 mutations.

TET2 guards against unchecked BATF3-induced CAR T cell expansion.

Further advances in cell engineering are needed to increase the efficacy of chimeric antigen receptor (CAR) and other T cell-based therapies1-5. As T cell differentiation and functional states are associated with distinct epigenetic profiles6,7, we hypothesized that epigenetic programming may provide a means to improve CAR T cell performance. Targeting the gene that encodes the epigenetic regulator ten-eleven translocation 2 (TET2)8 presents an interesting opportunity as its loss may enhance T cell memory9,10, albeit not cause malignancy9,11,12. Here we show that disruption of TET2 enhances T cell-mediated tumour rejection in leukaemia and prostate cancer models. However, loss of TET2 also enables antigen-independent CAR T cell clonal expansions that may eventually result in prominent systemic tissue infiltration. These clonal proliferations require biallelic TET2 disruption and sustained expression of the AP-1 factor BATF3 to drive a MYC-dependent proliferative program. This proliferative state is associated with reduced effector function that differs from both canonical T cell memory13,14 and exhaustion15,16 states, and is prone to the acquisition of secondary somatic mutations, establishing TET2 as a guardian against BATF3-induced CAR T cell proliferation and ensuing genomic instability. Our findings illustrate the potential of epigenetic programming to enhance T cell immunity but highlight the risk of unleashing unchecked proliferative responses.

Uncovering the Interaction Interface Between Harpin (Hpa1) and Rice Aquaporin (OsPIP1;3) Through Protein-Protein Docking: An In Silico Approach.

Hpa1 (a type of harpin) is involved in T3SS (Type III Secretion System) assembly in the infection mechanism by Xanthomonas Oryzae pv. oryzae (Xoo). Hpa1 interacts with the plasma membrane components of plants thereby assisting effector proteins toward the cytoplasm, wherein effectors execute their pathological functions. Independently, harpins also induce hypersensitive response and systemic acquired resistance in plants. However, lack of knowledge regarding the plant-harpin interaction mechanism constrains the pathway of its agricultural application. Although an in vitro study proved that Hpa1 protein can interact with OsPIP1;3, a rice aquaporin, the structural basis of the interaction is yet to be discovered. The presented work is the first of its kind where an in silico approach is used for the PPI (protein-protein interaction) of harpin protein. The study discovered participation of Hpa1 N-terminal amino acids at the interface. Besides, MD simulation studies were performed to assess the stability. RMSD values were 0.35 ± 0.049, 0.73 ± 0.11, and 0.50 ± 0.065 nm for OsPIP1;3, Hpa1, and Hpa1-OsPIP1;3 complex, respectively. Additionally, Residue-wise fluctuations have also been studied post-MDS. Taken together, these findings not only give a solid foundation for a deeper knowledge of various interacting target molecules with Harpin protein orthologs but also bring a new avenue for the structural-functional relationship study of harpin proteins.

Curcumin mediated dendritic cell maturation by modulating cancer associated fibroblasts-derived exosomal miRNA-146a.

BACKGROUND: Though cancer associated fibroblasts (CAFs), being a main component of tumor microenvironment (TME), are known to modulate immune response through secretion of various growth hormones, exosomes carrying miRNAs and cytokines; their effect on dendritic cells (DCs) are yet to be elucidated. Thus, aim of this study was to assess the effect of miRNAs and cytokines released by lung-CAFs and to evaluate immunomodulatory potential of curcumin on DC maturation through modulating their TME. MATERIAL AND METHODS: To check the effect of CAFs derived exosomes on DC maturation, we cultured imDCs in the presence of CAFs derived conditioned media (CAFs-CM) and characterized by the presence of maturation markers CD80, CD83, CD86 and CTLA4 using qRT-PCR. Additionally, expression of miR-221, miR-222, miR-155, miR-142-3p and miR-146a was assessed to evaluate the role of epigenetic regulators on DC maturation. Likewise, cytokine profiling of CAFs-CM as well as CAFs-CM treated with curcumin was also conducted using ELISA. RESULTS: Results revealed the generation of regulatory DCs which were characterized by decreased expression of maturation markers in the presence of CAFs-CM. In addition, such DCs showed higher expression of epigenetic regulator miR-146a which was positively correlated with increased expression of anti-inflammatory cytokines like IL-6, IL-10, TGF-ß and decreased expression of TNF-α (pro-inflammatory). Moreover, curcumin had the potential to convert regulatory DCs generated by CAFs into mDCs, which were characterized by high expression of co-stimulatory molecules, low expression of CTLA4, lower levels of immune suppressive cytokines production and lower levels of miR-146a. CONCLUSION: Collectively, these findings provide insight into understanding the immunomodulatory role of curcumin in targeting CAFs and modulating TME, thus enhancing antitumor immune response in DC based therapy.

An integrative analysis to enumerate candidate genes for clinical use in oral cancer.

Background: Oral cancer (OC) is the most pernicious sub-site of head and neck tumours with poor prognostic value that is largely ascribed to the lack of ideal biomarkers and therapeutic targets. This fact highlights an urgent need to identify biomarkers that can further aid in OC management. Aim: The aim of this study was to identify a gene panel with a maximum clinical utility for OC. Materials and Methods: Eight eligible datasets were downloaded from the Gene Expression Omnibus Database, containing 320OC samples and 173 normal samples. The data were processed by GeneSpring software to reveal differentially expressed genes between OC tissues and normal tissues in eight individual experiments. Functional enrichment and network analysis were performed using PANTHER and STRING databases for concordant genes (fold change >10; P ≤ 0.05). The selected genes were cross-validated in the cancer genome atlas (TCGA), Oncomine, and KaplanMeier (KM) plotter databases. Results: Totally, 65 concordant genes were identified, including 37 up-regulated genes and 28 down-regulated genes. A 13-gene panel CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, OASL, SERPINE1, SPP1, and PLAU was elected from the lists of functionally enriched genes, hub genes, and genes that showed high alterations for mutation, copy number variation, and mRNA expression status in 'Head and Neck Squamous Cell Carcinoma patients (n = 279; TCGA, Nature 2015)'. Further, validation in Oncomine database demonstrated significant over-expression of all elected genes in OC patients across multiple datasets. In addition, out of 13, six genes (CXCL8, CXCL10, FN1, PLAU, SERPINE1, and SPP1) showed significant association with the prognosis of Head and Neck cancer patients (n = 500) in the KM plotter database. Conclusions: Using an integrative analysis, our study investigated and validated a 13-gene panel for OC which can be used to improve current diagnostic, prognostic, and treatment approaches.

In vitro model of predicting metastatic ability using tumor derived extracellular vesicles; beyond seed soil hypothesis.

Lung cancer progression is often driven by metastasis, which has resulted in a considerable increase in lung cancer-related deaths. Cell-derived extracellular vesicles (EVs), particularly exosomes, serve key roles in cellular signal transmission via microenvironment, however, their biological relevance in cancer development and metastasis still needs to be clear. Here, we demonstrate that extracellular vesicles (EVs) derived from lung cancer bone metastatic patients exhibited a great capacity to promote the progression of lung cancer cells. We carried out a comprehensive meta-analysis to identify the gene expression profile of bone metastases using publicly available microarray datasets. Furthermore, mRNA expression of six identified genes was quantified by real time PCR in lung cancer with and without bone metastasis and healthy individual derived EVs. In addition, we utilized a very novel approach by to study how lung cancer cells uptake EVs by co-culturing EVs with lung cells. We observed that EVs obtained from bone metastases patients were efficiently ingested by lung cancer cells. Morevore, integration and uptake of these EVs lead to increased lung cancer cell proliferation, migration, invasion, and sphere formation. We discovered that EV uptake increase the expression of SPP1, CD44, and POSTN genes in lung cancer cells. The data obtained from this study, support to the possibility that circulating EVs play a significant role in the formation of the pre-metastatic niche, eventually leading to metastasis.

Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators.

P-glycoprotein (Pgp), an ATP binding cassette (ABC) transporter, is an ATP-dependent efflux pump responsible for cancer multidrug resistance. As part of efforts to identify human Pgp (hPgp) inhibitors, we prepared a series of novel triazole-conjugated dihydropyrimidinones using a synthetic approach that is well suited for obtaining compound libraries. Several of these dihydropyrimidinone derivatives modulate human P-glycoprotein (hPgp) activity with low micromolar EC50 values. Molecular docking studies suggest that these compounds bind to the M-site of the transporter.

Pascal's Triangle Fractal Symmetries.

We introduce a model of interacting bosons exhibiting an infinite collection of fractal symmetries-termed "Pascal's triangle symmetries"-which provides a natural U(1) generalization of a spin-(1/2) system with Sierpinski triangle fractal symmetries introduced in Newman et al., [Phys. Rev. E 60, 5068 (1999).PLEEE81063-651X10.1103/PhysRevE.60.5068]. The Pascal's triangle symmetry gives rise to exact degeneracies, as well as a manifold of low-energy states which are absent in the Sierpinski triangle model. Breaking the U(1) symmetry of this model to Z_{p}, with prime integer p, yields a lattice model with a unique fractal symmetry which is generated by an operator supported on a fractal subsystem with Hausdorff dimension d_{H}=ln(p(p+1)/2)/lnp. The Hausdorff dimension of the fractal can be probed through correlation functions at finite temperature. The phase diagram of these models at zero temperature in the presence of quantum fluctuations, as well as the potential physical construction of the U(1) model, is discussed.

Construction of Fractal Order and Phase Transition with Rydberg Atoms.

We propose the construction of a many-body phase of matter with fractal structure using arrays of Rydberg atoms. The degenerate low energy excited states of this phase form a self-similar fractal structure. This phase is analogous to the so-called "type-II fracton topological states." The main challenge in realizing fractonlike models in standard condensed matter platforms is the creation of multispin interactions, since realistic systems are typically dominated by two-body interactions. In this work, we demonstrate that the van der Waals interaction and experimental tunability of Rydberg-based platforms enable the simulation of exotic phases of matter with fractal structures, and the study of a quantum phase transition involving a fractal ordered phase.

Computational investigation of ginkgetin and theaflavin as potential inhibitors of heat shock protein 90 (Hsp90).

Heat shock protein 90 (Hsp90) is the prime molecular chaperone found to be overexpressed in cancer cells and pose as an anti-cancer therapeutic drug target for cancer chemotherapy. Even drugs are available which inhibit Hsp90, the associated side effects along with multi-drug regimen necessitate the identification of natural molecules to block the activity of Hsp90. In this present investigation, we performed virtual screening of Hsp90 inhibitors from a curated collection of natural molecules with proven pharmacological effects. This process helped in the identification of the top two scoring ligands, ginkgetin and theaflavin with favorable as well as crucial interactions with the Hsp90 ligand-binding pocket. Molecular dynamics simulations of these two natural molecules exhibited minimal fluctuations in the binding pattern of ginkgetin and theaflavin to Hsp90 which retained crucial contacts throughout the simulation time. We anticipate that ginkgetin and theaflavin could act as potent Hsp90 inhibitors which are under current investigation in our laboratory.Communicated by Ramaswamy H. Sarma.

Assessing the Protective Effect of Moringa oleifera Extract against Bone Metastasis: An In Vitro Simulated Digestion Approach.

Moringa oleifera possesses numerous advantageous effects like anti-microbial, antioxidant, and anti-inflammatory, leaves contain a high multiplicity of the bioactive compound; however, little is identified about its bioaccessibility. The objective of this study was to assess the bioefficacy, bioaccessible and anticancer activity of Moringa oleifera in a PC3 cell line before and after simulated in vitro digestion. Digested and non-digested extracts were prepared and evaluated for total polyphenols, flavonoids, and total antioxidant capacity by spectrophotometric analysis and LCMS analysis. Cell viability, apoptosis, colony formation, cell cycle, Glutathione level, and gene expression study were tested with Moringa oleifera (MO) and digested Moringa oleifera (DMO). Results revealed that total polyphenols, total flavonoids, and TAC were significantly (P < 0.05) reduced after in vitro digestion. Furthermore, biological activity against the PC3 cell line showed that DMO extracts significant cytotoxic and reduced cell vitality compared to the MO. In addition, DMO extract had a noteworthy effect in apoptosis and inhibiting the colony formation ability; while cell cycle was blocked in S phase by both extracts but significant effect showed in DMO. These studies have increased understanding of the influence of in vitro simulation digestion on the biological activity effect of M. oleifera against prostate cancer bone metastasis.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1933099 .

Targeting Bone Metastases Signaling Pathway Using Moringa oleifera Seed Nutri-miRs: A Cross Kingdom Approach.

Moringa oleifera is a medicinally important plant that has various medical and nutritional uses. Plant miRNAs are a class of non-coding endogenous small RNAs that regulate human-specific mRNA but the mechanistic actions are largely unknown. Here, in this study, we aim to explore the mechanistic action and influence of M. oleifera seed miRNAs on vital human target genes using computer based approaches. The M. oleifera seed miRNAs sequence was taken from published data and identified its human gene targets using a psRNA target analysis server. We identified 94 miRNAs that are able to significantly regulate 47 human target genes, which has enormous biological and functional importance. Out of 47 human targeted genes, 23 genes were found to be associated with PI3K-AKT, RUNX, and MAPK1/MAPK3 signaling pathway which has shown to play key roles in bone metastases during cancer progression. The M. oleifera seed miRNAs hold a strong potential for future research that might uncover the possibility of miRNA-facilitated cross-kingdom regulation and therapeutic targets for bone metastases.

Theaflavin-3-gallate, a natural antagonist for Hsp90: In-silico and in-vitro approach.

Poor prognosis and metastasis have been recognized as the major cause of breast cancer related deaths worldwide. Recent experimental evidence has shown that Hsp90, the prime chaperone, is overexpressed in many cancers and is responsible if reducing the 5-year survival rate of cancer patients. Therefore, targeted inhibition of Hsp90 may be a new and effective way to target cancer as well as enhancing therapeutic outcomes. In the present study, screening and simulation of potential natural compounds result in the identification of theaflavin-3-gallate as a promising inhibitory compound of Hsp90. Further in-vitro validation of the cytotoxic effect of theaflavin-3-gallate in human breast carcinoma cell line MCF7 and normal cell line MCF10A revealed that theaflavin-3-gallate significantly inhibited the cell proliferation of MCF7 cells whereas no cytotoxic effect was observed on MCF10A cells. We also found that theaflavin-3-gallate significantly induced programmed cell death by arresting cells in the G2/M phase of the cell cycle. A significant decrease in cell migration and colony formation by theaflavin-3-gallate treatment was also observed in MCF7 cells. Furthermore, theaflavin-3-gallate significantly downregulated the mRNA expression patterns of the HSP90, MMP9, VEGFA, and SPP1 genes. Collectively, our results demonstrated theaflavin-3-gallate as a potential natural Hsp90 inhibitor that can be used to enhance the therapeutic efficacy of existing breast cancer therapies and improve overall survival of breast cancer patients.

The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women's lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.

A Virtual Cardiovascular Care Program for Prevention of Heart Failure Readmissions in a Skilled Nursing Facility Population: Retrospective Analysis.

BACKGROUND: Patients with heart failure (HF) in skilled nursing facilities (SNFs) have 30-day hospital readmission rates as high as 43%. A virtual cardiovascular care program, consisting of patient selection, initial televisit, postconsultation care planning, and follow-up televisits, was developed and delivered by Heartbeat Health, Inc., a cardiovascular digital health company, to 11 SNFs (3510 beds) in New York. The impact of this program on the expected SNF 30-day HF readmission rate is unknown, particularly in the COVID-19 era. OBJECTIVE: The aim of the study was to assess whether a virtual cardiovascular care program could reduce the 30-day hospital readmission rate for patients with HF discharged to SNF relative to the expected rate for this population. METHODS: We performed a retrospective case review of SNF patients who received a virtual cardiology consultation between August 2020 and February 2021. Virtual cardiologists conducted 1 or more telemedicine visit via smartphone, tablet, or laptop for cardiac patients identified by a SNF care team. Postconsult care plans were communicated to SNF clinical staff. Patients included in this analysis had a preceding index admission for HF. RESULTS: We observed lower hospital readmission among patients who received 1 or more virtual consultations compared with the expected readmission rate for both cardiac (3% vs 10%, respectively) and all-cause etiologies (18% vs 27%, respectively) in a population of 3510 patients admitted to SNF. A total of 185/3510 patients (5.27%) received virtual cardiovascular care via the Heartbeat Health program, and 40 patients met study inclusion criteria and were analyzed, with 26 (65%) requiring 1 televisit and 14 (35%) requiring more than 1. Cost savings associated with this reduction in readmissions are estimated to be as high as US $860 per patient. CONCLUSIONS: The investigation provides initial evidence for the potential effectiveness and efficiency of virtual and digitally enabled virtual cardiovascular care on 30-day hospital readmissions. Further research is warranted to optimize the use of novel virtual care programs to transform delivery of cardiovascular care to high-risk populations.

A predictive biomarker panel for bone metastases: Liquid biopsy approach.

Bone metastases is one of the common metastatic site and leading cause of cancer-related mortality in progressive cancer patients. The purpose of the present study is to establish a liquid biopsy based multi-gene classifier and associated signalling pathways for early diagnosis of bone metastases. We used publically available microarray datasets and analysed them in a platform/chip-specific manner using GeneSpring software. Analyses of gene expression datasets identified 15 consistently over-expressed genes with statistical significance. Further, expression profile of same set of 15 genes were compared in breast and lung cancer exosome derived mRNA with (n = 10) and without (n = 10) bone metastases against healthy controls. ROC curve analysis performed individually for all the 15 genes shortlisted the 5 most relevant genes with significant sensitivity and specificity in both cancers. This liquid biopsy-based bone metastases predictor using multi-gene panel is a unique approach with potential clinical applications for effective management of aggressive cancers.