Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.

The mitochondria-localized protein OsNDB2 negatively regulates grain size and weight in rice

Grain size is a determinant of rice grain yield.In plants,mitochondria supply energy for cellular metabolism via the mitochondrial electron transport chain.Here we report that OsNDB2,which encodes a putative rotenone-insensitive typeⅡNAD(P)H dehydrogenase(ND),negatively regulates grain size and weight in rice.Six ND members representing three major types of rice were identified,and the predicted OsNDB2 protein was localized to mitochondria.Contents of OsNDB2 transcripts were higher in young panicles and leaf blades.OsNDB2 overexpression reduced grain length,grain width,and 1000-grain weight and moderately influenced plant height,while knockout of OsNDB2 increased grain size and 1000-grain weight.Allelic mutations of OsNDB2 were associated with diverse grain appearances.Cellular observations revealed that variations in grain size of transgenic lines were caused by change in cell expansion but not cell proliferation in spikelet hulls.Our study sheds light on OsNDB2 function and provides a new potential breeding approach for increasing rice grain size and weight.

CYP2C19 Polymorphism and Clinical Outcomes among Patients of Different Races Treated with Clopidogrel:A Systematic Review and Meta-Analysis

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease（CAD） treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention（PCI）. The primary outcome of our interest was the recurrence of major adverse cardiovascular events（MACE） in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30 th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.

A Positive Correlation between Elevated Altitude and Frequency of Mutant Alleles at the EPAS1 and HBB Loci in Chinese Indigenous Dogs

Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the genetic bases of adaption to high-altitude environments （Bigham et al., 2010; Simonson et al., 2010）. The domestic dog （Canisfamiliaris） is the first animal that developed an intimate relationship with human beings. Dogs migrated with human beings and have adapted to variety of ecological niches （Savolainen et al., 2002）. Our previous research revealed parallel evolution and convergent evolution in the adaptation of dogs and humans to the high-altitude environment of the Tibetan plateau （Wang et al., 2013, 2014）, suggesting that exploring the adaption of domestic dogs to high-altitude hypoxia is an interesting and important question.

Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions

Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy cells.Recently,programmable endonucleases such as clustered regularly interspaced short palindromic repeats(CRISPR)associated protein(Cas)and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions,enabling their detection with deep next generation sequencing(NGS).However,the enrichment level achievable with these assays is limited by futile binding events and off-target cleavage.To overcome these shortcomings,we conceived a new assay(Programmable Enzyme-Assisted Selective Exponential Amplification,PASEA)that combines the cleavage of wild type alleles with concurrent polymerase amplification.While PASEA increases the numbers of both wild type and mutant alleles,the numbers of mutant alleles increase at much greater rates,allowing PASEA to achieve an unprecedented level of selective enrichment of targeted alleles.By combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification,we converted samples with0.01%somatic mutant allele fractions(MAFs)to products with 70%MAFs in a single step within 20 min,enabling inexpensive,rapid genotyping with such as Sanger sequencers.Furthermore,PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA probes.Real-time PASEA'performance was proved equivalent to clinical amplification refractory mutation system(ARMS)-PCR and NGS when testing over hundred cancer patients'samples.This strategy has the potential to reduce the cost and time of cancer screening and genotyping,and to enable targeted therapies in resource-limited settings.