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Anxiety disorders are commonly diagnosed and cause substantial functional impairment. A mixture of pharmacologic and psychosocial treatments currently exists, but these treatments are not always tolerable and effective. For patients with anxiety resistant to standard therapy, psychedelics may be a promising alternative. This review assesses the therapeutic benefits and safety of psychedelics in treating anxiety disorders. We searched PubMed, Embase, PsycInfo, and CINAHL for clinical trials investigating psychedelics in patients with clinician-diagnosed generalized anxiety disorder, social anxiety disorder, specific phobia, separation anxiety disorder, selective mutism, panic disorder, agoraphobia, and anxiety attributable to another medical condition. We analyzed data from 9 independent psychedelic-assisted trials testing ayahuasca (1 study), ketamine (4 studies), lysergic acid diethylamide (LSD) (2 studies), 3,4-methylenedioxymethamphetamine (MDMA) (1 study), and psilocybin (1 study). Efficacy was assessed by measuring the change in outcome measures and the quality of life from baseline. The reviewed studies demonstrated encouraging efficacy in reducing anxiety symptoms, increasing self-perception, and increasing social function in patients with generalized anxiety disorder, social anxiety disorder, or anxiety attributable to another medical condition while establishing feasibility and evidence of safety. For many patients, the therapeutic effects of the psychedelic treatment lasted weeks, and no severe adverse events were reported. Based on the evidence of symptom reduction and safety, the current literature (2011 to 2021) shows that psychedelics could be considered for treating clinician-diagnosed anxiety disorders. Psychedelics may provide an alternative therapeutic option for patients resistant to current standard treatments.

Sensitive detection of low-abundance proteins in complex biological samples has typically been achieved by immunoassays that use antibodies specific to target proteins; however, de novo development of antibodies is associated with high costs, long development lead times, and high failure rates. To address these challenges, we developed an antibody-free strategy that involves PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing) for sensitive selected reaction monitoring (SRM)–based targeted protein quantification. The strategy capitalizes on high-resolution reversed-phase liquid chromatographic separations for analyte enrichment, intelligent selection of target fractions via on-line SRM monitoring of internal standards, and fraction multiplexing before nano–liquid chromatography-SRM quantification. Application of this strategy to human plasma/serum demonstrated accurate and reproducible quantification of proteins at concentrations in the 50–100 pg/mL range, which represents a major advance in the sensitivity of targeted protein quantification without the need for specific-affinity reagents. Application to a set of clinical serum samples illustrated an excellent correlation between the results obtained from the PRISM-SRM assay and those from clinical immunoassay for the prostate-specific antigen level.

Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA ‘microsatellite instability/CpG island methylation phenotype’ transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis - and trans -effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A (hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology. Proteome analysis of The Cancer Genome Atlas (TCGA) colorectal cancer specimens reveals that DNA- or RNA-level measurements cannot reliably predict protein abundance, colorectal tumours can be separated into distinct proteotypes, and that copy number alterations drive mRNA abundance changes but few extend to protein-level changes. Proteomics/genomics of colorectal tumours A team from the Clinical Proteomics Tumor Analysis Consortium has now analysed the proteomes of 95 colon and rectal tumours previously characterized by the Cancer Genome Atlas project. Integration of the proteomics with the original genomic data demonstrates that protein abundance cannot be reliably predicted from DNA- or RNA-level measurements, and that mRNA and protein levels are modestly correlated. Proteomics identified five colorectal cancer subtypes that reflect known biological characteristics, yet capture differences that are not evident at the transcriptome level. Integrated proteogenomic analysis of this type can provide functional context to interpret genomic abnormalities in terms of cancer biology.

Purpose Pathogenic variants affecting MLH1 , MSH2 , MSH6 , and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. Methods We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. Results There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. Conclusion Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

Sensitive detection of low-abundance proteins in complex biological samples has typically been achieved by immunoassays that use antibodies specific to target proteins; however, de novo development of antibodies is associated with high costs, long development lead times, and high failure rates. To address these challenges, we developed an antibody-free strategy that involves PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing) for sensitive selected reaction monitoring (SRM)–based targeted protein quantification. The strategy capitalizes on high-resolution reversed-phase liquid chromatographic separations for analyte enrichment, intelligent selection of target fractions via on-line SRM monitoring of internal standards, and fraction multiplexing before nano–liquid chromatography-SRM quantification. Application of this strategy to human plasma/serum demonstrated accurate and reproducible quantification of proteins at concentrations in the 50–100 pg/mL range, which represents a major advance in the sensitivity of targeted protein quantification without the need for specific-affinity reagents. Application to a set of clinical serum samples illustrated an excellent correlation between the results obtained from the PRISM-SRM assay and those from clinical immunoassay for the prostate-specific antigen level.

Capabilities in mass spectrometry are evolving rapidly, with recent improvements in sensitivity, data analysis and, most important from the standpoint of this review, much higher throughput, allowing analysis of many samples in a single day. This short review describes how these improvements in mass spectrometry can be used to dissect host-pathogen interactions using Salmonella as a model system. This approach has enabled direct identification of the majority of annotated Salmonella proteins, quantitation of expression changes under various in vitro growth conditions and new insights into virulence and expression of Salmonella proteins within host cells. One of the most significant findings is that a relatively high percentage of all the annotated genes (>20%) in Salmonella are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several Salmonella virulence regulators that involve protein-protein interactions, suggesting additional functions of these regulators in coordinating virulence expression. Overall high-throughput mass spectrometry provides a new view of host-pathogen interactions, emphasizing the protein products and defining how protein interactions determine the outcome of infection.

Capabilities in mass spectrometry are evolving rapidly, with recent improvements in sensitivity, data analysis and, most important from the standpoint of this review, much higher throughput, allowing analysis of many samples in a single day. This short review describes how these improvements in mass spectrometry can be used to dissect host-–pathogen interactions using as a model system. This approach has enabled direct identification of the majority of annotated proteins, quantitation of expression changes under various growth conditions and new insights into virulence and expression of proteins within host cells. One of the most significant findings is that a relatively high percentage of all the annotated genes (>20%) in are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several virulence regulators that involve protein-–protein interactions, suggesting additional functions of these regulators in coordinating virulence expression. Overall high-throughput mass spectrometry provides a new view of host-–pathogen interactions, emphasizing the protein products and defining how protein interactions determine the outcome of infection.

PurposePathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer.MethodsWe conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years.ResultsThere were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer.ConclusionManagement guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.