Development and application of an optimised Bayesian shrinkage prior for spectroscopic biomedical diagnostics.

BACKGROUND AND OBJECTIVE: Classification of vibrational spectra is often challenging for biological substances containing similar molecular bonds, interfering with spectral outputs. To address this, various approaches are widely studied. However, whilst providing powerful estimations, these techniques are computationally extensive and frequently overfit the data. Shrinkage priors, which favour models with relatively few predictor variables, are often applied in Bayesian penalisation techniques to avoid overfitting. METHODS: Using the logit-normal continuous analogue of the spike-and-slab (LN-CASS) as the shrinkage prior and modelling, we have established classification for accurate analysis, with the established system found to be faster than conventional least absolute shrinkage and selection operator, horseshoe or spike-and-slab. These were examined versus coefficient data based on a linear regression model and vibrational spectra produced via density functional theory calculations. Then applied to Raman spectra from saliva to classify the sample sex. RESULTS: Subsequently applied to the acquired spectra from saliva, the evaluated models exhibited high accuracy (AUC>90 %) even when number of parameters was higher than the number of observations. Analyses of spectra for all Bayesian models yielded high-classification accuracy upon cross-validation. Further, for saliva sensing, LN-CASS was found to be the only classifier with 100 %-accuracy in predicting the output based on a leave-one-out cross validation. CONCLUSIONS: With potential applications in aiding diagnosis from small spectroscopic datasets and are compatible with a range of spectroscopic data formats. As seen with the classification of IR and Raman spectra. These results are highly promising for emerging developments of spectroscopic platforms for biomedical diagnostic sensing systems.

Medically assisted hydration for adults receiving palliative care.

BACKGROUND: Many people receiving palliative care have reduced oral intake during their illness, and particularly at the end of their life. Management of this can include the provision of medically assisted hydration (MAH) with the aim of improving their quality of life (QoL), prolonging their life, or both. This is an updated version of the original Cochrane Review published in Issue 2, 2008, and updated in February 2011 and March 2014. OBJECTIVES: To determine the effectiveness of MAH compared with placebo and standard care, in adults receiving palliative care on their QoL and survival, and to assess for potential adverse events. SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, CANCERLIT, CareSearch, Dissertation Abstracts, Science Citation Index and the reference lists of all eligible studies, key textbooks, and previous systematic reviews. The date of the latest search conducted on CENTRAL, MEDLINE, and Embase was 17 November 2022. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) of studies of MAH in adults receiving palliative care aged 18 and above. The criteria for inclusion was the comparison of MAH to placebo or standard care. DATA COLLECTION AND ANALYSIS: Three review authors independently reviewed titles and abstracts for relevance, and two review authors extracted data and performed risk of bias assessment. The primary outcome was QoL using validated scales; secondary outcomes were survival and adverse events. For continuous outcomes, we measured the arithmetic mean and standard deviation (SD), and reported the mean difference (MD) with 95% confidence interval (CI) between groups. For dichotomous outcomes, we estimated and compared the risk ratio (RR) with 95% CIs between groups. For time-to-event data, we planned to calculate the survival time from the date of randomisation and to estimate and express the intervention effect as the hazard ratio (HR). We assessed the certainty of evidence using GRADE and created two summary of findings tables.  MAIN RESULTS: We identified one new study (200 participants), for a total of four studies included in this update (422 participants). All participants had a diagnosis of advanced cancer. With the exception of 29 participants who had a haematological malignancy, all others were solid organ cancers. Two studies each compared MAH to placebo and standard care. There were too few included studies to evaluate different subgroups, such as type of participant, intervention, timing of intervention, and study site. We considered one study to be at high risk of performance and detection bias due to lack of blinding; otherwise, risk of bias was assessed as low or unclear. MAH compared with placebo Quality of life One study measured change in QoL at one week using Functional Assessment of Cancer Therapy - General (FACT-G) (scale from 0 to 108; higher score = better QoL). No data were available from the other study. We are uncertain whether MAH improves QoL (MD 4.10, 95% CI -1.63 to 9.83; 1 study, 93 participants, very low-certainty evidence). Survival One study reported on survival from study enrolment to last date of follow-up or death. We were unable to estimate HR. No data were available from the other study. We are uncertain whether MAH improves survival (1 study, 93 participants, very low-certainty evidence).  Adverse events One study reported on intensity of adverse events at two days using a numeric rating scale (scale from 0 to 10; lower score = less toxicity). No data were available from the other study. We are uncertain whether MAH leads to adverse events (injection site pain: MD 0.35, 95% CI -1.19 to 1.89; injection site swelling MD -0.59, 95% CI -1.40 to 0.22; 1 study, 49 participants, very low-certainty evidence).  MAH compared with standard care Quality of life No data were available for QoL. Survival One study measured survival from randomisation to last date of follow-up at 14 days or death. No data were available from the other study. We are uncertain whether MAH improves survival (HR 0.36, 95% CI 0.22 to 0.59; 1 study, 200 participants, very low-certainty evidence).  Adverse events Two studies measured adverse events at follow-up (range 2 to 14 days). We are uncertain whether MAH leads to adverse events (RR 11.62, 95% CI 1.62 to 83.41; 2 studies, 242 participants, very low-certainty evidence).  AUTHORS' CONCLUSIONS: Since the previous update of this review, we have found one new study. In adults receiving palliative care in the end stage of their illness, there remains insufficient evidence to determine whether MAH improves QoL or prolongs survival, compared with placebo or standard care. Given that all participants were inpatients with advanced cancer at end of life, our findings are not transferable to adults receiving palliative care in other settings, for non-cancer, dementia or neurodegenerative diseases, or for those with an extended prognosis. Clinicians will need to make decisions based on the perceived benefits and harms of MAH for each individual's circumstances, without the benefit of high-quality evidence to guide them.

Spectroscopic molecular-fingerprint profiling of saliva.

Saliva analysis has been gaining interest as a potential non-invasive source of disease indicative biomarkers due to being a complex biofluid correlating with blood-based constituents on a molecular level. For saliva to cement its usage for analytical applications, it is paramount to gain underpinning molecular knowledge and establish a 'baseline' of the salivary composition in healthy individuals as well as characterize how these factors are impacting its performance as potential analytical biofluid. Here, we have systematically studied the molecular spectral fingerprint of saliva, including the changes associated with gender, age, and time. Via hybrid artificial neural network algorithms and Raman spectroscopy, we have developed a non-destructive molecular profiling approach enabling the assessment of salivary spectral changes yielding the determination of gender and age of the biofluid source. Our classification algorithm successfully identified the gender and age from saliva with high classification accuracy. Discernible spectral molecular 'barcodes' were subsequently constructed for each class and found to primarily stem from amino acid, protein, and lipid changes in saliva. This unique combination of Raman spectroscopy and advanced machine learning techniques lays the platform for a variety of applications in forensics and biosensing.

Electroporation and Mass Spectrometry: A New Paradigm for In Situ Analysis of Intact Proteins Direct from Living Yeast Colonies.

Yeasts constitute an oft-neglected class of pathogens among which the resistance to first-line treatments, attributed in part to mutations in efflux pumps, is rapidly emerging. Their thick, chitin-reinforced cell walls render cell lysis difficult, complicating their analysis and identification by methods routinely used for bacteria, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Liquid extraction surface analysis mass spectrometry (LESA-MS) has previously been applied to the analysis of intact proteins from Gram-positive and Gram-negative bacterial colonies sampled directly on solid nutrient media. To date, a similar analysis of yeast colonies has not proved possible. Here we demonstrate the rapid release of intact yeast proteins for LESA-MS by electroporation using a home-built high-voltage device designed to lyse cells grown in colonies on agar media. Detection and identification of previously inaccessible proteins from baker's yeast Saccharomyces cerevisiae, as well as two clinically relevant yeast species (Candida glabrata and Cryptococcus neoformans), is shown. The electroporation approach also has the potential to be translated to other mass spectrometric analysis techniques, including MALDI and various ambient ionization methods.