Palliative prognostic scores for survival prediction of cancer patients: a systematic review and meta-analysis.

BACKGROUND: The palliative prognostic score is the most widely validated prognostic tool for cancer survival prediction, with modified versions available. A systematic evaluation of palliative prognostic score tools is lacking. This systematic review and meta-analysis aimed to evaluate the performance and prognostic utility of palliative prognostic score, delirium-palliative prognostic score, and palliative prognostic score without clinician prediction in predicting 30-day survival of cancer patients and to compare their performance. METHODS: Six databases were searched for peer-reviewed studies and grey literature published from inception to June 2, 2023. English studies must assess palliative prognostic score, delirium-palliative prognostic score, or palliative prognostic score without clinician-predicted survival for 30-day survival in adults aged 18 years and older with any stage or type of cancer. Outcomes were pooled using the random effects model or summarized narratively when meta-analysis was not possible. RESULTS: A total of 39 studies (n = 10 617 patients) were included. Palliative prognostic score is an accurate prognostic tool (pooled area under the curve [AUC] = 0.82, 95% confidence interval [CI] = 0.79 to 0.84) and outperforms palliative prognostic score without clinician-predicted survival (pooled AUC = 0.74, 95% CI = 0.71 to 0.78), suggesting that the original palliative prognostic score should be preferred. The meta-analysis found palliative prognostic score and delirium-palliative prognostic score performance to be comparable. Most studies reported survival probabilities corresponding to the palliative prognostic score risk groups, and higher risk groups were statistically significantly associated with shorter survival. CONCLUSIONS: Palliative prognostic score is a validated prognostic tool for cancer patients that can enhance clinicians' confidence and accuracy in predicting survival. Future studies should investigate if accuracy differs depending on clinician characteristics. Reporting of validation studies must be improved, as most studies were at high risk of bias, primarily because calibration was not assessed.

Versatility of reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) from diagnosis of early pathological infection to mutation detection in organisms.

Loop-mediated isothermal amplification (LAMP) is a rapid, state-of-the-art DNA amplification technology, used primarily for the quick diagnosis and early identification of microbial infection, caused by pathogens such as virus, bacteria and malaria. A target DNA can be amplified within 30 min using the LAMP reaction, taking place at a steady temperature. The LAMP method uses four or six primers to bind eight regions of a target DNA and has a very high specificity. The devices used for conducting LAMP are usually simple since the LAMP method is an isothermal process. When LAMP is coupled with Reverse Transcription (RT), it allows direct detection of RNA in a sample. This greatly enhances the efficiency of diagnosis of RNA viruses in a sample. Recently, the rampant spread of COVID-19 demanded such a rapid, simple, and cost-effective Point of Care Test (PoCT) for the accurate diagnosis of this pandemic. Loop-mediated isothermal amplification (LAMP) assays are not only used for the detection of microbial pathogens, but there are various other applications such as detection of genetic mutations in food and various organisms. In this review, various implementations of RT-LAMP techniques would be discussed.

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review.

The emergence of antimicrobial resistance raises the fear of untreatable diseases. Antimicrobial resistance is a multifaceted and dynamic phenomenon that is the cumulative result of different factors. While Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile, were previously the most concerning issues in the field of public health, Gram-negative pathogens are now of prime importance. The World Health Organization's priority list of pathogens mostly includes multidrug-resistant Gram-negative organisms particularly carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and extensively drug-resistant Acinetobacter baumannii. The spread of Gram-negative bacterial resistance is a global issue, involving a variety of mechanisms. Several strategies have been proposed to control resistant Gram-negative bacteria, such as the development of antimicrobial auxiliary agents and research into chemical compounds with new modes of action. Another emerging trend is the development of naturally derived antibacterial compounds that aim for targets novel areas, including engineered bacteriophages, probiotics, metal-based antibacterial agents, odilorhabdins, quorum sensing inhibitors, and microbiome-modifying agents. This review focuses on the current status of alternative treatment regimens against multidrug-resistant Gram-negative bacteria, aiming to provide a snapshot of the situation and some information on the broader context.

Correlation between human gut microbiome and diseases.

Human gut microbiome is a major source of human bacterial population and a significant contribution to both positive and harmful effects. Due to its involvement in a variety of interactions, gut microorganisms have a great impact on our health throughout our lives. The impact of gut microbial population is been studied intensively in last two decades. Extensive literature survey focusing developments in the field were searched in English language Electronic Databases like PubMed, Google Scholar, Pubag, Google books, and Research Gate were mostly used to understand the role of human gut mirobiome and its role in different human diseases. Gut microbiome in healthy subjects differs from those who suffer from diseases. Type 2 diabetes, obesity, non-alcoholic liver disease, and cardiometabolic diseases have all been linked to dysbiosis of the gut microbiota. Pathogenesis of many disorders is also linked to changes in gut microbiota. Other diseases like cancer, arithritis, autism, depression, anxiety, sleep disorder, HIV, hypertension, and gout are also related to gut microbiota dysbiosis. We focus in this review on recent studies looking into the link between gut microbiome dysbiosis and disease etiology. Research on how gut microbiota affects host metabolism has been changed in past decades from descriptive analyses to high throughput integrative omics data analysis such as metagenomics and metabolomics. Identification of molecular mechanisms behind reported associations is been carried out in human, animals, and cells for measure of host physiology and mechanics. Still many the mechanisms are not completely understood.

Biochemical Characterization of a Mycobacteriophage Derived DnaB Ortholog Reveals New Insight into the Evolutionary Origin of DnaB Helicases.

The bacterial replicative helicases known as DnaB are considered to be members of the RecA superfamily. All members of this superfamily, including DnaB, have a conserved C- terminal domain, known as the RecA core. We unearthed a series of mycobacteriophage encoded proteins in which the RecA core domain alone was present. These proteins were phylogenetically related to each other and formed a distinct clade within the RecA superfamily. A mycobacteriophage encoded protein, Wildcat Gp80 that roots deep in the DnaB family, was found to possess a core domain having significant sequence homology (Expect value < 10-5) with members of this novel cluster. This indicated that Wildcat Gp80, and by extrapolation, other members of the DnaB helicase family, may have evolved from a single domain RecA core polypeptide belonging to this novel group. Biochemical investigations confirmed that Wildcat Gp80 was a helicase. Surprisingly, our investigations also revealed that a thioredoxin tagged truncated version of the protein in which the N-terminal sequences were removed was fully capable of supporting helicase activity, although its ATP dependence properties were different. DnaB helicase activity is thus, primarily a function of the RecA core although additional N-terminal sequences may be necessary for fine tuning its activity and stability. Based on sequence comparison and biochemical studies we propose that DnaB helicases may have evolved from single domain RecA core proteins having helicase activities of their own, through the incorporation of additional N-terminal sequences.

The mycobacteriophage D29 gene 65 encodes an early-expressed protein that functions as a structure-specific nuclease.

The genomes of mycobacteriophages of the L5 family, which includes the lytic phage D29, contain several genes putatively linked to DNA synthesis. One such gene is 65, which encodes a protein belonging to the RecA/DnaB helicase superfamily. In this study a recombinant version of the mycobacteriophage D29 gp65 was functionally characterized. The results indicated that it is not a helicase as predicted but an exonuclease that removes 3' arms from forked structures in an ATP-dependent manner. The gp65 exonuclease acts progressively from the 3' end, until the fork junction is reached. As it goes past, its progress is stalled over a stretch of seven to eight nucleotides immediately downstream of the junction. It efficiently acts on forked structures with single stranded arms. It also acts upon 5' and 3' flaps, though with somewhat relaxed specificity, but not on double-stranded forks. Sequence comparison revealed the presence of a KNRXG motif in the C-terminal half of the protein. This is a conserved element found in the RadA/Sms family of DNA repair proteins. A mutation (R203G) in this motif led to complete loss of nuclease activity. This indicated that KNRXG plays an important role in the nuclease function of not only gp65, but possibly other RadA/Sms family proteins as well. This is the first characterization of a bacteriophage-derived RadA/Sms class protein. Given its mode of action, it is very likely that gp65 is involved in processing branched replication intermediates formed during the replication of phage DNA.