Detecting Bacterial Species from Ancient Human Skeletal Samples

This paleopathological study aims to identify Mycobacterium tuberculosis complex (MTBC), Mycobacterium avium complex (MAC) and other Mycobacterium species in silico from skeletal samples that belonged to 28 Polish individuals in the Neolithic period under PRJNA422903 from the Sequence Read Archive (SRA). After next-generation sequencing (NGS), bioinformatics methods are heavily relied upon for identification of pathogens from complex samples. We implemented a bioinformatics pipeline, with custom-built databases, utilizing the following software tools: Trim Galore! and Kraken2. After adapter trimming, Kraken2 was used for taxonomic classifications. We have found that Mycobacterium is present in all 28 individuals. The average percentage of MAC present in the genus Mycobacterium, in all 28 individuals, is 6%. Reads from MTBC makes up an average of 7% of the Mycobacterium genus. We have identified previously unreported strains of MTBC and MAC such as Mycobacterium tuberculosis XDR1219, which is an extensively drug-resistance strain. Our analysis also revealed 14.8% of reads from MTBC belong to Mycobacterium avium hominissuis, which was commonly found in humans and pigs. Additionally, strains of Mycobacterium simiae complex were also discovered. Mycobacterium simiae has been commonly found among immunocompromised individuals. In conclusion, our bioinformatics pipeline has been more effective than other published approaches. This approach broadens the potential scope of paleoepidemiology both to older, sub-optimally preserved samples and to pathogens with difficult intrageneric taxonomy. It is therefore suitable for other studies in paleopathology using NGS technologies

Detecting bacterial species from ancient human skeletal samples

Diagnosis of tuberculosis (TB) via morphological analysis is difficult and often inconsistent. With next-generation sequencing (NGS), ancient host microbiomes can be subjected to metagenomic analyses for the detection of TB in silico. Suitable bioinformatic workflows are needed for reliable ancient DNA (aDNA) analysis of causative agents. This study aims to enhance available bioinformatic screening methods to create more suitable bioinformatic processes and generate insights in relation to TB. This research utilizes publicly available NGS data accessed through the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI). Initial quality control steps included adapter trimming with Trim Galore!. Kraken2 was then used for taxonomic classification with a custom-built database comprised of Mycobacterial genomes from the NCBI. Quantitation and visualization were carried out with Bracken and Krona, respectively. Our workflow was first applied to 28 Neolithic skeletons (SRA number PRJNA422903) representing the Middle Neolithic Brześć Kujawski Group of the Lengyel culture (∼4400–4000 BC, 26 individuals), and the Late Neolithic Globular Amphora culture (∼3100–2900 BC, 2 individuals). Three additional datasets have since been utilized in this research: mummified remains of 265 individuals from Hungary (1731–1838 CE; PRJNA795622), one calcified lung nodule from Lund, Sweden (17th century; PRJNA517266); and dental calculus of four individuals from the Iberian Peninsula (4500-5000 BP; PRJEB46022). Preliminary results for the 28 Neolithic skeletons revealed an average of 7% of the Mycobacterium genus sequencing reads mapping to Mycobacterium tuberculosis complex (MTBC) among all individuals. This work also revealed additional species of MTBC and Mycobacterium avium complex (MAC) that were previously unreported by the originator of datasets, including the extensively drug-resistant (XDR) Mycobacterium tuberculosis XDR1219 and Mycobacterium avium hominissuis. Our bioinformatic workflow has therefore been more effective than previously published approaches and is suitable for future paleopathological studies

Protein secretion systems in bacterial-host associations, and their description in the Gene Ontology

Protein secretion plays a central role in modulating the interactions of bacteria with their environments. This is particularly the case when symbiotic bacteria (whether pathogenic, commensal or mutualistic) are interacting with larger host organisms. In the case of Gram-negative bacteria, secretion requires translocation across the outer as well as the inner membrane, and a diversity of molecular machines have been elaborated for this purpose. A number of secreted proteins are destined to enter the host cell (effectors and toxins), and thus several secretion systems include apparatus to translocate proteins across the plasma membrane of the host also. The Plant-Associated Microbe Gene Ontology (PAMGO) Consortium has been developing standardized terms for describing biological processes and cellular components that play important roles in the interactions of microbes with plant and animal hosts, including the processes of bacterial secretion. Here we survey bacterial secretion systems known to modulate interactions with host organisms and describe Gene Ontology terms useful for describing the components and functions of these systems, and for capturing the similarities among the diverse systems

Genomic sequence of temperate phage Smp131 of Stenotrophomonas maltophilia that has similar prophages in xanthomonads

Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacterium previously named as Xanthomonas maltophilia. This organism is an important nosocomial pathogen associated with infections in immunocompromised patients. Clinical isolates of S. maltophilia are mostly resistant to multiple antibiotics and treatment of its infections is becoming problematic. Several virulent bacteriophages, but not temperate phage, of S. maltophilia have been characterized

Mean structure and fluctuations of the Kuroshio east of Taiwan from in situ and remote observations

Author Posting. © The Oceanography Society, 2015. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 28, no. 4 (2015): 74–83, doi:10.5670/oceanog.2015.83.The Kuroshio is important to climate, weather prediction, and fishery management along the northeast coast of Asia because it transports tremendous heat, salt, and energy from east of the Philippines to waters southeast of Japan. In the middle of its journey northward, the Kuroshio’s velocity mean and its variability east of Taiwan crucially affect its downstream variability. To improve understanding of the Kuroshio there, multiple platforms were used to collect intensive observations off Taiwan during the three-year Observations of the Kuroshio Transports and their Variability (OKTV) program (2012–2015). Mean Kuroshio velocity transects show two velocity maxima southeast of Taiwan, with the primary velocity core on the onshore side of the Kuroshio exhibiting a mean maximum velocity of ~1.2 m s–1. The two cores then merge and move at a single velocity maximum of ~1 m s–1 east of Taiwan. Standard deviations of both the directly measured poleward (v) and zonal (u) velocities are ~0.4 m s–1 in the Kuroshio main stream. Water mass exchange in the Kuroshio east of Taiwan was found to be complicated, as it includes water of Kuroshio origin, South China Sea Water, and West Philippine Sea Water, and it vitally affects heat, salt, and nutrient inputs to the East China Sea. Impinging eddies and typhoons are two of the principal causes of variability in the Kuroshio. This study’s models are more consistent with the observed Kuroshio than with high-frequency radar measurements.This study was sponsored by the Ministry of Science and Technology (MOST) of the ROC (Taiwan) under grants NSC 101-2611-M-002-018-MY3, NSC 101-2611- M-019-002, NSC 102-2611-M-002-017, NSC 102-2611- M-019-012, MOST 103-2611-M-002-014, and MOST 103-2611-M-002-018. MA was sponsored by the US Office of Naval Research under grant N00014- 12-1-0445. YHT was supported by NSF Earth System Model (EaSM) Grant 1419292

Comparison of antipsychotic dose equivalents for acute bipolar mania and schizophrenia

Are antipsychotic dose equivalents between acute mania and schizophrenia the same? Study selection and analysis Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre–post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia. Findings We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: −022, 95% CI −0.41 to –0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, –8.1%) and risperidone (p<0.001, –15.8%). Conclusions Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes

Trial sequential analysis and updated meta-analysis of fluvoxamine on clinical deterioration in adult patients with symptomatic COVID-19 infection

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59–1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56–1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified

Variability and efficacy in treatment effects on manic symptoms with lithium, anticonvulsants, and antipsychotics in acute bipolar mania: A systematic review and meta-analysis

Background: Acute mania is a psychiatric emergency requiring rapid management. However, randomised controlled trials (RCTs) have shown considerable individual differences in treatment effects on manic symptoms with antimanic drugs. Methods: We searched the MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov to identify RCTs without language restrictions from inception to April 19, 2022. We included double-blind RCTs of oral antimanic monotherapy versus placebo in adult patients. The primary outcome was variability in improvement of manic symptoms (assessed using the coefficient of variation ratio [CVR]). The secondary outcomes were overall improvement of manic symptoms and acceptability (i.e., discontinuation for any reason). The pooled effects of outcomes were calculated by random-effects meta-analyses using restricted maximum likelihood methods. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) Assessment Tool. This study was registered with OSF (DOI:10.17605/OSF.IO/G4JNY). Findings: We included 39 RCTs (N=12150; mean age=39·9 years, interquartile range [IQR]=38·7-41·1; mean proportion of female=48·6%, IQR=42·3%-52·3%) and investigated 14 antimanic drugs. We found that eight antimanic drugs compared to placebo were associated with lower CVRs (95% confidence interval [CI]; I2), including risperidone (0·51; 0·37-0·70; 0%), haloperidol (0·54; 0·44-0·67; 4%), olanzapine (0·59; 0·44-0·79; 47%), ziprasidone (0·61; 0·53-0·71; 0%), lithium (0·63; 0·52-0·76; 0%), quetiapine (0·65; 0·48-0·87; 2%), aripiprazole (0·68; 0·56-0·84; 25%), and cariprazine (0·70; 0·49-0·99; 28%). There were nine antimanic drugs associated with greater efficacy than placebo, including risperidone (reported as standardised mean difference; 95% CI; I2: 0·64; 0·31-0·97; 15%), haloperidol (0·57; 0·29-0·85; 64%), cariprazine (0·51; 0·24-0·78; 0%), olanzapine (0·44; 0·30-0·58; 0%), lithium (0·42; 0·29-0·55; 0%), ziprasidone (0·42; 0·26-0·58; 0%), quetiapine (0·40; 0·13-0·67; 0%), asenapine (0·40; 0·13-0·67; 0%), and aripiprazole (0·32; 0·14-0·49; 53%). Ziprasidone (reported as risk ratio; 95% CI; I2: 0·83; 0·79-0·89; 0%) and olanzapine (0·63; 0·49-0·80; 35%) were associated with better acceptability relative to placebo. Among the 39 RCTs, none had a high ROB. Interpretation: We demonstrated that eight antimanic drugs were associated with lower variability and better efficacy than placebo, suggesting that these antimanic drugs were associated with more homogenous and predictable improvements of manic symptoms in patients with acute mania

Treatment efficacy and acceptability of pharmacotherapies for dementia with lewy bodies: a systematic review and network meta-analysis

Introduction We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms (NPS), cognitive function, motor symptoms, and acceptability. Methods Electronic databases were searched from inception through June 5, 2019, for randomized controlled trials (RCTs) and open-label trials (OLTs) in patients with DLB. We performed a pairwise conventional meta-analysis (PWMA) and network meta-analysis (NMA) within a frequentist framework. The main outcomes were mean change scores in NPS, general cognition, motor symptoms and acceptability. The effect sizes and odds ratios with 95% confidence intervals (CIs) were calculated. This study was registered with PROSPERO (CRD42018096996). Results In total, we included 29 studies (9 RCTs and 20 OLTs). In the NMA with 9 RCTs, both high- (mean difference [MD] 2.00, 95% CIs, 0.69 to 3.31) and low-dose (1.86, 0.58 to 3.15) donepezil were associated with a greater cognitive improvement than placebo. High-dose zonisamide was associated with greater motor symptom improvement ( -4.10, -7.03 to -1.17]). No medications reached statistical significance regarding improving neuropsychiatric symptoms or developing intolerable adverse effects as compared to placebo. In the second NMA, with 29 studies as an exploratory analysis, aripiprazole and yokukansan may be effective for neuropsychiatric symptoms, while levodopa may be associated with cognitive impairment. Conclusions We report the most comprehensive evidence for the selection of pharmacotherapy for treating different clusters of DLB-related symptoms. Due to the limited availability of RCTs on DLB, more well-conducted RCTs are needed for MMA to warrant clinical efficacy in the future